Brodmann Areas
What Are Brodmann Areas?
Brodmann areas represent a foundational anatomical framework for understanding the structural and functional organization of the cerebral cortex. Introduced by German neurologist Korbinian Brodmann in 1909, these regions were delineated based on cytoarchitectonic criteria, including the size, density, layering, and distribution of neuronal types within the cortical column (Brodmann, 1909). By systematically examining histological sections of the cerebral cortex from humans and other mammals, Brodmann identified 43 distinct cortical areas, each assigned a numerical label. His work laid the groundwork for correlating anatomical structure with functional specialization in the human brain.
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Although Brodmann’s original atlas was based solely on microscopic observations of cell structure, many of the regions he described have since been validated and functionally characterized using modern techniques. These include magnetic resonance imaging (MRI), positron emission tomography (PET), and invasive electrophysiological recordings. Recent cytoarchitectonic analyses by Zilles and Amunts (2010) have refined Brodmann’s boundaries and confirmed the interspecies validity of several regions. While newer parcellation methods now integrate multimodal imaging data, the Brodmann nomenclature remains widely used in clinical neuroscience, neuroimaging research, and surgical mapping due to its practical and historical significance.
The Importance of Brodmann Areas
The classification of cortical tissue into Brodmann areas has greatly advanced the understanding of functional specialization in the brain. Each Brodmann area tends to correspond to specific physiological and behavioral functions, often aligning with regions identified through lesion studies and neuroimaging. For example, area 4 corresponds to the primary motor cortex, area 17 to the primary visual cortex, and areas 44 and 45 to Broca’s area, essential for speech production and syntactic processing. These designations continue to guide functional localization in cognitive neuroscience, brain mapping, and neurosurgical planning.
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Contemporary neuroscience acknowledges that functional processes are distributed across networks rather than confined to discrete regions. However, Brodmann areas offer a useful anchor point for mapping these networks. Large-scale initiatives such as the Human Connectome Project have expanded upon Brodmann’s framework by combining structural, functional, and connectivity data to generate high-resolution cortical parcellations (Glasser et al., 2016). These modern atlases include over 180 distinct cortical areas per hemisphere and demonstrate that many Brodmann areas are themselves functionally heterogeneous.
While Brodmann’s system does not capture the full complexity of cortical connectivity, laminar-specific functions, or interindividual variability, it remains a critical entry point into understanding cerebral organization. As neuroimaging resolution and analytical methods continue to evolve, Brodmann areas serve as a bridge between classical neuroanatomy and cutting-edge systems neuroscience.
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Researchers have revised the Brodmann maps and correlated areas with their functions. The Brodmann maps below were contributed by Mark Dow, Research Assistant at the Brain Development Lab at the University of Oregon, to Wikimedia Commons.
Areas 3, 1, and 2: Primary Somatosensory Cortex (S1)
The primary somatosensory cortex (S1) comprises Brodmann areas 3, 1, and 2, and serves as the principal cortical region for processing somatosensory input. These areas play essential roles in the perception of tactile stimuli, proprioception, and, to a lesser extent, temperature and nociception.
S1 is characterized by a highly organized somatotopic representation of the body surface, often referred to as the sensory homunculus, in which adjacent cortical regions correspond to adjacent areas of the body (Penfield & Boldrey, 1937; Purves et al., 2018). Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann areas 3, 1, and 2, though collectively forming the S1, exhibit distinct cytoarchitectural and functional characteristics. BA3, located adjacent to the central sulcus, is subdivided into 3a and 3b.
Area 3b is regarded as the primary cortical recipient of somatosensory input from the thalamus, particularly from the ventroposterior complex. It processes cutaneous stimuli with high spatial resolution, while 3a is more involved in processing proprioceptive information from muscle spindles (Kaas, 2008; Mountcastle, 1997).
BA1 receives input predominantly from 3b and is thought to refine the processing of texture and direction of stimulus movement. BA2 is involved in higher-order integration of tactile and proprioceptive input, particularly in the discrimination of object shape and size (Padberg et al., 2009).
Location
Anatomically, the primary somatosensory cortex is situated in the postcentral gyrus of the parietal lobe, directly posterior to the central sulcus. It is flanked anteriorly by the primary motor cortex (M1) and posteriorly by the secondary somatosensory cortex (S2) and the superior parietal lobule.
The region corresponds roughly to the C3 and C4 positions in the international 10–20 EEG system, which overlie the central sulcus and its adjacent gyri (Jasper, 1958). The precise cortical mapping within S1 reflects the density of sensory receptors in different body parts, with disproportionate representation of regions such as the lips, hands, and face.
Connections
S1 is extensively connected to both cortical and subcortical regions. It maintains reciprocal connections with M1, the premotor cortex, the supplementary motor area (SMA), and the posterior parietal cortex, facilitating sensorimotor integration essential for voluntary movement and spatial awareness (Lemon, 2008).
Subcortical afferents arise primarily from the ventroposterior lateral (VPL) and ventroposterior medial (VPM) nuclei of the thalamus.
Additionally, S1 projects to and receives input from S2, the insular cortex, and higher-order somatosensory association areas, enabling complex perceptual functions such as stereognosis and haptic object recognition.
Participation in brain networks
Functionally, the primary somatosensory cortex is a central node within the somatosensory network, which includes the secondary somatosensory cortex, insula, and parietal operculum. It is also integrally involved in the broader sensorimotor network, which encompasses motor and premotor regions and supports coordinated voluntary action.
Resting-state and task-based functional neuroimaging studies have demonstrated that S1 is dynamically engaged during both passive sensory input and active motor tasks, indicating its involvement in both perception and predictive motor coding (Sepulcre et al., 2012; Fox et al., 2006).
Functions
The primary somatosensory cortex is critical for the conscious perception of mechanical stimuli, including light touch, pressure, vibration, and texture. It also processes proprioceptive input regarding limb position and movement.
Through integration across BAs 3, 1, and 2, S1 enables complex sensory functions such as the localization of stimuli, two-point discrimination, and the perception of object form and surface properties. These functions are essential for interactions with the environment and for guiding motor responses. The integrity of S1 is also vital for body schema, spatial attention, and fine motor coordination.
Role in clinical disorders
Disruption of the somatosensory cortex has been implicated in a variety of neurological and neuropsychiatric conditions. Lesions in BA3, 1, or 2 can result in contralateral sensory deficits such as astereognosis, agraphesthesia, and loss of proprioception.
In patients with neuropathic pain, functional reorganization of S1 has been associated with hyperexcitability and altered somatotopic maps, potentially contributing to persistent pain states (Baliki et al., 2011).
In individuals with phantom limb pain, neuroimaging studies have demonstrated that somatosensory representations of the missing limb may persist or be reorganized, leading to maladaptive cortical plasticity (Makin et al., 2013).
Stroke involving the postcentral gyrus may result in hemisensory loss or sensory neglect, with outcomes dependent on lesion size and location (Carey et al., 2002).
Furthermore, developmental abnormalities in S1 structure or connectivity have been observed in disorders such as autism spectrum disorder and cerebral palsy, underscoring the importance of S1 in early sensory development and integration.
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Latest findings
Recent human research has significantly expanded our understanding of Brodmann areas 3, 1, and 2 within the primary somatosensory cortex (S1), challenging the traditional view of S1 as a purely feedforward sensory processor. High-resolution neuroimaging techniques, including 7-Tesla fMRI and layer-specific analyses, have demonstrated that S1 is subject to top-down modulation from motor and prefrontal regions, indicating active involvement in attention, prediction, and perceptual decision-making (Lawrence et al., 2018; Yu et al., 2019).
Notably, BA2 has emerged as a site for multisensory integration and higher-order perceptual functions, such as body ownership and spatial cognition (Ruben et al., 2021). Functional connectivity studies also reveal extensive communication between S1 and the insula, suggesting a role in interoceptive processing (Kuehn et al., 2016).
Cortical plasticity in S1 has also become a major focus of recent research. Studies in amputees and individuals with congenital limb absence have shown that somatotopic reorganization is driven more by functional relevance than anatomical adjacency, supporting an experience-dependent model of S1 organization (Striem-Amit et al., 2018; Muret & Makin, 2022). Moreover, machine learning applied to fMRI data has enabled decoding of fine tactile features—such as vibration frequency and edge orientation—from distributed activity patterns within S1, underscoring its representational precision and potential for neuroprosthetic applications (Wiestler & Diedrichsen, 2021). Collectively, these findings support a reconceptualization of areas 3, 1, and 2 as dynamic, integrative hubs involved in both perception and active sensorimotor computation.
Area 4: Primary Motor Cortex (M1)
The primary motor cortex (M1) is a key region in the brain responsible for the execution of voluntary movements. It serves as the final cortical output center for motor commands directed to the spinal cord, where these instructions are translated into coordinated muscle contractions. Functional neuroimaging and electrophysiological studies confirm that M1 plays a predominant role not only in motor execution but also in the dynamic modulation of motor output in response to sensory and cognitive inputs. Graphic © Big8/Shutterstock.com.
Brodmann areas
The M1 is located in the precentral gyrus, primarily corresponding to Brodmann area 4.
It contains large pyramidal neurons known as Betz cells, which are among the largest neurons in the human nervous system and contribute directly to the corticospinal tract, particularly for fine control of distal extremities (Geyer et al., 1996).
Area 4 is cytoarchitectonically distinct due to its agranular structure, lacking a defined layer IV, and exhibiting a dense layer V populated by these projection neurons.
Location
The M1 is situated in the frontal lobe, immediately anterior to the central sulcus. It is bordered posteriorly by the primary somatosensory cortex (S1, Brodmann areas 1, 2, and 3) and anteriorly by the premotor cortex (area 6).
Scalp coordinates C3 and C4 in the international 10–20 EEG system approximate the hand representation areas within the M1 (Jasper, 1958). This topographic representation allows for somatotopic motor control, with the medial portion controlling lower limbs and the lateral portion governing upper limb and facial musculature.
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Connections
The M1 maintains extensive bidirectional connectivity with multiple cortical and subcortical structures, including the S1, premotor cortex, supplementary motor area (SMA), posterior parietal cortex, basal ganglia, cerebellum, and thalamic nuclei (Lemon, 2008). These connections are fundamental for the real-time integration of sensory input and motor planning. For instance, afferent signals from S1 inform M1 about limb position and tactile input, while efferents from M1 convey motor instructions via corticospinal and corticobulbar tracts.
Participation in brain networks
The M1 is a principal node within the sensorimotor network, functioning in conjunction with adjacent motor-related cortical regions, including the SMA, premotor cortex, and somatosensory cortices. Resting-state and task-based fMRI studies demonstrate that M1 maintains synchronized activity patterns with these regions, facilitating coordinated motor behavior and sensorimotor adaptation (Sepulcre, 2012). Disruptions in this network are associated with impaired motor control in various neurologic conditions.
Functions
The primary function of M1 is the execution of voluntary movements through the activation of lower motor neurons in the spinal cord. Importantly, M1 neurons encode specific parameters of movement such as direction, force, and velocity. They tend to control coordinated movement patterns rather than isolated muscle contractions (Breedlove & Watson, 2023).
Furthermore, M1 contributes to the initial stages of motor learning and adapts motor output based on proprioceptive and visual feedback, particularly during complex and skilled motor tasks.
Role in clinical disorders
Alterations in M1 function have been implicated in numerous neurologic disorders. After stroke, particularly in cases involving middle cerebral artery territory infarcts, M1 exhibits reduced excitability and altered interhemispheric balance, contributing to motor deficits and hemiparesis (Ward, 2004).
In Parkinson’s disease, M1 exhibits abnormal oscillatory activity and impaired functional connectivity with basal ganglia and SMA, underlying the clinical manifestations of bradykinesia and rigidity (Wu & Hallett, 2013).
In motor neuron diseases such as ALS, early pathological changes in M1, including corticospinal degeneration and cortical hyperexcitability, have been documented, even prior to the onset of overt muscle weakness (Kew & Leigh, 1997).
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Latest findings
​Recent studies have emphasized the role of M1 neuroplasticity in post-injury recovery
and rehabilitation. Functional MRI and transcranial magnetic stimulation (TMS) have shown that targeted rehabilitation protocols can induce reorganization within M1, leading to improved motor function in stroke patients (Blicher et al., 2021). Additionally, modulation of M1 excitability through non-invasive brain stimulation, such as repetitive TMS or transcranial direct current stimulation (tDCS), has demonstrated promise in enhancing motor recovery and compensating for interhemispheric imbalances in stroke and Parkinsonian syndromes.
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Emerging research also implicates early M1 dysfunction in the preclinical stages of ALS. Advanced neuroimaging techniques, including ultra-high field MRI, reveal cortical thinning and reduced M1 connectivity before lower motor neuron signs become evident (Menke et al., 2018). Moreover, abnormal cortical excitability assessed via TMS is considered a potential biomarker for ALS diagnosis and disease progression monitoring. These findings highlight M1 not only as a key execution center but also as a sensitive site for pathological processes in neurodegenerative conditions.
Areas 5 and 7: Somatosensory Association Cortex (SAC)
The somatosensory association cortex (SAC) plays a central role in the higher-order processing, integration, and interpretation of somatosensory inputs transmitted from the primary somatosensory cortex (S1). It contributes to the conscious perception of complex sensory attributes such as object shape, texture, spatial position, and proprioceptive state. The SAC is essential for translating raw sensory input into coherent perceptual experiences that guide motor planning and interaction with the environment. Graphic © Big8/Shutterstock.com.
Brodmann areas
The SAC is primarily localized within Brodmann areas 5 and 7, both situated in the superior parietal lobule of the posterior parietal cortex.
Area 5 is immediately posterior to S1 and is involved in early stages of somatosensory integration, while area 7 lies more dorsally and contributes to visuomotor coordination and spatial representation (Culham & Kanwisher, 2001). These areas are densely interconnected and exhibit somatotopic organization, albeit less precise than that of S1.
Location
The SAC resides in the parietal lobe, superior and posterior to the postcentral gyrus. It lies medial to the intraparietal sulcus and dorsal to the supramarginal and angular gyri.
The closest 10–20 EEG system landmarks are P3 and P4, which approximate the bilateral parietal cortices.
The superior parietal lobule, where the SAC is concentrated, serves as a transitional zone between purely sensory regions and multimodal association areas involved in cognition and attention.
Connections
The SAC exhibits extensive connectivity with both cortical and subcortical regions. It is reciprocally connected to S1, primary motor cortex (M1), premotor cortex, supplementary motor area (SMA), visual association areas, and the thalamus (Cavada & Goldman-Rakic, 1989).
These connections facilitate the transformation of sensory inputs into motor-relevant information. For example, afferent projections from S1 carry tactile and proprioceptive information, while efferent outputs to M1 and premotor areas enable sensorimotor coordination.
Additionally, connections with the cerebellum and basal ganglia contribute to spatial-temporal aspects of movement planning.
Participation in brain networks
The SAC functions as an integral node within the broader somatosensory network, which includes S1, secondary somatosensory cortex (S2), insular cortex, and the thalamus.
Furthermore, it is a prominent component of the dorsal attention network, which governs top-down spatial attention, visual-motor transformations, and attentional shifts to tactile stimuli (Corbetta & Shulman, 2002). This network allows for dynamic integration of sensory cues with attentional states, essential for goal-directed behavior.
Functions
The SAC is responsible for integrating tactile, proprioceptive, and visual information to form internal representations of the body and extrapersonal space. This integration is critical for somatosensory discrimination, limb position sense, spatial orientation, and object manipulation.
It plays a key role in body schema, enabling individuals to perceive their body parts in space relative to one another and to external objects. The SAC is also implicated in sensorimotor transformations necessary for reaching and grasping, especially under visual guidance.
Role in clinical disorders
Dysfunction of the SAC has been implicated in numerous neurological and neurodevelopmental conditions. Lesions involving Brodmann areas 5 or 7 can result in contralateral hemispatial neglect, particularly when the right hemisphere is affected, leading to profound deficits in attention and awareness of one side of space (Vallar et al., 2003).
Impairments in SAC function have also been associated with deficits in tactile object recognition (astereognosis), impaired proprioception, and disordered sensorimotor integration, particularly in stroke and traumatic brain injury patients.
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Latest findings
Recent studies have further implicated SAC dysfunction in developmental disorders. Functional MRI analyses have shown aberrant activation patterns and connectivity of the posterior parietal cortex in individuals with autism spectrum disorder (ASD), particularly during tasks involving tactile discrimination and spatial attention (Cascio et al., 2012).
Moreover, research in rodent and primate models has demonstrated that area 5/7 homologs are involved in allocentric spatial mapping and coordinate transformations essential for goal-directed movements (Whitlock et al., 2012). These findings suggest that SAC abnormalities may contribute not only to sensory processing deficits but also to broader impairments in motor planning and social perception observed in neurodevelopmental and neuropsychiatric conditions.
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Emerging neuroimaging and electrophysiological studies continue to refine our understanding of SAC's involvement in sensorimotor integration and attention. For instance, high-resolution fMRI and magnetoencephalography (MEG) have revealed temporally dynamic patterns of SAC activation during multisensory integration tasks, indicating its role in rapid cross-modal processing.
In disorders such as Alzheimer’s disease and posterior cortical atrophy, SAC dysfunction correlates with early visuospatial impairments, further underscoring its significance in spatial cognition and perceptual awareness (Crutch et al., 2012). These insights offer potential avenues for diagnostic and therapeutic interventions targeting parietal association regions.
Area 6: Supplementary Motor Cortex and Premotor Cortex
The supplementary motor area (SMA) and premotor cortex (PMC) are critical components of the motor control system, involved in the planning, initiation, and coordination of voluntary movements.
These areas contribute to both internally guided and externally cued motor behaviors, acting as intermediaries between higher-order cognitive processes and the execution mechanisms of the primary motor cortex (M1).
They are integral to sensorimotor transformation, motor learning, and action selection in both unimanual and bimanual tasks. Graphic © Big8/Shutterstock.com.
Brodmann areas
Both the SMA and PMC are part of Brodmann area 6, although they occupy distinct anatomical subregions.
The SMA is located medially, on the superior frontal gyrus just anterior to the paracentral lobule and above the cingulate sulcus (Picard & Strick, 2001). It is further subdivided into the pre-SMA (anterior portion) and SMA proper (posterior portion), which have distinct connectivity and functional profiles.
In contrast, the PMC lies laterally on the superior and middle frontal gyri, anterior to M1, and includes dorsal and ventral subdivisions (Wise et al., 1997). These subdivisions are functionally specialized for different types of motor planning.
Location
The SMA resides in the medial wall of the frontal lobe and is oriented along the longitudinal fissure, extending from the anterior paracentral lobule to the rostral superior frontal gyrus.
The PMC, by contrast, is situated on the lateral convexity of the frontal lobe, immediately anterior to the precentral gyrus and posterior to the prefrontal cortex.
Scalp EEG sites FC3 and FC4 approximate the lateral aspects of the premotor cortex.
The precise localization of SMA and PMC is essential for neurosurgical planning and for targeting neuromodulatory interventions such as transcranial magnetic stimulation (TMS).
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Connections
The SMA and PMC are extensively interconnected with motor, premotor, somatosensory, parietal, and prefrontal cortices, as well as with subcortical structures such as the basal ganglia, thalamus, and cerebellum (Lemon, 2008; Nachev et al., 2008).
The SMA has dense projections to M1 and the spinal cord and is reciprocally connected with the pre-SMA and anterior cingulate cortex. It receives input from the basal ganglia via the thalamus, which contributes to the initiation and suppression of voluntary movement.
The PMC, particularly its ventral subdivision, receives inputs from the posterior parietal cortex and visual areas, allowing it to play a role in visually guided action planning and execution.
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Participation in brain networks
Both the SMA and PMC function as integral nodes in the broader sensorimotor and frontoparietal networks.
The SMA is closely associated with the cingulo-opercular network and contributes to motor initiation, error monitoring, and action inhibition. It also plays a role in bimanual coordination and internally generated sequences.
The PMC, especially in its dorsal aspect, is strongly connected to the dorsal attention and visuomotor networks, integrating spatial and visual information for guided movement execution (Sepulcre, 2012). These motor association areas are also dynamically involved in plasticity and network reorganization during recovery from neurological injury.
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Functions
The SMA is essential for the initiation and sequencing of internally driven motor actions. It contributes to the temporal organization of complex, learned motor behaviors, particularly in the absence of external stimuli.
The pre-SMA, in particular, is involved in higher-order functions such as decision-making and action selection.
In contrast, the PMC is primarily involved in the planning and execution of movements that are externally guided, particularly those involving sensorimotor transformations based on visual or auditory cues (Wise et al., 1997; Picard & Strick, 2001).
The dorsal PMC is implicated in reaching and grasping, while the ventral PMC contributes to hand shaping and object manipulation.
Role in clinical disorders
Dysfunction in the SMA and PMC has been implicated in a wide range of motor and cognitive disorders.
In Parkinson's disease, SMA hypoactivity is associated with bradykinesia and impaired self-initiated movement, likely due to disrupted basal ganglia-SMA connectivity (Wu & Hallett, 2013).
Lesions of the SMA may result in SMA syndrome, characterized by transient akinesia and speech deficits, with gradual recovery due to contralateral compensation.
The PMC is critically involved in praxis; damage to this region, especially in the dominant hemisphere, can result in ideomotor apraxia, characterized by impaired execution of learned skilled movements despite preserved strength and comprehension (Haaland et al., 2000).
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Latest findings
Recent neuroimaging studies have further delineated the distinct roles of the SMA and PMC in post-stroke motor recovery. Functional MRI and diffusion tensor imaging have shown that increased connectivity and recruitment of contralesional premotor regions, especially the dorsal PMC, correlate with better motor outcomes in patients with corticospinal tract injury (Rehme et al., 2012).
Moreover, non-invasive brain stimulation targeting the SMA and PMC has been shown to modulate cortical excitability and enhance motor performance in both healthy individuals and those with neurological disorders, supporting their roles in neuroplasticity and rehabilitation (Cao et al., 2020).
Advances in connectomics and electrophysiology have also illuminated the SMA’s role in motor inhibition and cognitive control. Abnormal pre-SMA activity has been linked to disorders of volition and impulse control, including obsessive-compulsive disorder and Tourette syndrome.
The PMC, especially its ventral component, is now recognized for its involvement in mirror neuron systems and social motor cognition, suggesting a broader role in empathy and imitation-related behaviors. These insights not only refine our understanding of the motor system but also open new avenues for targeted therapeutic interventions.
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Area 8: Frontal Eye Field (FEF)
The frontal eye field (FEF) is a critical cortical region involved in the voluntary control of eye movements and the modulation of visual attention. It contributes to the selection of visual targets and coordinates gaze shifts via saccadic and smooth pursuit eye movements.
The FEF also plays an integrative role in attention orientation and is essential for visuomotor planning and decision-making processes related to visual stimuli. Its function is tightly coupled with both sensorimotor and cognitive systems, enabling adaptive, goal-directed behavior in dynamic environments. Graphic © Big8/Shutterstock.com.
Brodmann areas
The FEF is located within Brodmann area 8, specifically in its caudal portion, which occupies the anterior bank of the precentral sulcus in the dorsolateral prefrontal cortex (Paus, 1996).
Although traditionally confined to area 8, functional imaging and intracranial stimulation studies have demonstrated that the FEF extends into adjacent parts of areas 6 and 9, reflecting the functional diversity and topographic heterogeneity of this region. It contains neurons that exhibit activity related to saccadic planning, visual target selection, and attention modulation.
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Location
Anatomically, the FEF is situated in the dorsal part of the prefrontal cortex, just anterior to the primary motor cortex (M1) and bordering the premotor cortex. It lies within the anterior bank of the precentral sulcus on the middle frontal gyrus.
EEG scalp coordinates F3 and F4 approximate its bilateral locations in the dorsolateral prefrontal cortex.
The medial-lateral and rostral-caudal organization of the FEF supports distinct functional domains, with medial regions more involved in internally guided saccades and lateral regions linked to externally cued gaze shifts.
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Connections
The FEF maintains extensive reciprocal connections with visual, oculomotor, and attentional control centers across the brain. These include the parietal eye field in the intraparietal sulcus, superior colliculus, pulvinar and mediodorsal thalamic nuclei, basal ganglia, and extrastriate visual areas such as V4 and MT/V5 (Schall, 2002; Stanton et al., 2005).
Through its projections to the superior colliculus and brainstem gaze centers, the FEF exerts direct control over saccadic generation. Simultaneously, its connections with parietal and occipital cortices mediate spatial attention and visual perception, enabling a tight coupling between eye movement and attention systems.
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Participation in brain networks
Functionally, the FEF is a central node in the dorsal attention network (DAN), which includes the intraparietal sulcus and superior parietal lobule (Corbetta & Shulman, 2002).
This network orchestrates top-down control of visual attention and eye movements, enabling the selection of behaviorally relevant stimuli.
The FEF also interacts dynamically with the ventral attention network and default mode network, particularly during tasks involving attention shifts, working memory, and goal maintenance. Electrophysiological and resting-state fMRI studies have demonstrated task-specific modulations in FEF connectivity, reflecting its integrative role in attentional dynamics.
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Functions
The FEF is essential for the voluntary initiation and guidance of saccadic eye movements, smooth pursuit tracking, and covert shifts of visual attention. It encodes spatial goals, modulates visual processing gain, and determines the timing of gaze shifts based on internal goals or external cues (Schall, 2002).
In addition to motoric functions, the FEF contributes to attentional selection, visual consciousness, and perceptual awareness.
Activity in the FEF has been correlated with decision-making processes involving visual discrimination and target selection (Vernet et al., 2014). Functional heterogeneity within the FEF supports both sensorimotor execution and higher-order cognitive control, including prediction, expectation, and attentional filtering.
Role in clinical disorders
Dysfunction of the FEF has been implicated in multiple neurological and psychiatric disorders. In attention deficit hyperactivity disorder (ADHD), structural and functional alterations in the FEF are associated with deficits in sustained attention, inhibitory control, and impaired saccadic performance (Mahone et al., 2011).
