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5-Min Science: EEG Biomarkers for Refractory Cases

BioSource Faculty

Updated: Feb 9


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This post summarizes Swatzyna and colleagues' (2024) "Evidentiary Significance of Routine EEG in Refractory Cases: A Paradigm Shift in Psychiatry," which was published in Clinical EEG and Neuroscience. Although we primarily summarize open-access articles, we believe this is a reference worth purchasing.

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We examine the significance of routine EEGs in refractory cases, focusing on the biomarkers of focal slowing (FS), spindling excessive beta (SEB), encephalopathy (EN), and isolated epileptiform discharges (IEDs).



Introduction


The evolving field of psychiatry has increasingly recognized the limitations of the Diagnostic and Statistical Manual (DSM), the primary manual used by clinicians and researchers to diagnose and classify mental disorders in accurately diagnosing and treating mental disorders. Traditional approaches, reliant on observable symptoms, often lead to trial-and-error medication regimens with suboptimal outcomes, particularly for refractory cases, instances where patients do not respond to standard treatments or medications.


Electroencephalograms (EEGs) provide a promising avenue for precision psychiatry by identifying objective biomarkers, measurable indicators of biological processes or conditions, often used to guide diagnosis and treatment, that elucidate the neurobiological underpinnings of psychiatric symptoms. This article examines the significance of routine EEGs in refractory cases, focusing on the biomarkers of focal slowing (FS), spindling excessive beta (SEB), encephalopathy (EN), and isolated epileptiform discharges (IEDs).



EEG Biomarkers for Refractory Cases


Four EEG biomarkers—FS, SEB, EN, and IEDs—provide crucial insights into medication failure in refractory cases. A medication failure is when patients fail three medication trials or experience adverse effects with two medications​. These biomarkers indicate underlying brain dysregulation undetectable through conventional psychiatric assessments.



Focal Slowing


Focal slowing (FS) reflects localized cerebral pathology, often associated with traumatic brain injury, ischemia, or structural abnormalities. This abnormality is identified as slowed wave activity in specific brain regions and reliably indicates focal dysfunction. FS can arise from diverse causes, such as congenital abnormalities, hemorrhagic and ischemic strokes, bacterial or viral infections (e.g., encephalitis), tumors, or neurodegenerative processes. FS serves as a marker of localized neural inefficiency. Importantly, the presence of FS may directly impair cognitive processes like memory or attention, depending on the affected brain region.



Spindling Excessive Beta


Spindling excessive beta (SEB), characterized by persistent high-frequency beta activity, may be caused by cortical irritability, possibly from viral or toxic encephalopathy, and benzodiazepine or barbiturate use. SEB has been linked to severe anxiety, impulse control issues, and sleep disturbances.



Encephalopathy


Encephalopathy (EN) is a global or localized dysfunction in brain activity. EN manifests as slow-wave patterns across the EEG and is a hallmark of systemic dysregulation that often presents as developmental delays in children or cognitive impairments in adults. EN can be produced by hypoxia or ischemia, metabolic dysregulation (e.g., hypothyroidism), toxic exposures (heavy metals, including lead and mold), and organ dysfunction (e.g., uremic or hepatic encephalopathy).



Isolated Epileptiform Discharges


Isolated epileptiform discharges (IEDs) represent transient patterns of neuronal hyperexcitability that do not meet the threshold for clinical seizures but are implicated in various psychiatric and cognitive disorders. Depending on their cortical localization, these discharges may correlate with specific symptoms, such as mood instability or cognitive decline. IEDs may be linked to neurodegenerative diseases (e.g., Alzheimer's), pubescent changes, or hormone-related epileptogenesis.



Analysis


Routine EEGs in refractory psychiatric patients offer a transformative approach to diagnosis and treatment. A recent replication study involving 1,233 refractory cases demonstrated that 53.4% of patients exhibited FS, 25.1% SEB, 10.9% EN, and 24.3% IEDs. These findings suggest that EEG biomarkers are not merely incidental but integral to understanding the neurobiological basis of treatment resistance.


The EEG can play an invaluable role in this investigative process when neurologists recognize the potential relevance of these biomarkers for treatment failures and recommend that the managing physician screen for their underlying causes.


However, the EEG's potential will be wasted if a neurologist only examines recordings for epileptiform activity and tumors and declares the EEG normal when they are not present.

