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. In this study, we investigated a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours. Methods: We analyzed 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 participants (n_female = 3, n_male = 2). This surgical setting allowed 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 that reflects the balance of activity across all frequency bands and may serve as a proxy for excitatory/inhibitory balance in the brain. Results: Our findings demonstrated that shifts in aperiodic slope correlated with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all 5 participants, particularly in the ventromedial prefrontal cortex. Conclusions: This biomarker offers a new way to track patient responses to major depressive disorder treatment, thus paving the way for individualized therapies in both intracranial and noninvasive monitoring contexts.