AUTHOR=Kasiri Maral , Vidmark Jessica , Hernandez-Martin Estefania , Seyyed Mousavi S. Alireza , Sanger Terence D. 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1592689

DOI=10.3389/fnins.2025.1592689

ISSN=1662-453X

ABSTRACT=IntroductionDeep brain stimulation (DBS) is a neuromodulation method for treatment of various neurological disorders. Research on DBS has often focused on local inhibition or excitation effects, at the site of stimulation. However, it is well-known that DBS can lead to robust evoked potentials (EP) not only at the stimulation site, representing the local effect, but also in distant brain regions, representing the effects on distant targets. While the significance of these EPs for therapeutic outcomes is not known, it appears that the electrical effects of DBS have a partial modulatory impact on downstream targets. Nonetheless, it partly remains unclear through what mechanism DBS pulses travel to the distant targets or what portion of the pulses travel along the normal pathways from the stimulation site. The possible scenarios include orthodromic or antidromic pathways, accessory pathways, normally inhibited pathways, and direct electromagnetic activation of distant sites. We hypothesize that the pathways that transmit DBS pulses include the pathways that transmit intrinsic neural signals.MethodsTo test this, we performed a transfer function analysis on deep brain recordings from children with dystonia, during DBS-off condition and compared its impulse response with the transmission of signals from electrical stimulation during DBS-on condition. We compared impulse responses derived from intrinsic neural signals during voluntary movement (DBS-off) to evoked potentials (EPs) recorded during electrical stimulation (DBS-on), focusing on directional transmission (orthodromic vs. antidromic).ResultsDBS EPs were more accurately predicted by impulse responses corresponding to direct axonal activation rather than somatic relay. Significant correlations between intrinsic signal transfer functions and EPs, particularly in orthodromic directions (p-value < 0.01) from pallidum to thalamus and subthalamic nucleus, support our hypothesis that DBS travels along physiological pathways.DiscussionThese results suggest that DBS engages existing motor pathways to reach distant targets, offering mechanistic insight into its network effects. This supports future approaches that could tailor treatment plans based on individual connectivity maps to improve clinical efficacy of DBS.