Atrophy and resting state connectivity in primary progressive aphasia

原发性进行性失语症的萎缩和静息态连接

• 批准号: 9752262
• 负责人: Borna Bonakdarpour
• 金额: $ 16.93万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-03 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752262
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Aphasia; Area; Atrophic; Biological Markers; Brain; Cell Death; Clinical; Cognitive; Collaborations; Communication; Complex; Data; Data Analyses; Development; Disease Progression; Frontotemporal Lobar Degenerations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Image; Impairment; Individual; Intervention; Knowledge; Language; Learning; Measurement; Measures; Mentored Patient-Oriented Research Career Development Award; Methodology; Methods; Nerve Degeneration; Neurobiology; Neurology; Neuronal Dysfunction; Pathology; Patients; Pattern; Pharmacology; Physiological; Physiology; Population; Primary Progressive Aphasia; Protocols documentation; Research; Research Personnel; Research Project Grants; Rest; Speech; Structure; Symptoms; Testing; Therapeutic Intervention; Thick; Time; Tissues; Training; Translational Research; Writing; base; brain tissue; candidate marker; career development; cerebral atrophy; design; effective therapy; improved; innovation; insight; language impairment; multimodality; neuroimaging; neuron loss; neuroregulation; novel; programs; public health relevance; repetitive transcranial magnetic stimulation; skills

 DESCRIPTION (provided by applicant): The purpose of the proposed project is to provide the candidate with additional career development training in areas of multimodal neuroimaging and characterization of Primary Progressive Aphasia (PPA) to enable the candidate to establish a productive research program geared towards the long-term goals of: 1) delineating the pathophysiology of PPA using resting state functional MRI (rs-fMRI) and brain volumetric measurements, and 2) designing an effective treatment for aphasia. To achieve this purpose, the project includes both career development activities and a research plan designed to advance insight into the brain physiologic and structural changes in PPA. Relatively little is known about the relationship between changes in the brain language network physiology, brain tissue loss (atrophy) and clinical findings of aphasia in PPA. Based on our recent finding that PPA symptoms can exist in the absence of significant brain atrophy, the first aim of this research program is to determine whether functional connectivity in PPA is decreased in the absence of detectable atrophy. Currently, it is not known to what extent atrophy reflects the loss of neuronal versus non- neuronal tissue. Therefore the relationship between brain atrophy and changes in language network is not well understood. Our second aim tests the hypothesis that increased atrophy results in a further decrease in network connectivity in PPA. This multimodal neuroimaging and clinical approach may enable further characterization of the language network disruption and can potentially be used to [investigate neurobiology of treatment responsiveness, gauge therapeutic interventions, and identify network targets for neuromodulatory interventions such as repetitive Transcranial Magnetic Stimulation (rTMS)]. In addition, if rs-fMRI proves to be able to identify language network change, it may prove to be a candidate biomarker to predict the path of atrophy and disease progression. Findings will also have significant impact on our understanding of aphasia and the language network in general. So far, as an investigator at the Northwestern Cognitive Neurology and Alzheimer Disease Center, I have acquired skills to analyze and interpret normal rs-fMRI data. However, to achieve the goals of this proposal and to develop autonomy, I need to advance my skills further with additional training from experts from Northwestern Clinical and Translational Imaging, and outstanding advisors outside Northwestern. With regards to volumetric measurements in PPA, I have not had the opportunity to acquire the necessary expertise. The K23 mechanism will provide protected time for me to learn volumetric measurements in PPA. The K23 mechanism will also provide the opportunity for me to collaborate with the outstanding group of experts outside Northwestern to improve my rs-fMRI and brain volumetric skills, and establish independent collaborations beyond Northwestern. [In this resubmission, in line with my long term goal, additional training components for treatment of PPA have been added. These include both speech/language, and neuromodulatory (rTMS) interventions, which eventually enable me to bridge findings from this study with language interventions]. In summary, the career development activities in this proposal aim at advancing my current knowledge and skills towards the goal of writing an R01 research grant addressing my long term goal.

 描述（由适用提供）：拟议项目的目的是为候选人提供更多的职业发展培训，以在多模式的神经影像学领域和主要进行性渐进性失语（PPA）的特征来使候选人能够建立一个针对以下的长期目标建立生产研究计划：1：1）使用RESS和BRAINTINECTINECTINECTINECTINECTINTICTION STARTINECTINTICTION and INTARITINCTINTICTINE STARTINTICTINTICTIONTINCTINTICTINTICTINACTINACTINTICTINTIC 2）设计有效的治疗方法。为了实现此目的，该项目既包括职业发展活动，又包括一项研究计划，旨在提高对PPA大脑生理和结构变化的见解。关于大脑语言网络生理学，脑组织损失（萎缩）和PPA失语症的临床发现之间的关系，知之甚少。根据我们最近的发现，即在没有明显的大脑萎缩的情况下可以存在PPA符号，该研究计划的第一个目的是确定在没有可检测到的萎缩的情况下，PPA中的功能连通性是否会降低。目前，尚不清楚萎缩在多大程度上反映了神经元与非神经元组织的丧失。因此，脑部萎缩与语言网络变化之间的关系尚不清楚。我们的第二个目标检验了增加萎缩的假设导致PPA网络连通性的进一步降低。这种多模式的神经影像学和临床方法可能能够进一步表征语言网络中断，并有可能用于[研究治疗反应能力，计量治疗干预措施的神经生物学，并确定用于神经调节干预措施（例如重复性经颅磁刺激（RTMS））的网络目标]。此外，如果RS-FMRI被证明能够识别语言网络的变化，则可能被证明是预测萎缩和疾病进展的途径的候选生物标志物。调查结果还将对我们对失语症和语言网络的理解产生重大影响。到目前为止，作为西北认知神经病学和阿尔茨海默氏病中心的研究者，我已经获得了分析和解释正常RS-FMRI数据的技能。但是，为了实现该提案的目标并建立自主权，我需要通过来自西北临床和转化成像的专家的额外培训以及西北西北部以外的杰出顾问进一步提高自己的技能。关于PPA的体积测量，我没有机会获得必要的专业知识。 K23机制将为我提供受保护的时间，以学习PPA中的体积测量。 K23机制还将为我提供与西北地区以外的杰出专家团体合作的机会，以提高我的RS-FMRI和脑力大量技能，并建立西北地区以外的独立合作。 [在此重新提交中，根据我的长期目标，已经添加了其他用于治疗PPA的培训组件。其中包括语音/语言和神经调节性（RTMS）干预措施，有时使我能够通过语言干预措施从这项研究中启动发现]。总而言之，该提案中的职业发展活动旨在提高我当前的知识和技能，以撰写R01研究赠款，以解决我的长期目标。