Subthalamic nucleus deep brain stimulation induces motor network BOLD activation: use of a high precision MRI guided stereotactic system for nonhuman primates

Abstract

Background: Functional magnetic resonance imaging (fMRI) is a powerful method for identifying in vivo network activation evoked by deep brain stimulation (DBS).

Objective: Identify the global neural circuitry effect of subthalamic nucleus (STN) DBS in nonhuman primates (NHP).

Method: An in-house developed MR image-guided stereotactic targeting system delivered a mini-DBS stimulating electrode, and blood oxygenation level-dependent (BOLD) activation during STN DBS in healthy NHP was measured by combining fMRI with a normalized functional activation map and general linear modeling.

Results: STN DBS significantly increased BOLD activation in the sensorimotor cortex, supplementary motor area, caudate nucleus, pedunculopontine nucleus, cingulate, insular cortex, and cerebellum (FDR < 0.001).

Conclusion: Our results demonstrate that STN DBS evokes neural network grouping within the motor network and the basal ganglia. Taken together, these data highlight the importance and specificity of neural circuitry activation patterns and functional connectivity.

Keywords: Deep brain stimulation; Functional magnetic resonance imaging; Motor cortex; Nonhuman primate; Pedunculopontine nucleus; Subthalamic nucleus.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. STN DBS (5V, 130Hz, and 150 μs)

(A) Areas of activation with STN stimulation (n=2, data set=4); (B) Event-related BOLD percent change during and after STN DBS. Error bars represent standard error; (C) Principal component analysis between functionally defined regions of interest for STN DBS. Abbreviations: AC, auditory cortex; AM, amygdala; BOLD, blood oxygen level dependent; C, contralateral; CB, cerebellum; CC, cingulate cortex; CD, caudate nucleus; CP, caudate nucleus and putamen; CS, central sulcus; DBS, deep brain stimulation; FDR, false discovery rate; I, ipsilateral; IC, insular cortex; MC, primary motor cortex; ML, medial lemniscus; PAG, pariaqueductal gray; PC, principal component; PCA, principal component analysis; PPH, parahippocampal gyrus; PPN, pedunculopontine nucleus; PU, putamen; SS, primary somatosensory cortex; Stim, stimulation; STN, subthalamic nucleus; TH, thalamus; VL, ventral lateral thalamic nucleus.