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

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. 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 (nfemale= 3, nmale = 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. 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. 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.