Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Intracranial Directed Connectivity Links Subregions of the Prefrontal Cortex to Major Depression. medRxiv 2024 Aug 08

Date

08/16/2024

Pubmed ID

39148826

Pubmed Central ID

PMC11326344

DOI

10.1101/2024.08.07.24311546

Abstract

Understanding the neural basis of major depressive disorder (MDD) is vital to guiding neuromodulatory treatments. The available evidence supports the hypothesis that MDD is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neural systems lead to diminished emotion regulation and intrusive ruminations. Recent research also points towards network changes in the brain, especially within the prefrontal cortex (PFC), as primary sources of MDD etiology. However, due to limitations in spatiotemporal resolution and clinical opportunities for intracranial recordings, this hypothesis has not been directly tested. We recorded intracranial EEG from the dorsolateral (dlPFC), orbitofrontal (OFC), and anterior cingulate cortices (ACC) in neurosurgical patients with MDD. We measured daily fluctuations in self-reported depression severity alongside directed connectivity between these PFC subregions. We focused primarily on delta oscillations (1-3 Hz), which have been linked to GABAergic inhibitory control and intracortical communication. Depression symptoms worsened when connectivity within the left vs. right PFC became imbalanced. In the left hemisphere, all directed connectivity towards the ACC, from the dlPFC and OFC, was positively correlated with depression severity. In the right hemisphere, directed connectivity between the OFC and dlPFC increased with depression severity as well. This is the first evidence that delta oscillations flowing between prefrontal subregions transiently increase intensity when people are experiencing more negative mood. These findings support the overarching hypothesis that MDD worsens with prefrontal disinhibition.

Author List

Myers J, Xiao J, Mathura R, Shofty B, Pirtle V, Adkinson J, Allawala AB, Anand A, Gadot R, Najera R, Rey HG, Mathew SJ, Bijanki K, Banks G, Watrous A, Bartoli E, Heilbronner SR, Provenza N, Goodman WK, Pouratian N, Hayden BY, Sheth SA

Author

Hernan Gonzalo Rey PhD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin