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

Deep brain stimulation (DBS) is a neuromodulation method for treatment of various neurological disorders. It is often assumed that the primary inhibition or excitation effect of DBS occurs at the site of stimulation. However, recent work has shown 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 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. The ability to record signals from brain regions provides an opportunity to determine the mechanism of DBS signal transmission. We hypothesize that the pathways that transmit DBS pulses include the pathways that transmit intrinsic neural signals. To test this, we performed a transfer function analysis on deep brain recordings during DBS-off condition and compared its impulse response with the transmission of signals from electrical stimulation during DBS-on condition. Our results support our claim that the electrical pulses travel partly along intrinsic neural pathways by showing that the propagation of DBS signals can be partially predicted by observation of intrinsic neural activity and measurement of DBS-EPs.