Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3
Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3
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DOI：
10.1002/hbm.23266
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发表时间：
2016-10-01
影响因子：
4.8
通讯作者：
Castelo-Branco, Miguel
中科院分区：
文献类型：
--
作者：
Duarte, Joao Valente;Faustino, Ricardo;Castelo-Branco, Miguel
Machado-Joseph病，遗传性3型脊髓小脑共济失调（SCA 3），是世界上最常见的形式。神经影像学和神经病理学一直显示小脑的改变。在这里，我们的目标是发现全脑功能生物标志物，基于参数性能水平依赖信号。我们评估了13名早期SCA 3患者和14名健康参与者。我们使用了一个组合的参数行为/功能神经成像设计，以调查疾病指纹，作为性能水平的函数，再加上结构MRI和基于体素的形态学。功能性磁共振成像（fMRI）的目的是参数分析行为和神经反应的音频起搏的双边拇指运动的时间频率为1，3和5赫兹。我们基于性能水平的设计探测运动协调的神经元相关性，使发现神经激活和行为显示出关键的参数调制损失，特别是在SCA 3，与频率依赖性皮层/皮层下激活/失活模式。小脑/皮质的频率依赖性分离模式可以清楚地区分组间的灰质损失无关。我们的研究结果表明，运动网络的功能重组，并表明功能磁共振成像作为一种工具，以监测疾病进展SCA 3的可能作用。因此，功能磁共振成像模式被证明是潜在的生物标志物在早期SCA 3，作为测试的行为和神经激活在不同的频率的接收器操作特性分析。基于BOLD信号的识别分析在单个感兴趣区域的敏感性和特异性通常达到80%以上，因此，基于小脑和皮质BOLD性能依赖信号调制的功能指纹可以组合为遗传性共济失调的诊断和/或治疗靶点。《脑地图》37：3656-3668，2016。(c)2016 Wiley Periodicals，Inc.
Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. (c) 2016 Wiley Periodicals, Inc.