Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals

Abstract

The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. The goal of this study was to trace DBS-induced global neuronal network activation in a large animal model by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus (STN) (n=7) and the entopeduncular nucleus (EN), the non-primate analogue of the primate globus pallidus interna (n=4). Using a normalized functional activation map for group analysis and the application of general linear modeling across subjects, we found that both STN and EN DBS significantly increased BOLD activation in the ipsilateral sensorimotor network (FDR < 0.001). In addition, we found differential, target-specific, non-motor network effects. In each group the activated brain areas showed a distinctive correlation pattern forming a group of network connections. Results suggest that the scope of DBS extends beyond an ablation-like effect and that it may have modulatory effects not only on circuits that facilitate motor function but also on those involved in higher cognitive and emotional processing. Taken together, our results show that the swine model for DBS fMRI, which conforms to human implanted DBS electrode configurations and human neuroanatomy, may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS.

Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

“…In a recent report studying normal, unlesioned pigs, widespread, positive BOLD signal changes were noted during DBS, without any evidence of suppressed regional activity during stimulation (Min et al, 2012). The motor and premotor cortices represented the first and second largest areas of BOLD activity, respectively, and were similarly active during stimulation of the internal globus pallidus (another common DBS target for movement disorders).…”

Modeling sequence and quasi-uniform assumption in computational neurostimulation

“…For these reasons, even presumably focal stimulation will produce brain-wide changes. Modern analysis of interventions such as TMS (Bestmann, 2008) and DBS (Kahan et al, 2014;Kent et al, 2015;Min et al, 2012) leverages characterization of these connections. On a local network scale, the ongoing activity of a network will fundamentally influence what actions electrical stimulation has; with highly organized processes such as oscillations, the effects of stimulation are almost entirely explained by how these processes are altered (Frohlich and McCormick, 2010;Kang and Lowery, 2013;Reato et al, 2010Reato et al, , 2013b.…”

Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease

“…27–32 To investigate the neural circuitry associated with basal ganglia stimulation, we previously developed a method for fMRI in swine 33 and NHP, 34 reporting increase activation in the sensorimotor associative and limbic networks by STN DBS.…”