Narvid J, Gorno-Tempini M L, Slavotinek A, Dearmond S J, Cha Y H, Miller B L, Rankin K
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA 94143, USA.
Neurocase. 2009 Jun;15(3):190-205. doi: 10.1080/13554790802632967.
Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick's disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A's abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A's genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can be dissociated from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD.
额颞叶痴呆（FTD）是一种临床综合征，其特征为社交行为逐渐衰退以及额叶和颞叶的局灶性损伤模式。其生物学基础仍知之甚少，但脑变性的局灶性为研究社会认知的认知和解剖学基础提供了一个有力模型。在此，我们介绍A博士，一位患有罕见遗传性骨病（遗传性多发性骨软骨瘤）和FTD（病理特征为皮克病）的患者，其表现出以获得性反社会人格为特征的严重行为障碍。我们进行了详细的基因、病理、神经影像学和认知研究，包括一系列旨在调查A博士理解情感线索以及推断他人心理状态和意图（心理理论）能力的测试。A博士的基因图谱表明，导致遗传性多发性骨软骨瘤的突变基因Ext2可能在额颞叶痴呆的神经变性模式中起作用，因为缺乏Ext基因家族成员Ext1的基因敲除小鼠表现出严重的中枢神经系统缺陷，包括嗅球缺失和大脑皮质异常小。尽管A博士的一般认知能力保持完好，但在情感理解、二阶心理理论、意图归因和共情方面表现出显著受损。基于体素的形态测量分析结构MRI图像显示，内侧和右侧眶额及颞前区域有明显萎缩，而背外侧额叶皮质未受影响。该病例表明，FTD中的社会和情感功能障碍可与经典执行功能任务中的保留表现相分离。VBM显示的特定解剖损伤模式强调了包括额上内侧回以及颞极区域在内的网络在调节社会认知和心理理论中的重要性。该病例为社会认知的神经基础提供了新证据，并提示了骨病与FTD之间可能的遗传联系。