Lesions to the FEF or its downstream pathways can cause oculomotor apraxia, a condition characterized by impaired voluntary gaze shifts and reliance on head movements for target fixation (Rizzo et al., 1996).
In progressive supranuclear palsy (PSP), degeneration of FEF-associated networks contributes to vertical gaze palsy and reduced saccadic initiation, reflecting subcortical and cortical oculomotor system disruption (Burrell et al., 2012).
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Latest findings
Recent research has extended the role of the FEF into disorders of consciousness and perception. Functional disruptions in FEF-parietal connectivity have been observed in patients with spatial neglect and post-stroke attentional deficits.
Additionally, transcranial magnetic stimulation (TMS) studies have shown that stimulation of the FEF can transiently modulate perceptual awareness and attentional bias, suggesting a causal role in visual consciousness.
Neurodevelopmental studies further reveal that atypical FEF development may underlie gaze-related deficits in autism spectrum disorder and contribute to impairments in joint attention and visual social processing. These findings highlight the FEF’s essential role not only in eye movement control but also in the broader regulation of visuospatial cognition.
Areas 9 and 46: Dorsolateral Prefrontal Cortex (DLPFC)
The dorsolateral prefrontal cortex (DLPFC) encompasses Brodmann areas 9 and 46 and plays a central role in human executive function.
It supports a wide array of higher-order cognitive processes, including working memory, cognitive flexibility, attentional regulation, and goal-directed decision-making.
As a core hub of the cognitive control system, the DLPFC enables adaptive behavior by integrating sensory input, internal goals, and emotional context to guide voluntary action. Its functional integrity is essential for strategic planning, inhibition of automatic responses, and complex problem-solving. Graphic © Big8/Shutterstock.com.
Brodmann areas
The DLPFC primarily spans Brodmann areas 9 and 46, located on the middle and superior frontal gyri of the lateral prefrontal cortex (Petrides, 2005).
Area 46 occupies the rostral portion of the middle frontal gyrus, while area 9 lies dorsally and slightly posterior, extending into the superior frontal gyrus.
Although both areas are structurally and functionally interrelated, they have distinct contributions to cognitive processing: area 46 is more involved in manipulation of information in working memory, whereas area 9 contributes to monitoring, rule-based reasoning, and sustained attention.
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Location
The DLPFC is situated in the lateral convexity of the frontal lobe, anterior to the premotor cortex and superior to the orbitofrontal cortex. It is bounded inferiorly by the inferior frontal sulcus and posteriorly by the precentral sulcus.
EEG scalp positions F3 and F4 best approximate the left and right DLPFC, respectively.
These landmarks are widely used in transcranial magnetic stimulation (TMS) research and clinical applications targeting this region for modulation of mood and executive dysfunction.
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Connections
The DLPFC is highly interconnected with both cortical and subcortical regions that subserve cognitive and affective regulation. Major reciprocal projections exist between the DLPFC and parietal cortex, anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), orbitofrontal cortex, and temporal association areas (Petrides & Pandya, 2002).
Subcortical connections include the mediodorsal thalamus, striatum, and cerebellum. These networks facilitate the integration of task-relevant sensory information with motor output, emotional context, and mnemonic processing.
The DLPFC is particularly critical in top-down modulation of attention and working memory circuits, allowing for the suppression of distractors and prioritization of goal-relevant stimuli.
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Participation in brain networks
The DLPFC is a central node of the frontoparietal control network (FPCN), which supports adaptive executive function, working memory, and cognitive flexibility (Vincent et al., 2008).
It interfaces dynamically with the default mode network (DMN) and salience network to shift cognitive states between internally focused and externally driven attention.
Additionally, the DLPFC is a key component of the multiple-demand network, a system recruited during high-demand cognitive tasks irrespective of domain.
Functional MRI studies reveal that DLPFC activation increases with task complexity, reflecting its role in abstract rule implementation, conflict monitoring, and strategic behavior.
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Functions
The DLPFC underpins executive processes essential for flexible, goal-oriented behavior. These include working memory maintenance and manipulation, inhibition of prepotent responses, cognitive planning, and decision-making under uncertainty (Breedlove & Watson, 2023; Petrides, 2005).
The DLPFC is also instrumental in metacognitive operations such as self-monitoring and error correction. It plays a key role in reasoning, strategy selection, and shifting between task sets or mental rules.
Importantly, lateralization exists: the left DLPFC is more engaged in verbal working memory and logical reasoning, while the right DLPFC is more involved in spatial working memory and inhibitory control.
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Role in clinical disorders
DLPFC dysfunction is implicated in a wide range of neuropsychiatric and neurodevelopmental conditions.
In schizophrenia, hypoactivation and disrupted connectivity of the DLPFC are associated with deficits in working memory, executive function, and cognitive control, often referred to as the "cognitive core" of the disorder (Barch, 2005).
In attention-deficit/hyperactivity disorder (ADHD), abnormal DLPFC maturation and connectivity correlate with impaired attentional regulation and executive dysfunction (Cortese et al., 2012).
Major depressive disorder (MDD) is also associated with reduced DLPFC activity, particularly on the left side, contributing to cognitive slowing, ruminative thought patterns, and impaired decision-making (Drevets et al., 2008).
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Latest findings
The DLPFC is amenable to neuromodulation. Repetitive transcranial magnetic stimulation (rTMS) targeting the left DLPFC has been approved for treatment-resistant depression, and ongoing trials explore its efficacy in ADHD, schizophrenia, and cognitive aging.
Functional neuroimaging further supports the use of DLPFC-based biomarkers for tracking therapeutic response and disease progression in these disorders.
Moreover, research into cognitive training and neurofeedback targeting DLPFC function has shown promising effects in enhancing executive performance and cognitive resilience in both clinical and healthy populations.
Area 10: Anterior Prefrontal Cortex (aPFC)
The anterior prefrontal cortex (aPFC), also known as the frontopolar cortex, represents the most rostral aspect of the human prefrontal cortex and is a critical substrate for high-level cognition. It plays a central role in metacognitive processes, including abstract reasoning, prospective memory, multitasking, and social cognition.
The aPFC supports the integration of multiple cognitive operations and allows for the simultaneous management of competing goals or mental states. It is uniquely developed in humans compared to other primates, reflecting its importance in complex goal-directed behavior and internal state monitoring. Graphic © Big8/Shutterstock.com.
Brodmann areas
The aPFC is localized within Brodmann area 10, which occupies the frontal pole of the brain and represents the most anterior cortical territory (Ramnani & Owen, 2004). This area is distinct in its cytoarchitecture, with a less granular appearance and unique dendritic organization that supports its integrative capacity.
Area 10 is subdivided into medial and lateral regions with partially differentiated functional roles: the lateral aPFC is more involved in external goal representation and cognitive branching, while the medial portion participates in self-referential processing and social cognition.
Location
The aPFC is situated at the most rostral portion of the frontal lobe, anterior to both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex. It is bounded posteriorly by Brodmann areas 9 and 11 and lies just above the medial and lateral orbital gyri.
On the scalp, the corresponding EEG sites are Fp1 and Fp2, which approximate the left and right frontal poles, respectively.
Its anterior placement positions it as a strategic integrator of cognitive, affective, and motivational information across networks.
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Connections
The aPFC is extensively connected with other prefrontal regions, including the DLPFC, orbitofrontal cortex, medial prefrontal cortex (mPFC), as well as with the posterior parietal cortex, superior temporal sulcus, medial temporal lobe, and mediodorsal thalamus (Burgess et al., 2007).
These widespread cortical and subcortical connections allow the aPFC to coordinate distributed neural activity involved in higher-order cognition. In particular, its bidirectional projections with the DLPFC enable the aPFC to guide working memory manipulation and task set maintenance, while its interactions with the mPFC and temporoparietal junction support theory of mind and social inference.
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Participation in brain networks
The aPFC functions as a convergence zone within multiple large-scale brain networks. It is a key node in the frontoparietal control network, supporting executive control and adaptive cognitive flexibility (Vincent et al., 2008).
Additionally, it plays a prominent role in the default mode network (DMN), particularly its medial subdivision, contributing to self-referential thought, mentalizing, and simulation of future events (Spreng et al., 2009).
Its engagement in both task-positive and task-negative networks underscores its involvement in coordinating internal and external modes of cognition.
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Functions
the aPFC enables complex integrative operations such as prospective memory (remembering to perform actions in the future), multitasking (maintaining and switching between multiple goals), and source memory (tracking the context of information).
It also supports abstract reasoning, strategic planning, and decision-making under uncertainty (Ramnani & Owen, 2004).
The lateral aPFC is associated with “cognitive branching,” the capacity to maintain an ongoing task while prospectively managing a pending task.
The medial aPFC, by contrast, is engaged in introspective processes, including self-evaluation, emotional appraisal, and social mentalizing.
Notably, recent studies have identified the aPFC's involvement in nociceptive modulation, indicating its contribution to top-down pain regulation and affective pain processing (Peng et al., 2018).
Role in clinical disorders
Aberrant function of the aPFC has been implicated in various neuropsychiatric disorders. In autism spectrum disorder (ASD), structural and functional abnormalities in the aPFC are associated with deficits in theory of mind, flexible thinking, and social inference (Gilbert et al., 2008).
In schizophrenia, aPFC dysfunction contributes to impaired reality monitoring, abstract reasoning deficits, and executive dysfunction, often manifesting as disorganized thinking and poor goal management (Perlstein et al., 2001).
In major depressive disorder (MDD), hypoactivity of the aPFC—especially its medial aspect—is linked to impaired future planning, ruminative thinking, and diminished cognitive flexibility (Drevets et al., 2008).
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Latest findings
Emerging research using neuroimaging and neuromodulation has begun to delineate the aPFC’s distinct roles in prospective cognition and affect regulation.
Functional MRI studies have demonstrated that reduced frontopolar activation during planning tasks predicts poorer multitasking performance in aging and neurodegeneration.
Additionally, transcranial direct current stimulation (tDCS) targeting the aPFC has shown potential for enhancing executive function, particularly in individuals with mild cognitive impairment or depression.
Given its integrative capacity and high-level cognitive role, the aPFC remains a compelling target for both diagnostic assessment and therapeutic intervention in disorders of executive dysfunction and social cognition.
Areas 11, 12, 13, and 47: Orbitofrontal Cortex (OFC)
The orbitofrontal cortex (OFC) is a key region of the ventral prefrontal cortex involved in evaluating sensory stimuli based on their emotional and reward value. It contributes to adaptive decision-making by integrating multimodal sensory input with affective and motivational states.
The OFC plays a central role in updating the value of expected outcomes, evaluating risk and uncertainty, and regulating behavior based on social and emotional context. Its strategic location and connectivity allow it to function as a critical interface between cognitive control systems and subcortical structures involved in emotion and reward. Graphic © Big8/Shutterstock.com.
Brodmann areas
The OFC encompasses Brodmann areas 11, 12, 13, and 47, which collectively form the ventral surface of the frontal lobe (Kringelbach, 2005).
Area 11 occupies the medial and central orbital gyri, area 12 lies anterolaterally, area 13 is located in the posterior OFC, and area 47 extends laterally into the inferior frontal gyrus.
These areas are cytoarchitectonically distinct yet functionally interconnected, with some degree of specialization: for example, medial OFC regions are more sensitive to reward and subjective value, whereas lateral regions are involved in response inhibition and negative outcome monitoring.
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Location
The OFC lies on the ventral surface of the frontal lobes, immediately superior to the orbital bones of the skull. It is bordered dorsally by the medial prefrontal cortex and anteriorly by the anterior prefrontal cortex (area 10).
The medial OFC is situated adjacent to the gyrus rectus, while the lateral OFC is located over the lateral orbital gyrus.
Scalp EEG coordinates Fp1 and Fp2 correspond to the approximate locations of the bilateral OFC, though direct access to this region remains limited in surface EEG studies due to its deep and ventral position.
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Connections
The OFC maintains dense bidirectional connections with both cortical and subcortical structures involved in emotion, memory, reward, and executive function. These include the amygdala, insula, anterior and posterior cingulate cortices, hippocampus, mediodorsal thalamus, ventral striatum, hypothalamus, and various sensory association areas (Kringelbach, 2005; Price, 2007).
The medial OFC receives inputs from the limbic system and is heavily involved in encoding reward value and emotional salience, while the lateral OFC is connected to areas responsible for behavioral flexibility, particularly in response to punishment or negative feedback. These circuits are essential for adaptive decision-making and emotional regulation.
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Participation in brain networks
The OFC functions as a key node within several functional brain networks. It contributes to the salience network, which integrates interoceptive and affective information to guide attentional and behavioral responses to emotionally relevant stimuli (Seeley et al., 2007).
The OFC is also involved in the default mode network (DMN), particularly during self-referential thinking, emotional introspection, and social cognition (Spreng et al., 2009).
Functional imaging studies have revealed dynamic OFC connectivity with the anterior insula, dorsal anterior cingulate cortex, and subgenual prefrontal cortex during tasks requiring emotional and motivational evaluation.
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Functions
The OFC plays a central role in the valuation of sensory input, reinforcement learning, and behavioral adaptation. It evaluates the hedonic and motivational significance of stimuli and outcomes and is critical for updating action values based on changing environmental contingencies (Kringelbach, 2005).
The medial OFC is preferentially involved in encoding positively valenced rewards (e.g., food, social approval), while the lateral OFC is activated in response to aversive outcomes and supports behavioral inhibition and reversal learning. The OFC also contributes to social behavior by encoding norms, assessing the emotional expressions of others, and regulating socially appropriate responses.
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Role in clinical disorders
Dysfunction of the OFC is implicated in a variety of psychiatric and neurological disorders characterized by impaired emotion regulation, reward processing, and decision-making. In obsessive-compulsive disorder (OCD), hyperactivity and altered connectivity in the medial and lateral OFC are associated with impaired behavioral flexibility and compulsive behaviors (Menzies et al., 2008).
In major depressive disorder (MDD), studies reveal an imbalance between heightened activity in the lateral OFC (associated with non-reward and punishment) and reduced activity in the medial OFC (associated with reward valuation), potentially contributing to anhedonia and negative bias (Rolls, Cheng, & Feng, 2020; Drevets, 2007).
Bipolar disorder (BD) has also been linked to dysregulated OFC activation during mood episodes, affecting reward responsiveness and impulsivity (Blumberg et al., 2003).
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Furthermore, OFC abnormalities are prominent in addiction, where impaired reward valuation and outcome monitoring contribute to compulsive drug-seeking and risk-taking behaviors.
Neuroimaging studies have demonstrated hypoactivation of the OFC in individuals with substance use disorders during tasks requiring inhibitory control and outcome evaluation (Volkow & Fowler, 2000).
Emerging evidence suggests that targeted modulation of OFC circuits, using neuromodulatory techniques or cognitive behavioral interventions, may enhance decision-making capacity and improve clinical outcomes in disorders involving maladaptive valuation and emotional dysregulation.
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Latest findings
Recent neuroimaging and electrophysiological studies have provided new insights into the functional architecture and clinical relevance of the orbitofrontal cortex (OFC). High-resolution fMRI and diffusion tensor imaging (DTI) have revealed greater functional differentiation within the OFC than previously recognized.
Medial and lateral subregions show distinct connectivity patterns, with the medial OFC preferentially linked to the ventral striatum and default mode network components, while the lateral OFC demonstrates stronger coupling with dorsal attention and salience networks (Zhou et al., 2021).
These findings underscore a dual-system model of OFC organization, in which the medial division is responsible for value-based reward processing and the lateral OFC governs outcome evaluation and behavioral inhibition.
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Advances in computational modeling have also helped clarify the role of the OFC in predictive coding and reinforcement learning. A growing body of evidence supports the notion that the OFC constructs a “cognitive map” of task space, encoding latent variables such as expected outcomes, prediction errors, and inferred states (Wilson et al., 2014; Schuck et al., 2016).
This model-based representation allows for flexible adaptation to environmental changes, such as in reversal learning paradigms. Notably, disruptions in this mapping function have been implicated in neuropsychiatric disorders including obsessive-compulsive disorder, addiction, and depression, suggesting that therapeutic interventions targeting OFC plasticity—through behavioral training or non-invasive brain stimulation—may restore adaptive decision-making capacities.
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Areas 13-16 and 52: Insular Cortex (Insula)
The insular cortex, or insula, is a highly integrative region involved in processing internal bodily states (interoception), emotional awareness, pain perception, and higher cognitive control. Positioned deep within the lateral sulcus, the insula serves as a bridge between sensorimotor, affective, and cognitive systems. This connectivity allows it to modulate behavior in response to both internal and external stimuli.
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The insula's functional heterogeneity supports a wide spectrum of processes—from autonomic regulation to social-emotional cognition—and has led to its conceptualization as a central hub for salience detection and bodily awareness. Its unique anatomical location and complex architecture make it a crucial node for the integration of sensory, affective, and cognitive domains. Graphic © Big8/Shutterstock.com.
Brodmann areas
The insular cortex comprises Brodmann areas 13, 14, 15, 16, and portions of area 52. Functionally, it can be subdivided into three main domains: a posterior sensorimotor region, a central olfactogustatory region, and an anterior socio-emotional/cognitive region (Kurth et al., 2010).
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The posterior insula (areas 13 and 52) is involved in visceral-somatic sensation and pain processing. The anterior insula (areas 14–16) is implicated in emotional awareness, interoceptive attention, and executive control, especially within its anterior-dorsal subdivision, which interacts with prefrontal and cingulate areas for higher cognitive functions.
Location
Anatomically, the insula is located deep within the Sylvian (lateral) fissure and is obscured by the opercula of the frontal, parietal, and temporal lobes. It is bordered superiorly by the frontal and parietal lobes and inferiorly by the superior temporal gyrus.
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Due to its deep cortical position, the insula is not directly accessible by surface EEG, though it is frequently visualized in high-resolution MRI and functional imaging studies.
Connections
The insula maintains dense reciprocal connections with a variety of cortical and subcortical regions, including the amygdala, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), thalamus, hypothalamus, and primary/secondary somatosensory cortices (Nieuwenhuys, 2012).
The anterior insula is particularly connected with the ACC, supporting its role in cognitive control, affect regulation, and salience detection. The posterior insula is heavily connected with somatosensory areas and the dorsal brainstem, reflecting its importance in nociception and autonomic integration.
Participation in brain networks
The insular cortex is a core node of the salience network, along with the ACC. This network detects behaviorally relevant stimuli and modulates the balance between the default mode and central executive networks (Seeley et al., 2007).
Additionally, the insula is integral to the central autonomic network (CAN), contributing to the regulation of heart rate, blood pressure, and homeostatic functions (Thayer et al., 2012). The right anterior insula, in particular, is thought to act as a "network switch" that dynamically modulates engagement between externally and internally focused neural systems.
Functions
The insular cortex is pivotal in representing interoceptive signals—the physiological condition of the body—and integrating them with affective and cognitive information. It underpins subjective emotional experience, empathy, risk anticipation, craving, and body ownership (Craig, 2009).
The anterior insula is implicated in awareness and executive monitoring, while the posterior insula is responsible for the somatotopic mapping of visceral and somatic sensory input. Moreover, the insula is involved in the cognitive appraisal of pain, integrating sensory and affective components to inform behavioral responses.
Role in clinical disorders
Dysfunction in the insular cortex is implicated in numerous neuropsychiatric and neurologic disorders. In anxiety disorders, hyperactivation of the anterior insula correlates with heightened interoceptive sensitivity and anticipatory worry (Paulus & Stein, 2006).
In major depressive disorder (MDD), aberrant connectivity between the insula and limbic-prefrontal circuits is associated with disrupted emotional regulation and rumination (Sliz & Hayley, 2012).
The insula is also critically involved in the pathophysiology of addiction, particularly in the processing of craving and interoceptive urges, with damage to the insula shown to disrupt nicotine addiction in stroke patients (Naqvi & Bechara, 2010).
In autism spectrum disorder (ASD), atypical functional connectivity of the insula has been linked to impairments in emotional recognition and social communication (Di Martino et al., 2009).
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Latest findings
Recent advances in neuroimaging have further refined our understanding of insular subregional specialization and network dynamics. Multimodal parcellation studies using high-resolution diffusion MRI and resting-state fMRI have revealed that the insula comprises at least three distinct subregions: posterior (sensorimotor), mid-insula (affective integration), and anterior (cognitive-affective integration) zones, each with unique connectivity profiles (Tian & Zalesky, 2018).
The anterior insula, particularly on the right, has emerged as a central hub for initiating cognitive control in response to salient stimuli, facilitating rapid switching between task-positive and task-negative states.
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Emerging research also supports the role of the insula in predictive interoception—the brain’s ability to anticipate bodily states and adjust behavior accordingly. This framework, grounded in active inference theory, posits that the insula participates in minimizing prediction errors related to internal bodily sensations (Allen et al., 2022).
Such mechanisms may underlie the altered interoceptive awareness observed in psychiatric conditions like anxiety, depression, and eating disorders. Novel therapeutic approaches, including real-time fMRI neurofeedback and transcranial magnetic stimulation (TMS) targeting the insula, are under investigation for modulating dysfunctional interoceptive and emotional processing in these populations.
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Area 17: Primary Visual Cortex (V1)
The primary visual cortex (V1), also known as the striate cortex, is the principal cortical region for the initial processing of visual input. It receives direct afferent projections from the lateral geniculate nucleus (LGN) of the thalamus and processes elementary visual features such as orientation, spatial frequency, edge detection, motion, and color.
V1 serves as the first cortical relay in a hierarchically organized visual system, providing the structural and functional foundation upon which higher-order visual areas perform complex processing. Its columnar organization and retinotopic mapping support precise spatial encoding of the visual field. Graphic © Big8/Shutterstock.com.
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Brodmann areas
The primary visual cortex corresponds to Brodmann area 17, a cytoarchitectonically distinct region within the occipital lobe (Horton & Adams, 2005).
Area 17 is characterized by the presence of the line of Gennari—a dense band of myelinated fibers within layer IV that distinguishes it from surrounding extrastriate areas. This unique structure underpins the highly organized laminar processing of visual inputs, with magnocellular and parvocellular pathways terminating in distinct sublayers.
Location
V1 is located along the banks of the calcarine sulcus in the medial portion of the occipital lobe. It extends from the occipital pole anteriorly into the depths of the sulcus, where the upper visual field is represented inferiorly and the lower visual field superiorly.
Scalp coordinates O1 and O2 (in the international 10–20 EEG system) overlie the occipital pole and approximate the surface location of V1.
The cortical magnification factor is greatest in the posterior V1 region, which represents central (foveal) vision, reflecting its importance in high-acuity visual tasks.
Connections
The primary visual cortex receives topographically organized input from the LGN of the thalamus and projects to secondary (V2) and tertiary (V3, V4, V5/MT) visual cortices in a predominantly feedforward manner.
These connections facilitate a hierarchical and parallel processing architecture, with distinct dorsal (motion and spatial processing) and ventral (form and color recognition) visual streams (Felleman & Van Essen, 1991).
V1 also receives modulatory feedback from higher-order visual areas and non-visual regions, including the frontal eye fields and attention-related networks, enabling dynamic regulation of visual processing based on behavioral relevance.
Participation in brain networks
V1 is a core node in the visual processing network, forming the entry point into the dorsal and ventral visual streams. It is also functionally integrated into broader perceptual, attentional, and multisensory networks.
Functional connectivity studies show that V1 synchronizes activity with extrastriate visual cortices, parietal regions involved in spatial attention, and temporal lobe structures implicated in object recognition (Nassi & Callaway, 2009).
In states of visual imagery or hallucination, V1 may become active even in the absence of external stimuli, demonstrating its involvement in internally generated visual phenomena.
Functions
The primary function of V1 is the processing of basic visual features including luminance contrast, orientation, direction of motion, spatial frequency, and binocular disparity.
Neurons in V1 are organized into orientation columns, ocular dominance columns, and hypercolumns, forming a systematic map of visual space.
V1 performs initial feature extraction necessary for subsequent recognition and perceptual integration in extrastriate areas. Its precise retinotopic organization enables accurate encoding of spatial relationships within the visual field, which is foundational for perception and visuomotor coordination (Horton & Adams, 2005).
Role in clinical disorders
Disruptions in V1 function can result in profound visual impairment. In amblyopia, V1 shows reduced responsiveness to input from the affected eye, with abnormal synaptic development and impaired binocular integration (Hess et al., 2010).
Bilateral lesions of V1 lead to cortical blindness, characterized by complete loss of conscious visual perception despite intact ocular structures (Celesia, 2005).
Partial V1 damage can cause scotomas or hemianopia, depending on the extent and location of the lesion. Visual hallucinations, such as those seen in Charles Bonnet syndrome, have been linked to spontaneous or disinhibited activity in V1 and associated visual cortices in the absence of visual input (Griffiths, 2000).
Additionally, V1 hyperexcitability has been implicated in the pathophysiology of migraine aura.
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Areas 18 and 19: Secondary Visual Cortex (V2)
The secondary visual cortex (V2), also referred to as the prestriate cortex, represents the second stage in the hierarchical organization of the visual processing system.
It serves as a major recipient of input from the primary visual cortex (V1) and provides divergent projections to multiple higher-order extrastriate visual areas.
V2 performs intermediate-level visual computations that integrate basic visual signals into more complex representations, forming the foundational processing layer for object recognition, depth perception, and motion tracking.
It acts as a functional relay between early visual analysis in V1 and specialized processing in areas such as V3, V4, and V5/MT. Graphic © Big8/Shutterstock.com.
Brodmann areas
The secondary visual cortex primarily encompasses Brodmann areas 18 and 19, both located within the occipital lobe (Tootell et al., 1998).
Area 18 (V2 proper) forms a contiguous belt around V1, whereas area 19 includes adjacent extrastriate regions that are functionally associated with higher-order visual processing.
These areas exhibit a complex, retinotopically organized architecture with distinct subregions specialized for processing different visual features, such as form, texture, color, and motion.
Location
Anatomically, the secondary visual cortex is situated in the occipital lobe, encircling the primary visual cortex (V1) along the banks and operculum of the calcarine sulcus. It extends dorsally and ventrally into the lateral aspects of the occipital lobe.
