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Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens.


ABSTRACT: 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.

SUBMITTER: Albaugh DL 

PROVIDER: S-EPMC5013271 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens.

Albaugh Daniel L DL   Salzwedel Andrew A   Van Den Berge Nathalie N   Gao Wei W   Stuber Garret D GD   Shih Yen-Yu Ian YY  

Scientific reports 20160907


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 stimul  ...[more]

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