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Increased Aperiodic Exponents Track Depression Symptom Severity
Mark R Libowitz1,2,3, Wendy Sun4, Rikki Rabinovich2
1Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA.
Biorxiv : the Preprint Server for Biology
|March 18, 2026
Summary
The aperiodic exponent in brain activity may serve as a novel biomarker for major depressive disorder (MDD) symptom severity. This neurophysiological marker could help guide treatment selection for treatment-resistant depression.
Area of Science:
- Neuroscience
- Computational Psychiatry
- Biomarkers
Background:
- Major depressive disorder (MDD) affects one-third of patients, leading to treatment resistance.
- Current diagnostic methods rely on subjective behavioral assessments, lacking objective neurophysiological markers.
- Identifying brain-based biomarkers is crucial for guiding treatment selection and tracking therapeutic response in real-time.
Purpose of the Study:
- To investigate the potential of the aperiodic exponent in intracranial EEG (iEEG) as a neurophysiological marker for depression symptom severity.
- To determine if the aperiodic exponent can differentiate between minimal and elevated depressive symptoms.
- To explore the association between the aperiodic exponent and specific symptom dimensions of depression.
Main Methods:
- Utilized iEEG data from 20 patients with refractory epilepsy, analyzing over 1,800 contacts.
- Estimated the aperiodic exponent (reflecting cortical excitability) across 10-100 Hz in local brain regions and cortical networks.
- Correlated aperiodic exponents with Beck Depression Inventory-II (BDI-II) scores using ordinary least squares regression.
Main Results:
- The whole-brain mean aperiodic exponent distinguished between minimal and elevated depression symptoms (AUC = 0.82).
- Higher exponents were observed in the orbitofrontal cortex, anterior cingulate cortex, insula, and amygdala in the elevated depression group.
- Aperiodic exponents positively correlated with BDI-II scores in these regions and in the Salience and Default networks, with the Salience network tracking anhedonia symptoms.
Conclusions:
- Intracranial aperiodic exponents in fronto-limbic and insular circuits are associated with depression symptom status and severity.
- The aperiodic exponent shows promise as a candidate neurophysiological marker for current depression burden.
- This marker has potential implications for personalized neuromodulation strategies in MDD treatment.
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