Cernera Stephanie, Shcherbakova Maria, Hammer Lauren H, Friedrich Maximilian, Peach Robert, Ip Chi Wang, Bledsoe Ian, Little Simon, Starr Philip A
Department of Neurological Surgery, University of California, San Francisco, California, United States.
Department of Neurology, University of California, San Francisco, California, United States.
J Neurophysiol. 2025 Aug 1;134(2):677-690. doi: 10.1152/jn.00198.2025. Epub 2025 Jul 28.
Dystonia is a movement disorder characterized by involuntary muscle contractions, often treated with bilateral pallidal deep brain stimulation (DBS). However, optimizing DBS therapy remains challenging due to delayed clinical effects and a lack of objective biomarkers in dystonia. Using an investigational sensing-enabled DBS device attached to both cortical and pallidal leads, we recorded over 500 h of neural activity in a patient with cervical dystonia before and during chronic stimulation therapy while the individual went about their normal daily life. During off-stimulation settings, we observed increased low-frequency power (3-12 Hz) and a distinct narrowband gamma oscillation (∼60 Hz) in the sensorimotor cortex, both of which correlated with the severity of dystonic head tremor. DBS suppressed both pathological low-frequency activity and narrowband gamma oscillations while inducing stimulation-entrained gamma oscillations at half the stimulation frequency (65 Hz). Reductions in low-frequency power and increases in entrained gamma power were associated with improvements in dystonia severity, as measured by blinded clinical assessments of home video and video-derived kinematics, including head tremor amplitude and head angle deviations. The amplitude of gamma entrainment depended on stimulation parameters, including amplitude, frequency, and electrode contact. These findings suggest that gamma oscillations and their entrainment by stimulation may serve as an objective marker of DBS effectiveness in dystonia. We recorded over 500 h of neural activity in a patient with cervical dystonia using a sensing-enabled DBS device-the most extensive dataset to date. Multisite recordings were paired with wearable and kinematic analysis of 100+ home videos. Low-frequency and narrowband gamma oscillations correlated with tremor and were suppressed by DBS, which also induced entrained gamma oscillations. These neural changes tracked with clinical and kinematic improvements, suggesting potential biomarkers of DBS effectiveness.
肌张力障碍是一种以不自主肌肉收缩为特征的运动障碍，通常采用双侧苍白球深部脑刺激（DBS）进行治疗。然而，由于临床效果延迟以及肌张力障碍缺乏客观生物标志物，优化DBS治疗仍然具有挑战性。我们使用一种连接到皮质和苍白球导联的具有传感功能的研究性DBS设备，在一名颈部肌张力障碍患者进行慢性刺激治疗之前和期间，记录了超过500小时的神经活动，同时该患者进行正常的日常生活。在非刺激状态下，我们观察到感觉运动皮层的低频功率（3 - 12赫兹）增加以及一种明显的窄带伽马振荡（约60赫兹），这两者都与肌张力障碍性头部震颤的严重程度相关。DBS抑制了病理性低频活动和窄带伽马振荡，同时以一半的刺激频率（65赫兹）诱导出与刺激同步的伽马振荡。低频功率的降低和同步伽马功率的增加与肌张力障碍严重程度的改善相关，这是通过对家庭视频和视频衍生运动学的盲法临床评估来衡量的，包括头部震颤幅度和头部角度偏差。伽马同步的幅度取决于刺激参数，包括幅度、频率和电极触点。这些发现表明，伽马振荡及其通过刺激的同步可能作为DBS治疗肌张力障碍有效性的客观标志物。我们使用一种具有传感功能的DBS设备，在一名颈部肌张力障碍患者中记录了超过500小时的神经活动——这是迄今为止最广泛的数据集。多部位记录与100多个家庭视频的可穿戴和运动学分析相结合。低频和窄带伽马振荡与震颤相关，并被DBS抑制，DBS还诱导出同步伽马振荡。这些神经变化与临床和运动学改善相关，表明可能是DBS有效性的生物标志物。
