1 Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0SZ, UK.
Brain. 2014 Jan;137(Pt 1):208-20. doi: 10.1093/brain/awt302. Epub 2013 Nov 29.
The volitional impairments of alien limb and apraxia are a defining feature of the corticobasal syndrome, but a limited understanding of their neurocognitive aetiology has hampered progress towards effective treatments. Here we combined several key methods to investigate the mechanism of impairments in voluntary action in corticobasal syndrome. We used a quantitative measure of awareness of action that is based on well-defined processes of motor control; structural and functional anatomical information; and evaluation against the clinical volitional disorders of corticobasal syndrome. In patients and healthy adults we measured 'intentional binding', the perceived temporal attraction between voluntary actions and their sensory effects. Patients showed increased binding of the perceived time of actions towards their effects. This increase correlated with the severity of alien limb and apraxia, which we suggest share a core deficit in motor control processes, through reduced precision in voluntary action signals. Structural neuroimaging analyses showed the behavioural variability in patients was related to changes in grey matter volume in pre-supplementary motor area, and changes in its underlying white matter tracts to prefrontal cortex. Moreover, changes in functional connectivity at rest between the pre-supplementary motor area and prefrontal cortex were proportional to changes in binding. These behavioural, structural and functional results converge to reveal the frontal network for altered awareness and control of voluntary action in corticobasal syndrome, and provide candidate markers to evaluate new therapies.
自愿运动障碍和失用症是皮质基底节综合征的一个明确特征，但对其神经认知病因的理解有限，阻碍了有效治疗方法的发展。在这里，我们结合了几种关键方法来研究皮质基底节综合征中自愿运动障碍的机制。我们使用了一种基于明确的运动控制过程、结构和功能解剖学信息的定量测量方法来评估对皮质基底节综合征的临床自愿障碍的意识。在患者和健康成年人中，我们测量了“意图绑定”，即自愿行为及其感觉效果之间感知的时间吸引力。患者表现出对行为感知时间向其效果的绑定增加。这种增加与异肢和失用症的严重程度相关，我们认为它们通过减少自愿行为信号的精度，共享运动控制过程中的核心缺陷。结构神经影像学分析表明，患者的行为变异性与补充运动前区灰质体积的变化以及其下的白质束与前额叶皮层的变化有关。此外，静息状态下补充运动前区和前额叶皮层之间功能连接的变化与绑定的变化成正比。这些行为、结构和功能结果的综合揭示了皮质基底节综合征中自愿意识和控制改变的额网络，并提供了候选标志物来评估新的治疗方法。
