The Clinician Detective: Intermittent Epileptiform Discharges (IEDs)

Dr. Ronald Swatzyna, Director and Chief Scientist of the Houston Neuroscience Brain Center, inspired our Clinician Detective series. In his Association for Applied Psychophysiology and Biofeedback (AAPB) Distinguished Scientist address, he reminded his audience that the DSM-5 requires that general medical conditions be systematically ruled out before assigning a psychiatric diagnosis to ensure diagnostic validity and appropriate treatment planning. He argued that in abrupt onset and refractory cases, EEG biomarkers should challenge neurofeedback providers and their medical colleagues to become detectives to identify its causes. This collaborative approach allows each professional to contribute to assessment while "staying in their lane."

Introduction

Intermittent epileptiform discharges (IEDs) are brief paroxysmal electroencephalographic events that typically manifest as spikes, sharp waves, or spike-and-wave complexes lasting less than 70 milliseconds.

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These waveforms reflect transient cortical hyperexcitability and are traditionally associated with epilepsy. However, mounting evidence reveals that IEDs may also occur in individuals without a history of seizures, particularly within pediatric and adolescent populations exhibiting neurodevelopmental or psychiatric symptoms (Swatzyna et al., 2020).

These findings challenge the conventional dichotomy that separates epileptic from non-epileptic disorders and instead support a dimensional understanding of cortical excitability across diagnostic boundaries. In individuals with psychiatric conditions, IEDs may not induce convulsive activity but can still contribute to clinically significant disturbances in cognition, mood, or behavior. As a result, they serve as important neurophysiological biomarkers that can elucidate treatment resistance and inform more precise, biologically grounded interventions.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), emphasizes phenomenological descriptions and symptom clusters in the classification of psychiatric disorders. This approach, while clinically pragmatic, lacks integration with objective biomarkers of brain function. The absence of physiological data in psychiatric diagnostics contributes to misclassification and overreliance on psychopharmacologic trial-and-error, particularly in cases that do not respond to first- or second-line therapies.

The National Institute of Mental Health (NIMH) has proposed the Research Domain Criteria (RDoC) framework to address this limitation by incorporating neurobiological measures into diagnostic models (Insel et al., 2010). In this context, EEG findings—especially IEDs—represent a valuable opportunity to align psychiatry with the broader movement toward precision medicine. They provide a means of “testing the organ we are treating,” and when interpreted within a clinical context, they offer critical insight into the functional dynamics of the brain that underpin psychiatric presentations (Swatzyna et al., 2024).

How to Recognize Intermittent Epileptiform Discharges (IEDs) in the EEG

Morphology and Misinterpretation in Standard Practice

IEDs are typically identified by their sudden emergence, distinct morphology, and deviation from the EEG background. Spikes last less than 70 milliseconds and have a steep rise and fall, while sharp waves are slightly broader, up to 200 milliseconds. Pediatric IED graphic courtesy of Papadelis et al. (2016).

Caption: 1 s of highlighted section that contains one sharp wave is presented on the right panels in an extended time scale display. Red dots indicate the peak of the IEDs.

Spike-and-wave complexes—often associated with generalized epileptiform activity—can also present focally. These discharges stand out from the ongoing rhythm, not only in shape but often in amplitude, and are usually followed by a slow wave or transient suppression of the background, a hallmark of cortical disruption. While most neurologists are trained to recognize these patterns, many do not attribute significance to them unless they meet stringent epilepsy criteria. This tendency to underreport or dismiss isolated discharges as "normal variants" reflects a disconnect between electrophysiology and clinical neuropsychiatry.

Anatomical Localization and Behavioral Expression

Swatzyna and Boutros argue that the location of IEDs is as important as their frequency. Discharges in the frontal lobes often correspond with symptoms of disinhibition, irritability, and executive dysfunction. Patients with these findings may be misdiagnosed with ADHD, conduct disorder, or even borderline personality disorder. Similarly, temporal lobe IEDs are frequently associated with emotional instability, memory disturbance, dissociation, or auditory hallucinations—symptoms that often lead to diagnoses of bipolar disorder or PTSD. In these cases, the EEG may reveal a physiological substrate that reframes the diagnosis and prompts a rethinking of pharmacologic strategy. Boutros has emphasized that even a single discharge in a behaviorally critical region may be responsible for substantial impairment, particularly when psychiatric symptoms fluctuate episodically and resist standard treatment.

State Dependence and the Limitations of Routine EEG

One key insight from Swatzyna’s work is that IEDs are often state-dependent. They are most likely to appear during drowsiness, early non-REM sleep, or following sleep deprivation—states that reduce cortical inhibition and unmask latent excitability. In clinical practice, this means that routine 20-minute awake EEGs may miss discharges entirely. Swatzyna’s studies have shown that adding sleep-deprived or overnight EEG protocols significantly improves detection rates, particularly in children and adolescents. Patients with previously "normal" EEGs often reveal clinically meaningful abnormalities when tested under these conditions. For individuals with treatment-resistant anxiety, mood instability, or aggression, an extended EEG can reveal a pattern that directly informs the choice of medication or neuromodulatory intervention.

Educational Gaps and the Role of the Neurologist

Despite this, IEDs are still frequently overlooked in psychiatry due to the enduring belief that "abnormal" EEG findings must correlate with overt seizures to be relevant. Neurologists may be reluctant to report infrequent or isolated discharges in non-epileptic patients, fearing overinterpretation or medicolegal implications. Boutros and Swatzyna have challenged this hesitation, arguing that EEG findings should be interpreted in the full clinical context—not in isolation. The neurologist, they suggest, must adopt the mindset of a clinical detective, asking not just whether the discharge is epileptiform, but whether it explains otherwise puzzling symptomatology.

