Increased aperiodic exponents track depressive symptom severity in refractory epilepsy

Area of Science:

• Neuroscience
• Computational Psychiatry

Background:

• Major depressive disorder (MDD) is a leading cause of disability, with a significant portion of patients developing treatment-resistant disease.
• Current personalized neuromodulation approaches for MDD are hindered by the absence of objective, brain-based biomarkers for guiding treatment and monitoring symptoms.
• This study investigates the potential of the aperiodic exponent in intracranial electroencephalography (EEG) local field potentials as a neurophysiological marker for current depressive symptom severity.

Purpose of the Study:

• To determine if the aperiodic exponent of intracranial EEG local field potentials can serve as a neurophysiological marker for current depressive symptom severity in patients with major depressive disorder.
• To identify specific brain regions and networks where the aperiodic exponent correlates with depressive symptoms.
• To assess the utility of the aperiodic exponent in differentiating between minimal and elevated depressive symptom states.

Main Methods:

• Analysis of resting-state intracranial EEG data from 20 patients with refractory epilepsy undergoing invasive monitoring.
• Utilized over 1,800 intracranial contacts to sample distributed cortical and subcortical regions.
• Quantified depressive symptoms immediately before EEG recording using the Beck Depression Inventory-II (BDI-II).

Main Results:

• Aperiodic exponent effects were localized to frontolimbic and insular circuits, including the orbitofrontal cortex, anterior cingulate cortex, insula, and amygdala.
• Aperiodic exponents within large-scale salience and default-mode networks scaled continuously with depressive symptom burden.
• The whole-brain mean aperiodic exponent demonstrated significant discrimination between minimal and elevated depressive symptom status (AUC = 0.82) and tracked anhedonia within the salience network.

Conclusions:

• Intracranial aperiodic exponents represent a scalable and circuit-relevant biomarker for current depressive symptom burden in major depressive disorder.
• These findings suggest potential utility for biomarker-informed, individualized neuromodulation strategies in treating MDD.
• The aperiodic exponent offers a promising neurophysiological marker for objective assessment and personalized treatment of depression.