Language

English

Publication Date

2-1-2025

Journal

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

DOI

10.1016/j.bpsc.2024.10.019

PMID

39547412

PMCID

PMC12694767

PubMedCentral® Posted Date

2-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

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 (nfemale = 3, nmale = 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.

Keywords

Humans, Depressive Disorder, Treatment-Resistant, Male, Female, Middle Aged, Prefrontal Cortex, Adult, Deep Brain Stimulation, Major Depressive Disorder, Severity of Illness Index, Electrodes, Implanted, Electrophysiology, intracranial, slope, biomarker, DBS, MDD

Published Open-Access

yes

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