Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study
Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study
复制标题
DOI：
10.1093/brain/awq017
复制
发表时间：
2010-03-01
期刊：
影响因子：
14.5
通讯作者：
Eidelberg, David
中科院分区：
文献类型：
--
作者：
Carbon, Maren;Argyelan, Miklos;Eidelberg, David
神经生理学研究已经提供了原发性肌张力障碍时初级运动皮层过度兴奋的证据，但一些功能成像研究表明并非如此。为了解决这个问题，我们测量了DYT 1肌张力障碍突变携带者和对照受试者在区域和网络水平上的感觉运动激活。我们使用（15）氧标记水和正电子发射断层扫描扫描9个表现DYT 1携带者，10个非表现DYT 1携带者和12个年龄匹配的对照，同时他们进行运动控制的运动任务;他们也在非运动视听控制条件下进行扫描。组内和组间对比采用统计参数图进行分析。对于网络分析，我们首先确定了一个正常的运动相关的激活模式，在一组39运动和视听扫描中获得的18名健康志愿者的独立队列。在每个基因携带者和对照中获得的运动和对照扫描中前瞻性地定量该模式的表达。用ANOVA和事后对比比较三组的网络值。DYT 1携带者和对照组的体素比较显示，前者的运动激活反应异常增加（P < 0.05，校正;统计参数映射），定位于感觉运动皮层、背侧运动前皮层、辅助运动区和下顶叶皮层。网络分析的规范推导队列显示了一个显着的正常的运动相关的激活模式的地形图（P < 0.0001），其特征是共变的神经活动的感觉运动皮层，背侧运动前皮层，辅助运动区和小脑。在研究队列中，在运动过程中测量的正常运动相关激活模式表达在表现基因携带者中异常升高（P < 0.001），但在其非表现对应物中没有。相反，在非运动控制条件下，两组基因携带者的网络活动均异常增加（P < 0.001）。在这种情况下，正常电机相关的激活模式的表达在非表现载体大于对照组，但低于受影响的运营商。在后一组中，视听条件下正常运动相关激活模式表达的测量值与独立肌张力障碍临床评分相关（r = 0.70，P = 0.04）。这些发现证实了感觉运动系统的过度兴奋是肌张力障碍的一个重要特征。在非运动条件下，正常运动相关激活模式表达升高，表明视听输入与感觉运动网络活动的异常整合是这种疾病的重要特征。最后，在个体病例中，正常运动相关激活模式表达的定量可能在肌张力障碍和相关疾病的新治疗试验中作为治疗反应的客观描述符具有实用性。
Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used (15)Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal increases in network activity were present in both groups of gene carriers (P < 0.001). In this condition, normal motor-related activation pattern expression in non-manifesting carriers was greater than in controls, but lower than in affected carriers. In the latter group, measures of normal motor-related activation pattern expression in the audio-visual condition correlated with independent dystonia clinical ratings (r = 0.70, P = 0.04). These findings confirm that overexcitability of the sensorimotor system is a robust feature of dystonia. The presence of elevated normal motor-related activation pattern expression in the non-motor condition suggests that abnormal integration of audio-visual input with sensorimotor network activity is an important trait feature of this disorder. Lastly, quantification of normal motor-related activation pattern expression in individual cases may have utility as an objective descriptor of therapeutic response in trials of new treatments for dystonia and related disorders.