Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor
Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor
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DOI：
10.1093/brain/awt304
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发表时间：
2014-01-01
期刊：
影响因子：
14.5
通讯作者：
Volkmann, Jens
中科院分区：
文献类型：
--
作者：
Groppa, Sergiu;Herzog, Jan;Volkmann, Jens
姿势性震颤是特发性震颤的主要症状，但在某些情况下会出现意向性震颤和肢体共济失调，并可能成为高度致残的特征。深部脑部刺激丘脑或丘脑底白质可改善震颤和共济失调；然而，底层的网络机制是神秘的。为了阐明原发性震颤的深部脑刺激机制，我们采用了一种多模式方法，结合了抓握运动的运动学测量、临床评估、神经元兴奋性的生理测量和扩散张量成像的概率纤维束成像。七名原发性震颤患者（年龄 62.9 +/- 10.3 岁，两名女性）接受丘脑深部脑刺激，并使用治疗和超治疗刺激参数对刺激结束时肢体震颤和共济失调的严重程度进行临床检查。还执行了基于声音提示的伸手抓握任务。为了检查目标结构的电特性，我们确定了被调节的神经元件的时间。对照组由 13 名健康受试者（年龄 56 +/- 7.6 岁，5 名女性）组成，在 3 T 下接受全脑扩散张量成像。在健康受试者中应用概率纤维束成像技术，从小脑和中脑的种子中重建丘脑底区的连接模式。患者刺激电极的位置被转换成概率图，并且连接值与临床结果测量相关。治疗性刺激主要在达到范式的目标期间改善共济失调和震颤（与停止刺激相比减少 63%）。值得注意的是，加速期 (29%) 和减速期 (41%) 得到了改善。相比之下，超治疗刺激在减速期间使共济失调恶化，空间变异性增加了 55%，同时保持对震颤的近乎完全抑制。 Chronaxie 测量在快速传导有髓纤维的范围内，对于治疗刺激的抗震颤作用（27 秒）和超治疗刺激的促共济失调作用（52 秒）具有显着不同的值。刺激电极处与齿状丘脑束的连接程度与治疗条件下震颤的减少显着相关。我们的数据表明，刺激引起的震颤减少和超治疗刺激引起的共济失调是由不同的纤维系统介导的。概率束成像将齿状丘脑束确定为震颤抑制的可能目标。刺激引起的共济失调可能是由于相邻纤维系统在较高振幅下的额外募集引起的。短脉冲持续时间的刺激可能有助于增加治疗窗并集中于抗震颤效果。
Postural tremor is the leading symptom in essential tremor, but in some cases intention tremor and limb ataxia emerge and can become highly disabling features. Deep brain stimulation of the thalamus or subthalamic white matter improve tremor and ataxia; however, the underlying network mechanisms are enigmatic. To elucidate the mechanisms of deep brain stimulation in essential tremor, we pursued a multimodal approach combining kinematic measures of reach-to-grasp movements, clinical assessments, physiological measures of neuronal excitability and probabilistic tractography from diffusion tensor imaging. Seven patients with essential tremor (age 62.9 +/- 10.3 years, two females) received thalamic deep brain stimulation and a clinical examination of severity of limb tremor and ataxia at off stimulation, using therapeutic and supratherapeutic stimulation parameters. A reach-to-grasp task based on acoustic cues was also performed. To examine the electrical properties of target structures, we determined the chronaxie of neural elements modulated. A control group of 13 healthy subjects (age 56 +/- 7.6 years, five females) underwent whole-brain diffusion tensor imaging at 3 T. Probabilistic tractography was applied in healthy subjects from seeds in cerebellum and midbrain to reconstruct the connectivity pattern of the subthalamic area. The positions of stimulation electrodes in patients were transferred into probability maps and connectivity values were correlated to clinical outcome measures. Therapeutic stimulation improved ataxia and tremor mainly during the target period of the reaching paradigm (63% reduction compared with off stimulation). Notably the acceleration (29%) and deceleration periods (41%) were improved. By contrast, supratherapeutic stimulation worsened ataxia during the deceleration period with a 55% increase of spatial variability, while maintaining near complete suppression of tremor. Chronaxie measures were in the range of rapidly-conducting myelinated fibres with significantly different values for the anti-tremor effect of therapeutic stimulation (27 s) and the pro-ataxic effect of supratherapeutic stimulation (52 s). The degree of connectivity to the dentato-thalamic tract at the stimulating electrode correlated significantly with the reduction of tremor in the therapeutic condition. Our data suggest that stimulation induced tremor reduction and induction of ataxia by supratherapeutic stimulation are mediated by different fibre systems. Probalistic tractography identified the dentato-thalamic tract as a likely target of tremor suppression. Stimulation-induced ataxia may be caused by additional recruitment of adjacent fibre systems at higher amplitudes. Stimulation with short pulse duration may help to increase the therapeutic window and focus on the anti-tremor effect.