Departments of Neurology and Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, Department of Neurology, University of Colorado Anschutz Medical Campus, Denver, Colorado 80045, and PET Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892.
J Neurosci. 2013 Sep 11;33(37):14705-14. doi: 10.1523/JNEUROSCI.0407-13.2013.
Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.
痉挛性发音障碍是一种原发性局灶性肌张力障碍，其特征是在言语产生过程中喉部肌肉出现不自主痉挛。痉挛性发音障碍的病理生理学被认为涉及基底节-丘脑-皮质回路的结构和功能异常；然而，支持这些异常的神经化学相关性及其与痉挛性发音障碍症状的关系仍然未知。我们使用放射性配体 [(11)C]raclopride (RAC) 的正电子发射断层扫描研究痉挛性发音障碍患者在静息状态下和产生有症状的句子以及无症状的手指敲击时纹状体多巴胺能神经传递。我们发现，与健康对照组相比，患者的平均双侧纹状体多巴胺 D2/D3 受体 RAC 结合潜能 (BP) 降低了 29.2%，这与在有症状的说话过程中左纹状体的 RAC 位移 (RAC ΔBP) 降低有关（组平均差异 10.2%），但在无症状敲击时双侧纹状体的 RAC ΔBP 增加（组平均差异 10.1%）。具有更严重的语音症状和亚临床更长时间启动敲击序列的患者具有更大的 RAC ΔBP 测量值，而痉挛性发音障碍的持续时间更长与任务诱导的 RAC ΔBP 减少有关。在有症状的言语产生过程中，多巴胺能传递的减少可能代表一种与症状产生有关的特定于疾病的病理生理特征，而在未受影响的任务表现期间多巴胺能功能的增加可能是由于黑质纹状体多巴胺能系统的代偿性适应，可能是由于纹状体 D2/D3 受体的可用性降低所致。这些变化可以与痉挛性发音障碍的临床和亚临床特征相关联，并且可能代表该疾病中基底节改变的神经化学基础。
