BRAIN AND BEHAVIOR IN DYSTONIA: A MULTICENTER STUDY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 0062 原发性扭转肌张力障碍(PTD)是一种慢性运动障碍，临床表现为局部或全身性持续性肌肉收缩、姿势和/或不自主运动，范围从动作诱发的肌张力障碍症状到致残性、全身性肌张力障碍。研究人员将对表达原发性肌张力障碍基因的受试者的功能/解剖连接进行深入的表征。这项工作的目的将是比较北美门诺派人群中与PTD、DYT1和DYT6突变相关的主要基因型的临床显性携带者和非显性携带者的学习和相关脑功能。根据我们的初步数据，我们的假设是PTD与额纹状体通路的功能/解剖障碍有关，并且与非显性肌张力障碍基因携带者相比，这种异常在受影响的患者中更广泛。在序列学习过程中，大脑功能组织的群体差异将使用正电子发射断层成像(PET)进行评估。将在相同的受试者中使用扩散张量成像(DTI)进行补充检查，这是一种磁共振成像(MRI)技术，用于评估纤维束的方向和完整性。纹状体D2受体结合在两个PTD突变携带者中在基底节输出通路和伴随表现中的功能异常的发展中的作用将被评估。最后，我们将使用我们的心理物理/PET方法结合脑深部刺激(DBS)来确定通过治疗可以逆转运动和非运动功能的程度。总之，这些研究将提供有关原发性扭转肌张力障碍的生理机制以及脑深部刺激可能的治疗效果的重要信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 0062 Primary torsion dystonia (PTD) is a chronic movement disorder manifested clinically by focal or generalized sustained muscle contractions, postures, and/or involuntary movements, ranging from action-induced dystonic symptoms to disabling, generalized dystonia. Investigators will perform an in-depth characterization of functional/anatomical connectivity in subjects expressing genes for primary dystonia. The goal of this work will be to compare learning and related brain function in clinically manifesting and non-manifesting carriers of the major genotypes associated with PTD, DYT1 and the DYT6 mutations in North American Mennonites. Our hypothesis, based on our preliminary data, is that PTD is associated with a functional/anatomical disorder of fronto-striatal pathways, and that this abnormality is more extensive in affecteds as compared with non-manifesting dystonia gene carriers. Group differences in the functional organization of the brain during sequence learning will be assessed using positron emission tomography (PET) imaging. Complementary examinations will be conducted in the same subjects using diffusion tensor imaging (DTI)an magnetic resonance imaging (MRI) technique for the assessment of the direction and integrity of fiber tracts. The role of striatal D2 receptor binding in the development of functional abnormalities in basal ganglia output pathways and in concomitant manifestations will be assessed in both PTD mutation carriers. Lastly, we will use our psychophysical/PET approach in conjunction with deep brain stimulation (DBS) to determine the degree to which motor and non-motor functioning can be reversed through treatment. Together, these studies will provide important information about the physiological mechanisms that underlie primary torsion dystonia, and the possible therapeutic effect of deep brain stimulation.