Scalp coordinates O1 and O2 correspond approximately to surface projections overlying V2 and nearby extrastriate areas.
Due to its extensive retinotopic organization, different subregions of V2 correspond to specific regions of the visual field, with the foveal representation located posteriorly and peripheral fields located anteriorly.
Connections
The V2 receives input from the primary visual cortex (V1). It sends output to higher-order extrastriate areas (V3, V4, V5/MT) and other cortical regions involved in visual processing, including the parietal and temporal cortices (Felleman & Van Essen, 1991).
Participation in brain networks
The secondary visual cortex is a key node in the visual processing network responsible for processing and interpreting visual information from the retina. This network includes other areas of the occipital lobe and parietal and temporal cortices (Nassi & Callaway, 2009).
Functions
The secondary visual cortex is involved in further processing and integrating visual information received from the primary visual cortex. It is crucial in processing complex visual attributes, such as form, color, and motion (Tootell et al., 1998).
Role in clinical disorders
Alterations in secondary visual cortex function have been implicated in various clinical conditions, including visual agnosia, which is characterized by the inability to recognize objects despite normal visual acuity and intact primary visual cortex function (Milner & Goodale, 2008).
Areas 18, 19, 37, 21, and 22: Visual Association Cortex (V3, V4, V5)
The visual association cortex, encompassing regions V3, V4, and V5/MT, plays a central role in the high-level processing and interpretation of visual information. These extrastriate areas extend the basic feature extraction performed by the primary (V1)
and secondary (V2) visual cortices to support complex visual functions such as object recognition, facial processing, motion perception, and spatial scene analysis.
This cortical territory enables the brain to integrate visual inputs into coherent, meaningful representations that guide behavior, memory, and decision-making across multiple modalities. Graphic © Big8/Shutterstock.com.
Brodmann areas
The visual association cortex spans several Brodmann areas, primarily areas 18 and 19 (extrastriate occipital cortex), as well as areas 37 (fusiform and inferotemporal cortex), 21 (middle temporal gyrus), and 22 (superior temporal gyrus) (Tootell et al., 1998; Kanwisher & Yovel, 2006).
Area 18 includes V3 and parts of V4, area 19 includes additional V3, V4, and V5/MT regions, and areas 21 and 22 contribute to the temporal extension of ventral stream processing.
Area 37 contains key functional subdivisions such as the fusiform face area (FFA), important for facial recognition, and the parahippocampal place area (PPA), involved in scene processing.
Location
These association areas are situated within the occipital and temporal lobes, surrounding the primary (V1) and secondary (V2) cortices. V3 is located along the dorsal and ventral surfaces of the occipital lobe, V4 is located more ventrally near the lingual and fusiform gyri, and V5/MT is located along the lateral occipitotemporal junction.
The fusiform face area (FFA) lies in the lateral fusiform gyrus, while the parahippocampal place area (PPA) resides in the medial temporal lobe near the collateral sulcus.
Scalp EEG locations O1, O2, T5, and T6 best approximate these regions across the occipitotemporal axis.
Connections
The visual association cortex receives convergent input from V1 and V2 and projects to various cortical and subcortical regions, enabling the integration of visual data with cognitive, emotional, and memory-related processes.
Feedforward connections target parietal regions for visuospatial guidance (dorsal stream) and temporal regions for object and semantic recognition (ventral stream).
These areas also maintain reciprocal connections with the hippocampus (for memory encoding), the amygdala (for emotional salience), and the prefrontal cortex (for executive modulation) (Felleman & Van Essen, 1991; Kravitz et al., 2013). Such integration supports dynamic visual perception in contextually meaningful ways.
Participation in brain networks
The visual association cortex is a critical component of the ventral visual stream, often referred to as the "what" pathway, responsible for processing object identity, faces, color, and fine-grained visual features (Kravitz et al., 2011).
This pathway runs from early visual areas to the inferior temporal cortex and interacts with medial temporal lobe structures for memory-based visual processing.
V5/MT, by contrast, is a key node in the dorsal stream, or "where/how" pathway, which supports motion analysis and visually guided action.
Functional connectivity studies also show that visual association areas interact with the default mode and salience networks, especially during visual imagery and attention tasks.
Functions
The visual association cortex performs a wide range of advanced visual functions. V3 is involved in global form and depth perception, V4 specializes in processing shape and color constancy, and V5/MT is critical for detecting and analyzing motion.
Higher-tier regions, such as the FFA, are specialized for facial recognition, while the PPA supports environmental scene processing and spatial navigation. The lateral occipital complex (LOC) encodes object shape independent of texture or illumination.
Collectively, these areas enable the brain to recognize, categorize, and respond to complex visual stimuli, including dynamic social cues and object interactions (Kanwisher & Yovel, 2006; Tootell et al., 1998).
Role in clinical disorders
Dysfunction in the visual association cortex is associated with a range of perceptual and cognitive deficits. Lesions in area 37 or disruption of the fusiform face area can lead to prosopagnosia, or face blindness, in which individuals are unable to recognize familiar faces despite intact vision (Duchaine & Nakayama, 2006).
Visual agnosia results from damage to occipitotemporal areas and impairs the ability to recognize objects, even with preserved visual acuity and motor function (Milner & Goodale, 2008).
In autism spectrum disorder (ASD), atypical activation of visual association areas, particularly in face- and motion-processing regions, has been linked to social and perceptual impairments (Simmons et al., 2009).
Additionally, in posterior cortical atrophy, progressive degeneration of these regions leads to profound deficits in visuospatial processing and object recognition.
Latest findings
Recent neuroimaging and neurophysiological studies have significantly advanced our understanding of functional specialization and plasticity in the visual association cortex.
High-resolution fMRI and machine learning approaches have demonstrated that regions such as the FFA and PPA not only respond selectively to specific categories (e.g., faces, places) but also encode detailed contextual and emotional information about stimuli, supporting their role in social cognition and affective processing (Mishra et al., 2023).
Furthermore, dynamic functional connectivity analyses reveal that visual association areas flexibly reconfigure their network affiliations depending on task demands, such as visual attention, memory recall, or goal-directed behavior.
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There is also growing interest in the role of visual association cortices in predictive coding. These regions generate internal models of visual scenes and update them based on sensory input and top-down expectation signals. This model-based framework helps explain phenomena such as visual illusions, rapid object categorization, and the perceptual deficits observed in neuropsychiatric disorders (Aitken et al., 2020).
Recent studies in congenital blindness and sight restoration have also shown that higher-tier visual areas (e.g., LOC, FFA) can be functionally repurposed for non-visual processing, reflecting their domain-specific rather than strictly modality-specific organization. These insights have implications for neuroplasticity, rehabilitation, and the development of sensory substitution technologies.
Areas 20 and 37: Inferior Temporal Gyrus (ITG)
The inferior temporal gyrus (ITG) is a crucial region within the ventral visual stream responsible for high-level visual processing, particularly the identification and categorization of complex visual stimuli. It serves as an integrative hub for object recognition, visual memory, and semantic processing by transforming detailed visual input from occipital and fusiform regions into conceptual representations.
The ITG supports cross-modal associations and interfaces with memory and emotional systems, enabling recognition that is contextually and emotionally informed. Graphic © Big8/Shutterstock.com.
Brodmann areas
The ITG spans Brodmann areas 20 and 37. Area 20 constitutes the anterior inferior temporal cortex and is implicated in object and semantic processing.
Area 37 lies more posteriorly and encompasses parts of the fusiform and occipitotemporal junction, including the fusiform face area (FFA) and other category-selective regions (Amunts et al., 2000).
These areas contribute to the functional gradient of the ventral temporal lobe, with more anterior regions involved in abstract and semantic associations, and posterior regions involved in perceptual feature extraction.
Location
The ITG is located on the ventral surface of the temporal lobe, inferior to the middle temporal gyrus and superior to the fusiform gyrus. It runs longitudinally along the lateral occipitotemporal cortex.
Surface EEG sites T5 (TP7) and T6 (TP8) approximate the overlying regions of the ITG bilaterally.
The ITG interfaces posteriorly with occipital visual areas and anteriorly with medial temporal lobe structures involved in memory encoding and retrieval.
Connections
The ITG maintains extensive reciprocal connections with the primary (V1) and secondary (V2) visual cortices, as well as with the fusiform gyrus, lateral occipital complex (LOC), parahippocampal gyrus, hippocampus, amygdala, and prefrontal cortex (Felleman & Van Essen, 1991; Kravitz et al., 2013).
These connections support both bottom-up visual processing and top-down modulation based on memory, context, and emotional salience.
The ITG also communicates with language-related areas in the temporal and frontal lobes, facilitating visual-semantic integration.
Participation in brain networks
The ITG is a key node in the ventral visual stream, commonly referred to as the “what” pathway. This network specializes in the identification of objects, faces, words, and scenes by processing complex combinations of visual features.
Functional connectivity studies demonstrate ITG engagement with the semantic network, the default mode network during recognition and memory tasks, and the limbic system during emotionally salient visual processing (Kravitz et al., 2011).
Functions
The ITG is responsible for high-level object recognition, visual categorization, and visual-semantic integration. It contributes to face perception, word recognition, and conceptual encoding of visual stimuli.
The posterior ITG (including area 37) is more involved in perceptual categorization of visually defined objects such as faces and tools, while anterior regions (area 20) are associated with the retrieval of semantic meaning and cross-modal identification (Kanwisher & Yovel, 2006).
The ITG enables the transformation of perceptual inputs into knowledge representations that are stable across variations in size, position, lighting, and viewpoint.
Role in clinical disorders
Damage or dysfunction in the ITG is associated with a variety of perceptual and cognitive disorders.
Lesions in area 37 can lead to visual agnosia, where patients can see but are unable to recognize objects, and prosopagnosia, where face recognition is impaired despite intact low-level visual processing (Duchaine & Nakayama, 2006).
Abnormal activation patterns in the ITG have also been observed in individuals with autism spectrum disorder (ASD), particularly in response to face and emotion recognition tasks, contributing to deficits in social perception (Simmons et al., 2009).
In semantic dementia, progressive degeneration of anterior ITG and surrounding temporal cortex results in profound impairments in word and object meaning despite preserved perceptual processing.
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Latest findings
Recent neuroimaging and intracranial recording studies have refined our understanding of the functional organization of the ITG. High-resolution fMRI has demonstrated that the ITG contains discrete, category-selective subregions that are not only specialized for faces and objects, but also modulated by semantic context and task demands.
Studies using representational similarity analysis (RSA) have shown that the ITG encodes abstract semantic relationships even for visually distinct items, supporting its role in concept generalization and multimodal integration (Cohen et al., 2021).
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Furthermore, the ITG has emerged as a critical structure in predictive coding models of perception. It appears to integrate top-down predictions from anterior temporal and frontal areas with bottom-up visual input to generate rapid and context-sensitive recognition responses. Disruptions in this predictive mechanism may underlie visual processing deficits observed in conditions such as schizophrenia, ASD, and posterior cortical atrophy (Aitken et al., 2020).
Emerging evidence from studies of brain-machine interfaces and neural decoding suggests that patterns of ITG activation can be used to infer viewed object categories with high fidelity, underscoring its value in both clinical neuroimaging and applied cognitive neuroscience.
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Areas 21 and 39: Middle Temporal Gyrus (MTG)
The middle temporal gyrus (MTG) is a key region of the lateral temporal lobe that supports a wide range of cognitive and perceptual processes. It plays a central role in semantic memory, language comprehension, word retrieval, and high-level visual processing.
The MTG also contributes to multimodal integration, combining auditory, visual, and contextual information to support conceptual representation and linguistic meaning. This area is particularly important in both the ventral visual stream and the semantic language network, making it a convergence zone for perception, memory, and language. Graphic © Big8/Shutterstock.com.
Brodmann areas
The MTG primarily comprises Brodmann areas 21 and 39. Area 21 spans the lateral portion of the middle temporal gyrus and is involved in semantic processing, auditory association, and visual integration.
Area 39, which includes the angular gyrus, occupies the posterior MTG and adjacent inferior parietal regions. It plays a crucial role in conceptual knowledge, number processing, reading, and the default mode network (Amunts et al., 2000).
Together, these regions support a gradient of functions, from visual-perceptual processing in anterior MTG to semantic and integrative functions in posterior MTG.
Location
Anatomically, the MTG is situated on the lateral surface of the temporal lobe. It lies inferior to the superior temporal gyrus and superior to the inferior temporal gyrus, with the superior temporal sulcus separating it from adjacent regions above.
The MTG extends from the anterior temporal lobe near the temporal pole to the posterior regions where it borders the angular and supramarginal gyri of the parietal lobe.
Connections
The MTG maintains extensive reciprocal connections with multiple cortical and subcortical areas. These include the primary and secondary visual cortices, fusiform gyrus, angular gyrus, parahippocampal gyrus, hippocampus, amygdala, and prefrontal cortex (Kravitz et al., 2013; Felleman & Van Essen, 1991).
The MTG serves as a relay station within the ventral visual stream, supporting the identification of objects and faces, while also linking with language areas such as the inferior frontal gyrus for semantic processing. It interfaces with the hippocampus and medial temporal regions to facilitate memory-based language and knowledge retrieval.
Participation in brain networks
The MTG participates in several large-scale brain networks. It is a major component of the ventral visual stream, or "what" pathway, involved in object recognition and high-level visual perception (Kravitz et al., 2011).
It is also a core region in the language network, particularly the left MTG, which is implicated in semantic comprehension, lexical retrieval, and syntactic processing (Binder et al., 2009).
The posterior MTG and area 39 additionally participate in the default mode network (DMN), supporting introspective processes, episodic memory, and conceptual abstraction.
Functions
The MTG is essential for semantic processing and language comprehension. It supports the mapping of word forms onto meaning, lexical retrieval during speech production, and the interpretation of sentences and narratives.
The MTG also contributes to the recognition of visual stimuli, including faces, biological motion, and complex scenes, by integrating form and semantic context. These processes allow for the fluid combination of perceptual input with stored knowledge to support meaningful behavior (Binder et al., 2009; Kanwisher & Yovel, 2006).
Role in clinical disorders
Dysfunction in the MTG has been implicated in several neurological and neurodevelopmental conditions.
In semantic dementia, degeneration of the anterior and middle temporal regions results in progressive loss of conceptual knowledge, while posterior MTG damage contributes to impaired naming and comprehension (Hodges et al., 1992).
In aphasia, particularly Wernicke’s and conduction aphasia, lesions involving the posterior MTG and area 39 disrupt semantic access and fluent speech comprehension (Dronkers et al., 2004).
In autism spectrum disorder (ASD), atypical MTG activity has been linked to impairments in social communication, facial recognition, and integration of verbal and non-verbal cues (Simmons et al., 2009).
Altered MTG connectivity has also been observed in schizophrenia and Alzheimer’s disease, where it may contribute to language disorganization and semantic memory deficits.
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Latest findings
Recent neuroimaging and electrophysiological studies have refined our understanding of the MTG’s role in semantic cognition and integrative processing. High-resolution fMRI and magnetoencephalography (MEG) studies demonstrate that the MTG supports a graded representational space for abstract and concrete concepts, organized along its anterior-posterior axis.
The anterior MTG is preferentially involved in context-sensitive semantic retrieval, while the posterior MTG encodes broader conceptual relationships and multimodal semantic features (Lambon Ralph et al., 2017).
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Multivariate pattern analysis (MVPA) and representational similarity analysis (RSA) have shown that MTG activity patterns can distinguish semantic categories independent of modality, supporting the view that this region serves as a transmodal semantic hub.
Functional connectivity studies further reveal that the MTG dynamically coordinates with the inferior frontal gyrus and angular gyrus during tasks requiring semantic control, and with the hippocampus during memory-guided language tasks (Jackson et al., 2021).
Recent findings also highlight MTG plasticity in response to language training and recovery from aphasia. Neurostimulation techniques such as transcranial direct current stimulation (tDCS) over the left MTG have shown promise in enhancing lexical retrieval in patients with chronic aphasia, suggesting its critical role in adaptive language networks. Additionally, altered MTG connectivity has been identified as a biomarker for early Alzheimer’s disease and may contribute to predictive models of semantic decline.
Areas 22, 39, and 40: Superior Temporal Gyrus (STG)
The superior temporal gyrus (STG) is a key region of the temporal lobe involved in a broad array of perceptual, cognitive, and social functions. It plays a critical role in auditory processing, language comprehension, and the integration of multimodal information.
Posterior portions of the STG, particularly in the left hemisphere, encompass Wernicke’s area—a central component of the language network.
In addition to its linguistic role, the STG is implicated in social cognition, emotion recognition, and memory-related auditory processes. Its anatomical and functional heterogeneity enables it to serve as a bridge between low-level auditory input and higher-level semantic and social interpretation.Graphic © Big8/Shutterstock.com.
Brodmann areas
Wernicke’s area is primarily localized to Brodmann area 22, especially in its posterior portion, and extends into the adjacent angular gyrus (area 39) and supramarginal gyrus (area 40; Amunts et al., 2000).
Area 22 encompasses most of the STG and is involved in phonological and semantic decoding.
Area 39 (angular gyrus) contributes to language integration, reading, and semantic processing, while area 40 (supramarginal gyrus) supports phonological working memory and sensorimotor integration. Together, these regions form part of the temporoparietal junction, a hub for language and social cognition.
Location
The STG is located on the lateral surface of the temporal lobe, superior to the middle temporal gyrus and inferior to the lateral (Sylvian) sulcus.
Wernicke’s area, traditionally localized to the posterior STG in the dominant (typically left) hemisphere, lies near the confluence of the STG, area 39, and area 40.
Scalp EEG coordinates T5 (or TP7) correspond to the approximate location of Wernicke’s area in the left hemisphere. Anterior regions of the STG are adjacent to primary auditory cortex, while posterior portions interface with the inferior parietal lobule.
Connections
The STG and Wernicke’s area are richly interconnected with several regions involved in auditory, language, memory, and social processing. Key projections include reciprocal connections with Broca’s area (areas 44/45) via the arcuate fasciculus and superior longitudinal fasciculus (Friederici, 2009).
The STG also connects to the middle and inferior temporal gyri, angular gyrus, insula, auditory cortices, medial prefrontal cortex, and limbic structures such as the hippocampus and amygdala. These connections allow it to serve as an integrative node for phonological decoding, semantic association, and social signal interpretation.
Participation in brain networks
The STG, particularly Wernicke’s area, is a core component of the perisylvian language network and the broader semantic system.
It plays a central role in the dorsal language pathway (linking auditory perception to speech production) and the ventral stream (mapping sound to meaning) (Binder et al., 2009).
Additionally, the STG contributes to the auditory processing network, including pitch and rhythm perception, and the social cognition network, supporting emotion recognition and theory of mind through its connections with temporoparietal and prefrontal areas.
Functions
The STG is involved in the hierarchical processing of auditory stimuli, progressing from basic acoustic features to phonemic decoding, lexical access, and sentence-level comprehension.
Wernicke’s area specifically supports the comprehension of spoken and written language, semantic processing, and syntactic parsing.
Beyond language, the STG contributes to processing prosody, voice identity, and socially relevant auditory cues, such as emotional tone and intention in speech (Price, 2012). Its posterior portions are also implicated in integrating auditory input with memory and visuospatial representations, making it essential for multimodal understanding.
Role in clinical disorders
Damage to Wernicke’s area results in Wernicke’s aphasia, characterized by fluent yet nonsensical speech, impaired comprehension, and semantic paraphasias. The STG more broadly is implicated in language-related disorders such as conduction aphasia, dyslexia, and auditory verbal agnosia.
Abnormal structure or function of the STG is also linked to autism spectrum disorder (ASD), particularly in relation to deficits in prosody perception, social auditory processing, and speech comprehension (Boddaert et al., 2004).
In schizophrenia, STG abnormalities—especially volume loss and hypoactivation—have been associated with auditory hallucinations and thought disorganization.
Moreover, disruptions in STG connectivity have been noted in Alzheimer’s disease and frontotemporal dementia, where they contribute to semantic memory impairments and language decline.
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Latest findings
Recent neuroimaging, electrophysiological, and connectomic studies have expanded our understanding of the STG’s functional architecture. High-resolution fMRI has revealed distinct subregions within the STG specialized for phonological, lexical-semantic, and syntactic processing, with fine-grained lateralization patterns supporting left-dominant language functions.
MEG and intracranial EEG studies have shown that the posterior STG rapidly engages within 100–200 milliseconds during word recognition, suggesting its role in early access to phonological and semantic representations.
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Advanced diffusion imaging has further refined the understanding of dorsal and ventral language pathways, highlighting distinct subcomponents of the arcuate fasciculus that link posterior STG with Broca’s area and anterior temporal regions (Dick et al., 2014).
Additionally, studies of functional reorganization post-stroke have demonstrated compensatory recruitment of right hemisphere homologues of Wernicke’s area in individuals recovering from aphasia, underscoring the plasticity of the STG in language networks.
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Beyond language, research has emphasized the role of the STG in social auditory cognition. For instance, the right posterior STG is increasingly recognized for its role in detecting vocal emotional cues and sarcasm, while its connectivity with medial prefrontal areas supports mental state attribution.
Functional abnormalities in these circuits are now considered potential neurobiological markers in disorders of social communication, including ASD and schizophrenia. Ongoing work using neuromodulation (e.g., transcranial magnetic stimulation) has begun to explore the therapeutic potential of targeting STG subregions to enhance language comprehension or reduce auditory hallucinations in clinical populations.
Area 23: Ventral Posterior Cingulate Cortex (vPCC)
The ventral posterior cingulate cortex (vPCC) is a subregion of the posterior cingulate cortex and plays a central role in the integration of memory, emotional context, and internally directed cognition.
As part of the limbic system, it is critically involved in the processing of autobiographical memory, self-referential thought, and emotional salience. Its functional role in internal cognition is supported by its extensive connectivity with medial temporal and prefrontal structures.
The vPCC is functionally distinct from the dorsal posterior cingulate cortex (dPCC), with a stronger emphasis on affective memory and self-related processing. Graphic © Big8/Shutterstock.com.
Brodmann areas
The vPCC is primarily located within Brodmann area 23 (Vogt et al., 2006). Area 23 extends along the posterior cingulate gyrus and is functionally subdivided into ventral and dorsal components.
The ventral division is associated more closely with affective and mnemonic functions, while the dorsal division plays a greater role in attentional control and cognitive integration.
Location
The vPCC is situated medially, ventral to the precuneus and dorsal to the splenium of the corpus callosum. It lies within the posterior cingulate gyrus and is bordered by the retrosplenial cortex and parahippocampal regions.
On the scalp, EEG sites Pz and CPz approximate its medial parietal location, although its depth and curvature require advanced neuroimaging for precise assessment.
Connections
The vPCC maintains extensive reciprocal connections with the medial prefrontal cortex (mPFC), hippocampus, parahippocampal gyrus, lateral parietal cortex, and temporal pole (Leech & Sharp, 2014; Utevsky et al., 2014).
These connections enable it to serve as a central hub for integrating autobiographical memory with emotional and self-relevant content. It also communicates with subcortical structures involved in affective regulation, including the thalamus and basal forebrain.
Participation in brain networks
The vPCC is a key node in the default mode network (DMN), a large-scale brain network most active during internally directed mental activity such as mind-wandering, introspection, and autobiographical memory retrieval (Raichle et al., 2001; Buckner et al., 2008).
The vPCC specifically anchors the posterior DMN subsystem and interacts with the mPFC and angular gyrus to support self-referential processing and simulation of future events.
Functions
The vPCC plays a vital role in self-related cognition, emotional evaluation of memory content, and context-sensitive memory retrieval.
It supports autobiographical memory by linking affective salience to personal experiences and integrating them into a coherent narrative self.
It also contributes to social cognition, including perspective-taking and empathy, through its participation in the DMN and its connectivity with limbic and paralimbic structures (Leech & Sharp, 2014).
Role in clinical disorders
Abnormal activity or connectivity of the vPCC has been implicated in numerous neuropsychiatric and neurodegenerative disorders.
In Alzheimer's disease, early metabolic decline and hypoconnectivity in the vPCC are hallmark findings, reflecting its vulnerability in the progression of cortical atrophy (Buckner et al., 2005).
In major depressive disorder, hyperconnectivity within the DMN, particularly between the vPCC and mPFC, has been associated with ruminative thought patterns and impaired cognitive flexibility (Sheline et al., 2010).
In autism spectrum disorder (ASD), altered vPCC activation correlates with deficits in self-processing and reduced DMN connectivity, contributing to impairments in social cognition and theory of mind (Padmanabhan et al., 2017).
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Latest findings
Recent studies using dynamic functional connectivity and high-resolution fMRI have revealed that the vPCC is not a functionally uniform region but consists of multiple subunits with distinct roles.
While the core vPCC integrates emotional memory and self-referential processing, adjacent transitional zones toward the retrosplenial cortex exhibit more spatial navigation and contextual encoding functions. These findings refine the traditional DMN model by showing that the vPCC dynamically interacts with different subnetworks depending on cognitive demands.
Additionally, machine learning classifiers trained on vPCC activity patterns now reliably distinguish between healthy controls and individuals with mild cognitive impairment or early Alzheimer’s disease, highlighting its potential as a sensitive biomarker for early diagnosis.
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Another emerging area of research involves the vPCC’s involvement in consciousness and awareness. Intracranial EEG and neurostimulation studies suggest that vPCC activity decreases reliably during anesthetic-induced unconsciousness and in disorders of consciousness such as vegetative states. This observation aligns with the hypothesis that the vPCC serves as a central hub for integrating internal cognitive states.
Furthermore, transcranial stimulation studies targeting the vPCC are under investigation for their ability to modulate self-referential thought in depression and to improve autobiographical memory in aging populations. These developments underscore the vPCC’s pivotal role in both health and disease, particularly in relation to internal mentation and memory-based self-awareness.
Areas 24 and 25: Ventral Anterior Cingulate Cortex (vACC)
The ventral anterior cingulate cortex (vACC) is a subregion of the anterior cingulate cortex, located within the medial prefrontal cortex and forming part of the limbic system.
It plays a central role in emotional regulation, autonomic control, decision-making, and the integration of affective and cognitive processes.
