The nature of tremor circuits in parkinsonian and essential tremor.
The nature of tremor circuits in parkinsonian and essential tremor.
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DOI：
10.1093/brain/awu250
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Brown P
中科院分区：
文献类型：
--
作者：
Cagnan H;Little S;Foltynie T;Limousin P;Zrinzo L;Hariz M;Cheeran B;Fitzgerald J;Green AL;Aziz T;Brown P
见Arkadir等人。(DOI：)获取本文的科学评论。震颤产生的机制尚不清楚。Cagnan等人。在患者自己的震颤频率处或附近使用丘脑或丘脑底核的脑深部刺激，以调查帕金森症和特发性震颤的网络。结果揭示了这两种震颤背后的电路的不同。震颤是帕金森氏病和特发性震颤的基本特征，是两种最常见的运动障碍。然而，震颤产生的机制在很大程度上仍不清楚。我们假设，以与患者自身震颤频率非常匹配的频率驱动脑深部刺激电极，应该与导致震颤的神经活动相互作用，并且刺激对震颤的影响应该揭示不同的脑深部刺激目标在震颤产生中的作用。此外，震颤对刺激的反应可能揭示帕金森病患者和特发性震颤回路之间的病理生理学差异。15例帕金森病患者(男13例，女2例，年龄50~77岁)和10例特发性震颤患者(男9例，女1例，年龄34~74岁)分别用丘脑或丘脑下部电极进行刺激。在接近震颤频率的刺激下，三组患者均出现震颤(帕金森病患者丘脑腹外侧部刺激，P=0.0078；帕金森病患者丘脑底核刺激，P=0.0312；特发性震颤患者丘脑腹外侧部刺激，P=0.0137；双尾配对Wilcoxon符号等级检验)。然而，只有特发性震颤的丘脑腹外侧部刺激根据刺激脉冲相对于震颤周期的时间来调制姿势震颤的幅度(例如，震颤放大的P=0.0002，双尾Wilcoxon秩和检验)。帕金森病患者的休息和基本的姿势震颤严重程度(即震颤幅度)在不施加刺激时对震颤频率的自发变化的相对耐受性不同。具体地说，帕金森静止性震颤的幅度保持不变，尽管震颤频率发生了自发变化，而当震颤频率偏离中位数时，原发性姿势震颤的幅度降低。根据这些结果，我们认为帕金森静止性震颤是由一个神经网络驱动的，该神经网络包括丘脑底核和丘脑腹外侧部，具有广泛的频率-幅度耐受性。我们认为，正是这种对震颤频率变化的耐受性决定了帕金森病静止性震颤可能会被低频刺激显著地夹带，而不是刺激时序依赖的幅度调制。相反，在特发性震颤中，受低频丘脑刺激影响的回路具有较窄的频率-幅度耐受性，因此通过外在驱动的震颤夹带必然伴随着幅度调制。帕金森病患者休息和特发性震颤的这种差异将对未来选择闭合环深部脑刺激控制震颤的策略非常重要。
See Arkadir et al. (doi:) for a scientific commentary on this article. The mechanisms underlying tremor generation remain unclear. Cagnan et al. use deep brain stimulation of the thalamus or subthalamic nucleus at/near a patient's own tremor frequency to investigate the networks responsible for parkinsonian and essential tremor. The results reveal differences in the circuitry underlying these two tremor types. Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that parkinsonian rest tremor is driven by a neural network, which includes the subthalamic nucleus and ventrolateral thalamus and has broad frequency-amplitude tolerance. We propose that it is this tolerance to changes in tremor frequency that dictates that parkinsonian rest tremor may be significantly entrained by low frequency stimulation without stimulation timing-dependent amplitude modulation. In contrast, the circuit influenced by low frequency thalamic stimulation in essential tremor has a narrower frequency-amplitude tolerance so that tremor entrainment through extrinsic driving is necessarily accompanied by amplitude modulation. Such differences in parkinsonian rest and essential tremor will be important in selecting future strategies for closed loop deep brain stimulation for tremor control.
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影响因子：
2.9
作者：
Ermentrout, B
通讯作者：
Ermentrout, B
影响因子：
9.2
作者：
Brittain, John-Stuart;Probert-Smith, Penny;Aziz, Tipu Z.;Brown, Peter
通讯作者：
Brown, Peter
DOI：
10.1093/brain/awt239
发表时间：
2013-10
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Cagnan H;Brittain JS;Little S;Foltynie T;Limousin P;Zrinzo L;Hariz M;Joint C;Fitzgerald J;Green AL;Aziz T;Brown P
通讯作者：
Brown P
影响因子：
11.2
作者：
Helmich, Rick C.;Janssen, Marcel J. R.;Toni, Ivan
通讯作者：
Toni, Ivan
影响因子：
14.5
作者：
Hirschmann, Jan;Hartmann, Christian J.;Schnitzler, Alfons
通讯作者：
Schnitzler, Alfons