Toward Functional and Narrative EEG Reporting

To facilitate this shift, both Swatzyna and Boutros advocate for narrative EEG reports that integrate the electrophysiological data with behavioral and cognitive symptoms. Rather than simply labeling a study “normal” or “abnormal,” the report should describe the location of discharges, the states in which they appeared, and their potential relevance to the patient’s clinical picture. For example, identifying left temporal IEDs in a patient with language impairment and emotional lability provides diagnostic and therapeutic direction. This kind of integrative reporting aligns EEG interpretation with the goals of precision psychiatry, where brain-based biomarkers inform personalized treatment strategies.

The EEG as a Tool of Neuropsychiatric Discovery

Ultimately, recognizing IEDs in the EEG is not just a matter of technical proficiency—it is a clinical act of discovery. Swatzyna’s model reframes EEG interpretation from a static exercise in pattern recognition to a dynamic investigation into the functional integrity of the brain. By embracing this model, clinicians and neurologists alike can uncover hidden sources of dysfunction, correct misdiagnoses, and tailor interventions to the true neurophysiological architecture of the patient. In this light, IEDs become not an incidental curiosity, but a critical biomarker—one that, when properly understood, opens the door to a radically improved standard of care in psychiatry.

Prevalence Across Diagnostic Categories

The presence of IEDs in psychiatric populations is far more common than previously assumed and significantly exceeds the background prevalence in the general population. In neurologically healthy children, the prevalence of IEDs detected on routine EEG is estimated to range between 0.5% and 5% (Doose & Baier, 1988). However, among children and adolescents with neuropsychiatric disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), these figures are markedly elevated.

For example, Swatzyna et al. (2020) reported that more than 25% of patients with ADHD and up to 63% of those with ASD displayed IEDs on routine EEG. Other studies using sleep-deprived or extended EEG protocols have reported even higher detection rates—up to 85% in individuals with ASD—suggesting that standard wake EEG may underestimate the true prevalence (Hara, 2007; Tuchman & Rapin, 2002).

This high prevalence is not uniformly distributed across psychiatric conditions. IEDs appear more commonly in disorders characterized by early neurodevelopmental disruption, emotional dysregulation, and treatment resistance. In contrast, individuals with primary mood disorders or anxiety disorders without neurodevelopmental features generally exhibit lower rates of IEDs—approximately 3% in major depressive disorder, for instance (Swatzyna et al., 2020). These findings suggest that IEDs may reflect a shared neurobiological substrate across several DSM-5 categories, particularly where standard treatments fail or produce paradoxical reactions.

Importantly, Swatzyna and colleagues (2017) emphasized that the presence of IEDs did not align neatly with any one psychiatric diagnosis but instead functioned as a transdiagnostic biomarker indicative of underlying cortical dysregulation. This has significant implications for clinical assessment and treatment planning, encouraging clinicians to consider EEG evaluation in refractory or atypical psychiatric presentations.

Cognitive and Behavioral Manifestations

IEDs can produce subtle but clinically meaningful impairments in brain function, even in the absence of overt seizures. These discharges disrupt local and global cortical processing, causing transient deficits in attention, memory, language, or emotional regulation depending on their topographical location. For instance, discharges in the left temporal lobe may interfere with verbal working memory and language fluency, while right frontal IEDs may impair impulse control and social decision-making. These manifestations are often episodic and context-dependent, making them difficult to detect through routine clinical interviews or behavioral observations alone (Boutros et al., 2016). Nonetheless, their impact can be profound, especially when IEDs are frequent or occur during critical periods of cognitive engagement, such as school tasks or interpersonal interactions.

These paroxysmal disruptions often mimic primary psychiatric symptoms and are thus misattributed to mood or behavioral disorders. For example, a child with frequent frontal IEDs may exhibit poor frustration tolerance, emotional outbursts, and distractibility, leading to a diagnosis of ADHD or oppositional defiant disorder. However, the underlying pathophysiology may be neuroelectric instability rather than a pure behavioral or developmental etiology.

In a study of children with ASD, Swatzyna et al. (2017) found that 36% exhibited isolated epileptiform discharges (IEDs) on EEG despite having no clinical history of seizures. These discharges were associated with treatment-resistant aggression and mood lability, and symptom improvement was observed following the introduction of neurostabilizing interventions. This underscores the critical importance of recognizing IEDs as potential contributors to complex psychiatric profiles. Without EEG screening, these individuals risk being misdiagnosed, subjected to inappropriate medication regimens, and deprived of targeted neurophysiological treatment strategies.

Topographic Distribution and Symptom Profiles

The clinical relevance of IEDs is heavily influenced by their neuroanatomical location. IEDs arise from specific cortical regions, and their behavioral manifestations often reflect the functions of those regions. Frontal lobe discharges, for example, are frequently associated with impairments in executive functioning, including poor planning, disinhibition, reduced frustration tolerance, and impulsivity—core features commonly mistaken for ADHD or bipolar disorder. Temporal lobe IEDs, by contrast, may be linked to episodic memory disturbances, emotional dysregulation, derealization, and even hallucinations (Swatzyna et al., 2024). In some cases, temporal IEDs in the dominant hemisphere have been associated with language impairments or word retrieval difficulties, while those in the non-dominant hemisphere may result in behavioral rigidity or social cue misinterpretation—features that overlap substantially with ASD (Tuchman & Rapin, 2002).

