Spooner Rachel K, Hizli Baccara J, Bahners Bahne H, Schnitzler Alfons, Florin Esther
Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
NPJ Parkinsons Dis. 2024 Mar 8;10(1):53. doi: 10.1038/s41531-024-00663-9.
Subthalamic deep brain stimulation (STN-DBS) is an effective therapy for alleviating motor symptoms in people with Parkinson's disease (PwP), although some may not receive optimal clinical benefits. One potential mechanism of STN-DBS involves antidromic activation of the hyperdirect pathway (HDP), thus suppressing cortical beta synchrony to improve motor function, albeit the precise mechanisms underlying optimal DBS parameters are not well understood. To address this, 18 PwP with STN-DBS completed a 2 Hz monopolar stimulation of the left STN during MEG. MEG data were imaged in the time-frequency domain using minimum norm estimation. Peak vertex time series data were extracted to interrogate the directional specificity and magnitude of DBS current on evoked and induced cortical responses and accelerometer metrics of finger tapping using linear mixed-effects models and mediation analyses. We observed increases in evoked responses (HDP ~ 3-10 ms) and synchronization of beta oscillatory power (14-30 Hz, 10-100 ms) following DBS pulse onset in the primary sensorimotor cortex (SM1), supplementary motor area (SMA) and middle frontal gyrus (MFG) ipsilateral to the site of stimulation. DBS parameters significantly modulated neural and behavioral outcomes, with clinically effective contacts eliciting significant increases in medium-latency evoked responses, reductions in induced SM1 beta power, and better movement profiles compared to suboptimal contacts, often regardless of the magnitude of current applied. Finally, HDP-related improvements in motor function were mediated by the degree of SM1 beta suppression in a setting-dependent manner. Together, these data suggest that DBS-evoked brain-behavior dynamics are influenced by the level of beta power in key hubs of the basal ganglia-cortical loop, and this effect is exacerbated by the clinical efficacy of DBS parameters. Such data provides novel mechanistic and clinical insight, which may prove useful for characterizing DBS programming strategies to optimize motor symptom improvement in the future.
丘脑底核深部脑刺激（STN-DBS）是缓解帕金森病患者（PwP）运动症状的有效疗法，尽管有些人可能无法获得最佳临床疗效。STN-DBS的一种潜在机制涉及对超直接通路（HDP）的逆向激活，从而抑制皮层β同步性以改善运动功能，尽管最佳DBS参数背后的确切机制尚不完全清楚。为了解决这个问题，18名接受STN-DBS治疗的PwP在脑磁图（MEG）检查期间完成了对左侧STN的2Hz单极刺激。使用最小范数估计在时频域对MEG数据进行成像。提取峰值顶点时间序列数据，以使用线性混合效应模型和中介分析来研究DBS电流对诱发和诱导的皮层反应以及手指敲击的加速度计指标的方向特异性和大小。我们观察到，在刺激部位同侧的初级感觉运动皮层（SM1）、辅助运动区（SMA）和额中回（MFG），DBS脉冲开始后诱发反应增加（HDP约3-10毫秒），β振荡功率同步（14-30Hz，10-100毫秒）。DBS参数显著调节神经和行为结果，与次优触点相比，临床有效触点引起中潜伏期诱发反应显著增加、诱导的SM1β功率降低以及更好的运动表现，通常与施加的电流大小无关。最后，HDP相关的运动功能改善以依赖于设置的方式由SM1β抑制程度介导。总之，这些数据表明，DBS诱发的脑-行为动力学受基底神经节-皮层环路关键枢纽中β功率水平的影响，并且这种效应因DBS参数的临床疗效而加剧。这些数据提供了新的机制和临床见解，可能有助于未来表征DBS编程策略以优化运动症状改善。
