Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI.
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.
Department of Neurology, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Medical Image and Signal Processing Group, Ghent University, Ghent, Belgium.
Nathalie
N
Van Den Berge
Department of Neurology, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC, USA.
Daniel L
DL
Albaugh
Biomedical Imaging Research Institute, Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Andrew
A
Salzwedel
Medical Image and Signal Processing Group, Ghent University, Ghent, Belgium.
Christian
C
Vanhove
Medical Image and Signal Processing Group, Ghent University, Ghent, Belgium.
Roel
R
Van Holen
Biomedical Imaging Research Institute, Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Wei
W
Gao
Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC, USA; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Garret D
GD
Stuber
Department of Neurology, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC, USA; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA. Electronic address: shihy@unc.edu.
Yen-Yu Ian
YI
Shih
D000818:Animals; D001921:Brain / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D004558:Electric Stimulation; D005917:Globus Pallidus / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D065841:Pars Reticulata / Q000502:physiology*; D017207:Rats, Sprague-Dawley
Deep brain stimulation; External globus pallidus; Rat; Striatum; Substantia nigra pars reticulata; fMRI