The location-dependent symptomatology of IEDs offers a critical window into cortical network function and dysfunction. Zimmerman and Konopka (2015) demonstrated that IEDs located in behaviorally salient regions such as the anterior temporal or inferior frontal gyri were significantly more likely to produce observable psychiatric symptoms than those arising from parieto-occipital areas. Moreover, they found that patients with focal IEDs confined to a single lobe often exhibited more severe psychiatric symptoms than those with more diffuse or multifocal activity, contradicting traditional assumptions about the risks associated with generalized discharges. This suggests that not all IEDs are created equal—both the location and context in which they occur matter profoundly. Such specificity underscores the importance of trained electroencephalographers who can interpret not only the morphology but also the localization and clinical significance of the discharges. For clinicians, recognizing that a pattern of symptoms may be topographically mapped onto cortical regions where IEDs are recorded opens new avenues for diagnosis, prognosis, and intervention.

Case Identification and Misdiagnosis

The failure to recognize IEDs as etiologically significant often results in misdiagnosis and inappropriate treatment. Patients who present with episodic mood swings, irritability, attentional deficits, or aggression are frequently labeled with mood, behavioral, or personality disorders without adequate consideration of neurological substrates. For instance, a teenager with episodic aggression and poor affect regulation might be diagnosed with intermittent explosive disorder or conduct disorder, when in fact their symptoms are manifestations of temporal lobe discharges that transiently impair emotional control circuits.

In a review of 386 treatment-refractory cases, Swatzyna et al. (2015) found that IEDs were present in 45% of patients and contributed significantly to failed medication trials and adverse drug reactions. These findings challenge the sufficiency of DSM-5 criteria in explaining refractory presentations and highlight the necessity of integrating EEG findings into psychiatric diagnostics.

Compounding the diagnostic challenge is the clinical silence of IEDs in many individuals—they do not cause seizures or visible neurological events, making them invisible to the unaided eye. As a result, these discharges may be mistaken for non-compliance, attention-seeking behavior, or even malingering.

Psychiatric medications that influence cortical excitability—particularly SSRIs, stimulants, and antipsychotics—can exacerbate symptoms in patients with underlying IEDs, further confusing the diagnostic picture and reinforcing incorrect labels such as treatment-resistant depression or atypical bipolar disorder (Swatzyna et al., 2020).

Clinical case studies demonstrate that patients mislabeled as having personality disorders or refractory ADHD often experience dramatic improvement in symptoms when the underlying IEDs are treated with anticonvulsants or neuromodulatory approaches. These transformations, though often surprising to clinicians, emphasize the degree to which EEG findings can revise psychiatric understanding and direct more effective therapeutic strategies.

Detection Techniques and Methodological Limitations

The identification of IEDs relies primarily on standard or extended EEG studies, yet current clinical practice underutilizes this tool in psychiatric populations. Routine EEGs conducted during wakefulness with eyes closed may fail to detect discharges that only appear during transitions between sleep stages or during non-REM sleep, when cortical disinhibition allows latent epileptiform activity to emerge. Swatzyna et al. (2020) demonstrated that sleep-deprived EEG protocols dramatically increased the diagnostic yield of IEDs in children and adolescents with psychiatric symptoms, particularly those with ASD and impulsive aggression. Unfortunately, sleep protocols are seldom included in routine psychiatric workups, leading to missed diagnoses and false reassurance.

Further complicating EEG utility is the overreliance on automated spike detection algorithms or insufficient training among EEG readers. Subtle discharges may be overlooked by general practitioners or misclassified as benign variants. Moreover, some waveforms that appear epileptiform may be normal for age or state (e.g., vertex sharp transients in sleep), requiring expert interpretation to avoid overdiagnosis. Therefore, accurate detection of IEDs necessitates not only extended or sleep-enhanced EEG protocols but also interpretation by board-certified neurophysiologists with clinical context.

Even in optimal settings, however, the paroxysmal and intermittent nature of IEDs makes them difficult to capture in a single routine study. This has led some experts to advocate for more widespread use of ambulatory EEG or inpatient monitoring in complex psychiatric presentations, especially when symptoms are episodic, refractory, or poorly characterized (Boutros et al., 2016). These approaches, though resource-intensive, may yield vital insights into otherwise enigmatic clinical profiles.

Bridging the Interpretive Gap: Rethinking the Role of the Neurologist in Psychiatric EEG Evaluation

One of the persistent challenges in leveraging EEG findings for psychiatric care is the interpretive variability among neurologists, particularly in how IEDs are characterized in patients without overt seizures. Many general neurologists are trained within a framework that emphasizes seizure diagnosis and epilepsy syndromes. In this context, isolated or infrequent IEDs—especially those without clinical correlates—are often dismissed as benign variants or incidental findings with “no clinical significance.”

This approach stems from a longstanding belief that EEG abnormalities, in the absence of seizures, are not actionable unless they occur with high frequency or in a known epileptogenic pattern (Gregory et al., 2008). Consequently, discharges that could explain fluctuating cognition, mood instability, or treatment resistance in psychiatric populations may be overlooked or downplayed in EEG reports.

Furthermore, the “normal variant” designation is sometimes based on the assumption that if the patient has no prior seizure history, discharges are not pathologic. However, this interpretation neglects the growing body of evidence showing that IEDs can interfere with real-time cognitive and affective processing and may reflect underlying cortical instability that contributes to psychiatric symptoms—even in the absence of seizures (Boutros et al., 2016; Swatzyna et al., 2020). This epistemological gap between epilepsy-focused neurology and neuropsychiatric application underscores the need for a paradigm shift in how EEGs are interpreted for psychiatric purposes.

Differential Diagnosis and Pathophysiology

The discovery of IEDs on EEG should prompt a thorough differential diagnostic process that extends beyond epilepsy. While these discharges may indeed reflect a subclinical epileptogenic focus, they can also occur secondary to broader cortical dysregulation, metabolic encephalopathy, neurotoxic exposure, or structural brain abnormalities. In children and adolescents, causes of intermittent discharges can include perinatal hypoxia, prior concussions, infections such as viral encephalitis, or even genetic syndromes that affect ion channel function (Swatzyna et al., 2020).

