Oza Chintan S, Brocker David T, Behrend Christina E, Grill Warren M
Department of Biomedical Engineering, Duke University , Durham, North Carolina.
School of Medicine, Duke University , Durham, North Carolina.
J Neurophysiol. 2018 Nov 1;120(5):2410-2422. doi: 10.1152/jn.00929.2017. Epub 2018 Aug 8.
Deep brain stimulation (DBS) is an effective therapy for movement disorders, including Parkinson's disease (PD), although the mechanisms of action remain unclear. Abnormal oscillatory neural activity is correlated with motor symptoms, and pharmacological or DBS treatment that alleviates motor symptoms appears to suppress abnormal oscillations. However, whether such oscillatory activity is causal of motor deficits such as tremor remains unclear. Our goal was to generate abnormal oscillatory activity in the cortex-basal ganglia loop using patterned subthalamic nucleus DBS and to quantify motor behavior in awake healthy rats. Stimulation patterns were designed via model-based optimization to increase power in the low-frequency (7-11 Hz) band because these oscillations are associated with the emergence of motor symptoms in the 6-hydroxydopamine lesioned rat model of parkinsonism. We measured motor activity using a head-mounted accelerometer, as well as quantified neural activity in cortex and globus pallidus (GP), in response to 5 stimulation patterns that generated a range of 7- to 11-Hz spectral power. Stimulation patterns induced oscillatory activity in the low-frequency band in the cortex and GP and caused tremor, whereas control patterns and regular 50-Hz DBS did not generate any such effects. Neural and motor-evoked responses observed during stimulation were synchronous and time-locked to stimulation bursts within the patterns. These results identified elements of irregular patterns of stimulation that were correlated with tremor and tremor-related neural activity in the cortex and basal ganglia and may lead to the identification of the oscillatory activity and structures associated with the generation of tremor activity. NEW & NOTEWORTHY Subthalamic nucleus deep brain stimulation is a promising therapy for movement disorders such as Parkinson's disease. Several groups reported correlation between suppression of abnormal oscillatory activity in the cortex-basal ganglia and motor symptoms, but it remains unclear whether such oscillations play a causal role in the emergence of motor symptoms. We demonstrate generation of tremor and pathological oscillatory activity in otherwise healthy rats by stimulation with patterns that produced increases in low-frequency oscillatory activity.
深部脑刺激（DBS）是治疗运动障碍（包括帕金森病（PD））的一种有效疗法，但其作用机制仍不清楚。异常的振荡性神经活动与运动症状相关，而减轻运动症状的药物治疗或DBS治疗似乎能抑制异常振荡。然而，这种振荡活动是否是震颤等运动缺陷的病因仍不清楚。我们的目标是通过对丘脑底核进行模式化DBS在皮质-基底神经节环路中产生异常振荡活动，并对清醒健康大鼠的运动行为进行量化。刺激模式通过基于模型的优化设计，以增加低频（7-11Hz）频段的功率，因为这些振荡与帕金森病6-羟基多巴胺损伤大鼠模型中运动症状的出现有关。我们使用头戴式加速度计测量运动活动，并量化皮质和苍白球（GP）中的神经活动，以响应5种产生7至11Hz频谱功率范围的刺激模式。刺激模式在皮质和GP中诱导了低频带的振荡活动并引起了震颤，而对照模式和常规50Hz DBS没有产生任何此类效应。在刺激期间观察到的神经和运动诱发反应是同步的，并且与模式内的刺激脉冲时间锁定。这些结果确定了与震颤以及皮质和基底神经节中与震颤相关的神经活动相关的不规则刺激模式的要素，并可能导致识别与震颤活动产生相关的振荡活动和结构。新进展与值得关注之处：丘脑底核深部脑刺激是治疗帕金森病等运动障碍的一种有前景的疗法。几个研究小组报告了皮质-基底神经节中异常振荡活动的抑制与运动症状之间的相关性，但尚不清楚这种振荡是否在运动症状的出现中起因果作用。我们通过用产生低频振荡活动增加的模式进行刺激，证明了在其他方面健康的大鼠中产生了震颤和病理性振荡活动。