Case evidence supports this investigative approach. For instance, apparent treatment-resistant depression may actually stem from chronic inflammatory response syndrome (CIRS) due to mold exposure, while sudden-onset obsessive-compulsive symptoms might indicate PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) or autoimmune encephalitis. Similarly, new-onset attention deficits resistant to standard treatments might result from environmental toxin exposure or nutrient deficiencies rather than primary ADHD.


This may involve evaluation for mold exposure, testing for inflammatory markers, assessment of nutrient status, or screening for environmental toxins. The goal is to identify and address the underlying cause rather than simply managing symptoms through psychiatric medication.


This approach requires a paradigm shift from treating DSM-5 diagnoses to treating underlying pathophysiology. While DSM-5 criteria remain valuable for classification and communication, they should not constrain the search for root causes when clinical presentation or treatment response suggests deeper issues.


Objective findings such as EEG abnormalities should particularly prompt investigation of environmental or systemic causes, even when presenting symptoms appear purely psychiatric. By adopting this investigative mindset, clinicians can identify and address root causes that might otherwise go undetected, potentially leading to more effective and lasting therapeutic outcomes. This approach may require additional time and resources initially, but it can prevent years of ineffective symptom management and improve long-term patient outcomes.




Key Takeaways


  1. EEG Biomarkers as Diagnostic Tools: Routine EEGs reveal objective markers—focal slowing, spindling excessive beta, encephalopathy, and isolated epileptiform discharges—that uncover hidden neural dysregulation in refractory psychiatric cases.

  2. Paradigm Shift in Diagnostic Approach: Integrating EEG biomarkers into psychiatric evaluation shifts the focus from purely symptom-based diagnoses to precision medicine, yet it demands careful interpretation to avoid misattribution.

  3. Personalized Treatment Strategies: EEG-derived insights enable tailored interventions that move beyond trial-and-error medication regimens, targeting the underlying neurophysiology of treatment resistance.

  4. Interdisciplinary Collaboration for Accurate Diagnosis: Effective use of EEG findings requires collaboration between neurologists and psychiatrists to thoroughly investigate environmental, infectious, or systemic contributors to refractory symptoms.

  5. Enhancement of Non-Pharmacological Interventions: EEG insights refine non-invasive therapies like neurofeedback, ensuring that interventions address the root neurophysiological disturbances rather than merely alleviating observable symptoms.



Conclusion


Incorporating routine EEGs into psychiatric practice represents a paradigm shift toward precision medicine. By identifying biomarkers such as FS, SEB, EN, and IEDs, clinicians can tailor interventions to the underlying neurobiology, improving outcomes for refractory cases. EEG data can inform medication choices and provide critical insights for non-pharmacological interventions, such as biofeedback and neurofeedback, enabling practitioners to address the root causes of dysfunction.


The clinical implications are clear: when standard treatments fail or symptoms appear abruptly, clinicians should look beyond the presenting symptoms to investigate potential environmental, infectious, or systemic causes.

While this article addressed medication failures, we can generalize it to neurofeedback. Clinicians should collaborate with neurologists and managing physicians to investigate biomarker causes before initiating treatment or after treatment has failed. For example, neurofeedback to increase posterior dominant rhythm power to improve executive functioning will be wasted if the underlying cause is lead poisoning.


"Insanity is doing the same thing over and over again and expecting different results."



Google Illuminate Discussion


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Article


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, 15500594231221313. Advance online publication. https://doi.org/10.1177/15500594231221313



Glossary


biomarkers: measurable indicators of biological processes or conditions, often used to guide diagnosis and treatment. Diagnostic and Statistical Manual (DSM): The controversial manual used by clinicians and researchers to diagnose and classify mental disorders. encephalopathy (EN): a spectrum of brain dysfunctions caused by metabolic, toxic, or hypoxic processes.

electroencephalogram (EEG): a diagnostic tool that records electrical activity in the brain.

epileptiform discharges (IEDs): transient patterns of hyperexcitable neuronal activity associated with cognitive and behavioral abnormalities.

focal slowing (FS): localized slowing in EEG activity, indicative of cerebral pathology. medication failure: when patients fail three medication trials or experience adverse effects with two medications​.

precision medicine: a medical approach that tailors treatment to the individual characteristics of each patient. RDoC (Research Domain Criteria): a framework developed by the National Institute of Mental Health (NIMH) to integrate biological, psychological, and behavioral dimensions into mental health research and diagnosis.

spindling excessive beta (SEB): high-frequency beta wave activity linked to anxiety, cortical irritability, and poor medication response.




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