Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens.
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.
Department of Neurology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, 27599, USA.|Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC, 27599, USA.
Daniel L
DL
Albaugh
Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, 27599, USA.|Department of Radiology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Biomedical Imaging Research Institute, Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Andrew
A
Salzwedel
Department of Neurology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, 27599, USA.|Medical Image and Signal Processing Group, Ghent University, Ghent, 9000, Belgium.
Nathalie
N
Van Den Berge
Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, 27599, USA.|Department of Radiology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Biomedical Imaging Research Institute, Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Wei
W
Gao
Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Department of Psychiatry, University of North Carolina, Chapel Hill, NC, 27599, USA.
Garret D
GD
Stuber
Department of Neurology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, 27599, USA.|Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, 27599, USA.
Yen-Yu Ian
YY
Shih
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D046690:Deep Brain Stimulation / Q000379:methods*; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D017397:Prefrontal Cortex / Q000502:physiology; D017207:Rats, Sprague-Dawley