Aperiodic neural activity is a biomarker for depression severity.

A reliable physiological biomarker for Major Depressive Disorder (MDD) is necessary to improve treatment success rates by shoring up variability in outcome measures. In this study, we establish a passive biomarker that tracks with changes in mood on the order of minutes to hours. We record from intracranial electrodes implanted deep in the brain - a surgical setting providing exquisite temporal and spatial sensitivity to detect this relationship in a difficult-to-measure brain area, the ventromedial prefrontal cortex (VMPFC). The aperiodic slope of the power spectral density captures the balance of activity across all frequency bands and is construed as a putative proxy for excitatory/inhibitory balance in the brain. This study demonstrates how shifts in aperiodic slope correlate with depression severity in a clinical trial of deep brain stimulation for treatment-resistant depression (TRD). The correlation between depression severity scores and aperiodic slope is significant in N=5 subjects, indicating that flatter (less negative) slopes correspond to reduced depression severity, especially in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient response to MDD treatment, facilitating individualized therapies in both intracranial and non-invasive monitoring scenarios.

Déclaration de conflit d'intérêts

Competing interests: CH, KB, and MM are inventors of a planned patent on the electrophysiology biomarker reported in the current manuscript. KB is inventor of an issued patent on an unrelated method of electrical stimulation to treat depression, anxiety, and pain. SAS has consulting agreements with Boston Scientific, Neuropace, Abbott, and Zimmer Biomet. WKG has received donated devices from Medtronic and has consulting agreements with Biohaven Pharmaceuticals. SJM is supported through the use of resources and facilities at the Michael E. Debakey VA Medical Center, Houston, Texas and receives support from The Menninger Clinic. SJM has received research support from Biohaven Pharmaceuticals, Janssen, Merck, NeuroRx, Sage Therapeutics, and VistaGen Therapeutics. SJM has served as a consultant to the following companies outside the scope of the submitted work: Almatica Pharma, Axsome Therapeutics, BioXcel Therapeutics, Boehringer-Ingelheim, Clexio Biosciences, COMPASS Pathways, Delix Therapeutics, Douglas Pharmaceuticals, Eleusis, Engrail Therapeutics, Levo Therapeutics, Neumora, Neurocrine, Perception Neurosciences, Praxis Precision Medicines, Relmada Therapeutics, Seelos Therapeutics, Signant Health, Sunovion, and XW Pharma. The remaining authors declare no competing interests.