Intracranial Directed Connectivity Links Subregions of the Prefrontal Cortex to Major Depression

Publication date: Aug 07, 2024

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.

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Concepts Keywords
Email Acc
Neuropsychiatric Al
Texas Connectivity
Depression
Directed
Dlpfc
Hemisphere
Left
Mdd
Medrxiv
Ofc
Pfc
Preprint
Severity
Subregions

Semantics

Type Source Name
disease MESH major depressive disorder
disease MESH etiology
drug DRUGBANK Ramipril
disease MESH mood disorders
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Oxygen
pathway REACTOME Metabolism
disease MESH inflammation
disease MESH oxidative stress
drug DRUGBANK gamma-Aminobutyric acid
drug DRUGBANK Somatostatin
disease MESH sleep disorders
disease MESH panic attacks
drug DRUGBANK Albendazole
disease MESH treatment resistant depression
drug DRUGBANK Proline
disease MESH stroke
drug DRUGBANK Tilmicosin
disease MESH bipolar disorder

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