Johnson Vinith, Wilt Robert, Gilron Roee, Anso Juan, Perrone Randy, Beudel Martijn, Piña-Fuentes Dan, Saal Jeremy, Ostrem Jill L, Bledsoe Ian, Starr Philip, Little Simon
Movement Disorders and Neuromodulation Centre, University of California San Francisco, San Francisco, CA, USA.
Department of Neurology, Amsterdam Neuroscience Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Exp Neurol. 2021 Nov;345:113825. doi: 10.1016/j.expneurol.2021.113825. Epub 2021 Jul 28.
Dystonia is a disabling movement disorder characterized by excessive muscle contraction for which the underlying pathophysiology is incompletely understood and treatment interventions limited in efficacy. Here we utilize a novel, sensing-enabled, deep brain stimulator device, implanted in a patient with cervical dystonia, to record local field potentials from chronically implanted electrodes in the sensorimotor cortex and subthalamic nuclei bilaterally. This rechargeable device was able to record large volumes of neural data at home, in the naturalistic environment, during unconstrained activity. We confirmed the presence of theta (3-7 Hz) oscillatory activity, which was coherent throughout the cortico-subthalamic circuit and specifically suppressed by high-frequency stimulation. Stimulation also reduced the duration, rate and height of theta bursts. These findings motivated a proof-of-principle trial of a new form of adaptive deep brain stimulation - triggered by theta-burst activity recorded from the motor cortex. This facilitated increased peak stimulation amplitudes without induction of dyskinesias and demonstrated improved blinded clinical ratings compared to continuous DBS, despite reduced total electrical energy delivered. These results further strengthen the pathophysiological role of low frequency (theta) oscillations in dystonia and demonstrate the potential for novel adaptive stimulation strategies linked to cortico-basal theta bursts.
肌张力障碍是一种致残性运动障碍，其特征为肌肉过度收缩，目前对其潜在病理生理学的理解尚不完整，治疗干预的效果也有限。在此，我们利用一种新型的、具备传感功能的深部脑刺激器装置，将其植入一名颈部肌张力障碍患者体内，以记录双侧感觉运动皮层和丘脑底核中长期植入电极的局部场电位。这种可充电装置能够在自然环境中、患者无拘束活动期间在家中记录大量神经数据。我们证实了θ波（3 - 7赫兹）振荡活动的存在，这种活动在整个皮质 - 丘脑底核回路中具有一致性，并被高频刺激特异性抑制。刺激还减少了θ波爆发的持续时间、频率和幅度。这些发现促使开展了一项新形式的适应性深部脑刺激的原理验证试验——由运动皮层记录到的θ波爆发活动触发。这有助于在不诱发运动障碍的情况下提高刺激峰值幅度，并且与持续深部脑刺激相比，尽管输送的总电能减少，但盲法临床评分有所改善。这些结果进一步强化了低频（θ波）振荡在肌张力障碍中的病理生理作用，并证明了与皮质 - 基底节θ波爆发相关的新型适应性刺激策略的潜力。
