Journal
NEUROIMAGE
Volume 146, Issue -, Pages 1050-1061Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2016.10.049
Keywords
Deep brain stimulation; fMRI; External globus pallidus; Substantia nigra pars reticulata; Striatum; Rat
Funding
- National Institute of Neurological Disorders and Stroke (NINDS) [F31NS087909]
- Research Foundation Flanders
- Klarman Family Foundation
- Brain and Behavior Research Foundation
- Foundation for Prader-Willi Research
- Foundation of Hope
- National Institute on Drug Abuse [R01DA032750, R01DA038168]
- Department of Psychiatry at UNC Chapel Hill
- NINDS [R21NS088975, R01NS091236]
- Cedars-Sinai Medical Center
- National Institute of Mental Health [R01MH111429, R41MH113252, R21MH106939]
- National Institute on Alcohol Abuse and Alcoholism [U01AA020023, R01AA025582]
- National Institute of Health [UL1TR001111, 550KR81420, 550KR91413]
- Brain and Behavior Foundation Young Investigator Award as Ellen Schapiro & Gerald Axelbaum Investigator Fund
- American Heart Association Scientist Development Award [15SDG23260025]
- Department of Neurology
- Biomedical Research Imaging Center at UNC Chapel Hill
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The substantia nigra pars reticulata (SNr) and external globus pallidus (GPe) constitute the two major output targets of the rodent striatum. Both the SNr and GPe converge upon thalamic relay nuclei (directly or indirectly, respectively), and are traditionally modeled as functionally antagonistic relay inputs. However, recent anatomical and functional studies have identified unanticipated circuit connectivity in both the SNr and GPe, demonstrating their potential as far more than relay nuclei. In the present study, we employed simultaneous deep brain stimulation and functional magnetic resonance imaging (DBS-fMRI) with cerebral blood volume (CBV) measurements to functionally and unbiasedly map the circuit- and network level connectivity of the SNr and GPe. Sprague-Dawley rats were implanted with a custom-made MR-compatible stimulating electrode in the right SNr (n=6) or GPe (n=7). SNr- and GPe-DBS, conducted across a wide range of stimulation frequencies, revealed a number of surprising evoked responses, including unexpected CBV decreases within the striatum during DBS at either target, as well as GPe-DBS-evoked positive modulation of frontal cortex. Functional connectivity MRI revealed global modulation of neural networks during DBS at either target, sensitive to stimulation frequency and readily reversed following cessation of stimulation. This work thus contributes to a growing literature demonstrating extensive and unanticipated functional connectivity among basal ganglia nuclei.
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