In such cases, the discharges are not primary but rather secondary markers of underlying cerebral pathology. For example, lead toxicity, which affects calcium channels in the brain, has been shown to potentiate cortical excitability and result in IEDs—findings that resolve with chelation therapy and environmental detoxification (Swatzyna et al., 2015). Similarly, magnesium deficiency, which impairs NMDA receptor modulation, can exacerbate epileptiform activity and psychiatric symptoms.

In addition, chronic exposure to psychotropic medications may induce or unmask IEDs in susceptible individuals. Benzodiazepines, SSRIs, and psychostimulants, through their modulation of GABAergic or monoaminergic pathways, may disrupt cortical excitability thresholds, leading to paradoxical worsening of behavioral symptoms. For this reason, when IEDs are present, medication history must be carefully reviewed to assess for iatrogenic contributions. Moreover, the presence of IEDs in individuals with no prior seizure history introduces the possibility of interictal epileptiform activity—a condition in which abnormal discharges occur between seizures or in the complete absence of clinically overt convulsions.

While not traditionally considered “epilepsy” in the absence of seizures, such discharges may still impair daily functioning and require medical management (Swatzyna et al., 2024). Ultimately, EEG abnormalities must be evaluated in tandem with clinical symptoms, laboratory tests, and imaging to construct a cohesive pathophysiological model and avoid both under- and over-treatment.

Association with Neurodevelopmental Disorders

Among all psychiatric conditions, autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) exhibit the highest known prevalence of IEDs. This association is not incidental, as both disorders are characterized by cortical developmental abnormalities that predispose to neuronal disorganization and excitability.

Multiple studies have confirmed that children with ASD are several times more likely to exhibit IEDs than typically developing peers—even when they have no seizure history. For example, in a sample of 140 nonepileptic individuals with ASD, Swatzyna et al. (2017) found that 36% exhibited isolated epileptiform discharges, primarily in frontal and temporal regions. These discharges were significantly associated with symptoms such as irritability, aggression, and language regression.

In longitudinal research, Hara (2007) found that children with ASD and IEDs were at significantly higher risk of developing seizures later in adolescence, suggesting that these discharges may indicate not only current dysfunction but also future epileptogenic vulnerability.

Similarly, in ADHD populations, IEDs have been observed in up to 30% of patients, especially those who have failed multiple medication trials or who exhibit paradoxical reactions to stimulants. These children may show transient disruptions in attention and impulse control that correlate temporally with the occurrence of discharges—effects that are often dismissed as behavioral inconsistency.

Boutros et al. (2016) emphasized that in such cases, psychiatric symptoms may reflect an epiphenomenon of cerebral dysfunction rather than a primary psychiatric condition. Importantly, IEDs in neurodevelopmental disorders are often focal, and their presence does not necessarily indicate the need for antiepileptic therapy. However, their identification does demand a tailored treatment approach—one that avoids seizure-threshold-lowering agents and emphasizes neurophysiological stabilization through either pharmacologic or neuromodulatory means.

Implications for Pharmacological Treatment

The presence of IEDs should significantly influence medication selection, especially in patients with treatment-resistant symptoms. Numerous commonly prescribed psychotropics—particularly selective serotonin reuptake inhibitors (SSRIs), psychostimulants, and benzodiazepines—are known to alter cortical excitability and, in vulnerable individuals, may worsen or unmask IEDs. This is especially problematic when these medications are administered empirically to children or adolescents with aggressive or impulsive symptoms in the absence of EEG assessment.

Swatzyna et al. (2020) reported that up to one-third of children with refractory ADHD and mood disorders had previously worsened on standard psychopharmacological regimens that failed to account for underlying IEDs. In such cases, the observed medication “failure” may not indicate diagnostic inaccuracy but rather unrecognized cortical instability.

Conversely, the introduction of low-dose anticonvulsants such as valproate, oxcarbazepine, or lamotrigine has been shown to stabilize cortical rhythms and reduce both EEG abnormalities and psychiatric symptoms. These agents are particularly effective when IEDs are localized to the frontal or temporal lobes, where discharges are more likely to interfere with behavior, mood, and cognition.

In some studies, including those by Swatzyna et al. (2015), children misdiagnosed with bipolar disorder or conduct disorder experienced dramatic symptom resolution after being transitioned to neurostabilizing agents informed by EEG findings. Moreover, adjunctive treatments such as magnesium supplementation, zinc repletion, and correction of vitamin D deficiency have been shown to reduce IED frequency and enhance overall cortical stability, especially in pediatric populations with nutritional deficits or toxic exposures. Thus, medication decisions in the presence of IEDs must be approached with both caution and precision, balancing symptomatic relief with the risk of exacerbating neuronal excitability.

Neurofeedback and Neuromodulation

For patients with IEDs who are either medication-refractory or medication-intolerant, non-pharmacological strategies such as neurofeedback and neuromodulation offer promising alternatives. Neurofeedback, a form of operant conditioning using real-time EEG monitoring, allows individuals to gain voluntary control over aberrant brain activity.

In patients with identified IEDs, tailored neurofeedback protocols can be developed to suppress paroxysmal activity or enhance inhibitory rhythms, such as sensorimotor rhythm (SMR) or alpha coherence, in the affected cortical regions (Thibault et al., 2016).