Functionally, the vACC is critical for adaptive behavioral responses to emotional and motivational stimuli, linking internal affective states to behavioral output.
It is distinguished from the dorsal anterior cingulate cortex (dACC) by its stronger involvement in emotion-related processes rather than cognitive control.
Graphic © Big8/Shutterstock.com.
Brodmann areas
The vACC primarily includes Brodmann areas 24 and 25. Area 24 lies ventrally within the cingulate gyrus and transitions into area 25 (subgenual cingulate cortex), which is positioned directly beneath the genu of the corpus callosum (Vogt, 2005).
Area 25, in particular, has been closely linked to mood regulation and is a target of interest in depression research and treatment.
Location
The vACC is situated in the medial frontal lobe, anterior and ventral to the dACC, lying
in the subcallosal and pregenual regions of the anterior cingulate cortex.
Area 25 lies beneath the genu of the corpus callosum, while area 24 occupies the more rostral and dorsal portions of the vACC.
EEG sites FCz and Cz approximate its position on the scalp, although its deep location makes it more effectively studied through neuroimaging modalities such as fMRI or PET.
Connections
The vACC has robust connections with multiple limbic, prefrontal, and subcortical structures.
It receives afferent input from the amygdala, hippocampus, and insula, and projects to the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), nucleus accumbens, and hypothalamus (Bush et al., 2000; Etkin et al., 2011). These connections support its role in integrating emotional salience with autonomic and motivational responses, and in shaping emotional memory and mood regulation.
Participation in brain networks
The vACC is a key node within the salience network, which includes the anterior insula and dACC and is responsible for detecting behaviorally relevant stimuli and coordinating shifts in attention and control (Seeley et al., 2007; Menon, 2011).
The vACC also interacts with the default mode network during self-referential and emotional processing and has reciprocal communication with the limbic system to support affective valuation and internal state monitoring.
Functions
The vACC is involved in emotional appraisal, empathy, decision-making under uncertainty, conflict monitoring, and the regulation of autonomic responses to emotional stimuli. It plays a central role in detecting emotionally salient events and adapting behavioral responses accordingly.
Area 25, in particular, is implicated in processing negative affect and maintaining emotional homeostasis.
The vACC also contributes to social cognition by integrating emotional cues into prosocial and empathic responses (Etkin et al., 2011).
Role in clinical disorders
Abnormal structure and function of the vACC have been consistently linked to psychiatric disorders.
In major depressive disorder, increased activity and metabolic hyperconnectivity of area
25 are associated with rumination, negative affect, and treatment resistance (Drevets et al., 2008).
The vACC is also implicated in anxiety disorders, where hyperresponsiveness to threat cues may underlie excessive worry and autonomic dysregulation.
In schizophrenia and bipolar disorder, altered vACC connectivity contributes to emotional dysregulation and impaired social cognition.
Dysfunctional vACC activity is further observed in ADHD and autism spectrum disorder, where it may reflect deficits in emotional regulation and self-referential processing (Etkin et al., 2010).
Areas 25 and 24b: Subgenual Ventromedial Prefrontal Cortex (vmPFC)
The subgenual region of the ventromedial prefrontal cortex (vmPFC) is a critical structure within the medial prefrontal cortex that is deeply involved in emotional regulation, valuation, and self-referential cognition. It functions as an integrative hub linking affective, autonomic, and motivational processes, and plays a pivotal role in modulating behavioral responses based on internal emotional states. This region is particularly relevant for understanding affective disorders due to its regulatory influence over subcortical limbic circuits. Graphic © Big8/Shutterstock.com.
Brodmann areas
The subgenual region of the vmPFC primarily consists of Brodmann areas 25 and 24b (Ongür et al., 2003).
Location
The subgenual vmPFC comprises primarily Brodmann areas 25 and 24b.
Area 25, also known as the subgenual cingulate cortex, is located beneath the genu of the corpus callosum, while area 24b lies dorsally and forms part of the ventral anterior cingulate cortex (Ongür et al., 2003). These areas are distinct in cytoarchitecture and connectivity but functionally converge to support affective homeostasis and mood regulation.
Connections
This region maintains dense reciprocal connections with the amygdala, hippocampus, hypothalamus, nucleus accumbens, insula, and dorsolateral prefrontal cortex (Ongür et al., 2003; Price & Drevets, 2010). These connections support its role in linking affective valence with decision-making, modulating stress responses, and integrating interoceptive signals.
The subgenual vmPFC is also connected with key components of the serotonergic and dopaminergic systems, which underlie its influence on mood regulation and reward processing.
Participation in brain networks
The subgenual vmPFC is a central node in the default mode network (DMN), where it participates in self-referential thought, valuation, and autobiographical memory (Buckner et al., 2008).
It also contributes to the affective network, interacting with the limbic system to regulate mood and affective salience (Rudebeck et al., 2014).
Its dual role in internally directed cognition and affective evaluation positions it as a key interface between cognitive control and emotional processing systems.
Functions
The subgenual vmPFC is critical for emotion regulation, value-based decision-making, and the encoding of personal relevance or affective meaning.
It modulates autonomic and endocrine responses to stress and integrates affective input into goal-directed behavior.
The vmPFC also plays a role in empathy, social valuation, and introspection, supporting its involvement in higher-order social and moral cognition (Roy et al., 2012).
Role in clinical disorders
Dysregulation of the subgenual vmPFC is strongly implicated in mood and anxiety disorders.
In major depressive disorder (MDD), hyperactivity and metabolic dysregulation of area 25 are consistently reported and are correlated with treatment-resistant symptoms and ruminative thought (Mayberg, 2003). This region is also a primary target for deep brain stimulation (DBS) in treatment-resistant depression.
In bipolar disorder and PTSD, altered connectivity between the subgenual vmPFC and limbic structures such as the amygdala and hippocampus contributes to mood instability and dysregulated fear responses.
Dysfunctional vmPFC activity has also been associated with impaired reward valuation in substance use disorders and altered emotional insight in schizophrenia.
Latest findings
Recent advances in neuroimaging and neuromodulation have further clarified the distinct role of the subgenual vmPFC in emotional homeostasis.
High-resolution fMRI studies have identified altered functional connectivity between the subgenual vmPFC and the amygdala, dorsal anterior cingulate cortex, and insula in individuals with major depressive disorder and generalized anxiety disorder. These findings suggest that the subgenual vmPFC acts as a regulatory gate, dampening hyperactive limbic responses to emotional stimuli.
Moreover, resting-state connectivity analyses have shown that the degree of subgenual vmPFC–DMN coupling predicts symptom severity in depression and social withdrawal, highlighting its importance in affective network integrity.
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Importantly, the subgenual vmPFC has also become a focal point for neuromodulatory interventions. Deep brain stimulation (DBS) of area 25 has shown sustained antidepressant effects in treatment-resistant depression, with response rates linked to modulation of vmPFC–amygdala and vmPFC–striatum circuits (Mayberg et al., 2005).
Non-invasive techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) targeting medial prefrontal networks have begun to show promise in modulating subgenual activity indirectly.
Additionally, computational modeling of value-based decision-making has identified the subgenual vmPFC as a central node in encoding subjective value under uncertainty, particularly in the context of emotionally charged or socially relevant choices.
These findings position the subgenual vmPFC not only as a clinical biomarker but also as a potential target for precision neuromodulation and cognitive-affective rehabilitation strategies.
Area 27: Piriform (Pyriform) Cortex
The piriform cortex, often referred to as the primary olfactory cortex, is a key structure in the processing of olfactory information. Unlike the neocortex, it is part of the allocortex, specifically the paleocortex, and lacks the six-layered organization typical of isocortical regions.
The piriform cortex receives direct monosynaptic input from the olfactory bulb, bypassing the thalamus, making it unique among primary sensory areas. It plays a critical role not only in odor detection and discrimination but also in the association of odors with memory and emotional salience, functioning as a major node in olfactory-limbic circuitry. Graphic © Big8/Shutterstock.com.
Brodmann areas
The piriform cortex does not correspond to a specific Brodmann area, as it resides within the allocortical domain, which was not extensively mapped in Brodmann’s original scheme.
However, it is often functionally associated with regions adjacent to Brodmann area 27, which includes the presubiculum and entorhinal cortex (Shepherd, 2007). Its classification within the paleocortex reflects its phylogenetic antiquity and fundamental role in olfaction.
Location
The piriform cortex is situated in the medial temporal lobe. It lies anterior to the perirhinal cortex and lateral to the amygdala, extending from the olfactory tubercle to the entorhinal cortex. It includes both anterior and posterior subdivisions, which differ in connectivity and function. Its proximity to limbic structures facilitates rapid olfactory-emotional integration (Neville & Haberly, 2004).
Connections
The piriform cortex has widespread reciprocal connections with the olfactory bulb, anterior olfactory nucleus, amygdala, hippocampus, thalamus, hypothalamus, and orbitofrontal cortex (Gottfried, 2010). These connections allow it to serve as a convergence point for sensory, mnemonic, and affective information.
It projects directly to the amygdala and hippocampus, supporting odor-driven emotional and memory-related behaviors. The piriform cortex also communicates with the orbitofrontal cortex, where conscious odor perception and discrimination are refined.
Participation in brain networks
The piriform cortex is a central component of the olfactory network, functioning in tandem with limbic and frontal regions. It participates in networks related to sensory integration, emotional salience, and reward-based learning.
In particular, its interactions with the amygdala and hippocampus enable the formation of odor–emotion and odor–memory associations. It also plays a role in modulating behavior in response to olfactory cues, contributing to feeding, mating, and threat avoidance behaviors.
Functions
The piriform cortex is essential for the perception and discrimination of odors. It is involved in encoding odor identity, generalization, and associative odor memory.
The anterior piriform cortex is specialized for pattern separation and odor discrimination, while the posterior region supports generalization and integration of olfactory experiences.
Additionally, the piriform cortex contributes to behavioral and emotional responses to odors, including the formation of aversive or appetitive odor associations, often without conscious awareness (Neville & Haberly, 2004).
Role in clinical disorders
Dysfunction of the piriform cortex has been implicated in several neurological and psychiatric conditions.
In Alzheimer’s disease and Parkinson’s disease, early olfactory deficits often precede cognitive and motor symptoms, suggesting early involvement of olfactory pathways including the piriform cortex (Doty, 2008).
In schizophrenia, aberrant piriform cortex activity has been linked to impaired odor identification and emotional processing, possibly reflecting broader disruptions in sensory-limbic integration.
Additionally, epileptic foci in the piriform cortex have been associated with olfactory auras and temporal lobe epilepsy, underscoring its susceptibility to hyperexcitability and seizure generation.
Latest findings
Recent research using high-resolution functional imaging and optogenetics has provided deeper insights into the functional architecture of the piriform cortex. Studies show that odor representations in the piriform cortex are spatially distributed and non-topographic, distinguishing it from other sensory cortices. This distributed coding scheme enables robust pattern recognition and generalization across different odor contexts.
Furthermore, the piriform cortex exhibits experience-dependent plasticity: exposure to odorants or associative learning tasks reshapes synaptic responses in a manner that enhances odor discrimination and predictive coding. These findings suggest that the piriform cortex functions as both a sensory and associative hub, integrating olfactory cues with context and expectation.
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Another area of investigation concerns the piriform cortex’s role in consciousness and multisensory integration.
Functional connectivity studies have demonstrated that the piriform cortex engages with the salience network during odor-evoked attention and interacts dynamically with the default mode network during rest and olfactory imagery.
Additionally, recent work has implicated the piriform cortex in interoceptive-olfactory coupling, particularly in disorders such as depression and anxiety, where olfactory deficits may reflect altered emotional homeostasis. In translational research, the piriform cortex is gaining attention as a potential target for neuromodulation and early detection in neurodegenerative diseases, with olfactory testing increasingly used as a biomarker for prodromal pathology.
Area 28: Ventral Entorhinal Cortex (vEC)
The ventral entorhinal cortex (vEC) is a major hub within the medial temporal lobe memory system, serving as a principal gateway between the neocortex and the hippocampus.
Functionally and anatomically distinct from its dorsal counterpart, the vEC plays a critical role in processing non-spatial information related to objects, context, and episodic content. It integrates multimodal sensory input and relays processed signals to the hippocampal formation for the encoding and retrieval of episodic memories.
The vEC, as part of the allocortex, exhibits a three-layered structure and is especially vulnerable to early pathological changes in neurodegenerative diseases. Graphic © Big8/Shutterstock.com.
Brodmann areas
The entorhinal cortex has historically been associated with Brodmann area 28, although its classification within the allocortex sets it apart from the six-layered isocortical regions typically mapped in Brodmann’s system (Witter et al., 2000).
Area 28 encompasses the anterior portion of the parahippocampal gyrus and includes both the ventral and dorsal entorhinal subdivisions. The vEC is defined primarily by its position along the ventromedial surface of the temporal lobe and its unique input-output circuitry with perirhinal and hippocampal structures.
Location
The vEC is located in the anterior medial temporal lobe, situated ventrally to the hippocampal formation and posterior to the perirhinal cortex. It lies adjacent to the amygdala and is bordered anteriorly by the olfactory cortex and posteriorly by the parahippocampal cortex. This strategic position supports its role in integrating object, contextual, and affective information for downstream hippocampal processing.
Connections
The vEC maintains dense reciprocal connections with several key regions involved in episodic memory and cognition. Its primary afferents arise from the perirhinal cortex, orbitofrontal cortex, insula, and amygdala.
It projects to the dentate gyrus and CA3/CA1 fields of the hippocampus via the perforant pathway and receives return projections from the subiculum.
The vEC also maintains connections with the parahippocampal cortex and medial prefrontal cortex, facilitating the binding of memory representations with emotional and executive signals (van Strien et al., 2009; Witter et al., 2000).
Participation in brain networks
The vEC is a central node in the medial temporal lobe memory system and participates in broader networks subserving episodic memory, familiarity recognition, and spatial navigation.
It is part of the anterior limbic system and interfaces with both the default mode network and medial prefrontal circuits involved in memory-guided decision-making. Its connectivity with the hippocampus underlies its role in the dynamic reactivation of memory traces and temporal sequence coding.
Functions
The vEC is involved in the encoding and retrieval of episodic and contextual memories, object-place associations, and memory for temporal order.
While the dorsal entorhinal cortex is more associated with spatial mapping via grid cell activity, the vEC is specialized for processing content-rich, non-spatial components of memory such as object identity and affective context (Hafting et al., 2005; Eichenbaum et al., 2007).
The vEC also contributes to novelty detection and serves as a relay for emotionally salient information from the amygdala to the hippocampus.
Role in clinical disorders
The vEC is among the earliest regions affected in Alzheimer’s disease, with neurofibrillary tangles and synaptic dysfunction appearing in layer II neurons of the entorhinal cortex during the preclinical stages (Braak & Braak, 1991).
Degeneration in this area leads to progressive impairments in episodic memory and spatial orientation.
The vEC is also involved in temporal lobe epilepsy, often serving as a seizure initiation or propagation site due to its strong excitatory connectivity with hippocampal structures.
In schizophrenia, alterations in entorhinal connectivity and volume have been linked to episodic memory impairments and cognitive disorganization (Du et al., 2017). These pathologies underscore the vEC’s centrality in memory circuitry and its vulnerability to network-level dysfunction.
Latest findings
Recent advances in high-resolution neuroimaging and single-cell electrophysiology have expanded our understanding of the functional heterogeneity within the entorhinal cortex. Distinct neuronal populations within the vEC have been shown to support object-specific memory coding, including cells that selectively fire for object identity, emotional valence, and task context.
In contrast to the dorsal entorhinal cortex, which encodes spatial information via grid cells, the vEC appears to integrate affective and perceptual input to generate object-context associations essential for episodic memory. Studies using in vivo calcium imaging in rodents and ultra-high-field MRI in humans demonstrate that vEC activity predicts successful memory encoding and supports memory reinstatement during retrieval, even in the absence of spatial cues.
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In the context of neurodegeneration, recent biomarker studies using tau-PET imaging have confirmed that early pathological tau accumulation in the vEC precedes hippocampal involvement in Alzheimer's disease. These findings position the vEC as a critical site for early detection and intervention.
Moreover, connectomic analyses in individuals with mild cognitive impairment (MCI) show that reduced vEC–hippocampal connectivity correlates with poorer performance on delayed recall tasks. In translational neuroscience, modulation of vEC activity through deep brain stimulation and non-invasive neuromodulation is being explored as a means of restoring hippocampal network function in memory-impaired populations.
These findings reinforce the vEC's role as a critical bottleneck in memory processing and highlight its potential as a biomarker and therapeutic target in aging and neuropsychiatric disorders.
Areas 28 and 34: Dorsal Entorhinal Cortex (dEC)
The dorsal entorhinal cortex (dEC) is a critical structure within the medial temporal lobe that contributes to spatial memory, navigation, and contextual information processing.
As part of the entorhinal cortex (EC), the dEC acts as a major input/output interface between the neocortex and the hippocampus. Its unique role in the medial temporal lobe memory system involves the encoding of spatial maps and the integration of environmental cues to support navigation and memory-guided behavior. Graphic © Big8/Shutterstock.com.
Brodmann areas
The entorhinal cortex is traditionally associated with Brodmann areas 28 and 34, though these cytoarchitectonic designations do not capture the full complexity of its organization.
Area 28 encompasses the main body of the EC, including both dorsal and ventral subdivisions, while area 34 corresponds to the more anterior portion of the parahippocampal gyrus, adjacent to the amygdala (Van Strien et al., 2009).
Despite its inclusion in Brodmann’s system, the EC is considered allocortical, with a simpler three-layered structure compared to the six-layered isocortex.
Location
The dEC is situated in the medial temporal lobe, dorsally to the ventral entorhinal cortex (vEC) and posterior to the perirhinal cortex. It borders the subiculum and the presubiculum and lies adjacent to the parahippocampal cortex. This dorsal position facilitates its preferential involvement in spatial and contextual information processing, in contrast to the vEC’s role in object-related memory.
Connections
The dEC maintains robust bidirectional connections with the hippocampus—particularly the dentate gyrus, CA3, and CA1 fields—via the perforant path (Witter et al., 2000). It also receives inputs from the parahippocampal and retrosplenial cortices and projects to various cortical regions involved in visuospatial perception and memory integration. These connections enable the dEC to relay spatially coded information from cortical association areas to the hippocampus, forming a core component of the hippocampal-entorhinal loop.
Participation in brain networks
The dEC is a key node in the medial temporal lobe memory network, especially within the hippocampal formation's extended spatial processing system.
It is part of the network supporting egocentric-to-allocentric transformations, grid cell activity, and spatial learning. Functionally, it interfaces with the posterior default mode network and with navigation-related hubs such as the retrosplenial and posterior parietal cortices (Eichenbaum, 2000).
Functions
The dEC plays a vital role in spatial navigation, contextual memory, and the encoding of location-specific information.
It is especially notable for containing grid cells—neurons that fire at regular intervals as an animal traverses an environment, forming a coordinate system used to track spatial location independently of external cues (Hafting et al., 2005). This grid-based coding mechanism is essential for path integration and cognitive mapping, forming the neural basis for complex spatial representation.
Role in clinical disorders
The dEC is among the earliest cortical regions affected in Alzheimer’s disease, with pathological tau accumulation and functional disconnection observed prior to widespread cortical degeneration (Khan et al., 2014). Impairments in spatial navigation and orientation, common in the early stages of Alzheimer’s, have been linked to dEC dysfunction.
In temporal lobe epilepsy, the entorhinal cortex, including the dorsal region, is often implicated in seizure onset or propagation.
Abnormal dEC function has also been associated with schizophrenia, particularly in the context of disrupted hippocampal-prefrontal connectivity and working memory deficits.
Latest findings
Recent neurophysiological and imaging studies have significantly advanced our understanding of the dEC's microcircuitry and function. In vivo recordings in rodents and humans have confirmed that the dEC contains not only grid cells but also head direction cells, border cells, and speed-modulated cells, all of which contribute to a robust internal map of space.
High-resolution 7T fMRI in humans has shown activation patterns in the dEC that correlate with self-location and heading direction during virtual navigation tasks. Furthermore, the functional differentiation between the dEC and vEC is now well-established, with the dEC playing a more prominent role in the encoding of allocentric spatial frameworks and temporal sequences.
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At the clinical interface, recent studies using tau-PET imaging have shown that tau pathology in the dEC precedes hippocampal and neocortical involvement in Alzheimer’s disease, highlighting its importance as a potential early biomarker.
Functional connectivity analyses in mild cognitive impairment (MCI) patients reveal disrupted dEC–hippocampus coupling during spatial memory tasks, and performance on virtual navigation paradigms correlates strongly with dEC integrity.
Additionally, neurostimulation targeting dEC-hippocampal circuits is under investigation for enhancing spatial memory and navigation abilities in aging populations. These findings collectively underscore the dEC’s central role in spatial cognition and its emerging relevance in early detection and intervention strategies for neurodegenerative and psychiatric disorders.
Areas 29 and 30: Ectosplenial Retrosplenial Cerebral Cortex
The retrosplenial cortex (RSC), comprising Brodmann areas 29 and 30, is a pivotal component of the medial posterior cerebral cortex. It plays an essential role in memory, spatial orientation, and higher-order cognitive functions.
While the term “ectosplenial” has been used in comparative neuroanatomy—particularly in rodents and non-human primates—to refer to lateral subdivisions of the retrosplenial area, it is not a widely recognized or formally defined anatomical term in human neuroanatomy.
Nonetheless, the retrosplenial cortex as a whole is a functionally and structurally conserved region across species, critically involved in spatial cognition, episodic memory, and scene processing. Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann areas 29 and 30 form the cytoarchitectonic core of the retrosplenial cortex. Area 29, often referred to as granular retrosplenial cortex, is located medially and demonstrates a prominent layer IV.
Area 30, the agranular component, lies laterally and transitions into the posterior cingulate cortex. Both regions are situated within the caudal portion of the cingulate gyrus, forming a bridge between limbic and neocortical networks (Vogt et al., 2006).
Location
The retrosplenial cortex is located in the posterior medial parietal lobe, directly posterior to the splenium of the corpus callosum. It is bounded medially by the callosal sulcus and laterally by the precuneus. The RSC lies adjacent to, and is often continuous with, the posterior cingulate cortex, particularly in area 23. In EEG studies, approximate scalp correlates include midline electrodes such as Pz, CPz, and Oz (Jasper, 1958), although these provide only rough localization of underlying cortical structures.
Connections
The retrosplenial cortex exhibits extensive reciprocal connectivity with a broad array of cortical and subcortical regions. It maintains strong projections to and from the hippocampus—especially the subiculum and presubiculum—as well as the entorhinal cortex and parahippocampal cortex. It is also interconnected with the anterior thalamic nuclei, anterior and posterior cingulate cortices, medial prefrontal cortex, and lateral parietal regions. This pattern of connectivity places the RSC at the intersection of limbic, memory, and visuospatial networks (Vann et al., 2009; Kobayashi & Amaral, 2003).
Participation in brain networks
The RSC is a core component of the default mode network (DMN), a large-scale brain system implicated in self-referential thought, autobiographical memory, and future planning.
Within this network, the RSC appears to serve as a functional bridge between the medial temporal lobe memory system and other default mode network nodes, such as the medial prefrontal cortex and posterior cingulate cortex (Buckner et al., 2008). The RSC also interacts with the dorsal attention network during tasks involving spatial navigation and memory-guided attention.
Functions
The retrosplenial cortex is involved in a range of cognitive processes, including spatial navigation, episodic memory retrieval, scene construction, and contextual learning. It plays a crucial role in translating between egocentric (self-referenced) and allocentric (world-referenced) spatial frameworks, enabling individuals to navigate both familiar and novel environments.
Functional imaging studies consistently show retrosplenial activation during tasks requiring mental scene construction and autobiographical recall (Epstein, 2008; Vann et al., 2009). Moreover, the RSC is engaged during visual-spatial imagery, suggesting its role in linking perception with memory-guided behavior.
Role in clinical disorders
Disruption of retrosplenial structure or function has been observed in several neurological and psychiatric disorders, with significant clinical consequences. In Alzheimer’s disease, the RSC exhibits early hypometabolism and structural atrophy, which correlate with impairments in spatial navigation and autobiographical memory. These changes may occur before overt hippocampal degeneration, highlighting the region’s value as a potential early biomarker (Minoshima et al., 1997).
Bilateral lesions of the retrosplenial cortex, although rare, are associated with profound topographical disorientation and anterograde amnesia.
The RSC has also been implicated in schizophrenia, where functional dysconnectivity within the default mode network may contribute to disordered self-referential processing, and in depression, where altered retrosplenial activity correlates with rumination and maladaptive memory retrieval (Maguire, 2001; Mendez & Cherrier, 2003).
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Latest findings
Recent studies have expanded our understanding of the retrosplenial cortex, both in terms of functional specialization and clinical relevance. Using ultra-high field 7T MRI, Schaefer et al. (2023) have identified distinct subregions within areas 29 and 30, each with unique patterns of structural connectivity and functional activation. These findings suggest that the retrosplenial cortex is not a homogenous structure, but rather a functionally heterogeneous hub, integrating information across cognitive domains.
Longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) have confirmed that retrosplenial atrophy precedes hippocampal degeneration in individuals with early amyloid pathology. Notably, tau PET imaging has demonstrated that the RSC is one of the initial cortical sites of tau deposition in preclinical Alzheimer’s disease, even in the absence of overt cognitive symptoms (Guzmán-Vélez et al., 2024).
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In the realm of spatial cognition, studies employing immersive virtual reality environments have demonstrated that the RSC is critical for allocentric-to-egocentric transformations, a fundamental process in flexible navigation (Chrastil et al., 2023). These findings are consistent with lesion and inactivation studies in animal models.
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Moreover, neuromodulation research has begun exploring the therapeutic potential of targeting the retrosplenial cortex using non-invasive brain stimulation. Preliminary data suggest that repetitive transcranial magnetic stimulation (rTMS) targeting retrosplenial-parietal circuits can enhance memory retrieval in healthy adults and may offer future clinical applications in early cognitive decline (Benoit et al., 2024).
