Kasiri Maral, Vidmark Jessica, Hernandez-Martin Estefania, Seyyed Mousavi S Alireza, Sanger Terence D
Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, United States.
Department of Electrical Engineering and Computer Science, University of California, Irvine, Irvine, CA, United States.
Front Neurosci. 2025 Jul 24;19:1592689. doi: 10.3389/fnins.2025.1592689. eCollection 2025.
Deep 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.
To 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).
DBS 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 (-value < 0.01) from pallidum to thalamus and subthalamic nucleus, support our hypothesis that DBS travels along physiological pathways.
These 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.
深部脑刺激（DBS）是一种用于治疗各种神经系统疾病的神经调节方法。对DBS的研究通常集中在刺激部位的局部抑制或兴奋作用。然而，众所周知，DBS不仅能在刺激部位诱发强烈的诱发电位（EP），代表局部效应，还能在远处的脑区诱发，代表对远处靶点的影响。虽然这些EP对治疗结果的意义尚不清楚，但似乎DBS的电效应会对下游靶点产生部分调节作用。尽管如此，DBS脉冲通过何种机制传至远处靶点，或者有多少脉冲沿着从刺激部位出发的正常路径传播，部分仍不清楚。可能的情况包括顺行或逆行路径、附属路径、正常受抑制的路径以及远处部位的直接电磁激活。我们假设传递DBS脉冲的路径包括传递内在神经信号的路径。
为验证这一点，我们对肌张力障碍儿童在DBS关闭状态下的深部脑记录进行了传递函数分析，并将其脉冲响应与DBS开启状态下电刺激信号的传输进行比较。我们将自愿运动（DBS关闭）期间内在神经信号产生的脉冲响应与电刺激（DBS开启）期间记录的诱发电位（EP）进行比较，重点关注方向传输（顺行与逆行）。
与直接轴突激活而非躯体中继相对应的脉冲响应能更准确地预测DBS诱发的EP。内在信号传递函数与EP之间存在显著相关性，特别是在从苍白球到丘脑和底丘脑核的顺行方向（p值<0.01），这支持了我们的假设，即DBS沿着生理路径传播。
这些结果表明，DBS利用现有的运动通路到达远处靶点，为其网络效应提供了机制性见解。这支持了未来基于个体连接图谱制定治疗方案以提高DBS临床疗效的方法。
