Increased aperiodic exponents track depressive symptom severity in refractory epilepsy

BACKGROUND: Major depressive disorder remains a leading cause of disability, and approximately one-third of patients do not respond to standard treatments and develop treatment-resistant disease. Progress toward personalized neuromodulation has been limited by the lack of objective, brain-based biomarkers that can guide circuit target selection and track symptom burden in real time. Here we test whether the aperiodic exponent of intracranial EEG local field potentials provides a neurophysiological marker of current depressive symptom severity. METHODS: We analyzed resting-state intracranial EEG from a cohort of patients undergoing invasive monitoring for refractory epilepsy (N = 20), comprising >1,800 intracranial contacts sampling distributed cortical and subcortical regions, with depressive symptoms quantified immediately prior to recording using the Beck Depression Inventory-II. RESULTS: Region- and network-level analyses localized aperiodic exponent effects to frontolimbic and insular circuits-including orbitofrontal cortex, anterior cingulate cortex, insula, and amygdala-and to large-scale salience and default-mode networks, where exponents scaled continuously with symptom burden. In addition, exponents within the salience network tracked anhedonia. The whole-brain mean aperiodic exponent discriminated minimal versus elevated depressive symptom status (area under the curve = 0.82). CONCLUSIONS: Together, these results identify intracranial aperiodic exponents as a scalable, circuit-relevant marker of current depressive symptom burden, with potential utility for biomarker-informed, individualized neuromodulation in major depressive disorder.