Areas 35 and 36: Perirhinal Cortex (PRC)
The perirhinal cortex (PRC), encompassing Brodmann areas 35 and 36, is a pivotal region within the medial temporal lobe, critically involved in object recognition, associative memory, and familiarity-based memory processing. It functions as an interface between unimodal sensory cortices and the hippocampal formation, integrating perceptual information with mnemonic content. This region plays a fundamental role in enabling complex object representations and in resolving perceptual ambiguity, particularly when distinguishing between similar stimuli. Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann area 35 lies along the medial bank of the collateral sulcus and is characterized by a relatively agranular cortical architecture. Area 36 occupies the lateral bank and exhibits a more differentiated laminar structure. Together, these areas form the perirhinal cortex, which serves as a transitional zone between the highly processed sensory information arriving from the ventral visual stream and the entorhinal-hippocampal memory system. Early anatomical work by Van Hoesen and Pandya (1975) identified these regions as integral to the organization of the medial temporal lobe.
Location
The perirhinal cortex is situated in the anterior medial temporal lobe, extending along the collateral sulcus. Medially, it borders the entorhinal cortex, and laterally it lies adjacent to the parahippocampal cortex and the fusiform gyrus. This location enables the PRC to receive input from high-order visual areas in the inferior temporal cortex, allowing it to process detailed object features before transmitting integrated representations to the hippocampus via the entorhinal cortex.
Connections
The PRC maintains extensive reciprocal connections with several key regions of the medial temporal lobe, including the entorhinal cortex, hippocampus, parahippocampal cortex, and the amygdala. It also projects to and receives input from the inferotemporal cortex, orbitofrontal cortex, and medial prefrontal cortex.
Suzuki and Amaral (1994) demonstrated that the PRC is uniquely positioned to receive converging inputs from polymodal sensory areas and to transmit this integrated information to memory-related structures. This connectivity profile supports the PRC’s involvement in both perceptual and mnemonic operations.
Participation in brain networks
The perirhinal cortex plays a critical role within the medial temporal lobe memory system. It supports familiarity-based recognition, object-context associations, and perceptual integration. The PRC contributes to the encoding of unique object features and their conjunctions, and to the retrieval of these representations in the absence of conscious recollection.
Eichenbaum and colleagues (2007) emphasized that the PRC is essential for distinguishing between similar stimuli and for maintaining information about the identity of objects over short and long timescales. It acts as a computational node where perceptual and mnemonic signals converge.
Functions
The cognitive functions of the PRC are tightly linked to its anatomical position and connectivity. It enables recognition memory by supporting familiarity judgments and is particularly involved when discriminating between objects with overlapping features.
Functional imaging studies have consistently shown PRC activation during tasks requiring complex visual object identification, especially when fine perceptual discrimination is needed.
Additionally, the PRC contributes to associative memory, allowing individuals to link objects with contextual or temporal information. This integrative function becomes increasingly important in environments requiring rapid and accurate object identification under uncertain conditions.
Role in clinical disorders
The PRC is among the first cortical areas to exhibit pathological changes in Alzheimer’s disease, particularly in Brodmann area 35. Tau pathology frequently begins in this region before spreading to the entorhinal cortex and hippocampus. As demonstrated by Khan et al. (2014), structural atrophy and metabolic decline in the PRC may serve as early biomarkers of preclinical Alzheimer’s disease. These changes are associated with impairments in object recognition and familiarity-based memory, even in the absence of global cognitive decline. T
he PRC is also implicated in temporal lobe epilepsy, where structural disruptions contribute to memory deficits and altered connectivity with the hippocampus and neocortex.
Furthermore, reduced volume and functional integrity of the PRC have been observed in semantic dementia and other conditions involving object knowledge degradation.
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Latest findings
Recent investigations have expanded our understanding of the perirhinal cortex by revealing its functional heterogeneity and its potential role as a biomarker in early neurodegeneration. High-resolution functional MRI and tractographic studies have delineated distinct subregions within the PRC, indicating that area 35 is preferentially involved in semantic processing and familiarity judgments, while area 36 is more responsive to complex perceptual discrimination tasks (Xie et al., 2023). These findings support the hypothesis that the PRC operates along a perceptual-to-mnemonic gradient.
Additionally, new research has demonstrated the PRC's capacity for crossmodal integration. Tanaka et al. (2024) reported that the PRC integrates visual, auditory, and olfactory inputs during associative learning, highlighting its role beyond traditional visual memory. Complementing these findings, computational models employing deep learning have successfully predicted PRC activity during object categorization tasks, suggesting a mechanistic correspondence between artificial neural networks and perirhinal coding (Yamins et al., 2023).
Clinically, the PRC has gained attention as a promising target for early detection of Alzheimer’s disease. Longitudinal imaging studies have confirmed that atrophy in area 35 precedes hippocampal involvement and correlates with subtle cognitive complaints in preclinical stages. Maass et al. (2024) demonstrated that tau deposition in the PRC is detectable in asymptomatic individuals at elevated risk for Alzheimer’s disease, supporting its value as a prodromal biomarker. These findings collectively underscore the perirhinal cortex’s central role in both health and disease, reinforcing its significance in cognitive neuroscience and clinical neurology.
Areas 37 and 19: Fusiform Gyrus
The fusiform gyrus is a key anatomical and functional structure of the ventral temporal lobe, playing a central role in high-level visual processing, particularly in object recognition, face perception, and visual word form processing.
Situated on the basal surface of the temporal and occipital lobes, the fusiform gyrus serves as an integral component of the ventral visual stream—often referred to as the “what” pathway—which is responsible for identifying and categorizing visual stimuli. Graphic © Big8/Shutterstock.com.
Brodmann areas
The fusiform gyrus encompasses parts of Brodmann areas 37 and 20, depending on its rostrocaudal location. Area 37, located more posteriorly, is implicated in visual recognition and semantic memory, while area 20, situated more anteriorly, contributes to complex perceptual integration. These cytoarchitectonic regions are interconnected and support the fusiform gyrus's involvement in both perceptual and associative functions.
Location
The fusiform gyrus is located on the ventral surface of the cerebral hemisphere, bounded medially by the parahippocampal gyrus and laterally by the inferior temporal gyrus. It lies between the collateral sulcus and the occipitotemporal sulcus, extending from the posterior occipital lobe into the anterior temporal lobe. This positioning allows the fusiform gyrus to receive high-order visual input from occipital areas and to relay processed visual information to temporal and limbic regions involved in memory and emotion.
Connections
The fusiform gyrus is richly interconnected with multiple cortical and subcortical structures. Posteriorly, it receives feedforward input from the primary and secondary visual cortices (V1/V2), while anteriorly, it projects to the anterior temporal lobe, amygdala, and prefrontal cortex. Notably, it is extensively connected to the superior temporal sulcus, inferior occipital gyrus, and parietal lobe, supporting multimodal integration. These anatomical connections enable the fusiform gyrus to participate in complex visual recognition tasks and to integrate visual input with emotional and semantic context.
Participation in brain networks
The fusiform gyrus is a critical node in the ventral visual processing stream, which specializes in the identification of faces, words, and complex visual stimuli. It also participates in broader semantic and limbic networks, facilitating interactions between visual perception, memory, and affective evaluation. Within this framework, the fusiform gyrus supports hierarchical object representation, moving from simple feature detection in early visual areas to integrated object-level and categorical representations.
Functions
Functionally, the fusiform gyrus is best known for its role in face perception, with the fusiform face area (FFA) located in its right lateral portion. The FFA shows selective activation to upright human faces and is sensitive to facial identity, expression, and gaze direction.
Additionally, the visual word form area (VWFA), located in the left mid-fusiform gyrus, is involved in the recognition of written words and orthographic patterns during reading. Beyond these domain-specific functions, the fusiform gyrus is implicated in object recognition, scene categorization, symbolic processing, and expert visual processing—such as in car or bird recognition in trained individuals.
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Neuropsychological and neuroimaging studies have demonstrated that damage to the fusiform gyrus can result in prosopagnosia, a deficit in face recognition, or pure alexia, an impairment in reading despite preserved language comprehension and writing abilities. These deficits highlight the functional specialization of subregions within the fusiform gyrus.
Role in clinical disorders
The fusiform gyrus is involved in a range of neurological and psychiatric disorders, reflecting its importance in perceptual and cognitive integration.
In developmental prosopagnosia, structural and functional abnormalities in the right fusiform face area are associated with impaired face perception despite normal vision and intelligence.
In autism spectrum disorder (ASD), reduced fusiform activation during face processing has been consistently reported and is thought to contribute to difficulties in social recognition and emotional responsiveness.
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In schizophrenia, hypoactivation of the fusiform gyrus during facial affect recognition is associated with social cognition deficits.
In Alzheimer’s disease, atrophy in the fusiform and adjacent temporal regions correlates with impairments in naming, semantic memory, and visual recognition.
Additionally, temporal lobe epilepsy involving the fusiform region can lead to deficits in word recognition and visual memory.
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Latest findings
Recent advances in high-resolution imaging, computational modeling, and connectivity analyses have refined the understanding of the fusiform gyrus’s functional architecture. Multimodal imaging studies have revealed that the fusiform gyrus comprises functionally distinct but anatomically overlapping modules, such as the FFA and VWFA, that exhibit experience-dependent plasticity. For example, fMRI studies have shown that the VWFA becomes increasingly specialized for orthographic stimuli with reading acquisition, supporting the idea that visual expertise shapes fusiform functional organization (Dehaene et al., 2023).
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Connectomic data from human diffusion-weighted imaging studies indicate that the fusiform gyrus acts as a relay hub connecting visual input with semantic and limbic areas. This hub-like role may explain why it is vulnerable to disconnection syndromes in both degenerative and acquired brain disorders (Smith et al., 2024).
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In the domain of machine learning and neuroinformatics, recent work has demonstrated that deep convolutional neural networks trained on object or face recognition tasks can predict activity patterns within the fusiform gyrus, supporting computational models of hierarchical visual representation that mirror human cortical organization (Kietzmann et al., 2023).
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Additionally, early diagnostic research in Alzheimer’s disease has shown that atrophy in the fusiform gyrus is detectable in the preclinical phase, particularly in individuals with impairments in naming and visual semantic processing. This suggests that fusiform degeneration may be a marker of early-stage semantic decline in neurodegenerative disease progression (Rabinovici et al., 2024).
Area 38: Temporopolar Area (Temporal Pole)
The temporal pole, corresponding to Brodmann area 38 (BA38), is a structurally and functionally complex region located at the most anterior aspect of the temporal lobe. Often referred to as the temporopolar cortex, this area plays a crucial integrative role in emotional processing, semantic memory, and social cognition.
Owing to its rich anatomical connectivity and involvement in multiple cognitive domains, the temporal pole is increasingly recognized as a convergence zone linking perceptual, emotional, and conceptual processing streams. Graphic © Big8/Shutterstock.com.
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Brodmann areas
Brodmann area 38 is defined cytoarchitectonically as the most anterior portion of the temporal lobe. It lacks a granular layer IV and is considered part of the limbic allocortex, sharing similarities with paralimbic regions such as the orbitofrontal cortex and anterior cingulate cortex.
Öngür et al. (2003) emphasized that area 38 is positioned at the intersection of the neocortex and limbic system, functioning as a heteromodal association region that integrates higher-order sensory input with emotional and contextual relevance.
Location
The temporal pole is located at the anterior extremity of the temporal lobe, lying rostral to the superior, middle, and inferior temporal gyri. It forms the anterior boundary of the temporal cortex and is bounded medially by the entorhinal and perirhinal cortices and laterally by the anterior portions of the temporal gyri. Although largely obscured from the lateral surface view by the temporal lobe curvature, it is anatomically and functionally distinct from the more posterior temporal cortices (Öngür et al., 2003).
Connections
The temporopolar area maintains dense reciprocal connections with multiple brain regions, including the amygdala, hippocampus, orbitofrontal cortex, insula, and ventromedial prefrontal cortex, as well as with other parts of the anterior and posterior temporal lobes. These connections are supported by both short-range U-fibers and long-range white matter tracts such as the uncinate fasciculus, which links the temporal pole to the frontal lobe (Olson et al., 2007). Through these connections, the temporal pole serves as a critical interface for integrating emotional valence, autobiographical memory, and semantic knowledge.
Participation in brain networks
The temporal pole is a participant in several major large-scale brain networks, including the default mode network (DMN) and the salience network.
Within the DMN, the temporal pole contributes to semantic integration, self-referential cognition, and autobiographical memory retrieval.
Within the salience network, its interactions with the anterior insula and amygdala support emotional salience attribution, social behavior, and affective empathy (Roy et al., 2009). These roles position the temporal pole at the intersection of affective and cognitive neural processing streams.
Functions
The temporal pole, corresponding to Brodmann area 38, is involved in a diverse array of high-level cognitive and affective processes. Functionally, it plays a key role in semantic memory, particularly in the integration and retrieval of conceptual knowledge that carries emotional or social significance. Neuroimaging studies have consistently demonstrated activation of the temporal pole during tasks that require access to abstract or socially embedded semantic information, including person-specific knowledge, moral concepts, and emotionally valenced language.
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In the domain of emotional processing, the temporal pole interacts closely with the amygdala, orbitofrontal cortex, and anterior insula to attribute emotional significance to sensory and mnemonic stimuli. It contributes to the representation of affectively charged experiences and to the contextual modulation of emotional responses. Functional MRI findings have shown that the temporal pole is especially engaged during autobiographical memory retrieval involving emotionally salient content, underscoring its role in binding memory and affect.
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The temporal pole is also centrally involved in social cognition, particularly in the construction of mental models about others’ emotions, intentions, and beliefs—often referred to as theory of mind. In this context, it supports the comprehension of social narratives, moral reasoning, and empathic engagement. This is reflected in increased temporal pole activation during tasks that involve interpreting social cues or making judgments about social appropriateness and interpersonal meaning.
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Moreover, the temporal pole facilitates the integration of multimodal sensory inputs into coherent conceptual representations, functioning as a heteromodal convergence zone. It receives processed information from visual, auditory, and somatosensory cortices, synthesizing these inputs into unified semantic constructs. This capacity allows the temporal pole to bridge perceptual experiences with linguistic, emotional, and autobiographical frameworks, thus enabling complex cognition grounded in personal and social meaning.
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Overall, the temporopolar cortex serves as a uniquely integrative structure, linking semantic knowledge, emotional significance, and social understanding within a coherent neurocognitive framework. Its multifaceted role across these domains reflects its widespread anatomical connectivity and its involvement in large-scale brain networks dedicated to internal mentation, social interaction, and memory.
Role in clinical disorders
Dysfunction of the temporal pole has been observed in a range of neurodegenerative, psychiatric, and seizure-related disorders.
In frontotemporal dementia (FTD)—particularly the semantic variant of primary progressive aphasia (svPPA)—the temporal pole shows early and prominent atrophy, correlating with impairments in semantic memory and naming.
Alzheimer’s disease also involves temporal pole degeneration, though typically at a later stage than in FTD, often associated with autobiographical memory loss.
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In temporal lobe epilepsy, the anterior temporal lobe, including area 38, is frequently a site of seizure onset. Surgical resection of this region is associated with postoperative deficits in emotion recognition and autobiographical memory.
Additionally, in major depressive disorder and schizophrenia, aberrant connectivity of the temporal pole with limbic and prefrontal regions has been linked to deficits in emotional regulation, social cognition, and semantic coherence (Seeley et al., 2009).
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Latest findings
Recent research has advanced our understanding of the temporal pole’s microstructural, functional, and clinical relevance. High-resolution structural MRI and diffusion tensor imaging (DTI) have revealed that the temporal pole possesses a unique pattern of microstructural organization, characterized by high local connectivity and long-range projections through the uncinate fasciculus and inferior longitudinal fasciculus. These connections underpin its role as a semantic-affective hub (Bajada et al., 2023).
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Functional MRI studies using naturalistic stimuli (e.g., film, autobiographical narratives) have demonstrated increased temporal pole activation during socially and emotionally rich episodes, supporting its role in narrative-based emotion processing and moral reasoning (Zaki et al., 2023). This reflects a growing understanding that the temporal pole may integrate not only semantic content but also social-emotional context in real-world cognition.
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In clinical neuroscience, temporal pole atrophy has emerged as a predictive biomarker in the differential diagnosis of semantic variant frontotemporal dementia versus Alzheimer’s disease. Specifically, studies show that left temporal pole atrophy is more severe in svPPA, while bilateral involvement occurs in later-stage AD (Irish et al., 2024).
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Emerging neuromodulation research has begun exploring targeted transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) of the anterior temporal lobe to enhance semantic retrieval and emotional memory processing, with early-phase trials showing promise for therapeutic application in primary progressive aphasia and post-traumatic affective disorders (Sliwinska et al., 2024).
Area 39: Angular Gyrus
The angular gyrus, corresponding to Brodmann area 39, is a prominent heteromodal association area of the posterior parietal cortex. It is essential for integrating visual, auditory, and somatosensory information and plays a central role in a variety of higher cognitive functions, including language, semantic memory, numerical cognition, attention, and theory of mind.
As part of the posterior inferior parietal lobule, the angular gyrus is situated at a functional crossroads of perception and conceptual reasoning, allowing it to contribute to the abstract representation of symbolic and socially relevant knowledge. Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann area 39 is defined cytoarchitectonically as part of the inferior parietal lobule. It occupies a transitional zone between unimodal sensory areas and the heteromodal association cortices.
Caspers et al. (2006) described subregional variation within BA39, which reflects the functional diversity of the angular gyrus across different cognitive domains. Its involvement in multimodal integration is supported by its laminar structure and widespread anatomical connectivity.
Location
The angular gyrus is located in the posterior portion of the inferior parietal lobule, at the intersection of the parietal, temporal, and occipital lobes. It lies posterior to the supramarginal gyrus, wraps around the posterior end of the superior temporal sulcus, and is bordered dorsally by the lateral occipital cortex.
The region is situated beneath the P3 and P4 electrode sites in the International 10–20 EEG system (Jasper, 1958), although scalp-level recordings do not allow precise spatial localization due to the cortical folding in this region.
Connections
The angular gyrus exhibits extensive bidirectional connections with several cortical and subcortical areas. It is interconnected with the prefrontal cortex, posterior cingulate cortex, precuneus, superior temporal sulcus, and hippocampus, in addition to neighboring regions within the parietal cortex. This anatomical configuration enables the angular gyrus to integrate sensory input with linguistic, mnemonic, and social information.
Through both short-range and long-range white matter tracts—such as the superior longitudinal fasciculus—it supports distributed cognitive operations that involve cross-domain processing (Seghier, 2013).
Participation in brain networks
The angular gyrus exhibits extensive bidirectional connections with several cortical and subcortical areas. It is interconnected with the prefrontal cortex, posterior cingulate cortex, precuneus, superior temporal sulcus, and hippocampus, in addition to neighboring regions within the parietal cortex. This anatomical configuration enables the angular gyrus to integrate sensory input with linguistic, mnemonic, and social information. Through both short-range and long-range white matter tracts—such as the superior longitudinal fasciculus—it supports distributed cognitive operations that involve cross-domain processing (Seghier, 2013).
Functions
Functionally, the angular gyrus supports a wide spectrum of cognitive activities. It plays a central role in semantic processing, particularly in the retrieval and integration of lexical and conceptual knowledge. It is also implicated in numerical cognition, contributing to arithmetic fact retrieval, magnitude representation, and symbolic calculation. Furthermore, the angular gyrus is active during reading, language comprehension, and the use of metaphorical or abstract language.
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In addition to linguistic and numerical domains, the angular gyrus is involved in spatial cognition, visual imagery, and theory of mind, supporting mentalizing and perspective-taking tasks. Functional imaging consistently shows angular gyrus activation during episodic memory retrieval, especially in contexts involving the reconstruction of autobiographical experiences and the mental simulation of future events. These diverse roles reflect its capacity to act as a convergence zone for multimodal integration.
Role in clinical disorders
Lesions or dysfunction in the angular gyrus have been associated with a number of neurological and developmental disorders.
In the left hemisphere, damage to this region is a hallmark of Gerstmann syndrome, which includes agraphia, acalculia, finger agnosia, and left–right disorientation.
Angular gyrus involvement has also been implicated in anomic and conduction aphasias, where individuals exhibit impaired lexical retrieval and repetition despite intact comprehension.
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In developmental dyslexia, abnormalities in the angular gyrus contribute to difficulties with grapheme–phoneme integration, particularly during reading acquisition. The region also shows disrupted connectivity in autism spectrum disorder, schizophrenia, and Alzheimer’s disease, where deficits in memory, semantic processing, and self-referential cognition are prominent (Hoeft et al., 2007; Seghier, 2013).
Area 40: Supramarginal Gyrus
The supramarginal gyrus, corresponding to Brodmann area 40, is a multimodal association region in the inferior parietal lobule that plays a central role in integrating sensory information with motor, linguistic, attentional, and social cognitive processes.
Due to its anatomical location at the interface of auditory, somatosensory, and visual cortices, it acts as a critical hub for cross-modal processing, particularly in functions requiring real-time coordination of perception and action.
The supramarginal gyrus also contributes significantly to emotional prosody and empathy, emphasizing its role in social cognition as well. Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann area 40 defines the cytoarchitectonic boundaries of the supramarginal gyrus. It lies anterior to area 39 (angular gyrus) and is part of the inferior parietal lobule. Caspers et al. (2006) identified internal subdivisions within area 40 using postmortem microstructural analysis, reflecting its diverse functional contributions. These subdivisions correlate with its involvement in different cognitive domains, such as language, attention, and imitation.
Location
The supramarginal gyrus is located at the posterior end of the Sylvian fissure, wrapping around its terminal portion. It is bordered anteriorly by the postcentral gyrus (primary somatosensory cortex), posteriorly by the angular gyrus, and superiorly by the superior parietal lobule.
It lies deep to the P3 and P4 electrode sites of the International 10–20 EEG system (Jasper, 1958), although due to its folded and variable anatomy, scalp-based localization lacks precision for functional mapping.
Connections
The supramarginal gyrus maintains extensive reciprocal connections with frontal, parietal, temporal, and insular cortices. It is structurally connected to the dorsolateral and ventrolateral prefrontal cortex, posterior cingulate cortex, insula, and superior temporal sulcus, in addition to neighboring parietal regions. These connections allow the gyrus to act as an interface between sensory perception and cognitive control, coordinating language output, attentional shifts, and motor planning (Caspers et al., 2011).
Participation in brain networks
The supramarginal gyrus participates in several large-scale brain networks, including the frontoparietal control network, dorsal attention network, and ventral language network.
Within the dorsal attention network, it contributes to the orienting of attention toward task-relevant stimuli.
Within the frontoparietal network, it is involved in adaptive control, working memory, and error monitoring.
Its role in the ventral language network supports sublexical processing and speech articulation, particularly in coordination with the inferior frontal gyrus and superior temporal gyrus.
Functions
The supramarginal gyrus is essential for language processing, particularly in phonological working memory, verbal repetition, and speech production. It is strongly activated during tasks that require the transformation of auditory information into articulatory output. In addition, it supports sensorimotor integration, enabling the execution of skilled motor tasks by linking somatosensory feedback with motor intentions—an essential function in praxis and imitation.
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The gyrus is also involved in attention regulation, especially in reorienting attention based on changing environmental demands.
Moreover, the right supramarginal gyrus has been implicated in social cognition, including empathic responses and perspective-taking, possibly due to its interaction with somatosensory regions and the mirror neuron system. This is further supported by its role in recognizing vocal emotion (prosody) and interpreting social gestures.
Role in clinical disorders
Dysfunction in the supramarginal gyrus has been associated with a range of neurodevelopmental, neurological, and neuropsychiatric disorders.
In developmental dyslexia, reduced activation and gray matter volume in the left supramarginal gyrus are linked to impairments in phonological decoding and reading fluency (Hoeft et al., 2007).
In apraxia, particularly ideomotor apraxia, damage to the left supramarginal gyrus impairs the ability to perform skilled actions on command, reflecting its role in motor sequencing.
In aphasic syndromes, particularly conduction aphasia, supramarginal damage leads to disrupted phonological short-term memory, affecting repetition and fluency.
The right supramarginal gyrus has also been implicated in autism spectrum disorder, where atypical activation may contribute to difficulties in empathy, imitation, and social interpretation.
Lesions or hypoperfusion in this region are frequently observed in stroke-related language disorders and are predictive of poor recovery in repetition and naming tasks.
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Latest findings
Recent neuroimaging and neuromodulation studies have significantly expanded our understanding of the supramarginal gyrus. High-resolution fMRI and connectivity-based parcellation approaches have demonstrated functional dissociation between anterior and posterior subregions of the gyrus. The anterior portion is primarily engaged during phonological and verbal working memory tasks, while posterior regions show greater activity during social-emotional processing, imitation, and empathy.
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Transcranial magnetic stimulation (TMS) studies have provided causal evidence of these functions. Disruption of activity in the left supramarginal gyrus results in impaired phoneme manipulation and verbal rehearsal, while stimulation of the right supramarginal gyrus has been shown to enhance empathic accuracy, particularly in tasks involving emotional prosody.
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Resting-state fMRI studies have also demonstrated altered supramarginal connectivity in children with language delay and reading disorders, identifying this region as a potential early biomarker for neurodevelopmental risk. In post-stroke aphasia, lesion-symptom mapping has confirmed that damage to the supramarginal gyrus predicts long-term deficits in repetition and naming, supporting its inclusion in targeted rehabilitation programs.
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Emerging computational models now simulate the supramarginal gyrus’s role in auditory-motor mapping, modeling how sensory input is transformed into action during speech and imitation. These models align with empirical findings and reinforce the gyrus’s function as a cross-modal hub essential for both linguistic and praxis-related functions.
Areas 41 and 42: Auditory Cortex
The auditory cortex is the primary cortical region responsible for the perception and interpretation of auditory information. It plays a critical role in the detection, discrimination, and contextual integration of acoustic stimuli, encompassing both basic sound processing and higher-order auditory functions such as speech perception and music cognition.
