Narasimham Shruti, McGovern Eavan M, Quinlivan Brendan, Killian Owen, Beck Rebecca, O'Riordan Sean, Hutchinson Michael, Reilly Richard B
Trinity Centre for Bioengineering, Trinity College Dublin, University of Dublin, Dublin, Ireland.
School of Engineering, Trinity College Dublin, University of Dublin, Dublin, Ireland.
Front Integr Neurosci. 2019 Mar 12;13:8. doi: 10.3389/fnint.2019.00008. eCollection 2019.
An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms. To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD. Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses. Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination. Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance.
颈部肌张力障碍（CD）中异常的时间辨别阈值被认为是一种中介性内表型；在未受影响的亲属中，据推测这表明存在未表现出症状的基因携带情况。这种病症的发病机制仍然未知。对参与时间辨别障碍的神经网络进行研究可能会揭示其病理机制。为了检查时间辨别正常和异常的CD患者未受影响亲属的静息态脑功能。我们假设，内表型，即异常的时间辨别，将表现为亲属中与CD相关区域的连接性改变，从而阐明时间辨别与CD之间联系的神经基础。对两个性别和年龄匹配的队列进行了静息态功能磁共振成像（rs-fMRI）数据分析：16名时间辨别正常的CD患者未受影响亲属和16名时间辨别异常的CD患者未受影响亲属。通过独立成分分析（ICA）、局部一致性（ReHo）和低频振幅（ALFF）分析提取区域和全脑功能连接测量值。与时间辨别正常的亲属相比，我们的ICA分析显示，时间辨别异常的亲属在执行控制网络和小脑网络内的连接性增加，而在感觉运动网络内的连接性降低。ReHo和ALFF分析补充了这些结果，并证明在时间辨别异常的未受影响亲属中，与运动规划、运动协调、视觉信息处理和眼球运动相对应的区域存在连接性差异。时间辨别异常的未受影响亲属中连接性紊乱揭示了内表型表达的神经基础，并支持了这样一种假设，即遗传决定的异常连接性，当后来与未知的环境触发因素相结合时，可能导致疾病的外显。
