School of Psychology, Macquarie University, Sydney, Australia.
Brain and Mind Centre, The University of Sydney, Australia.
J Alzheimers Dis. 2018;61(2):521-535. doi: 10.3233/JAD-170809.
Impaired capacity for Theory of Mind (ToM) represents one of the hallmark features of the behavioral variant of frontotemporal dementia (bvFTD) and is suggested to underpin an array of socioemotional disturbances characteristic of this disorder. In contrast, while social processing typically remains intact in Alzheimer's disease (AD), the cognitive loading of socioemotional tasks may adversely impact mentalizing performance in AD. Here, we employed the Frith-Happé animations as a dynamic on-line assessment of mentalizing capacity with reduced incidental task demands in 18 bvFTD, 18 AD, and 25 age-matched Controls. Participants viewed silent animations in which geometric shapes interact in Random, Goal-Directed, and ToM conditions. An exclusive deficit in ToM classification was observed in bvFTD relative to Controls, while AD patients were impaired in the accurate classification of both Random and ToM trials. Correlation analyses revealed robust associations between ToM deficits and carer ratings of affective empathy disruption in bvFTD, and with episodic memory dysfunction in AD. Voxel-based morphometry analyses further identified dissociable neural correlates contingent on patient group. A distributed network of medial prefrontal, frontoinsular, striatal, lateral temporal, and parietal regions were implicated in the bvFTD group, whereas the right hippocampus correlated with task performance in AD. Notably, subregions of the cerebellum, including lobules I-IV and V, bilaterally were implicated in task performance irrespective of patient group. Our findings reveal new insights into the mechanisms potentially mediating ToM disruption in dementia syndromes, and suggest that the cerebellum may play a more prominent role in social cognition than previously appreciated.
心智理论（Theory of Mind，ToM）能力受损是额颞叶痴呆（frontotemporal dementia，FTD）行为变异型（behavioral variant of frontotemporal dementia，bvFTD）的标志性特征之一，据推测这一特征是该疾病一系列社会情感障碍的基础。相比之下，尽管阿尔茨海默病（Alzheimer's disease，AD）患者的社会认知处理通常保持完整，但社会情感任务的认知负荷可能会对 AD 患者的心智化表现产生不利影响。在这里，我们使用 Frith-Happé 动画作为一种动态的在线心智化能力评估方法，该方法具有较低的偶然任务需求，在 18 名 bvFTD 患者、18 名 AD 患者和 25 名年龄匹配的对照组中进行了评估。参与者观看无声动画，其中几何形状在随机、目标导向和 ToM 条件下相互作用。与对照组相比，bvFTD 患者在 ToM 分类方面存在明显缺陷，而 AD 患者在准确分类随机和 ToM 试验方面存在障碍。相关分析显示，在 bvFTD 中，ToM 缺陷与照顾者对情感共情障碍的评分之间存在强有力的关联，而在 AD 中，与情景记忆功能障碍之间存在关联。基于体素的形态测量学分析进一步确定了依赖于患者组的分离神经相关物。内侧前额叶、额眶回、纹状体、外侧颞叶和顶叶区域的分布式网络与 bvFTD 组有关，而右侧海马与 AD 患者的任务表现相关。值得注意的是，小脑的一些亚区，包括双侧的 I-IV 叶和 V 叶，与任务表现有关，而与患者组无关。我们的研究结果揭示了潜在机制，这些机制可能介导痴呆综合征中的 ToM 破坏，并表明小脑在社会认知中可能发挥比以前认识到的更重要的作用。
