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Intracranial directed connectivity links subregions of the prefrontal cortex to major depression

Author

Listed:
  • John Myers

    (Baylor College of Medicine)

  • Jiayang Xiao

    (Baylor College of Medicine)

  • Raissa K. Mathura

    (Baylor College of Medicine)

  • Ben Shofty

    (Baylor College of Medicine)

  • Victoria Gates

    (Baylor College of Medicine)

  • Joshua Adkinson

    (Baylor College of Medicine)

  • Anusha B. Allawala

    (Brown University)

  • Adrish Anand

    (Baylor College of Medicine)

  • Ron Gadot

    (Baylor College of Medicine)

  • Ricardo Najera

    (Baylor College of Medicine)

  • Hernan G. Rey

    (Baylor College of Medicine)

  • Sanjay J. Mathew

    (Baylor College of Medicine)

  • Kelly Bijanki

    (Baylor College of Medicine)

  • Garrett Banks

    (Baylor College of Medicine)

  • Andrew Watrous

    (Baylor College of Medicine)

  • Eleonora Bartoli

    (Baylor College of Medicine)

  • Sarah R. Heilbronner

    (Baylor College of Medicine)

  • Nicole Provenza

    (Baylor College of Medicine)

  • Wayne K. Goodman

    (University of Texas: Southwestern)

  • Nader Pouratian

    (University of Texas: Southwestern)

  • Benjamin Y. Hayden

    (Baylor College of Medicine)

  • Sameer A. Sheth

    (Baylor College of Medicine)

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.

Suggested Citation

  • John Myers & Jiayang Xiao & Raissa K. Mathura & Ben Shofty & Victoria Gates & Joshua Adkinson & Anusha B. Allawala & Adrish Anand & Ron Gadot & Ricardo Najera & Hernan G. Rey & Sanjay J. Mathew & Kell, 2025. "Intracranial directed connectivity links subregions of the prefrontal cortex to major depression," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61487-6
    DOI: 10.1038/s41467-025-61487-6
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    References listed on IDEAS

    as
    1. Sankaraleengam Alagapan & Ki Sueng Choi & Stephen Heisig & Patricio Riva-Posse & Andrea Crowell & Vineet Tiruvadi & Mosadoluwa Obatusin & Ashan Veerakumar & Allison C. Waters & Robert E. Gross & Sinea, 2023. "Cingulate dynamics track depression recovery with deep brain stimulation," Nature, Nature, vol. 622(7981), pages 130-138, October.
    2. Armita Golkar & Tina B Lonsdorf & Andreas Olsson & Kara M Lindstrom & Jonathan Berrebi & Peter Fransson & Martin Schalling & Martin Ingvar & Arne Öhman, 2012. "Distinct Contributions of the Dorsolateral Prefrontal and Orbitofrontal Cortex during Emotion Regulation," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-9, November.
    3. Thilo Womelsdorf & Pascal Fries & Partha P. Mitra & Robert Desimone, 2006. "Gamma-band synchronization in visual cortex predicts speed of change detection," Nature, Nature, vol. 439(7077), pages 733-736, February.
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