Structurally and functionally complex, the auditory cortex supports dynamic auditory scene analysis, language processing, and auditory attention through its hierarchical and tonotopic organization. Graphic © Big8/Shutterstock.com.
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Brodmann areas
The primary auditory cortex is localized to Brodmann areas 41 and 42, situated on the transverse temporal gyri (also known as Heschl’s gyri) of the superior temporal plane.
Area 41 corresponds to the core auditory cortex, which exhibits precise tonotopic organization and receives direct input from the thalamic medial geniculate nucleus (MGN). Brodmann area 42 represents the belt region, part of the secondary auditory cortex, which integrates more complex auditory features and connects with multimodal association cortices.
Surrounding these primary regions, Brodmann area 22, which includes the posterior superior temporal gyrus (notably Wernicke’s area in the left hemisphere), is involved in the comprehension of spoken language and prosody (Morosan et al., 2001).
Location
The auditory cortex is located in the superior temporal gyrus, extending medially into the lateral sulcus (Sylvian fissure) and lying on the transverse temporal gyri. These gyri run mediolaterally on the dorsal surface of the temporal lobe and are hidden from the lateral cortical surface.
Area 41 occupies the medial portion of the transverse gyrus, while area 42 lies laterally and merges with the surrounding superior temporal cortex. This topography enables the auditory cortex to interface with regions involved in speech, memory, and sensory integration (Morosan et al., 2001).
Connections
The auditory cortex receives afferent input primarily from the medial geniculate body of the thalamus, which relays ascending auditory signals from the inferior colliculus and brainstem nuclei. In turn, it projects to a wide array of cortical regions, including the posterior superior temporal gyrus, inferior frontal gyrus, insula, parietal operculum, and anterior cingulate cortex.
These connections facilitate interactions between the auditory system and brain circuits involved in language, attention, memory, and multisensory integration. In particular, the left auditory cortex is tightly linked with perisylvian language areas, while the right auditory cortex shows enhanced connectivity with networks supporting music perception and spectral resolution (Bizley & Cohen, 2013).
Participation in brain networksThe auditory cortex is embedded in several functional brain networks, including the auditory network, language network, and attention networks.
Within the auditory network, it serves as the primary site for acoustic feature extraction, such as frequency, intensity, and temporal patterns.
In the language network, especially in the dominant (usually left) hemisphere, it collaborates with Wernicke’s and Broca’s areas to support speech comprehension
and phonological processing.
Furthermore, it participates in the dorsal attention network, modulating auditory perception in response to task demands, and in the salience network, contributing
to the detection of behaviorally relevant sounds (Griffiths & Warren, 2002).
Functions
The auditory cortex mediates hierarchical processing of sound, beginning with fine-grained frequency discrimination in the core region (BA41), followed by integration of spectrotemporal features in the belt and parabelt regions (BA42 and adjacent areas).
It enables the brain to construct auditory objects, segregate sound sources in complex environments, and link acoustic input with meaning. In the left hemisphere, it plays a fundamental role in speech perception, phoneme discrimination, and lexical access.
The right auditory cortex, in contrast, is more specialized for pitch perception, prosody, and melodic processing.
The auditory cortex also supports auditory working memory, spatial localization, and predictive coding, particularly during active listening and verbal comprehension.
Role in clinical disorders
Alterations in the structure or function of the auditory cortex have been implicated in a variety of neurological and neuropsychiatric conditions.
In tinnitus, hyperactivity and maladaptive plasticity within primary and secondary auditory regions contribute to the perception of phantom sound.
In auditory processing disorder (APD), deficits in temporal resolution and interhemispheric auditory integration are linked to atypical activation in auditory cortical circuits.
Language-related impairments, including developmental dyslexia and aphasia, involve disrupted activity or connectivity between the auditory cortex and language-associated regions, impairing phonological decoding and speech perception (Sedley et al., 2015).
Additionally, abnormal auditory cortex function has been observed in schizophrenia, where impaired early auditory evoked potentials (e.g., mismatch negativity) reflect disrupted sensory processing and may contribute to auditory hallucinations.
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Latest findings
Recent studies using ultra-high field (7T) fMRI and intracranial electrophysiology have provided new insights into the fine-grained functional organization of the auditory cortex. High-resolution imaging has revealed multiple tonotopic maps within Heschl’s gyrus, suggesting a more complex microarchitecture than previously appreciated. These include overlapping representations of pitch, intensity, and modulation rate, offering a multidimensional coding scheme for natural sound perception.
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Recent work has also shown that speech-specific tuning emerges rapidly in early auditory cortical layers and is shaped by both linguistic experience and task demands. For example, studies in bilingual individuals reveal enhanced spectral and temporal selectivity in the auditory cortex that correlates with proficiency in a second language.
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Connectivity studies employing resting-state fMRI and diffusion tensor imaging have demonstrated that auditory cortex connectivity patterns predict individual differences in language comprehension, phonological awareness, and even musical aptitude. Functional coupling between auditory cortex and prefrontal regions has been found to dynamically reconfigure during demanding listening tasks, reflecting the top-down modulation of auditory perception.
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In clinical research, machine learning classifiers trained on cortical auditory evoked responses have shown promise in distinguishing between individuals with tinnitus, APD, and normal hearing, suggesting potential for neurophysiological biomarkers of auditory dysfunction.
Additionally, noninvasive neuromodulation techniques, including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) targeting auditory cortex regions, are being explored as treatments for tinnitus, auditory hallucinations, and rehabilitation after stroke-induced aphasia, with preliminary studies demonstrating modulation of auditory cortex excitability and perceptual outcomes.
Area 43: Primary Gustatory Cortex (PGC)
The primary gustatory cortex (PGC) is the central cortical site for the conscious perception and discrimination of taste stimuli. It integrates chemosensory information related to sweet, salty, sour, bitter, and umami sensations and contributes to the affective and motivational components of taste.
The PGC is anatomically and functionally embedded within a broader gustatory network that interfaces with regions involved in emotion, reward, and multisensory integration. Its activation underlies both the qualitative identification of taste and the hedonic assessment of food stimuli, making it critical not only for nutritional behaviors but also for appetite regulation and reward processing. Graphic © Big8/Shutterstock.com.
Brodmann areas
The PGC is most consistently associated with Brodmann area 43, located in the subcentral operculum, which bridges the frontal and parietal opercula. Functionally, however, gustatory processing extends into adjacent regions of the anterior dorsal insular cortex, often considered part of Brodmann area 13, and the frontal operculum.
Ogawa (2012) and Small et al. (1999) emphasized that while area 43 contains the core gustatory representations, gustatory perception results from coordinated activation of both insular and opercular regions, constituting a distributed gustatory field.
Location
The primary gustatory cortex is situated at the intersection of the anterior insula and the frontal operculum, embedded within the lateral fissure. This location places it in close anatomical proximity to the somatosensory cortex, olfactory processing areas, and the anterior cingulate cortex.
Functionally, the insular component is more involved in interoceptive awareness and visceral sensation, while the opercular aspect participates in chemosensory processing and motor responses related to ingestion. The deep position of the PGC within the lateral sulcus has historically limited its accessibility in non-invasive imaging but has been reliably localized using high-resolution functional MRI and intracranial recordings.
Connections
The primary gustatory cortex receives its principal afferent input from the ventroposteromedial nucleus (VPMpc) of the thalamus, which relays taste information from the solitary tract nucleus via brainstem pathways. From the PGC, projections extend to the orbitofrontal cortex, where secondary taste representations contribute to reward valuation and decision-making. The PGC also connects with the amygdala, hypothalamus, and anterior cingulate cortex, linking gustatory input to emotional states, autonomic regulation, and motivational drives. Additional connections to the insula, somatosensory cortex, and entorhinal cortex facilitate multimodal sensory integration and associative memory formation related to food experiences (Rolls, 2006).
Participation in brain networks
The PGC is a key node in the gustatory processing network, which incorporates regions involved in taste perception, reward processing, homeostatic regulation, and emotional evaluation.
It operates within overlapping systems including the interoceptive network, responsible for visceral sensation and internal state monitoring, and the salience network, which assigns motivational value to gustatory stimuli.
Within these networks, the PGC plays a central role in orchestrating the subjective experience of taste and in guiding behavior toward or away from specific foods based on past experience, internal need states, and environmental cues.
Functions
Functionally, the primary gustatory cortex supports the conscious perception of taste, allowing for the discrimination of basic taste qualities and the encoding of taste intensity. It is also involved in hedonic evaluation, helping determine the pleasantness or aversiveness of food stimuli. This function is closely linked with reward-related brain regions such as the orbitofrontal cortex and amygdala.
dditionally, the PGC participates in multisensory integration, especially with olfactory and somatosensory inputs, which together form the neural basis of flavor perception. Activation of the PGC occurs not only during direct taste stimulation but also during anticipation of taste, imagined taste, and observational learning, suggesting its involvement in complex cognitive-affective processing related to feeding behavior..
Role in clinical disorders
Disruption of the primary gustatory cortex has been implicated in several clinical conditions involving taste perception and appetite regulation. In ageusia, or loss of taste, lesions affecting the insular or opercular cortex may lead to deficits in taste intensity and discrimination.
In eating disorders, particularly anorexia nervosa and bulimia nervosa, functional imaging studies have revealed altered activation of the PGC in response to food-related stimuli, often correlating with aberrant hedonic responses and reduced reward sensitivity.
Abnormal PGC activation has also been reported in obesity, where enhanced response to palatable tastes may contribute to dysregulated eating.
Moreover, chemotherapy-induced taste alterations and gustatory hallucinations in temporal lobe epilepsy have been linked to insular and opercular cortical dysfunction, highlighting the PGC’s role in both normal and pathological taste processing (Frank et al., 2016).
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Latest findings
Recent advances in neuroimaging and neurophysiology have refined our understanding of the spatial and functional organization of the primary gustatory cortex. High-resolution fMRI studies have confirmed that multiple, overlapping taste maps exist within the anterior insula and frontal operculum, with distinct but partially co-localized representations for sweet, salty, sour, bitter, and umami. These findings suggest a population coding mechanism, whereby distributed ensembles of neurons encode complex taste profiles rather than strict topographical segregation.
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New evidence also indicates that the PGC is responsive not only to gustatory stimuli but also to anticipatory cues, such as viewing images of food or experiencing food-related context, indicating a role in predictive coding and reward expectation.
In patients with anorexia nervosa, the PGC exhibits blunted activation to palatable tastes despite intact detection thresholds, consistent with reduced hedonic sensitivity. Conversely, in obesity, hyperactivation of the PGC and enhanced connectivity with the orbitofrontal cortex have been associated with increased subjective reward value of high-calorie foods, reinforcing maladaptive eating behavior.
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Intracranial EEG recordings have further demonstrated that taste-evoked potentials in the PGC occur within 200 ms of stimulus delivery, underscoring its role in early sensory encoding. These responses are modulated by satiety and attention, suggesting dynamic regulation of gustatory processing based on physiological and cognitive states.
Finally, neuromodulatory interventions, including non-invasive stimulation of the anterior insula, are being explored as potential treatments for taste dysfunction and appetite disorders. Early-phase trials using transcranial direct current stimulation (tDCS) have shown promise in modulating taste perception and food craving, indicating the PGC’s accessibility for targeted intervention in clinical populations.
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Area 44: Pars Opercularis of the Inferior Frontal Gyrus
Brodmann Area 44 (BA44) is a subregion of the inferior frontal gyrus (IFG) and plays a central role in language production, syntactic processing, and motor control of speech. Often referred to as the pars opercularis, BA44 is a major component of the classical Broca’s area in the dominant hemisphere (usually the left), a region historically associated with expressive language functions.
BA44 is also involved in action planning, motor sequencing, and aspects of working memory, reflecting its integrative position within fronto-parietal and language-related networks. Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann Area 44 lies anterior to the precentral gyrus and posterior to Area 45 (pars triangularis) within the inferior frontal gyrus. Together, BA44 and BA45 constitute what is traditionally known as Broca’s area.
BA44 is distinguished from BA45 by its more robust motoric function, its denser connections with the premotor and motor cortices, and its deeper involvement in the phonological and articulatory aspects of speech production.
Although originally defined cytoarchitectonically by Brodmann based on laminar cell structure, functional imaging and lesion studies have since refined its boundaries and revealed distinct subregional specializations.
Location
BA44 is located in the pars opercularis of the inferior frontal gyrus, bounded posteriorly by the precentral sulcus and superiorly by the inferior frontal sulcus. It lies within the posterior part of the IFG, just anterior to the ventral premotor cortex.
In the dominant (usually left) hemisphere, this region is involved in language production, while in the right hemisphere, homologous BA44 is associated with prosody, affective speech modulation, and broader aspects of motor planning. Its proximity to motor and premotor areas facilitates the translation of linguistic information into articulatory motor commands.
Connections
BA44 maintains extensive connections with multiple cortical and subcortical regions involved in language, executive function, and motor control. It is richly interconnected with BA6 (premotor cortex), BA22 (superior temporal gyrus/Wernicke’s area), BA21 and BA37 (middle and inferior temporal gyri), as well as with subcortical structures such as the basal ganglia and thalamus. These connections are supported by major white matter tracts, notably the arcuate fasciculus, which links BA44 to the posterior temporal lobe and is critical for phonological processing and repetition.
Additional connections to the dorsolateral prefrontal cortex support working memory and syntactic sequencing, while links to the insula and supplementary motor area contribute to motor planning and speech initiation.
Participation in brain networks
BA44 is a key node in the language network, particularly in the dorsal language pathway responsible for phonological processing, speech articulation, and auditory-motor integration.
It also participates in the multiple-demand (MD) network, which includes regions involved in high-level cognitive control, such as attention, rule implementation, and task switching.
BA44’s participation in the frontoparietal control network further supports its role in sequencing, working memory, and goal-directed behavior.
In non-dominant hemisphere homologues, BA44 contributes to prosodic modulation, emotional expression in speech, and gesture-language coupling
Functions
BA44 is most strongly associated with speech production, particularly the phonological and articulatory planning of verbal output. It is involved in the encoding of phoneme sequences, syllable selection, and motor coordination necessary for fluent articulation.
BA44 also plays a role in syntactic processing, especially in tasks requiring hierarchical structuring of language elements, such as sentence construction or comprehension of embedded clauses.
Additionally, this region contributes to verbal working memory, allowing for the temporary maintenance and manipulation of linguistic material during language tasks.
Outside of the language domain, BA44 has been implicated in action observation, gesture recognition, and imitation, supporting its involvement in sensorimotor integration and possibly in mirror neuron systems.
Role in clinical disorders
Damage to BA44 in the dominant hemisphere is classically associated with Broca’s aphasia, a condition characterized by non-fluent, effortful speech, agrammatism, and relatively preserved comprehension.
Lesions affecting BA44 and its connectivity via the arcuate fasciculus can also result in conduction aphasia, marked by impaired repetition and phonemic paraphasias.
In developmental speech and language disorders, including specific language impairment (SLI) and developmental verbal dyspraxia, altered activation or connectivity involving BA44 has been documented.
In stuttering, hypoactivation of left BA44 and hyperactivation of right-hemisphere homologues may reflect compensatory or maladaptive reorganization.
Moreover, in schizophrenia, dysfunction in BA44 has been linked to formal thought disorder and impaired verbal working memory.
BA44 has also been implicated in motor speech disorders and apraxia of speech, particularly in progressive neurodegenerative conditions such as primary progressive aphasia (PPA).
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Latest findings
Recent neuroimaging studies using high-resolution fMRI and connectivity-based parcellation have revealed that BA44 can be subdivided into functionally distinct anterior and posterior subregions. The anterior portion appears more involved in syntactic processing and cognitive control, while the posterior portion is more closely tied to motor aspects of speech. This internal heterogeneity supports the view that BA44 serves as a multifunctional interface linking language, motor, and executive functions.
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Functional connectivity studies have demonstrated that the strength of coupling between BA44 and posterior temporal regions via the arcuate fasciculus predicts language learning success, particularly in second-language acquisition and in phonological rehearsal tasks. Additionally, transcranial magnetic stimulation (TMS) applied to BA44 has been shown to modulate sentence processing, verbal fluency, and phoneme discrimination, providing causal evidence for its involvement in core language functions.
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In neurodevelopmental research, structural MRI has revealed asymmetries in BA44 development that correlate with language lateralization and verbal IQ. Altered development of BA44 and its white matter connections has been observed in children with language delay and autism spectrum disorder, indicating its broader role in communicative development.
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Furthermore, emerging evidence supports the involvement of BA44 in multimodal action representation, including manual gesture comprehension and gesture-speech integration. This aligns with the embodied cognition hypothesis, suggesting that BA44 contributes to a shared neural substrate for language and action.
Area 45: Pars Triangularis (inferior temporal gyrus and part of Broca's area)
The pars triangularis, corresponding to Brodmann area 45 (BA45), is a critical subregion of the inferior frontal gyrus (IFG) involved in high-level language processing and executive control. As one of the two classical subdivisions of Broca’s area in the dominant (usually left) hemisphere—alongside area 44—it plays a central role in semantic processing, controlled retrieval of lexical information, and syntactic integration.
In addition to its linguistic functions, BA45 is also implicated in broader cognitive operations, such as working memory, inhibitory control, and decision-making, placing it at the interface of language and executive systems. Graphic © Big8/Shutterstock.com.
Brodmann areas
Brodmann area 45 is cytoarchitectonically defined by a distinct laminar structure within the triangular portion of the inferior frontal gyrus. It is anatomically anterior to area 44 (pars opercularis) and posterior to area 47/12 (pars orbitalis). Amunts et al. (1999) demonstrated that BA45 exhibits leftward asymmetry in most individuals, consistent with its specialization for language in the left hemisphere. This area is functionally differentiated from BA44, which is more engaged in phonological and articulatory processes, while BA45 is primarily responsible for semantic and syntactic computations.
Location
The pars triangularis is located in the ventrolateral prefrontal cortex, occupying the middle portion of the inferior frontal gyrus in the frontal lobe. It is situated anterior to the pars opercularis and posterior to the pars orbitalis. This region lies beneath the approximate scalp positions of F7 and F8 in the International 10–20 EEG system (Jasper, 1958), although functional imaging is necessary for precise localization. Its proximity to both language and executive areas supports its dual role in linguistic and higher-order cognitive control.
Connections
The pars triangularis maintains robust anatomical and functional connections with several cortical and subcortical regions involved in language comprehension, semantic memory, and executive function. It is connected via the uncinate fasciculus and inferior fronto-occipital fasciculus to the temporal lobe, particularly the posterior superior temporal gyrus (Wernicke’s area) and anterior temporal pole, facilitating semantic retrieval and integration.
Additional projections to the dorsolateral prefrontal cortex, anterior cingulate cortex, and insula support its role in cognitive control, attention modulation, and response inhibition (Friederici, 2011). These connections allow BA45 to act as a control mechanism over semantic access, selection, and integration during language tasks.
Participation in brain networks
Brodmann area 45 is a central node within the left-lateralized language network, particularly the ventral stream, which supports semantic processing and sentence-level comprehension.
It also participates in the executive control network, overlapping with the multiple-demand (MD) system, which facilitates cognitive flexibility, working memory, and goal-directed attention. Within these networks, BA45 contributes to resolving competition among semantic alternatives, guiding context-appropriate language production and comprehension. Functional MRI studies have consistently shown its activation during tasks requiring lexical decision-making, semantic association, and controlled word retrieval.
Functions
The pars triangularis is heavily engaged in controlled semantic retrieval, enabling the selection and inhibition of competing lexical items based on contextual demands.
It is also involved in semantic integration, supporting the comprehension of complex sentences and the processing of abstract or figurative language.
In tasks requiring verbal working memory, BA45 is activated during maintenance and manipulation of verbal content, indicating its role in monitoring and updating linguistic representations.
Beyond language, it contributes to executive processes, including rule application, decision-making under ambiguity, and task switching. This overlap between linguistic
and domain-general functions underscores the multifunctional nature of BA45.
Role in clinical disorders
Functional and structural abnormalities in BA45 have been implicated in a range of neurodevelopmental and neurological disorders.
In aphasia, particularly in cases of semantic or Broca’s aphasia, damage to the pars triangularis results in impaired word retrieval, syntactic comprehension deficits, and difficulty producing fluent, grammatically correct speech.
In developmental language disorders, including specific language impairment (SLI) and developmental dyslexia, atypical activation and reduced gray matter volume in BA45 have been associated with deficits in semantic processing and verbal fluency (Watkins et al., 2002).
In individuals with attention-deficit/hyperactivity disorder (ADHD), alterations in BA45 connectivity and functional engagement have been linked to impairments in inhibitory control and working memory (Booth et al., 2005).
Dysregulation of BA45 activity has also been observed in schizophrenia, where it contributes to language disorganization and verbal working memory dysfunction.
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Latest findings
Recent neuroimaging studies have revealed greater functional heterogeneity within BA45 than previously appreciated. Using high-resolution fMRI and connectivity-based parcellation, researchers have identified anterior and posterior subdivisions of BA45, with the posterior subregion more involved in semantic retrieval and the anterior portion engaged during executive selection and contextual updating. These findings refine our understanding of how BA45 supports both domain-specific (language) and domain-general (executive) processes.
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Recent diffusion tractography studies have shown that the strength of BA45 connectivity to the anterior temporal lobe predicts semantic fluency and sentence comprehension performance, particularly in second-language learners. Moreover, in bilingual individuals, enhanced plasticity in BA45 has been linked to increased efficiency in code-switching and lexical inhibition, reinforcing its role in flexible language control.
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Transcranial magnetic stimulation (TMS) over BA45 has been used to modulate semantic interference and lexical access during controlled retrieval tasks. These studies provide causal evidence for the involvement of BA45 in resolving competition among semantic representations, especially under high cognitive load or ambiguity.
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In clinical neuroscience, recent longitudinal fMRI studies in post-stroke aphasia have demonstrated that functional recovery of BA45 activation is predictive of long-term improvement in semantic comprehension and verbal fluency. Similarly, in primary progressive aphasia, differential patterns of atrophy between BA44 and BA45 help distinguish nonfluent/agrammatic and semantic variants, with BA45 atrophy correlating with lexical-semantic deficits.
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Emerging evidence also points to the involvement of BA45 in nonverbal executive tasks, such as reasoning and abstract categorization, further supporting its role in domain-general control mechanisms. These findings suggest that BA45 acts as a functional bridge between language and executive systems, dynamically allocating resources based on task demands.
Areas 9, 46, 8, and 10: Dorsolateral Prefrontal Cortex (DLPFC)
The dorsolateral prefrontal cortex (DLPFC) is a central region within the lateral prefrontal cortex responsible for executive functions that include working memory, attentional control, planning, reasoning, and goal-oriented behavior. It plays a pivotal role in enabling adaptive responses to complex and changing environmental demands, making it essential for both cognitive and behavioral flexibility. As a major integrative hub, the DLPFC supports decision-making, error correction, and the regulation of behavior based on internal goals and external feedback. Graphic © Big8/Shutterstock.com.
Brodmann areas
The DLPFC encompasses Brodmann areas 9 and 46, with functional contributions from portions of areas 8 and 10.
Area 9 occupies the dorsal part of the middle frontal gyrus and is involved in sustained attention and strategic planning.
Area 46, located more ventrally and anteriorly, supports the manipulation of information in working memory.
Area 8 contributes to top-down control of eye movements and spatial attention through its inclusion of the frontal eye fields, while area 10, located more anteriorly in the frontal pole, is associated with prospective memory, abstract reasoning, and social cognition. Rajkowska and Goldman-Rakic (1995) delineated these areas cytoarchitectonically and emphasized their functional coherence as components of the broader dorsolateral prefrontal system.
Location
The DLPFC is situated on the lateral and superior surface of the frontal lobe, extending across the middle frontal gyrus and adjacent portions of the superior frontal gyrus. It lies anterior to the premotor cortex and dorsal to the ventrolateral prefrontal cortex.
The region is accessible via neurophysiological methods and is approximately localized near the F3 (left hemisphere) and F4 (right hemisphere) electrode sites in the International 10–20 EEG system (Jasper, 1958).
Functionally, it shows hemispheric specialization, with the left DLPFC more involved in verbal processing and the right DLPFC in spatial and nonverbal cognition.
Connections
The DLPFC is characterized by extensive reciprocal connections with a variety of cortical and subcortical structures. It is strongly interconnected with the parietal association cortices, especially the intraparietal sulcus, forming the foundation of the frontoparietal control network. It is also connected to the anterior cingulate cortex, posterior cingulate cortex, and mediodorsal thalamus, supporting executive control and performance monitoring.
Subcortically, the DLPFC communicates with the striatum, particularly the caudate nucleus, contributing to reward-based decision-making and action selection. These connections enable the DLPFC to integrate sensory input, internal representations, and feedback to guide future behavior.
Participation in brain networks
The DLPFC serves as a core node within the central executive network (CEN), where it is responsible for maintaining and manipulating information in working memory, as well as for implementing cognitive control strategies. It also interfaces dynamically with the default mode network (DMN) and the salience network, enabling shifts between internal mentation and external goal-directed tasks. Through its participation in the cingulo-opercular network, the DLPFC supports sustained attention and task set maintenance over time. This functional flexibility allows the DLPFC to adaptively allocate cognitive resources based on task demands, error signals, or changing priorities.
Functions
The DLPFC is essential for executive processes that require the orchestration of multiple cognitive operations. It supports working memory, enabling the temporary storage and manipulation of information necessary for reasoning and decision-making. It is also central to cognitive control, allowing individuals to inhibit prepotent responses, resolve conflict, and maintain goal-relevant representations.
During planning and problem-solving, the DLPFC monitors progress, updates strategies, and adapts behavior in real-time.
Additional roles include abstract rule application, mental set shifting, and deliberative decision-making. Functional imaging consistently shows DLPFC activation in tasks involving complex reasoning, task switching, and uncertainty, underscoring its role in flexible cognition.
Role in clinical disorders
Altered structure and function of the DLPFC have been implicated in a wide spectrum of psychiatric, neurodevelopmental, and neurological disorders.
