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Cell. 2018 Mar 22;173(1):166-180.e14. doi: 10.1016/j.cell.2018.02.012.

Brain-wide Electrical Spatiotemporal Dynamics Encode Depression Vulnerability.

Author information

1
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
2
Department of Electrical and Computer Engineering, Duke University, Durham, NC 22208, USA.
3
Department of Psychological and Brain Sciences, Villanova University, Villanova, PA, 19085, USA.
4
Department of Civil and Electrical Engineering, Biostatistics and Bioinformatics, Duke University, Durham, NC 22208, USA.
5
Fishberg, Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
6
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
7
Departments of Neurobiology, Psychiatry & Behavioral Sciences and Psychology, Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
8
Departments of Bioengineering and Psychiatry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
9
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
10
Department of Electrical and Computer Engineering, Duke University, Durham, NC 22208, USA. Electronic address: lcarin@duke.edu.
11
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Center for Neuroengineering, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA; Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 22208, USA. Electronic address: kafui.dzirasa@duke.edu.

Abstract

Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional pathology. Using machine learning, we discover a spatiotemporal dynamic network that predicts the emergence of major depressive disorder (MDD)-related behavioral dysfunction in mice subjected to chronic social defeat stress. Activity patterns in this network originate in prefrontal cortex and ventral striatum, relay through amygdala and ventral tegmental area, and converge in ventral hippocampus. This network is increased by acute threat, and it is also enhanced in three independent models of MDD vulnerability. Finally, we demonstrate that this vulnerability network is biologically distinct from the networks that encode dysfunction after stress. Thus, these findings reveal a convergent mechanism through which MDD vulnerability is mediated in the brain.

KEYWORDS:

brain; depression; electricity; ketamine; networks; oscillations; spatiotemporal dynamics; stress

Comment in

PMID:
29502969
PMCID:
PMC6005365
DOI:
10.1016/j.cell.2018.02.012
[Indexed for MEDLINE]
Free PMC Article

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