Multidisciplinary Study of Social Behavior and Emotion in Frontotemporal Dementia

描述（由申请人提供）：额颞叶痴呆（FTD）是一种与年龄相关的神经退行性疾病，其特征是社会和道德行为障碍。FTD是解读老年社会行为的神经生物学基础的独特窗口。FTD的早期症状反映了自我参照的社会行为（如尴尬）、对他人的情感意识（如共情）和道德情感体验（如公平）的下降。这些行为变异的FTD患者也被去抑制，无法调节他们的社会行为。这些干扰的共同潜在机制可能是驱动社会和道德行为的情绪受损（Fiske, 2002； Olsson和Ochsner， 2008）。我们的研究表明，社会环境会改变自主情绪反应（Gehricke和Shapiro， 2001），而右半球负责这些反应（Spence等，1996）和bvFTD中主要的区域脑萎缩（McMurtray等，2006；Mendez等，2008）。总之，这些研究表明，特定的右额颞叶区域调节特定的社会道德情绪（SME）。为了这个应用，一个由社会科学家和神经科学家组成的多学科团队聚集在一起研究bvFTD中的SME。该团队在自然环境中观察社会道德行为，这是最明显的，为bvFTD构建了一个“Ethogram”或行为词典，用行为和心理生理学测量方法对其进行测试，并研究了涉及皮质映射技术的大脑区域。此应用程序将定义与阿尔茨海默病（AD）患者和正常对照相比，bvFTD患者的SME及其干扰。它将招募33名早期bvFTD患者，并将他们与33名AD患者和33名正常对照者在三个特定目标上进行比较。具体目标1将评估由试点数据生成的预测心电图。这一特定目标将应用人种学方法，对患者在家中的互动进行参与者观察，通过对话分析来理解他们的口头互动，并进行补充行为实验和量表。在具体目标2中，应用程序将进一步评估这些行为的特异性与心理生理措施。对于这两个特定目标，与对照组相比，该应用程序预测了bvFTD患者在社会道德情感行为方面更大、更具体的障碍。在具体目标3中，该应用将把SME的评估与区域异常和磁共振成像（MRI）的三维皮质映射联系起来。该应用预测，大多数SME障碍将与右侧腹内侧额叶区域的萎缩相关，而抑制解除和失调则对应于右侧眼窝额叶前部颞叶区域。其他特定的大脑行为定位可能会被这种创新的神经成像所揭示。最终，这一应用可以阐明老年神经退行性疾病如何影响社会和道德行为，并可以大大加快我们对社会行为的神经科学的理解。

DESCRIPTION (provided by applicant): Frontotemporal dementia (FTD) is an age-related neurodegenerative disorder characterized by disturbances in social and moral behavior. FTD is a singularly unique window to deciphering the neurobiological basis of social behavior in older age. The earliest symptoms of FTD reflect declines in self-referential social behavior (e.g., embarrassment), in emotional awareness of others (e.g., empathy), and in moral emotional experiences (e.g., fairness). These behavioral variant FTD patients are also disinhibited and unable to regulate their social behavior. The common, underlying mechanism for these disturbances may be impairment in the emotions that drive social and moral behavior (Fiske, 2002; Olsson and Ochsner, 2008). Our work has shown that social context alters autonomic emotional responses (Gehricke and Shapiro, 2001) and that the right hemisphere is responsible for both these responses (Spence et al, 1996) and the predominant regional brain atrophy in bvFTD (McMurtray et al, 2006; Mendez et al, 2008a). Together, these studies suggest that specific right frontotemporal regions mediate in specific in sociomoral emotions (SME). For this application, a multidisciplinary team of social scientists and neuroscientists have come together to study SME in bvFTD. This team takes observations of sociomoral behavior in a naturalistic setting, where it is most evident, constructs an "Ethogram" or behavioral dictionary for bvFTD, tests it with behavioral and psychophysiologic measures, and investigates the brain regions involved with cortical mapping techniques. This application will define the SME and their disturbances in patients with bvFTD, compared to patients with Alzheimer's disease (AD) and normal controls. It will recruit 33 patients with early bvFTD and compare them to33 patients with AD and 33 normal controls on three Specific Aims. Specific Aim 1 will evaluate the predicted Ethogram, generated by pilot data. This Specific Aim will apply ethnographic methods for participant observation of patient interactions in their homes, conversational analysis to understand their verbal interactions, and supplemental behavior experiments and scales. In Specific Aim 2, the application will further evaluate the specificity of these behaviors with psychophysiologic measures. For these two Specific Aims, this application predicts greater and more specific disturbances in sociomoral emotional behaviors among patients bvFTD, in comparison to controls. In Specific Aim 3, this application will correlate the assessments of SME with regional abnormalities and three-dimensional cortical mapping on magnetic resonance imaging (MRI). This application predicts that most SME disturbances will correlate with atrophy in the right ventromedial frontal regions, whereas disinhibition and dysregulation corresponds to right orbitofrontal-anterior temporal regions. Other specific brain-behavior localizations may be revealed by this innovate neuroimaging. Ultimately, this application can elucidate how neurodegenerative diseases of aging impact social and moral behavior and can greatly accelerate our understanding of the neuroscience of social behavior. PUBLIC HEALTH RELEVANCE: Many mental or brain disorders have disturbances in social behavior or interpersonal interactions. This application combines many specialists to study disturbed social behavior in frontotemporal dementia. The results of the project can clarify how social behavior is altered by mental disorders or brain diseases.