期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep31613
关键词
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资金
- National Institute of Neurological Disorders and Stroke (NINDS) [NS087909]
- Research Foundation Flanders
- Klarman Family Foundation
- Brain and Behavior Research Foundation
- Foundation for Prader-Willi Research
- Foundation of Hope
- National Institute on Drug Abuse [DA032750, DA038168]
- Department of Psychiatry at UNC Chapel Hill
- NINDS [NS088975]
- Cedars-Sinai Medical Center
- NINDS da [NS091236]
- National Institute of Mental Health [MH106939]
- National Institute on Alcohol Abuse and Alcoholism [AA020023]
- National Institute of Health [UL1TR001111, 550KR81420, 550KR91413]
- Brain and Behavior Foundation Young Investigator Award as the Ellen Schapiro & Gerald Axelbaum Investigator
- American Heart Association Scientist Development Award [15SDG23260025]
- Department of Neurology
- Biomedical Research Imaging Center at UNC Chapel Hill
Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked-and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action.
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