Swatzyna et al. (2015) documented cases in which patients with frontally dominant IEDs exhibited improved emotional regulation and attention after 20–40 sessions of protocol-driven neurofeedback targeting dysregulated frontal beta activity. While randomized controlled trials remain limited, clinical reports and observational data suggest that symptom improvements may parallel reductions in IED frequency, making neurofeedback a viable adjunct in comprehensive treatment planning.

In addition to neurofeedback, emerging technologies such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have demonstrated potential for cortical modulation in psychiatric disorders, particularly depression and ADHD. Though most studies have focused on their effects on mood and cognition, pilot investigations suggest that these modalities may also modulate epileptiform activity by influencing cortical excitability thresholds (Snyder et al., 2010). Importantly, however, such techniques should be used cautiously in patients with known IEDs, especially in the absence of continuous EEG monitoring.

Combining neuromodulation with EEG allows clinicians to monitor the electrophysiological impact of treatment and avoid inducing seizures or worsening instability. In this context, the integration of brain-based therapies and EEG biomarkers facilitates an individualized medicine approach that aligns with the principles of the NIMH’s RDoC initiative and the broader movement toward biologically informed psychiatry (Insel et al., 2010; Swatzyna et al., 2024).

Predictive Value and Longitudinal Outcomes

Beyond their role in symptom genesis, IEDs have important prognostic value. Several longitudinal studies have demonstrated that children with isolated IEDs—especially those with neurodevelopmental diagnoses—have a significantly elevated risk of developing epilepsy in adolescence or adulthood. Hara (2007) followed children with ASD and no seizure history for over a decade and found that 25% of those with IEDs eventually developed generalized or focal seizures.

This predictive relationship reinforces the need to monitor children with documented discharges over time, even if they remain clinically asymptomatic. Furthermore, persistent IEDs have been linked to neurocognitive stagnation or regression, particularly in language development, social functioning, and academic skills. These findings are consistent with the concept of electroclinical mismatch, where overt behavior may not reflect the extent of underlying neural dysfunction unless continuous EEG data are integrated into the clinical picture.

From a practical standpoint, the presence of IEDs in a child with psychiatric symptoms should raise clinical suspicion for neurodevelopmental vulnerability and justify closer follow-up. Even in cases where anticonvulsant therapy is not immediately indicated, lifestyle modifications—such as ensuring adequate sleep, managing stress, correcting nutritional deficiencies, and avoiding proconvulsant substances—may play a protective role.

Swatzyna et al. (2020) emphasize the importance of family education and ongoing neurological surveillance in patients with persistent IEDs. This not only improves long-term outcomes but also shifts the clinical focus from reactive symptom management to anticipatory neurodevelopmental care. When considered in this broader context, IEDs transition from obscure EEG anomalies to high-value markers of clinical risk that can inform both immediate intervention and long-term prognosis.

Relevance to Precision Psychiatry and Clinical Integration

The integration of EEG and IED analysis into psychiatric workflows represents a critical step toward the realization of precision psychiatry. Historically, psychiatry has operated within a phenomenological model, relying heavily on symptom clusters, narrative history, and behavioral observation. While valuable, this model fails to account for biological heterogeneity and often obscures the underlying neurophysiological mechanisms that contribute to mental illness. IEDs provide an accessible and reproducible biomarker of cortical instability that transcends DSM-5 diagnostic boundaries and offers direct insight into brain function. As Swatzyna et al. (2024) have shown, incorporating EEG into the routine evaluation of treatment-resistant psychiatric patients uncovers correctable etiologies in a significant percentage of cases and reduces unnecessary medication exposure.

Despite its promise, EEG remains underutilized in psychiatry due to barriers such as cost, lack of training, and skepticism about its clinical utility. Yet the data are unequivocal: up to 68% of refractory psychiatric patients exhibit EEG abnormalities—including IEDs, focal slowing, and encephalopathic patterns—that materially affect diagnosis and treatment outcomes (Swatzyna et al., 2024).

These findings call for a paradigm shift in psychiatric education, training, and practice. Psychiatrists must become competent consumers of EEG data and collaborate closely with neurophysiologists, neurologists, and neuropsychologists to develop integrated models of care. This collaborative framework is not only clinically effective but ethically imperative, ensuring that psychiatric diagnoses are informed by the same objective standards applied throughout the rest of medicine.

In Dr. Swatzyna's words, EEG allows clinicians to finally “test the organ they are treating,” bringing psychiatry into alignment with contemporary standards of biologically grounded healthcare.

Structured Diagnostic Checklist: Intermittent Epileptiform Discharges (IEDs) Evaluation and Management

I. Initial Clinical Assessment

☐ Comprehensive Clinical History ☐ Symptom onset, duration, and progression (episodic mood swings, irritability, confusion) ☐ Family history of epilepsy, developmental delay, or psychiatric disorders ☐ History of dissociative events, perceptual distortions, or nocturnal awakenings ☐ Failed treatment attempts (≥2 medications with paradoxical or worsening effects) ☐ Medication history including stimulants, SSRIs, anticonvulsants, and adverse reactions ☐ Exposure to neurotoxic substances (e.g., lead, mercury, solvents)

☐ Behavioral and Cognitive Screening ☐ ADHD symptom inventory (focused on attentional lapses and behavioral inconsistency) ☐ Mood and affect regulation assessment (e.g., CDRS-R, YMRS, MFQ) ☐ Anxiety screening tools (e.g., GAD-7, SCARED) ☐ Sleep disturbance questionnaires (e.g., PSQI, SDSC) ☐ Developmental history and ASD screening (e.g., SRS-2, SCQ)

☐ Neurological and Functional Examination ☐ Full neurological exam (gait, reflexes, eye movements) ☐ Basic cognitive screening (verbal fluency, working memory, response inhibition) ☐ Screening for aura-like symptoms or subtle seizures (e.g., déjà vu, visual changes)

