Neuroanatomy of social Function in FTD

该提案的目的是支持候选人发展必要的技能，以进行以患者为导向的行为神经科学研究。培训内容包括各种定量MRI分析方法的技能指导发展，包括行为神经学，高级生物统计学，神经网络建模以及科学严谨和负责任的研究行为的课程和指导培训。这些神经学/医学技能旨在补充申请人以前在心理和神经心理学评估和研究方面的培训。拟议的研究计划将支持候选人的这些技能的发展，让她有机会调查社会行为的神经解剖学和神经心理学基础， 额颞叶痴呆（FTD）患者。虽然这种疾病会导致社会功能的早期变化，而且往往是戏剧性的变化，沿着额叶、颞叶和杏仁核的不同模式的脑萎缩，但很少有人系统地量化社会变化或将社会特征与特定的大脑区域联系起来。通过该提案，将使用社会认知的神经心理学测试、对家庭成员进行的问卷调查和临床行为观察，收集75名FTD患者和25名健康对照的社会和人际功能数据。这些受试者的MRI扫描将提供给候选人，以便使用手动和自动感兴趣区域（ROI）和基于体素的形态测定（VBM）分析进行定量分析。加州大学旧金山分校记忆与衰老中心的受试者一般神经心理学评估数据也将用于分析 结合社会数据。具体的假设是：1）右前颞叶体积的减少将对应于人际温暖和对他人的移情定向的丧失，2）右背外侧前额叶皮质体积的减少将对应于社会推理的扭曲和对社会情境的不准确解释。还假设3）共情的变化和4）自信的变化将通过与假设的认知模型相对应的认知功能的神经心理学测试的分数来预测，并且这些模型可以通过结合脑组织损失的形态测量学分析来验证。

The objective of this proposal is to support the candidate's development of skills necessary to perform patient-oriented research in behavioral neuroscience. The training component includes the mentored development of skills in various methods of quantitative MRI analysis, and includes coursework and mentored training in behavioral neurology, advanced biostatistics, neural network modeling, and the scientifically rigorous and responsible conduct of research. These neurologic/medical skills are intended to complement the applicant's previous training in psychological and neuropsychological assessment and research. The proposed research plan will support the candidate's development of these skills by giving her the opportunity to investigate the neuroanatomical and neuropsychological substrates of social behavior with frontotemporal dementia (FTD) patients. Though this disease causes early and often dramatic changes in social functioning along with diverse patterns of brain atrophy in the frontal lobes, temporal lobes, and amygdala, little has been done to either systematically quantify the social changes or to link social features to specific brain areas. Through this proposal, data on social and interpersonal functioning will be collected on 75 FTD patients and 25 healthy controls using neuropsychological tests of social cognition, questionnaires administered to family members, and clinical behavioral observation. These subjects' MRI scans will be made available to the candidate for quantitative analysis using manual and automated region of interest (ROI) and voxel-based morphometry (VBM) analyses. Data from subjects' general neuropsychological evaluations at the UCSF Memory and Aging Center will also made available for analysis in conjunction with the social data. The specific hypotheses are that 1) decreased right anterior temporal lobe volume will correspond with loss of interpersonal warmth and empathic orientation to others, 2) Decreased right dorsolateral prefrontal cortex volume will correspond to distortion of social reasoning and inaccurate interpretation of social situations. It is also hypothesized that 3) variance in empathy, and 4) variance in assertiveness, will be predicted by scores on neuropsychological tests of cognitive functions corresponding to hypothesized cognitive models, and that these models can be validated via analysis in conjunction with morphometry analyses of brain tissue loss.