Journal Article

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

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

2013

Overview

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 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 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 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Biology / Brain / Brain Mapping / Brain research / Computed tomography / Cortex (cingulate) / Cortex (insular) / Deep Brain Stimulation / Depression (Mood disorder) / Functional magnetic resonance imaging / Health aspects / Hogs / Internal Capsule - physiology / Lead / Magnetic resonance / Magnetic Resonance Imaging / Male / Medical imaging / Medicine / Mental depression / Mental disorders / Modulation / Neural networks / Neuroimaging / Neuromodulation / NMR / Nuclear magnetic resonance / Nuclei / Nucleus accumbens / Nucleus Accumbens - physiology / Obsessive compulsive disorder / Oxygenation / Parahippocampal gyrus / Prefrontal cortex / Prefrontal Cortex - physiology / Reproducibility of Results / Rodents / Stimulation / Sus scrofa / Thalamus / Veterinary Science