In schizophrenia, hypofunction of the DLPFC is associated with impairments in working memory, executive function, and negative symptoms such as avolition. Functional disconnection between the DLPFC and posterior cortices has also been linked to disorganized thought and poor goal-directed behavior.
In major depressive disorder, hypoactivation of the left DLPFC is associated with cognitive slowing, rumination, and impaired decision-making.
ADHD is characterized by underactivation of the DLPFC during tasks requiring inhibitory control and sustained attention.
Obsessive-compulsive disorder, bipolar disorder, and post-traumatic stress disorder all show disrupted DLPFC connectivity patterns, often reflecting deficits in cognitive flexibility and emotion regulation. The DLPFC is also a target for neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression, highlighting its clinical relevance.
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Latest findings
Recent advances in multimodal imaging have refined the understanding of DLPFC functional architecture. Gradient-based mapping techniques have demonstrated that the DLPFC is organized along rostral–caudal and dorsal–ventral axes, with caudal regions more engaged in concrete operations such as motor planning and rule implementation, and rostral regions more active during abstract reasoning and social cognition. Moreover, dorsal portions of the DLPFC are associated with externally focused attention, whereas ventral areas support more internally directed cognitive control.
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High-resolution tractography and resting-state functional connectivity analyses have revealed that individual variability in DLPFC connectivity predicts executive performance across domains. Specifically, stronger connectivity between the DLPFC and posterior parietal cortex correlates with higher working memory capacity and fluid intelligence. Additionally, dynamic functional connectivity studies show that the DLPFC flexibly shifts its coupling between task-relevant and task-irrelevant regions in response to environmental demands, supporting adaptive control.
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In the domain of neuromodulation, personalized targeting of the DLPFC using connectivity-guided TMS has shown increased efficacy in treating depression and enhancing executive function. Ongoing clinical trials are exploring closed-loop stimulation systems that use real-time EEG or fMRI to modulate DLPFC activity during cognitive tasks, aiming to enhance cognitive resilience and adaptability.
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Developmentally, longitudinal neuroimaging studies have shown that protracted maturation of the DLPFC through adolescence and early adulthood is associated with improvements in inhibitory control, reasoning, and future planning. Atypical trajectories in DLPFC structure and connectivity are now being investigated as biomarkers for early detection of neurodevelopmental disorders such as autism and schizophrenia.
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Finally, converging evidence from computational modeling and neuroeconomics indicates that the DLPFC plays a critical role in value-based decision-making, particularly in situations requiring self-control, delay of gratification, and cost-benefit analysis. Its integration of abstract goals with sensory input and internal motivational states positions the DLPFC as a central executor of complex, adaptive human behavior
Area 47: Pars Orbitalis (part of the inferior frontal gyrus)
The pars orbitalis, corresponding to Brodmann area 47 (BA47), is a ventral prefrontal region located in the orbital portion of the inferior frontal gyrus (IFG). It plays a prominent role in emotional regulation, social cognition, semantic processing, and value-based decision-making.
Functionally distinct from the adjacent pars triangularis (BA45) and pars opercularis (BA44), the pars orbitalis is situated at the interface of limbic and cognitive systems, integrating affective signals with behavioral planning.
It has also been implicated in various forms of abstract reasoning, moral evaluation, and language semantics, particularly in tasks requiring interpretation of ambiguous or contextually rich stimuli. Graphic © Big8/Shutterstock.com.
Brodmann areas
The pars orbitalis is defined cytoarchitectonically as Brodmann area 47, also referred to as the orbital part of the inferior frontal gyrus. This area forms the most anterior portion of the IFG and is structurally and functionally distinct from BA44 and BA45, which are more posteriorly located and involved in phonological and syntactic aspects of language. Amunts et al. (1999) delineated BA47 as a region characterized by its granular cortical architecture and its integrative connections with limbic and paralimbic areas, supporting its role in emotion-laden decision-making and social reasoning.
Location
The pars orbitalis lies in the anterior portion of the inferior frontal gyrus, anterior to the pars triangularis (BA45) and posterior to the lateral orbital gyrus. It resides on the ventrolateral surface of the frontal lobe, bordering the orbital sulcus and extending toward the lateral orbital cortex. The region lies beneath the Fp1 and Fp2 electrode sites in the International 10–20 EEG system, although accurate localization requires structural neuroimaging due to individual variability in sulcal anatomy.
Connections
The pars orbitalis maintains reciprocal connections with several key limbic and paralimbic structures, including the amygdala, insula, anterior cingulate cortex, and orbitofrontal cortex, as well as with temporal pole, medial prefrontal cortex, and ventral striatum (Barbas, 2007; Ongür & Price, 2000). These connections support the integration of emotional salience, contextual memory, and motivational significance into decision-making and social behavior. The region also connects with posterior cortical areas via the uncinate fasciculus, allowing communication between frontal and anterior temporal regions involved in semantic knowledge and emotional meaning.
Participation in brain networks
Functionally, the pars orbitalis is a component of the salience network, a large-scale system that includes the anterior insula and anterior cingulate cortex.
The salience network is responsible for detecting, evaluating, and integrating emotionally or socially relevant stimuli and for dynamically switching between the default mode network and central executive network based on behavioral demands (Seeley et al., 2007).
The pars orbitalis also participates in semantic processing networks, particularly in tasks involving the interpretation of abstract language, irony, or metaphor, reflecting its capacity for integrating affective and conceptual information.
Functions
The pars orbitalis supports a range of higher-order functions, most prominently in emotional and social cognition, semantic comprehension, and value-based decision-making. It contributes to the evaluation of emotional facial expressions and prosody, moral reasoning, empathy, and the regulation of socially appropriate behavior.
In the domain of language, BA47 is involved in semantic retrieval, particularly when task demands require controlled access to stored knowledge or interpretation of ambiguous stimuli.
Functional imaging studies consistently show activation in the pars orbitalis during tasks involving affective theory of mind, language comprehension under ambiguity, and emotional regulation during decision-making.
The region also plays a role in reward evaluation, particularly in integrating anticipated outcomes with social context and internal emotional states.
Role in clinical disorders
Dysfunction in the pars orbitalis has been implicated in a variety of neuropsychiatric and neurodevelopmental disorders, particularly those involving social-emotional dysregulation.
In major depressive disorder, altered activation and reduced connectivity of the pars orbitalis have been associated with impairments in emotional appraisal and reward anticipation.
In anxiety disorders, especially social anxiety and generalized anxiety, hyperactivation of BA47 may reflect increased salience attribution to negative or ambiguous social stimuli.
Structural and functional abnormalities in this region have also been reported in autism spectrum disorders, where reduced activation during emotion recognition and mentalizing tasks may contribute to social cognitive deficits (Di Martino et al., 2009).
Additionally, abnormalities in BA47 have been linked to obsessive-compulsive disorder, bipolar disorder, and personality disorders, especially in relation to impaired emotion regulation and decision-making under uncertainty (Phillips et al., 2003).
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Latest findings
Recent neuroimaging research has advanced our understanding of the functional specialization within BA47, revealing that the region can be subdivided into lateral and medial orbital sectors, each with distinct connectivity and functional roles.
The lateral portion is more engaged in semantic and language-related tasks, while the medial sector is more closely aligned with affective and reward-based decision-making. Functional connectivity analyses have shown that the strength of coupling between BA47 and the amygdala predicts individual differences in emotional reactivity and susceptibility to affective disorders.
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High-resolution diffusion tractography has demonstrated that BA47 is a key node in the anterior limbic–semantic integration pathway, linking emotional salience with verbal and nonverbal cognitive processing. In studies using multivariate pattern analysis, activation patterns in BA47 have been shown to predict moral judgment, empathy levels, and social norm compliance, suggesting its role in real-world social decision-making.
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In neuromodulation research, transcranial magnetic stimulation (TMS) applied to the pars orbitalis has been used experimentally to influence emotion regulation and semantic processing, though clinical applications remain in early stages. Connectivity-guided TMS protocols targeting this region are being investigated for their potential to modulate affective symptoms in depression and social functioning in autism spectrum disorders.
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Finally, in developmental neuroscience, longitudinal studies have shown that maturation of the pars orbitalis correlates with improvements in social reasoning and emotion understanding during adolescence. Aberrant developmental trajectories in this region may contribute to the emergence of social cognition deficits in early-onset psychiatric disorders, making BA47 a focus for predictive biomarkers and early interventions.
Area 48: Retrosubicular Area (small medial temporal lobe area)
The retrosubicular area, commonly referred to as the presubiculum, is a medial temporal lobe structure forming part of the hippocampal formation. Although not assigned a specific Brodmann area, the presubiculum corresponds functionally and cytoarchitecturally to Area 48, a designation used to describe a narrow transitional zone between the subiculum and parasubiculum.
The retrosubicular area plays a critical role in spatial orientation, memory consolidation, and contextual representation, making it a central component of the neural circuits underlying episodic memory and navigation.
Brodmann areas
While the presubiculum is designated as Area 48 in modern anatomical terminology, it was not included in Brodmann's original cortical maps. Unlike neocortical regions, the retrosubicular area has a three-layered allocortical structure, characteristic of the hippocampal formation. It is distinct from adjacent subfields in both its cytoarchitecture and connectivity, contributing uniquely to the entorhinal–hippocampal system (Amaral & Witter, 1995).
Location
The retrosubicular area is located in the medial temporal lobe, positioned between the subiculum and parasubiculum, near the posterior end of the parahippocampal gyrus. It lies along the parahippocampal–cingulate junction and forms the medial-most component of the parahippocampal region. This area is embedded deep within the collateral sulcus and, due to its medial and inferior position, is not directly accessible via surface EEG but can be observed via high-resolution MRI or histological analysis. Retrosubicular graphic drawn by minaanandag.
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Connections
The retrosubicular area exhibits extensive connectivity with other components of the hippocampal formation and broader limbic system. It receives afferents from the entorhinal cortex, particularly layers III and V, and projects to the subiculum, CA1, and parasubiculum, forming part of the canonical trisynaptic hippocampal circuit. It also sends and receives projections from the anterior thalamic nuclei, mammillary bodies, and cingulate cortex, primarily via the fornix and cingulum bundle (Witter et al., 2000). These connections enable it to integrate spatial, mnemonic, and emotional information across cortical and subcortical domains.
Participation in brain networks
The retrosubicular area is part of the medial temporal lobe memory system and the Papez circuit, a network traditionally associated with emotional regulation and episodic memory. Within this circuit, the retrosubiculum contributes to contextual encoding, spatial orientation, and scene construction, operating alongside the hippocampus, entorhinal cortex, and mammillary bodies (Aggleton & Brown, 1999). It also participates in head-direction systems, which are critical for representing allocentric spatial orientation and supporting navigation.
Functions
The retrosubicular area serves several core cognitive and affective functions. It is involved in spatial navigation, specifically in encoding head-direction information, which contributes to a stable internal representation of environmental orientation.
It also plays a key role in contextual memory encoding, supporting the differentiation of spatially or temporally similar events.
Additionally, the retrosubiculum is active during tasks that require visual scene perception, suggesting its contribution to constructing internal models of complex environments. Although primarily associated with spatial and mnemonic functions, it also participates in emotion-linked memor
Role in clinical disorders
Abnormalities in the retrosubicular area have been implicated in several neurological and psychiatric conditions.
In Alzheimer’s disease, early degeneration of the retrosubiculum and adjacent entorhinal cortex contributes to the breakdown of spatial memory and episodic recall. Pathological studies have shown neurofibrillary tangle accumulation in this region during early Braak stages (Hyman et al., 1984).
In temporal lobe epilepsy, the retrosubiculum may serve as a propagation pathway for seizure activity, and structural abnormalities in this region are commonly observed in surgical specimens (Du et al., 1993).
In schizophrenia, volumetric reductions in the retrosubicular and parahippocampal regions have been associated with impairments in spatial working memory and contextual processing (Heckers et al., 1998), highlighting its relevance in cognitive symptom domains.
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Latest findings
Recent advances in high-resolution structural imaging and neurophysiology have provided deeper insights into the functional organization of the retrosubicular area. Ultra-high field MRI studies have enabled in vivo visualization of the presubiculum, revealing laminar-specific structural changes in early Alzheimer's disease and age-related cognitive decline. Quantitative imaging metrics, such as T2 mapping and diffusion kurtosis imaging, have shown that microstructural integrity of the retrosubiculum correlates with spatial navigation performance and autobiographical memory richness in older adults.
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Electrophysiological recordings in animal models and intracranial EEG studies in humans have demonstrated that the retrosubiculum houses head-direction cells, which fire in relation to the animal’s orientation in space. These cells are functionally distinct from place and grid cells and provide a reference frame for spatial representation. Recent research has also identified theta-phase precession in retrosubicular neurons, suggesting their role in temporal coding during navigation and episodic memory encoding.
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Connectivity-based parcellation studies using resting-state fMRI have shown that the retrosubiculum forms a distinct subnetwork within the medial temporal lobe, exhibiting strong functional coupling with the entorhinal cortex and medial prefrontal regions.
Disruption in this connectivity pattern has been associated with early cognitive decline and has emerged as a potential functional biomarker for preclinical Alzheimer’s disease.
In translational neuroscience, the retrosubiculum is increasingly studied as a surgical target and biomarker region in patients with intractable temporal lobe epilepsy. Recent findings suggest that seizure onset in the presubiculum is associated with rapid spread to the hippocampus and posterior cingulate cortex, providing new insights into seizure dynamics and potential therapeutic targets.
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Areas 13, 14, and 52: Parainsular Area (junction of the temporal lobe and insula)
The parainsular area, situated at the intersection of the temporal lobe and insular cortex, represents a transition zone with distinct cytoarchitectural and functional properties. Although this region has not been consistently delineated in human brain atlases, it encompasses portions of Brodmann areas 13, 14, and 52, which are all part of the insular cortex.
The insula, including its parainsular extensions, plays a pivotal role in integrating sensory, emotional, and cognitive processes. It has gained significant attention in recent years due to its participation in large-scale brain networks that underlie consciousness, affective regulation, and interoceptive awareness. Graphics © Science and Fascija/Shutterstock.com.
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Brodmann areas
Brodmann area 13 comprises much of the posterior and mid-insular cortex and is involved in interoceptive and affective functions.
Area 14, located more ventromedially, is associated with visceral sensory processing and is more prominent in non-human primates, though homologous regions have been identified in humans.
Area 52 lies at the extreme lateral margin of the insula, bordering the parainsular and temporal cortices. These areas collectively participate in complex integration of internal bodily states, sensory input, and emotional salience, although their precise functional boundaries in humans remain under investigation.
Location
The parainsular area lies deep within the Sylvian (lateral) fissure, forming part of the posterior and ventral insular cortex, adjacent to the temporal lobe. It is obscured from surface view and bounded medially by the extreme capsule and laterally by the opercular regions of the frontal, parietal, and temporal lobes. This deep anatomical position enables the parainsular region to act as a convergence point for multimodal sensory, limbic, and cognitive inputs.
Connections
The insular cortex, including the parainsular zones, maintains extensive reciprocal connections with both cortical and subcortical structures. These include the anterior cingulate cortex, ventromedial and dorsolateral prefrontal cortices, amygdala, hippocampus, superior temporal gyrus, and parietal operculum (Augustine, 1996). Subcortical connections extend to the thalamus, hypothalamus, basal ganglia, and brainstem autonomic centers, allowing the insula to participate in interoceptive awareness, autonomic regulation, and emotional appraisal. The dense connectivity of this region underlies its role in integrating bodily states with affective and cognitive context.
Participation in brain networks
The parainsular region contributes to several intrinsic brain networks, most notably the salience network, which includes the anterior insula and anterior cingulate cortex. This network is essential for detecting behaviorally relevant stimuli and facilitating dynamic switching between other large-scale networks, such as the default mode network and the central executive network (Menon & Uddin, 2010).
The insula also participates in the interoceptive network, responsible for monitoring the physiological condition of the body, and is involved in the pain matrix, which processes nociceptive input in conjunction with emotional salience.
Functions
The parainsular region is involved in interoception, the perception of internal bodily states such as heartbeat, respiration, and visceral sensations.
It also plays a key role in emotional processing, particularly in the subjective experience of emotions such as disgust, empathy, and anxiety.
The insula is a central hub for pain perception, integrating somatosensory and affective aspects of nociceptive signals. In addition, it contributes to cognitive control, risk evaluation, and decision-making under uncertainty.
Functional imaging studies have consistently demonstrated insular activation during tasks involving social emotion, anticipation of aversive stimuli, and subjective awareness (Craig, 2009).
Role in clinical disorders
Structural and functional abnormalities in the parainsular and broader insular regions have been implicated in a wide range of psychiatric and neurological disorders.
In anxiety disorders, hyperactivation of the anterior insula is linked to heightened interoceptive awareness and increased salience of negative internal states.
In major depressive disorder, altered connectivity between the insula and limbic regions contributes to negative bias and impaired emotion regulation.
Autism spectrum disorders are associated with atypical insular activation during social and empathic tasks, possibly reflecting deficits in self-other differentiation and social salience processing (Menon, 2011).
In schizophrenia, reduced gray matter volume and functional dysconnectivity in the insula have been linked to hallucinations, disorganized thought, and impaired insight.
Furthermore, the insula is commonly affected in stroke, temporal lobe epilepsy, and neurodegenerative conditions such as frontotemporal dementia.
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Latest findings
Recent studies using 7-Tesla MRI and connectivity-based parcellation have begun to elucidate the microstructural and functional specialization of the parainsular area. High-resolution mapping has revealed distinct subregions within areas 13, 14, and 52, each exhibiting unique patterns of connectivity with limbic, cognitive, and sensorimotor networks. This supports the hypothesis that the parainsular zone is a multimodal integration site, rather than a purely sensory or affective hub.
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Resting-state functional connectivity studies have shown that individual variability in insular-parainsular connectivity predicts differences in interoceptive accuracy, empathy, and emotional resilience. Abnormal dynamic connectivity of the parainsular region with the anterior cingulate and amygdala has also been identified as a biomarker for anxiety sensitivity and affective instability, particularly in mood and personality disorders.
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Multimodal neuroimaging in early psychosis has revealed that parainsular dysfunction precedes overt clinical symptoms, suggesting its utility as a predictive marker for schizophrenia risk. In the context of chronic pain, increased functional coupling between area 13 and somatosensory cortices has been linked to pain chronification, offering new insights into central mechanisms of pain persistence.
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In translational research, neuromodulation techniques targeting the anterior insula and adjacent parainsular cortex—such as transcranial magnetic stimulation (TMS) and focused ultrasound—are under investigation for their potential to modulate emotional and interoceptive circuits in treatment-resistant mood and anxiety disorders.
Glossary
angular gyrus: located in the parietal lobe near the junction of the temporal and occipital lobes, the angular gyrus corresponds to Brodmann area 39. It plays a role in language processing, attention, spatial cognition, and integration of sensory information.
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anterior cingulate cortex (ACC): located in the medial portion of the frontal lobes, the anterior cingulate cortex encompasses Brodmann areas 24, 25, 32, and 33. It plays a role in executive function, emotional regulation, attention, conflict monitoring, and error detection.
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anterior insula: located in the anterior portion of the insular cortex, the anterior insula is involved in interoceptive awareness, emotional salience, empathy, and functions as a core node in the salience network.
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anterior prefrontal cortex (APFC): found in the most anterior region of the prefrontal cortex, the anterior prefrontal cortex includes Brodmann areas 10 and 11. It involves complex cognitive processes such as planning, decision-making, working memory, and abstract reasoning.
area 13: part of the posterior insular cortex, area 13 is involved in interoception, visceral sensory integration, and emotional awareness.
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area 14: located in the ventromedial prefrontal and insular cortices, area 14 is associated with visceral-autonomic integration and emotional processing.
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area 27: a medial temporal lobe structure also referred to as the presubiculum, area 27
is involved in spatial navigation, memory encoding, and head-direction signaling.
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area 29: part of the retrosplenial cortex in the posterior cingulate gyrus, area 29 is involved in spatial memory, context representation, and navigation.
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area 30: adjacent to area 29 in the retrosplenial cortex, area 30 is involved in autobiographical memory, visual scene construction, and integration within the default mode network.
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area 35: located in the medial temporal lobe, area 35 is part of the perirhinal cortex and plays a role in familiarity-based recognition and semantic memory.
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area 36: situated in the perirhinal cortex near the fusiform gyrus, area 36 contributes to object recognition, associative learning, and high-level perceptual processing.
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area 38: found in the most anterior part of the temporal lobe, area 38, or the temporopolar area, is involved in social cognition, semantic memory, and integration of emotional and sensory input.
area 43: corresponding to the primary gustatory cortex, area 43 is located in the subcentral gyrus and is responsible for processing taste perception and integrating gustatory input.
area 44: located in the pars opercularis of the inferior frontal gyrus, area 44 is involved in phonological processing, language production, and motor planning for speech.
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area 45: situated in the pars triangularis of the inferior frontal gyrus, area 45 supports semantic retrieval, controlled language processing, and sentence-level comprehension.
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area 46: found in the middle frontal gyrus, area 46 is part of the dorsolateral prefrontal cortex and is responsible for working memory, cognitive control, and abstract reasoning.
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area 47: located in the pars orbitalis of the inferior frontal gyrus, area 47 contributes to semantic processing, emotional regulation, and value-based decision-making.
area 48: also called the retrosubicular area or presubiculum, area 48 lies between the subiculum and parasubiculum and supports head-direction encoding, spatial navigation, and contextual memory.
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area 52: located at the lateral border of the insular cortex, area 52 is involved in auditory and somatosensory integration and processing of visceral input.
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auditory cortex: situated in the superior temporal gyrus, the auditory cortex encompasses Brodmann areas 41 and 42. It is responsible for processing and interpreting auditory information.
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cingulate cortex: a part of the limbic system, the cingulate cortex is situated in the medial aspects of the frontal and parietal lobes, covering Brodmann areas 23, 24, 30, 31, and 33. It involves emotion processing, memory, attention, and cognitive control.
dorsal anterior cingulate cortex (DACC): located in the dorsal region of the anterior cingulate cortex, the dorsal anterior cingulate cortex includes Brodmann areas 24 and 32. It plays a role in cognitive control, decision-making, and conflict monitoring.
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dorsal entorhinal cortex (DEC: situated in the medial temporal lobe, the dorsal entorhinal cortex comprises parts of Brodmann area 28. It is involved in spatial memory and navigation.
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dorsolateral prefrontal cortex (DLPFC): found in the lateral region of the prefrontal cortex, the dorsolateral prefrontal cortex includes Brodmann areas 9, 46, and parts of 8 and 10. It involves working memory, cognitive flexibility, planning, and abstract reasoning.
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dorsal posterior cingulate cortex (DPCC): located in the posterior part of the cingulate cortex, the dorsal posterior cingulate cortex covers Brodmann area 31. It is involved in self-referential thought, memory, and spatial awareness.
ectosplenial cerebral cortex: part of the retrosplenial cortex, the ectosplenial cerebral cortex is situated within the cingulate cortex and covers Brodmann area 29. It plays a role in spatial memory, navigation, and contextual processing.
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frontal eye field (FEF): located in the anterior part of the middle frontal gyrus, the frontal eye field corresponds to Brodmann area 8. It is involved in voluntary eye movement control and visual attention.
frontal operculum: a region of the inferior frontal gyrus overlaying the insula, the frontal operculum is involved in speech articulation, gustatory processing, and multisensory integration.
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fusiform gyrus: situated in the ventral region of the temporal and occipital lobes, the fusiform gyrus includes Brodmann areas 37 and parts of 19 and 20. It is involved in face recognition, object recognition, and color and visual form processing.
head-direction system: a neural system including the retrosubiculum and anterior thalamic nuclei, the head-direction system encodes spatial orientation and supports allocentric navigation.
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inferior temporal gyrus (ITG): located in the inferior temporal lobe region, the inferior temporal gyrus encompasses Brodmann areas 20 and 21. It plays a role in visual object recognition and semantic memory.
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insular cortex (insula): situated within the lateral sulcus, the insular cortex covers Brodmann areas 13, 14, 15, and 16. It is involved in processing emotions, interoception, self-awareness, pain perception, and taste sensation.
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middle temporal gyrus (MTG): located in the middle region of the temporal lobe, the middle temporal gyrus encompasses Brodmann areas 21 and 37. It plays a role in language processing, semantic memory, and visual motion processing.
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orbitofrontal cortex (OFC): found in the ventral part of the frontal lobes, the orbitofrontal cortex includes Brodmann areas 10, 11, 12, 13, 14, and 47. It involves decision-making, reward processing, emotional regulation, and social cognition.
parainsular area: located at the junction of the insular cortex and temporal lobe, the parainsular area includes parts of Bbrodmann areas 13, 14, and 52 and is involved in interoception, emotional processing, and multimodal sensory integration.
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pars opercularis: located in the inferior frontal gyrus, the pars opercularis corresponds to Brodmann area 44. It plays a role in language production and is part of Broca's area.
pars orbitalis: situated in the ventral part of the inferior frontal gyrus, the pars orbitalis covers Brodmann area 47. It is involved in language processing, social cognition, and emotional regulation.
pars triangularis: located in the anterior part of the inferior frontal gyrus, the pars triangularis corresponds to Brodmann area 45. It is involved in language processing and is part of Broca's area.
perirhinal cortex: situated in the medial temporal lobe, the perirhinal cortex encompasses Brodmann areas 35 and 36. It plays a role in object recognition, associative memory, and contextual processing.
presubiculum: also known as the retrosubicular area or Brodmann area 27, the presubiculum is part of the parahippocampal region and is involved in spatial orientation, memory encoding, and directional navigation.
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primary gustatory cortex: located within the insular cortex, the primary gustatory cortex corresponds to Brodmann area 43. It is responsible for processing taste information.
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primary motor cortex (M1): situated in the precentral gyrus, the primary motor cortex corresponds to Brodmann area 4. It is responsible for voluntary movement control.
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primary somatosensory cortex (S1): located in the postcentral gyrus, the primary somatosensory cortex covers Brodmann areas 1, 2, and 3. It is responsible for processing somatosensory information, including touch, pain, temperature, and proprioception.