II. Neurophysiological Evaluation

☐ Routine and Extended EEG ☐ Standard wakeful EEG (minimum 20 minutes) ☐ Sleep-deprived or overnight EEG (to increase IED yield) ☐ Confirm presence of IEDs (spikes, sharp waves, spike-and-wave complexes) ☐ Document discharge localization (e.g., temporal, frontal) and frequency ☐ Determine sleep potentiation of IEDs or presence of subtle seizure patterns

☐ EEG Interpretation ☐ Conducted by board-certified neurophysiologist ☐ Distinguish true epileptiform activity from benign variants ☐ Evaluate for co-existing biomarkers (e.g., SEB, focal slowing, encephalopathy)

III. Laboratory and Imaging Workup

☐ Toxicology and Metabolic Testing ☐ Whole blood lead levels ☐ Urinary heavy metal screening (e.g., mercury, arsenic) ☐ Comprehensive metabolic panel (renal, hepatic, glucose, electrolytes) ☐ Thyroid function tests (TSH, T3, T4) ☐ Nutrient levels (magnesium, zinc, vitamin D, B12, folate)

☐ Neuroimaging ☐ MRI brain with FLAIR and DTI sequences ☐ Rule out structural lesions, periventricular abnormalities, encephalomalacia

☐ Neuropsychological Testing ☐ Evaluation of executive function, language processing, memory, attention ☐ Identify discrepancies between verbal and nonverbal intelligence ☐ Assess academic and adaptive functioning

IV. Differential Diagnosis Considerations

☐ Diagnostically re-evaluate for the following ☐ Subclinical epilepsy or interictal epileptiform disorder ☐ Toxic/metabolic encephalopathy ☐ Cortical dysplasia or previous head trauma ☐ Atypical bipolar spectrum disorder or mixed mood states ☐ Autism spectrum disorder with neurophysiological instability ☐ Psychotropic-induced cortical hyperexcitability (iatrogenic causes)

V. Treatment Strategy

☐ Etiological Interventions   ☐ Eliminate environmental neurotoxins (e.g., chelation therapy for lead) ☐ Correct nutritional deficiencies (magnesium, zinc, vitamin D) ☐ Initiate anti-inflammatory or neuroprotective protocols if indicated ☐ Psychoeducation for patient and family regarding IEDs

☐ Pharmacologic Management ☐ Withdraw medications that may lower seizure threshold (SSRIs, stimulants, antipsychotics) ☐ Trial of low-dose anticonvulsants (e.g., valproate, lamotrigine, oxcarbazepine) ☐ Monitor clinical and EEG response to therapy over 3–6 months

☐ Non-Pharmacologic Management ☐ Neurofeedback targeting discharge location and rhythm instability ☐ Cognitive remediation for executive dysfunction ☐ Sleep hygiene interventions to reduce discharge frequency ☐ Behavioral support and accommodations in academic settings

☐ Follow-Up and Reassessment ☐ Repeat EEG at 3–6 months to monitor resolution or persistence of IEDs ☐ Re-administer neuropsychological tests to assess cognitive recovery ☐ Re-evaluate psychiatric diagnosis post-treatment; revise if symptom resolution occurs  ☐ Continue neurologic monitoring if IEDs persist or if seizure activity emerges

Illustrative Case Study: “Elena” – A Diagnostic Turning Point

Elena, a 16-year-old female with a two-year history of psychiatric instability, presented with mood swings, impulsivity, anxiety, and emotional outbursts that defied conventional diagnostic categories. Initially diagnosed with generalized anxiety disorder, she was subsequently reclassified as having bipolar II disorder after she failed to respond to SSRIs and exhibited agitation following administration of lamotrigine and quetiapine. Over time, her condition worsened: stimulant trials triggered insomnia and irritability, while antidepressants exacerbated her mood lability. She experienced intermittent visual distortions, nocturnal awakenings, and dissociative episodes—all interpreted as psychosomatic or trauma-related. Her school performance deteriorated, and behavioral interventions yielded minimal results.

At this point, a clinician familiar with the neurobiomarker model proposed an EEG evaluation. The study revealed frequent left temporal intermittent epileptiform discharges (IEDs), especially during drowsiness, along with lower-amplitude frontal spikes not previously detected. These findings were suggestive of underlying cortical hyperexcitability affecting emotional regulation, language integration, and executive function.

Additional testing revealed elevated urinary lead levels and marginal magnesium deficiency—both factors associated with increased neuronal irritability. Based on these discoveries, Elena's psychotropics were withdrawn and replaced with a low-dose valproate regimen. She was also started on a medically supervised chelation protocol, magnesium repletion, and cognitive remediation targeting working memory deficits.

Within six months, Elena showed marked clinical improvement. Her mood stabilized, sleep normalized, and she re-engaged with academic and social activities. A repeat EEG demonstrated a near-complete resolution of IEDs. Notably, her psychiatric symptoms no longer met DSM-5 criteria for any specific disorder.

Elena’s case exemplifies how hidden neurophysiological pathology—detected only through EEG—can masquerade as refractory psychiatric illness and be reversed through targeted intervention. It highlights the urgent need to integrate brain-based diagnostics into standard psychiatric workflows, particularly in complex or treatment-resistant cases (Swatzyna et al., 2020; Swatzyna et al., 2024).

Conclusion

Intermittent epileptiform discharges represent a transformative diagnostic lens in psychiatry—one that challenges traditional models of symptom-based classification and ushers in an era of biologically informed care. As demonstrated across a wide spectrum of disorders—including ASD, ADHD, and treatment-resistant mood and anxiety disorders—IEDs are not incidental EEG findings, but markers of transient cortical dysfunction that disrupt cognition, emotion, and behavior. Their identification often provides the missing piece in complex diagnostic puzzles, illuminating why certain patients fail to respond to standard medications and why others show paradoxical reactions to pharmacologic agents.

