title: Nucleus accumbens deep brain stimulation results in insula and prefrontal activation: a large animal FMRI study.
abstract: BACKGROUND
  Deep Brain Stimulation (DBS) of the nucleus accumbens (NAc) has previously been investigated clinically for the treatment of several psychiatric conditions, including obsessive-compulsive disorder and treatment resistant depression. However, the mechanism underlying the therapeutic benefit of DBS, including the brain areas that are activated, remains largely unknown. Here, we utilized 3.0 T functional Magnetic Resonance Imaging (fMRI) changes in Blood Oxygenation Level-Dependent (BOLD) signal to test the hypothesis that NAc/internal capsule DBS results in global neural network activation in a large animal (porcine) model
  
  
  METHODS
  Animals (n = 10) were implanted in the NAc/internal capsule with DBS electrodes and received stimulation (1, 3, and 5 V, 130 Hz, and pulse widths of 100 and 500 µsec). BOLD signal changes were evaluated using a gradient echo-echo planar imaging (GRE-EPI) sequence in 3.0 T MRI. We used a normalized functional activation map for group analysis and applied general linear modeling across subjects (FDR<0.001). The anatomical location of the implanted DBS lead was confirmed with a CT scan
  
  
  RESULTS
  We observed stimulation-evoked activation in the ipsilateral prefrontal cortex, insula, cingulate and bilateral parahippocampal region along with decrease in BOLD signal in the ipsilateral dorsal region of the thalamus. Furthermore, as the stimulation voltage increased from 3 V to 5 V, the region of BOLD signal modulation increased in insula, thalamus, and parahippocampal cortex and decreased in the cingulate and prefrontal cortex. We also demonstrated that right and left NAc/internal capsule stimulation modulates identical areas ipsilateral to the side of the stimulation
  
  
  CONCLUSIONS
  Our results suggest that NAc/internal capsule DBS results in modulation of psychiatrically important brain areas notably the prefrontal cortex, cingulate, and insular cortex, which may underlie the therapeutic effect of NAc DBS in psychiatric disorders. Finally, our fMRI setup in the large animal may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS.
authors: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Emily J
authors: EJ
authors: Knight
authors: Hoon-Ki
authors: HK
authors: Min
authors: Sun-Chul
authors: SC
authors: Hwang
authors: Michael P
authors: MP
authors: Marsh
authors: Seungleal
authors: S
authors: Paek
authors: Inyong
authors: I
authors: Kim
authors: Joel P
authors: JP
authors: Felmlee
authors: Osama A
authors: OA
authors: Abulseoud
authors: Kevin E
authors: KE
authors: Bennet
authors: Mark A
authors: MA
authors: Frye
authors: Kendall H
authors: KH
authors: Lee
mesh_terms: D000818:Animals; D001931:Brain Mapping; D046690:Deep Brain Stimulation; D020772:Internal Capsule / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D015203:Reproducibility of Results; D034421:Sus scrofa