Deep brain stimulation in globus pallidus internus travels to thalamus and subthalamic nuclei along physiological pathways

Abstract

Deep brain stimulation (DBS) is used for targeted neuromodulation in the treatment of patients with movement disorders. It is often assumed that the primary effect of DBS occurs at the site of stimulation, potentially blocking or distorting intrinsic abnormal signals. However, despite the similarity of DBS to the effects of lesions in early studies, recent work has shown that DBS leads to robust evoked potentials (EP) in multiple brain regions connected to the stimulation site. While the significance of these EPs for therapeutic outcomes is not known, it appears that the electrical effects of DBS are having at least a partial modulatory effect on downstream targets. The availability of EP recordings from DBS provides an opportunity to investigate functional connectivity between deep brain regions. An understanding of functional and structural connectivity in patients with movement disorders is critical for determining the mechanism of DBS. This study aims to examine and shed light on how electrical stimulation from DBS pulses is carried along neural pathways. We hypothesize that the pathways that transmit external electrical stimulation include the pathways that transmit intrinsic neural signals, and are more likely to travel in the direction of intrinsic signals. To test this hypothesis, we acquired intrinsic brain signals and EPs through depth electrodes in seven children with dystonia. Transfer function analysis was performed to compare the transmission of signals from external electrical stimulation, along orthodromic and antidromic pathways, with the transmission of intrinsic brain signals. The methodology described offers a tool for predicting the transmission of DBS through deep brain networks. Further studies are necessary to confirm the feasibility of detecting differences between anatomic and non-anatomic pathways.