The incorporation of the EEG and interpretation of IEDs must become foundational in psychiatric practice, especially for patients with refractory symptoms, developmental delays, or atypical presentations. This shift demands interdisciplinary collaboration, education reform, and the willingness to integrate objective physiological data into psychiatric reasoning.

When properly utilized, the EEG offers not only diagnostic clarity but also a pathway to targeted interventions that restore function, reverse misdiagnosis, and alleviate unnecessary suffering. In a field too often constrained by clinical heuristics and medication algorithms, EEG—and specifically IED identification—offers a long-overdue reorientation toward the core principle of all medical disciplines: treat the organ you diagnose, and diagnose the organ you treat.

Key Takeaways

1. IEDs are present in over 25–60% of children with ASD or ADHD, even in the absence of seizures.

2. They can cause transient disruptions in mood, attention, language, and behavior, mimicking psychiatric disorders.

3. Standard psychotropics may worsen symptoms if underlying IEDs are unrecognized, necessitating EEG-informed treatment.

4. Neurofeedback, anticonvulsants, and targeted supplements can reduce IEDs and resolve treatment-resistant symptoms.

5. Routine EEG evaluation in refractory psychiatric cases enhances diagnostic precision and supports individualized care.

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Glossary

ADHD (Attention-Deficit/Hyperactivity Disorder): a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity, often beginning in childhood and persisting into adulthood.

affective regulation: the brain’s ability to modulate and control emotional responses; impairments can result in mood instability, irritability, or inappropriate affect.

ambulatory EEG: a prolonged, portable form of electroencephalographic monitoring performed over 24–72 hours in a non-hospital setting to capture transient or episodic brain activity.

anticonvulsant: a medication that reduces abnormal electrical activity in the brain, used to treat seizures and sometimes psychiatric symptoms linked to cortical hyperexcitability.

ASD (Autism Spectrum Disorder): a neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive patterns of behavior; frequently comorbid with cognitive and sensory abnormalities.

automated spike detection: a computerized algorithm used in EEG software to identify candidate epileptiform discharges; may require confirmation by a trained EEG reader due to false positives or misclassifications.

benzodiazepines: a class of psychoactive drugs that enhance GABA-A receptor activity, producing anxiolytic, sedative, and muscle-relaxing effects; chronic use can exacerbate cortical dysregulation.

cognitive remediation: a therapeutic intervention aimed at improving cognitive functions such as attention, memory, and executive control through structured exercises and behavioral techniques.

conduct disorder: a psychiatric diagnosis involving persistent patterns of aggressive, antisocial, or rule-violating behavior typically diagnosed in childhood or adolescence.

cortical excitability: a neurophysiological term referring to how easily neurons in the cerebral cortex are activated; excessive excitability may lead to epileptiform discharges or behavioral dyscontrol.

cortical hyperexcitability: an abnormally heightened responsiveness of cortical neurons, often underlying epileptiform discharges or irritability in mood and behavior.

DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition): the standard classification of mental disorders used by clinicians and researchers in the United States, based on observable symptom clusters.

drowsiness (in EEG): a transitional state between wakefulness and sleep, during which epileptiform activity—especially IEDs—is often more prominent.

electroclinical mismatch: a phenomenon in which significant EEG abnormalities occur without corresponding clinical symptoms, often seen in patients with IEDs and no seizures.

electroencephalography (EEG): a non-invasive diagnostic procedure that measures electrical activity in the brain via scalp electrodes to assess cortical function and identify abnormalities.

emotional lability: rapid and exaggerated changes in mood or affect, often disproportionate to contextual triggers; may be driven by cortical instability or frontal discharges.

encephalopathy: a general term describing diffuse brain dysfunction caused by metabolic, toxic, infectious, or structural insults; often associated with diffuse EEG slowing.

epileptiform discharge: a transient waveform seen on EEG—such as spikes or sharp waves—that suggests the presence of neuronal hyperexcitability and is often seen in epilepsy or cortical dysfunction.

executive function: a set of cognitive processes including planning, working memory, impulse control, and flexible thinking; commonly impaired by frontal lobe IEDs or injury.

focal slowing: a localized reduction in EEG frequency typically indicating cerebral dysfunction in a specific brain region; may reflect structural damage or inflammation.

frontal lobe: the brain region involved in executive function, motor planning, impulse control, and behavior regulation; a frequent site of IEDs linked to psychiatric symptoms.

GABA (gamma-aminobutyric acid): the brain’s primary inhibitory neurotransmitter; alterations in GABAergic signaling can influence seizure thresholds and mood regulation.

IED (intermittent epileptiform discharge): brief, abnormal paroxysmal waveforms seen on EEG that reflect transient cortical instability and may be subclinical or associated with behavioral changes.

impulsivity: a tendency to act without adequate forethought, often observed in ADHD and associated with frontal lobe dysfunction or discharges.

interictal activity: EEG abnormalities that occur between clinical seizures, often including IEDs; can cause cognitive and behavioral effects even without overt seizures.

irritability: a symptom characterized by a low threshold for frustration or aggression, often linked to cortical dysregulation, especially in the temporal lobes.

lead toxicity: exposure to lead—often from environmental sources—that disrupts neurological development and cortical function; a known risk factor for IEDs.

magnesium deficiency: a nutritional imbalance that affects neurotransmitter regulation and can exacerbate neuronal hyperexcitability and EEG abnormalities.

mood lability: frequent and unpredictable shifts in mood, often associated with temporal or frontal IEDs and misdiagnosed as bipolar disorder.

