Nucleus Accumbens Deep Brain Stimulation Results in Insula and Prefrontal Activation: A Large Animal fMRI Study

Emily J. Knight, Hoon Ki Min, Sun Chul Hwang, Michael P. Marsh, Seungleal Paek, Inyong Kim, Joel P. Felmlee, Osama A. Abulseoud, Kevin E. Bennet, Mark A Frye, Kendall H Lee

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere56640
JournalPLoS One
Volume8
Issue number2
DOIs
StatePublished - Feb 18 2013

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Deep Brain Stimulation
Nucleus Accumbens
magnetic resonance imaging
Brain
Animals
Chemical activation
Magnetic Resonance Imaging
brain
Internal Capsule
Oxygenation
animals
Prefrontal Cortex
Capsules
Blood
Gyrus Cinguli
Thalamus
thalamus
blood
Psychiatry
Treatment-Resistant Depressive Disorder

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Nucleus Accumbens Deep Brain Stimulation Results in Insula and Prefrontal Activation : A Large Animal fMRI Study. / Knight, Emily J.; Min, Hoon Ki; Hwang, Sun Chul; Marsh, Michael P.; Paek, Seungleal; Kim, Inyong; Felmlee, Joel P.; Abulseoud, Osama A.; Bennet, Kevin E.; Frye, Mark A; Lee, Kendall H.

In: PLoS One, Vol. 8, No. 2, e56640, 18.02.2013.

Research output: Contribution to journalArticle

Knight, EJ, Min, HK, Hwang, SC, Marsh, MP, Paek, S, Kim, I, Felmlee, JP, Abulseoud, OA, Bennet, KE, Frye, MA & Lee, KH 2013, 'Nucleus Accumbens Deep Brain Stimulation Results in Insula and Prefrontal Activation: A Large Animal fMRI Study', PLoS One, vol. 8, no. 2, e56640. https://doi.org/10.1371/journal.pone.0056640
Knight, Emily J. ; Min, Hoon Ki ; Hwang, Sun Chul ; Marsh, Michael P. ; Paek, Seungleal ; Kim, Inyong ; Felmlee, Joel P. ; Abulseoud, Osama A. ; Bennet, Kevin E. ; Frye, Mark A ; Lee, Kendall H. / Nucleus Accumbens Deep Brain Stimulation Results in Insula and Prefrontal Activation : A Large Animal fMRI Study. In: PLoS One. 2013 ; Vol. 8, No. 2.
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