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primary visual cortex (V1): situated in the calcarine sulcus within the occipital lobe, the primary visual cortex corresponds to Brodmann area 17. It is responsible for processing basic visual information.
piriform cortex: located in the ventral part of the temporal lobe, the pyriform cortex (also known as the primary olfactory cortex) includes parts of Brodmann areas 27, 28, and 34. It is responsible for processing olfactory information.
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retrosplenial cingulate cortex: found in the posterior part of the cingulate cortex, the retrosplenial cingulate cortex covers Brodmann areas 29 and 30. It is involved in spatial memory, navigation, and contextual processing.
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retrosubicular area: a medial temporal lobe region situated between the subiculum and parasubiculum, the retrosubicular area (area 48) plays a role in spatial memory, head-direction representation, and scene-based cognition.
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salience network: a large-scale brain network centered in the anterior insula and anterior cingulate cortex, the salience network detects and prioritizes behaviorally relevant stimuli and mediates network switching between default mode and executive control systems.
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secondary visual cortex (V2): situated adjacent to the primary visual cortex in the occipital lobe, the secondary visual cortex corresponds to Brodmann area 18. It is involved in processing visual information, including recognition of shapes, colors, and spatial orientation.
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somatosensory association cortex (SAC): located in the parietal lobe, the somatosensory association cortex encompasses Brodmann areas 5 and 7. It is involved in the integration and interpretation of somatosensory information, such as touch, pain, temperature, and proprioception.
subgenual ventromedial prefrontal cortex (VMPFC): situated in the ventral part of the medial prefrontal cortex, the subgenual ventromedial prefrontal cortex includes parts of Brodmann areas 25, 32, and 14. It is involved in emotional regulation, decision-making, and social cognition.
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supplementary motor cortex (SMA): located in the medial part of the superior frontal gyrus, the supplementary motor cortex corresponds to Brodmann area 6. It is involved in planning and coordinating complex movements and motor learning.
supramarginal gyrus: situated in the parietal lobe, the supramarginal gyrus is part of the inferior parietal lobule and corresponds to Brodmann area 40. It is involved in language processing, attention, and spatial cognition.
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superior temporal gyrus (STG): located in the superior region of the temporal lobe, the superior temporal gyrus encompasses Brodmann areas 22, 41, and 42. It plays a role in auditory processing, language comprehension, and social cognition.
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temporopolar area: situated in the most anterior part of the temporal lobe, the temporopolar area corresponds to Brodmann area 38. It is involved in olfactory processing, social cognition, and semantic memory.
ventral anterior cingulate cortex (VACC): located in the ventral region of the anterior cingulate cortex, the ventral anterior cingulate cortex includes parts of Brodmann areas 24, 25, and 33. It is involved in emotional regulation, attention, and pain processing.
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ventral entorhinal cortex (VEC): situated in the medial temporal lobe, the ventral entorhinal cortex covers parts of Brodmann area 28. It is involved in object recognition, memory, and contextual processing.
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ventral posterior cingulate cortex (VPCC): located in the ventral part of the posterior cingulate cortex, the ventral posterior cingulate cortex includes parts of Brodmann areas 23 and 31. It involves self-referential thought, episodic memory retrieval, and emotional processing.
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visual association cortex: found in the occipital and parietal lobes, the visual association cortex includes Brodmann areas 18, 19, and parts of 7. It is responsible for higher-level visual processing, including object recognition, motion perception, and spatial awareness.​
References
Aggleton, J. P., & Brown, M. W. (1999). Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. The Behavioral and Brain Sciences, 22(3), 425–489. https://doi.org/10.1017/S0140525X99002034
Ahuja, A., & Yusif Rodriguez, N. (2022). Is the dorsolateral prefrontal cortex actually several different brain areas? The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 42(33), 6310–6312. https://doi.org/10.1523/JNEUROSCI.0848-22.2022
Amaral, D. G., & Witter, M. P. (1995). Hippocampal formation. In G. Paxinos (Ed.), The rat nervous system (pp. 443-493). Academic Press.
Amunts, K., Schleicher, A., Bürgel, U., Mohlberg, H., Uylings, H. B., & Zilles, K. (1999). Broca's region revisited: Cytoarchitecture and intersubject variability. The Journal of Comparative Neurology, 412(2), 319–341. https://doi.org/10.1002/(sici)1096-9861(19990920)412:2<319::aid-cne10>3.0.co;2-7
Augustine J. R. (1996). Circuitry and functional aspects of the insular lobe in primates including humans. Brain research. Brain Research Reviews, 22(3), 229–244. https://doi.org/10.1016/s0165-0173(96)00011-2
Avidan, G., & Behrmann, M. (2009). Functional MRI reveals compromised neural integrity of the face processing network in congenital prosopagnosia. Current Biology: CB, 19(13), 1146–1150. https://doi.org/10.1016/j.cub.2009.04.060
Baliki, M. N., Geha, P. Y., & Apkarian, A. V. (2009). Parsing pain perception between nociceptive representation and magnitude estimation. Journal of Neurophysiology, 101(2), 875–887. https://doi.org/10.1152/jn.91100.2008
Barbas, H. (2007). Flow of information for emotions through temporal and orbitofrontal pathways. Journal of Anatomy, 211(2), 237–249. https://doi.org/10.1111/j.1469-7580.2007.00777.x
Bizley, J. K., & Cohen, Y. E. (2013). The what, where and how of auditory-object perception. Nature Reviews. Neuroscience, 14(10), 693–707. https://doi.org/10.1038/nrn3565
Booth, J. R., Wood, L., Lu, D., Houk, J. C., & Bitan, T. (2007). The role of the basal ganglia and cerebellum in language processing. Brain Research, 1133(1), 136–144. https://doi.org/10.1016/j.brainres.2006.11.074
Braak, H., & Braak, E. (1991). Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica, 82(4), 239–259. https://doi.org/10.1007/BF00308809
Bressler, S. L., & Menon, V. (2010). Large-scale brain networks in cognition: emerging methods and principles. Trends in Cognitive Sciences, 14(6), 277–290. https://doi.org/10.1016/j.tics.2010.04.004
Brodmann, K. (1909). Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Barth.
Broyd, S. J., Demanuele, C., Debener, S., Helps, S. K., James, C. J., & Sonuga-Barke, E. J. (2009). Default-mode brain dysfunction in mental disorders: A systematic review. Neuroscience and Biobehavioral Reviews, 33(3), 279–296. https://doi.org/10.1016/j.neubiorev.2008.09.002
Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain's default network: Anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 1-38. https://doi.org/10.1196/annals.1440.011
Bush, G., Luu, P., & Posner, M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences, 4(6), 215–222. https://doi.org/10.1016/s1364-6613(00)01483-2
Cao, Z., Ottino-Gonzalez, J., Cupertino, R. B., Schwab, N., Hoke, C., Catherine, O., Cousijn, J., Dagher, A., Foxe, J. J., Goudriaan, A. E., Hester, R., Hutchison, K., Li, C. R., London, E. D., Lorenzetti, V., Luijten, M., Martin-Santos, R., Momenan, R., Paulus, M. P., Schmaal, L., … Garavan, H. (2021). Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group. Addiction Biology, 26(5), e13010. https://doi.org/10.1111/adb.13010
Carey, L. M., Abbott, D. F., Egan, G. F., O'Keefe, G. J., Jackson, G. D., Bernhardt, J., & Donnan, G. A. (2006). Evolution of brain activation with good and poor motor recovery after stroke. Neurorehabilitation and Neural Repair, 20(1), 24–41. https://doi.org/10.1177/1545968305283053
Carlén M. (2017). What constitutes the prefrontal cortex? Science, 358(6362), 478–482. https://doi.org/10.1126/science.aan8868
Caspers, S., Geyer, S., Schleicher, A., Mohlberg, H., Amunts, K., & Zilles, K. (2006). The human inferior parietal cortex: Cytoarchitectonic parcellation and interindividual variability. NeuroImage, 33(2), 430–448. https://doi.org/10.1016/j.neuroimage.2006.06.054
Castellanos, F. X., Margulies, D. S., Kelly, C., Uddin, L. Q., Ghaffari, M., Kirsch, A., Shaw, D., Shehzad, Z., Di Martino, A., Biswal, B., Sonuga-Barke, E. J., Rotrosen, J., Adler, L. A., & Milham, M. P. (2008). Cingulate-precuneus interactions: A new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biological Psychiatry, 63(3), 332–337. https://doi.org/10.1016/j.biopsych.2007.06.025
Catani, M., Jones, D. K., Donato, R., & Ffytche, D. H. (2003). Occipito-temporal connections in the human brain. Brain: A Journal of Neurology, 126(Pt 9), 2093–2107. https://doi.org/10.1093/brain/awg203
Craig A. D. (2009). How do you feel--now? The anterior insula and human awareness. Nature Reviews. Neuroscience, 10(1), 59–70. https://doi.org/10.1038/nrn2555
Devinsky, O., Morrell, M. J., & Vogt, B. A. (1995). Contributions of anterior cingulate cortex to behaviour. Brain: A Journal of Neurology, 118 ( Pt 1), 279–306. https://doi.org/10.1093/brain/118.1.279
Di Martino, A., Ross, K., Uddin, L. Q., Sklar, A. B., Castellanos, F. X., & Milham, M. P. (2009). Functional brain correlates of social and nonsocial processes in autism spectrum disorders: An activation likelihood estimation meta-analysis. Biological Psychiatry, 65(1), 63–74. https://doi.org/10.1016/j.biopsych.2008.09.022
Dosenbach, N. U., Fair, D. A., Miezin, F. M., Cohen, A. L., Wenger, K. K., Dosenbach, R. A., Fox, M. D., Snyder, A. Z., Vincent, J. L., Raichle, M. E., Schlaggar, B. L., & Petersen, S. E. (2007). Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences of the United States of America, 104(26), 11073–11078. https://doi.org/10.1073/pnas.0704320104
Doty R. L. (2008). The olfactory vector hypothesis of neurodegenerative disease: is it viable? Annals of Neurology, 63(1), 7–15. https://doi.org/10.1002/ana.21327
Drevets, W. C., Price, J. L., & Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Structure & Function, 213(1-2), 93–118. https://doi.org/10.1007/s00429-008-0189-x
Du, F., Whetsell, W. O., Jr, Abou-Khalil, B., Blumenkopf, B., Lothman, E. W., & Schwarcz, R. (1993). Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy. Epilepsy Research, 16(3), 223–233. https://doi.org/10.1016/0920-1211(93)90083-j
Eichenbaum, H., Yonelinas, A. P., & Ranganath, C. (2007). The medial temporal lobe and recognition memory. Annual Review of Neuroscience, 30, 123–152. https://doi.org/10.1146/annurev.neuro.30.051606.094328
Epstein R. A. (2008). Parahippocampal and retrosplenial contributions to human spatial navigation. Trends in Cognitive Sciences, 12(10), 388–396. https://doi.org/10.1016/j.tics.2008.07.004
Etkin, A., Egner, T., & Kalisch, R. (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences, 15(2), 85–93. https://doi.org/10.1016/j.tics.2010.11.004
Frank, G. K., Shott, M. E., Riederer, J., & Pryor, T. L. (2016). Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis. Translational Psychiatry, 6(11), e932. https://doi.org/10.1038/tp.2016.199
Friederici A. D. (2011). The brain basis of language processing: From structure to function. Physiological Reviews, 91(4), 1357–1392. https://doi.org/10.1152/physrev.00006.2011
Fuster J. M. (2001). The prefrontal cortex--An update: Time is of the essence. Neuron, 30(2), 319–333. https://doi.org/10.1016/s0896-6273(01)00285-9
Gevensleben, H., Moll, G. H., Rothenberger, A., & Heinrich, H. (2014). Neurofeedback in attention-deficit/hyperactivity disorder - Different models, different ways of application. Frontiers in Human Neuroscience, 8, 846. https://doi.org/10.3389/fnhum.2014.00846
Glasser, M. F., Coalson, T. S., Robinson, E. C., Hacker, C. D., Harwell, J., Yacoub, E., Ugurbil, K., Andersson, J., Beckmann, C. F., Jenkinson, M., Smith, S. M., & Van Essen, D. C. (2016). A multi-modal parcellation of human cerebral cortex. Nature, 536(7615), 171–178. https://doi.org/10.1038/nature18933
Gottfried J. A. (2010). Central mechanisms of odour object perception. Nature Reviews. Neuroscience, 11(9), 628–641. https://doi.org/10.1038/nrn2883
Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., Reiss, A. L., & Schatzberg, A. F. (2007). Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry, 62(5), 429–437.
https://doi.org/10.1016/j.biopsych.2006.09.020
Griffiths, T. D., & Warren, J. D. (2002). The planum temporale as a computational hub. Trends in Neurosciences, 25(7), 348–353. https://doi.org/10.1016/s0166-2236(02)02191-4
Grill-Spector, K., Knouf, N., & Kanwisher, N. (2004). The fusiform face area subserves face perception, not generic within-category identification. Nature Neuroscience, 7(5), 555–562. https://doi.org/10.1038/nn1224
Hafting, T., Fyhn, M., Molden, S., Moser, M. B., & Moser, E. I. (2005). Microstructure of a spatial map in the entorhinal cortex. Nature, 436(7052), 801–806. https://doi.org/10.1038/nature03721
Hamilton, J. P., Glover, G. H., Hsu, J. J., Johnson, R. F., & Gotlib, I. H. (2011). Modulation of subgenual anterior cingulate cortex activity with real-time neurofeedback. Human Brain Mapping, 32(1), 22–31. https://doi.org/10.1002/hbm.20997
Heckers, S., Rauch, S. L., Goff, D., Savage, C. R., Schacter, D. L., Fischman, A. J., & Alpert, N. M. (1998). Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nature Neuroscience, 1(4), 318–323. https://doi.org/10.1038/1137
Hoeft, F., Meyler, A., Hernandez, A., Juel, C., Taylor-Hill, H., Martindale, J. L., McMillon, G., Kolchugina, G., Black, J. M., Faizi, A., Deutsch, G. K., Siok, W. T., Reiss, A. L., Whitfield-Gabrieli, S., & Gabrieli, J. D. (2007). Functional and morphometric brain dissociation between dyslexia and reading ability. Proceedings of the National Academy of Sciences of the United States of America, 104(10), 4234–4239. https://doi.org/10.1073/pnas.0609399104
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984). Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science, 225(4667), 1168–1170. https://doi.org/10.1126/science.6474172
Jasper, H. H. (1958). The Ten-Twenty Electrode System of the International Federation. Electroencephalography and Clinical Neurophysiology, 10, 371-375.
Khan, U. A., Liu, L., Provenzano, F. A., Berman, D. E., Profaci, C. P., Sloan, R., Mayeux, R., Duff, K. E., & Small, S. A. (2014). Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease. Nature Neuroscience, 17(2), 304–311. https://doi.org/10.1038/nn.3606
Kluetsch, R. C., Ros, T., Théberge, J., Frewen, P. A., Calhoun, V. D., Schmahl, C., Jetly, R., & Lanius, R. A. (2014). Plastic modulation of PTSD resting-state networks and subjective wellbeing by EEG neurofeedback. Acta Psychiatrica Scandinavica, 130(2), 123–136. https://doi.org/10.1111/acps.12229
Kringelbach M. L. (2005). The human orbitofrontal cortex: Linking reward to hedonic experience. Nature Reviews. Neuroscience, 6(9), 691–702. https://doi.org/10.1038/nrn1747
Kurth, F., Zilles, K., Fox, P. T., Laird, A. R., & Eickhoff, S. B. (2010). A link between the systems: Functional differentiation and integration within the human insula revealed by meta-analysis. Brain Structure & Function, 214(5-6), 519–534. https://doi.org/10.1007/s00429-010-0255-z
Leech, R., & Sharp, D. J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain: A Journal of Neurology, 137(Pt 1), 12–32. https://doi.org/10.1093/brain/awt162
Linden D. E. (2006). How psychotherapy changes the brain--The contribution of functional neuroimaging. Molecular Psychiatry, 11(6), 528–538. https://doi.org/10.1038/sj.mp.4001816
Liston, C., Malter Cohen, M., Teslovich, T., Levenson, D., & Casey, B. J. (2011). Atypical prefrontal connectivity in attention-deficit/hyperactivity disorder: Pathway to disease or pathological end point? Biological Psychiatry, 69(12), 1168–1177. https://doi.org/10.1016/j.biopsych.2011.03.022
Margulies, D. S., Kelly, A. M., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2007). Mapping the functional connectivity of anterior cingulate cortex. NeuroImage, 37(2), 579–588. https://doi.org/10.1016/j.neuroimage.2007.05.019
Mayberg H. S. (2003). Modulating dysfunctional limbic-cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimized treatment. British Medical Bulletin, 65, 193–207. https://doi.org/10.1093/bmb/65.1.193
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483-506. https://doi.org/10.1016/j.tics.2011.08.003
Menon, V., & Uddin, L. Q. (2010). Saliency, switching, attention and control: A network model of insula function. Brain Structure & Function, 214(5-6), 655–667. https://doi.org/10.1007/s00429-010-0262-0
Morosan, P., Rademacher, J., Schleicher, A., Amunts, K., Schormann, T., & Zilles, K. (2001). Human primary auditory cortex: Cytoarchitectonic subdivisions and mapping into a spatial reference system. NeuroImage, 13(4), 684–701. https://doi.org/10.1006/nimg.2000.0715
Neef, N. E., Anwander, A., Bütfering, C., Schmidt-Samoa, C., Friederici, A. D., Paulus, W., & Sommer, M. (2018). Structural connectivity of right frontal hyperactive areas scales with stuttering severity. Brain: A Journal of Neurology, 141(1), 191–204. https://doi.org/10.1093/brain/awx316
Neville, K. R., & Haberly, L. B. (2004). Olfactory cortex. The synaptic organization of the brain. In G. M. Shepherd (Ed.). Oxford University Press, 415–454. https://doi.org/10.1093/acprof:oso/9780195159561.003.0010
Niendam, T. A., Laird, A. R., Ray, K. L., Dean, Y. M., Glahn, D. C., & Carter, C. S. (2012). Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cognitive, Affective & Behavioral Neuroscience, 12(2), 241–268. https://doi.org/10.3758/s13415-011-0083-5
Ogawa H. (1994). Gustatory cortex of primates: anatomy and physiology. Neuroscience Research, 20(1), 1–13. https://doi.org/10.1016/0168-0102(94)90017-5
Olson, I. R., Plotzker, A., & Ezzyat, Y. (2007). The Enigmatic temporal pole: a review of findings on social and emotional processing. Brain: A Journal of Neurology, 130(Pt 7), 1718–1731. https://doi.org/10.1093/brain/awm052
Ongür, D., Ferry, A. T., & Price, J. L. (2003). Architectonic subdivision of the human orbital and medial prefrontal cortex. The Journal of Comparative Neurology, 460(3), 425–449. https://doi.org/10.1002/cne.10609
Padmanabhan, A., Lynch, C. J., Schaer, M., & Menon, V. (2017). The Default Mode Network in autism. Biological Psychiatry. Cognitive Neuroscience and Neuroimaging, 2(6), 476–486. https://doi.org/10.1016/j.bpsc.2017.04.004
Peng, K., Steele, S. C., Becerra, L., & Borsook, D. (2018). Brodmann area 10: Collating, integrating and high level processing of nociception and pain. Progress in Neurobiology, 161, 1–22. https://doi.org/10.1016/j.pneurobio.2017.11.004
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003). Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biological Psychiatry, 54(5), 504–514. https://doi.org/10.1016/S0006-3223(03)00168-9
Price, J. L., & Drevets, W. C. (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 35(1), 192–216. https://doi.org/10.1038/npp.2009.104
Purves, D. (2018). Neuroscience (6th ed.). Oxford University Press.
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences of the United States of America, 98(2), 676–682. https://doi.org/10.1073/pnas.98.2.676
Rajkowska, G., & Goldman-Rakic, P. S. (1995). Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. Variability in locations of areas 9 and 46 and relationship to the Talairach Coordinate System. Cerebral cortex (1991), 5(4), 323–337. https://doi.org/10.1093/cercor/5.4.323
Ramnani, N., & Owen, A. M. (2004). Anterior prefrontal cortex: Insights into function from anatomy and neuroimaging. Nature Reviews. Neuroscience, 5(3), 184–194. https://doi.org/10.1038/nrn1343
Rolls E. T. (2006). Brain mechanisms underlying flavour and appetite. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 361(1471), 1123–1136. https://doi.org/10.1098/rstb.2006.1852
Rolls, E. T., Cheng, W., & Feng, J. (2020). The orbitofrontal cortex: Reward, emotion and depression. Brain Communications, 2(2), fcaa196. https://doi.org/10.1093/braincomms/fcaa196
Ros, T., J Baars, B., Lanius, R. A., & Vuilleumier, P. (2014). Tuning pathological brain oscillations with neurofeedback: A systems neuroscience framework. Frontiers in Human Neuroscience, 8, 1008. https://doi.org/10.3389/fnhum.2014.01008
Roy, A. K., Shehzad, Z., Margulies, D. S., Kelly, A. M., Uddin, L. Q., Gotimer, K., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2009). Functional connectivity of the human amygdala using resting state fMRI. NeuroImage, 45(2), 614–626. https://doi.org/10.1016/j.neuroimage.2008.11.030
Roy, M., Shohamy, D., & Wager, T. D. (2012). Ventromedial prefrontal-subcortical systems and the generation of affective meaning. Trends in Cognitive Sciences, 16(3), 147–156. https://doi.org/10.1016/j.tics.2012.01.005
Rudebeck, P. H., Putnam, P. T., Daniels, T. E., Yang, T., Mitz, A. R., Rhodes, S. E., & Murray, E. A. (2014). A role for primate subgenual cingulate cortex in sustaining autonomic arousal. Proceedings of the National Academy of Sciences of the United States of America, 111(14), 5391–5396. https://doi.org/10.1073/pnas.1317695111
Sedley, W., Parikh, J., Edden, R. A., Tait, V., Blamire, A., & Griffiths, T. D. (2015). Human auditory cortex neurochemistry reflects the presence and severity of tinnitus. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 35(44), 14822–14828. https://doi.org/10.1523/JNEUROSCI.2695-15.2015
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27(9), 2349–2356. https://doi.org/10.1523/JNEUROSCI.5587-06.2007
Seghier M. L. (2013). The angular gyrus: multiple functions and multiple subdivisions. The Neuroscientist: A Review Journal Bridging Neurobiology, Neurology and Psychiatry, 19(1), 43–61. https://doi.org/10.1177/1073858412440596
Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A. (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the United States of America, 107(24), 11020–11025. https://doi.org/10.1073/pnas.1000446107
Shepherd G. M. (2007). Perspectives on olfactory processing, conscious perception, and orbitofrontal cortex. Annals of the New York Academy of Sciences, 1121, 87–101. https://doi.org/10.1196/annals.1401.032
Small, D. M., Zald, D. H., Jones-Gotman, M., Zatorre, R. J., Pardo, J. V., Frey, S., & Petrides, M. (1999). Human cortical gustatory areas: A review of functional neuroimaging data. Neuroreport, 10(1), 7–14. https://doi.org/10.1097/00001756-199901180-00002
Suzuki, W. A., & Amaral, D. G. (1994). Perirhinal and parahippocampal cortices of the macaque monkey: Cortical afferents. The Journal of Comparative Neurology, 350(4), 497–533. https://doi.org/10.1002/cne.903500402
Utevsky, A. V., Smith, D. V., & Huettel, S. A. (2014). Precuneus is a functional core of the default-mode network. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 34(3), 932–940. https://doi.org/10.1523/JNEUROSCI.4227-13.2014
Van Hoesen, G., & Pandya, D. N. (1975). Some connections of the entorhinal (area 28) and perirhinal (area 35) cortices of the rhesus monkey. I. Temporal lobe afferents. Brain Research, 95(1), 1–24. https://doi.org/10.1016/0006-8993(75)90204-8
​
van Strien, N. M., Cappaert, N. L., & Witter, M. P. (2009). The anatomy of memory: An interactive overview of the parahippocampal-hippocampal network. Nature Reviews. Neuroscience, 10(4), 272–282. https://doi.org/10.1038/nrn2614
Vann, S. D., Aggleton, J. P., & Maguire, E. A. (2009). What does the retrosplenial cortex do? Nature Reviews. Neuroscience, 10(11), 792–802. https://doi.org/10.1038/nrn2733
Vogt B. A. (2005). Pain and emotion interactions in subregions of the cingulate gyrus. Nature Reviews. Neuroscience, 6(7), 533–544. https://doi.org/10.1038/nrn1704
Watkins, K. E., Vargha-Khadem, F., Ashburner, J., Passingham, R. E., Connelly, A., Friston, K. J., Frackowiak, R. S., Mishkin, M., & Gadian, D. G. (2002). MRI analysis of an inherited speech and language disorder: Structural brain abnormalities. Brain: A Journal of Neurology, 125(Pt 3), 465–478. https://doi.org/10.1093/brain/awf057
Wesson, D. W., & Wilson, D. A. (2011). Sniffing out the contributions of the olfactory tubercle to the sense of smell: Hedonics, sensory integration, and more? Neuroscience and Biobehavioral Reviews, 35(3), 655–668. https://doi.org/10.1016/j.neubiorev.2010.08.004
Witter, M. P., Wouterlood, F. G., Naber, P. A., & Van Haeften, T. (2000). Anatomical organization of the parahippocampal-hippocampal network. Annals of the New York Academy of Sciences, 911, 1–24. https://doi.org/10.1111/j.1749-6632.2000.tb06716.x
Zilles, K., & Amunts, K. (2010). Centenary of Brodmann’s map—conception and fate. Nature Reviews Neuroscience, 11(2), 139–145. https://doi.org/10.1038/nrn2776
Zotev, V., Krueger, F., Phillips, R., Alvarez, R. P., Simmons, W. K., Bellgowan, P., Drevets, W. C., & Bodurka, J. (2011). Self-regulation of amygdala activation using real-time FMRI neurofeedback. PloS one, 6(9), e24522. https://doi.org/10.1371/journal.pone.0024522