neurodevelopmental disorders: a group of conditions with onset in the developmental period involving neurological deficits that impact behavior, cognition, and functioning (e.g., ASD, ADHD).

neurofeedback: a therapeutic intervention in which individuals learn to regulate their own brain activity via real-time EEG feedback, often used to reduce IEDs or improve self-regulation.

neuromodulation: the alteration of nerve activity through targeted delivery of stimuli (electrical or magnetic) to specific brain areas, used in treatments such as TMS or tDCS.

normal variant: a type of EEG waveform or pattern that mimics pathological activity—such as epileptiform discharges—but is actually a benign, physiologically typical finding for the patient’s age, state (e.g., sleep), or brain region. These waveforms may appear sharp or unusual in morphology but are not associated with cortical dysfunction, neurological disease, or psychiatric symptoms. Incorrectly labeling clinically significant discharges as normal variants can obscure the presence of treatable cortical dysregulation, contributing to diagnostic error, inappropriate medication use, and prolonged patient morbidity.

paroxysmal: describing symptoms or activity that appear suddenly and briefly, such as a spike on EEG or a behavioral outburst.

pharmaco-EEG: a technique that uses EEG to assess the impact of medications on brain activity, aiding in individualized treatment planning.

precision psychiatry: an emerging model of psychiatric care that integrates biological data (e.g., EEG, genetics, imaging) to tailor diagnosis and treatment to individual neurobiological profiles.

psychotropic medications: drugs that affect mood, cognition, or behavior, including antidepressants, antipsychotics, stimulants, and anxiolytics.

RDoC (Research Domain Criteria): a research framework developed by the National Institute of Mental Health that emphasizes dimensional, biologically based understanding of mental disorders.

seizure threshold: the level of cortical excitability at which seizures are likely to occur; some medications or metabolic states may lower this threshold.

sensorimotor rhythm (SMR): an EEG frequency (typically 12–15 Hz) associated with motor control and inhibition; training SMR is a common target in neurofeedback for impulsivity.

sharp wave: a type of epileptiform EEG waveform with a slightly slower rise and fall than a spike, also indicating cortical hyperexcitability.

sleep deprivation EEG: an EEG protocol in which the subject is partially or fully deprived of sleep to increase the yield of epileptiform activity, especially in subtle cases.

spike-and-wave complex: a specific epileptiform EEG pattern consisting of a sharp spike followed by a slower wave; often associated with absence seizures but can occur subclinically.

stimulants: a class of psychotropic drugs (e.g., methylphenidate, amphetamines) used primarily to treat ADHD but may exacerbate IEDs in susceptible patients.

subclinical: referring to biological or electrophysiological abnormalities that do not produce overt symptoms but may still affect functioning.

temporal lobe: a brain region involved in language, memory, and emotion; discharges in this area may produce aggression, hallucinations, or episodic dysphoria.

TMS (transcranial magnetic stimulation): a non-invasive neuromodulatory treatment that uses magnetic pulses to stimulate or inhibit brain regions, sometimes used for depression or impulsivity.

tDCS (transcranial direct current stimulation): a neuromodulatory method that delivers low-intensity electrical currents to the scalp to influence brain activity, being explored for various psychiatric uses.

treatment resistance: the failure to achieve adequate symptom control despite multiple trials of standard treatments, often signaling underlying biological factors such as IEDs.

valproate: a broad-spectrum anticonvulsant and mood stabilizer that enhances GABA activity and reduces cortical excitability; used in both epilepsy and psychiatry.

References

Boutros, N. N., Arns, M., Galderisi, S., Rogers, R., & Paul, M. (2016). EEG and clinical psychiatry: The persistent interface. Clinical EEG and Neuroscience, 47(2), 77–79. https://doi.org/10.1177/1550059416634425

Hara, H. (2007). Epileptic seizures in children with autism spectrum disorders: A 10-year follow-up study. Brain and Development, 29(8), 486–490. https://doi.org/10.1016/j.braindev.2007.01.005

Insel, T. R., Cuthbert, B. N., Garvey, M. A., Heinssen, R. K., Pine, D. S., Quinn, K. J., ... & Wang, P. (2010). Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167(7), 748–751. https://doi.org/10.1176/appi.ajp.2010.09091379

Papadelis, C., Tamilia, E., Stufflebeam, S., Grant, P. E., Madsen, J. R., Pearl, P. L., & Tanaka, N. (2016). Interictal high frequency oscillations detected with simultaneous magnetoencephalography and electroencephalography as biomarker of pediatric epilepsy. Journal of Visualized Experiments: JoVE, (118), 54883. https://doi.org/10.3791/54883

Swatzyna, R. J., Arns, M., Tarnow, J. D., Turner, R. P., Barr, E., MacInerney, E. K., Hoffman, A. M., & Boutros, N. N. (2020). Isolated epileptiform activity in children and adolescents: Prevalence, relevance, and implications for treatment. European Child & Adolescent Psychiatry, 30(11), 1731–1743. https://doi.org/10.1007/s00787-020-01597-2

Swatzyna, R. J., Morrow, L. M., Collins, D. M., Barr, E. A., Roark, A. J., & Turner, R. P. (2024). Evidentiary significance of routine EEG in refractory cases: A paradigm shift in psychiatry. Clinical EEG and Neuroscience. https://doi.org/10.1177/15500594231221313

Swatzyna, R. J., Tarnow, J. D., Tannous, J. D., Pillai, V., Schieszler, C., & Kozlowski, G. P. (2015). Pharmaco-EEG: A study of individualized medicine in clinical practice. Clinical EEG and Neuroscience, 46(3), 192–196. https://doi.org/10.1177/1550059414556120

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