A comparison of how deep brain stimulation in two targets with anti-compulsive efficacy modulates brain activity using fMRI in awake rats

Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment -refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS.Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accum-bens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypoth-esized that stimulation at both targets would result in partially overlapping BOLD responses.Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and con-nections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.

Automated summary

Deep brain stimulation (DBS) is an established treatment for otherwise treatment-refractory obsessive-compulsive disorder (OCD). By stimulating brain networks connecting basal ganglia and prefrontal cortex, DBS can alleviate OCD symptoms. Research on the effects of DBS on network changes and the role of internal capsule (IC) connections is important for improving DBS.