Aperiodic (1/f) neural activity robustly tracks symptom severity changes in treatment-resistant depression.

Background: A reliable physiological biomarker for Major Depressive Disorder is essential for developing and optimizing neuromodulatory treatment paradigms. This study investigates a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours.

Methods: We analyze brief recordings from intracranial electrodes implanted deep in the brain during a clinical trial of deep brain stimulation for treatment-resistant depression in 5 human subjects (n_female= 3, n_male = 2). This surgical setting allows for precise temporal and spatial sensitivity in the ventromedial prefrontal cortex, a challenging area to measure. We focused on the aperiodic slope of the power spectral density, a metric reflecting the balance of activity across all frequency bands and serving as a proxy for excitatory/inhibitory balance in the brain.

Results: Our findings demonstrate that shifts in aperiodic slope correlate with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all N=5 subjects, particularly in the ventromedial prefrontal cortex.

Conclusions: This biomarker offers a new way to track patient responses to Major Depressive Disorder treatment, paving the way for individualized therapies in both intracranial and non-invasive monitoring contexts.