Patterned low-frequency deep brain stimulation induces motor deficits and modulates cortex-basal ganglia neural activity in healthy rats.
Patterned low-frequency deep brain stimulation induces motor deficits and modulates cortex-basal ganglia neural activity in healthy rats.
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DOI：
10.1152/jn.00929.2017
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发表时间：
2018-11
影响因子：
2.5
通讯作者：
Chintan S. Oza;David T. Brocker;Christina E. Behrend;W. Grill
中科院分区：
文献类型：
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作者：
Chintan S. Oza;David T. Brocker;Christina E. Behrend;W. Grill
脑深部电刺激（DBS）是一种有效的治疗运动障碍，包括帕金森病（PD），虽然作用机制尚不清楚。异常的振荡神经活动与运动症状相关，并且减轻运动症状的药物或DBS治疗似乎可以抑制异常的振荡。然而，这种振荡活动是否是运动缺陷如震颤的原因仍不清楚。我们的目标是使用模式化的丘脑底核DBS在皮质-基底神经节回路中产生异常振荡活动，并量化清醒健康大鼠的运动行为。通过基于模型的优化设计刺激模式，以增加低频（7-11 Hz）带的功率，因为这些振荡与帕金森症6-羟基多巴胺损伤大鼠模型中运动症状的出现相关。我们使用头戴式加速度计测量运动活动，以及皮质和苍白球（GP）中的量化神经活动，以响应产生7至11 Hz频谱功率范围的5种刺激模式。刺激模式诱导皮层和GP低频带的振荡活动，并引起震颤，而控制模式和定期50赫兹DBS没有产生任何这样的效果。在刺激过程中观察到的神经和运动诱发的反应是同步的，并且时间锁定到模式内的刺激突发。这些结果确定了与震颤和震颤相关的神经活动在皮层和基底神经节的刺激的不规则模式的元素，并可能导致识别的振荡活动和结构与震颤活动的产生。新&值得注意的是丘脑底核脑深部刺激是一种有前途的治疗运动障碍，如帕金森氏病。几个研究小组报告了皮质基底神经节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。我们证明了震颤和病理振荡活动的产生，否则健康的大鼠刺激模式，产生低频振荡活动的增加。
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.