FMRI/Pathology/Anterior Cingulate/Frontoinsular Cortex

描述(申请人提供)：这是一份K08-阿尔茨海默病临床科学家发展奖的申请书，题为“FTLD和AD的前扣带回和额岛皮质的功能磁共振成像和病理学”。这项研究的主要目标是使用新的功能成像和病理学技术来探测植根于前扣带回(ACC)、前岛叶(Al)和眼眶额岛(F1)区域的神经回路，这些区域与阿尔茨海默病(AD)相比，在额颞叶痴呆(FTD)中是选择性脆弱的。 退行性痴呆的目标是特定的、功能相连的神经元网络。AD开始于内侧颞区，导致记忆功能障碍，而FTD累及ACC、A1和F1，导致社会行为紊乱。决定这些截然不同的解剖模式的力量仍然未知。这项研究的具体目的是(1)评估FTD、AD和年龄匹配的健康对照组ACCAI-FI网络内的静息状态fMRI连通性；(2)探索FTD和AD患者ACC-AI-FI网络与外周自主神经标记物的连通性；(3)确定FTD、AD和非神经对照的ACC和F1内新近进化的细胞群体-纺锤体神经元-的相对易感性。这项研究的主要假设是，仅FTD患者将具有与自主神经反应分离的、异常的ACC-AI-FI网络连接，并且FTD患者将表现出比AD患者更大的绝对和相对纺锤形神经元丢失。 作为拟议研究的一部分，申请人寻求以下方面的培训：(1)功能磁共振成像，包括功能连接技术，(2)基本自主神经生理学记录，(3)神经病理学，包括量化特定大脑区域内神经元亚型丧失的方法，(4)痴呆症的临床护理，(5)手稿准备和拨款撰写，以及(6)负责任的研究工作。拟议的研究计划、教学课程以及导师和顾问的辅导指导将促进申请者发展成为痴呆症神经科学的独立研究员。 退化性痴呆症给人类带来无法估量的痛苦，并对卫生保健资源造成越来越大的压力。这项拟议的研究旨在通过澄清痴呆症的生物学基础，最终促进痴呆症患者的早期诊断和更好的治疗，从而造福公众健康。

DESCRIPTION (provided by applicant): This is an application for a K08-Alzheimer's Disease Clinical Scientist Development Award, entitled "FMRI and Pathology of Anterior Cingulate and Frontoinsular Cortex in FTLD and AD." The primary goal of the proposed research is to use novel functional imaging and pathological techniques to probe a neural circuit rooted in anterior cingulate (ACC), anterior insular (Al), and orbital frontoinsular (Fl) regions known to be selectively vulnerable in frontotemporal dementia (FTD) compared with Alzheimer's Disease (AD). Degenerative dementias target specific, functionally-linked neuronal networks. AD begins in medial temporal areas, producing memory dysfunction, while FTD involves the ACC, Al, and Fl, leading to disordered social conduct. The forces that determine these contrasting anatomic patterns remain unknown. The specific aims of the proposed research are (1) To assess resting state fMRI connectivity within the ACCAI- FI network in FTD, AD, and healthy age-matched controls, (2) To explore connectivity of the ACC-AI-FI network to peripheral autonomic markers in FTD and AD, and (3) To determine the relative susceptibility of a recently evolved cellular population-the spindle neurons-within the ACC and Fl in FTD, AD, and nonneurological controls at autopsy. The overarching hypotheses of this research are that FTD patients alone will have diminished, aberrant ACC-AI-FI network connectivity that is uncoupled from autonomic responses, and that FTD patients will exhibit greater absolute and relative spindle neuron losses than those seen in AD. As part of the proposed research, the applicant seeks training in (1) fMRI, including functional connectivity techniques, (2) basic autonomic physiology recording, (3) neuropathology, including methods for quantifying loss of neuronal subtypes within specific brain regions, (4) clinical care of dementia, (5) manuscript preparation and grant writing and (6) the responsible conduct of research. The proposed research plan, didactic courses, and tutorial instruction from mentors and advisors will promote the applicant's development into an independent investigator in the neuroscience of dementia. Degenerative dementias cause immeasurable human suffering and impose a growing strain on health care resources. The proposed research seeks to benefit the public health by clarifying the biological basis of dementia, ultimately promoting earlier diagnosis and better treatments for dementia patients.