Staff and Researcher Publications

Language

English

Publication Date

7-9-2025

Journal

10.1038/s41467-025-61487-6

DOI

40628743

PMID

PMC12238457

PMCID

PMC12238457

PubMedCentral® Posted Date

7-9-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Research on the neural basis of major depressive disorder suggests that it is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neuronal systems lead to diminished emotion regulation and intrusive rumination. Subregions of the prefrontal cortex are thought to be sources of this disinhibition. However, due to limited opportunities for intracranial recordings from humans with major depression, this hypothesis has not been directly tested. Here, we use intracranial recordings from the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices from patients with major depression to measure daily fluctuations in self-reported depression symptom severity. Results indicate that directed connectivity within the delta frequency band, which has been linked to cortical inhibition, transiently increases intensity during negative mood. Symptom severity also shifts as connectivity patterns within the left and right prefrontal cortices become imbalanced. Our findings support the overarching hypothesis that depression worsens with prefrontal disinhibition and functional imbalance between hemispheres.

Keywords

Humans, Depressive Disorder, Major, Prefrontal Cortex, Male, Female, Adult, Middle Aged, Gyrus Cinguli, Magnetic Resonance Imaging

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.