TMS in Primary Progressive Aphasia: Modulation of Brain Networks and Language

TMS 在原发性进行性失语症中的应用：大脑网络和语言的调节

• 批准号: 10556429
• 负责人: Alexandra Touroutoglou
• 金额: $ 16.34万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10556429
• 关键词: Affect; Alzheimer' s disease related dementia; Aphasia; Atrophic; Behavior; Behavior assessment; Behavioral; Brain; Brain imaging; Case Study; Cephalic; Clinical; Clinical Research; Clinical Trials; Communication; Communities; Crossover Design; Data; Deterioration; Diffusion Magnetic Resonance Imaging; Double-Blind Method; Effectiveness; Frequencies; Functional Magnetic Resonance Imaging; Future; General Hospitals; Goals; Intervention; Language; Left; Magnetic Resonance Imaging; Massachusetts; Measures; Mentors; Mission; Modeling; Names; National Institute on Deafness and Other Communication Disorders; Nerve Degeneration; Neurodegenerative Disorders; Neuropsychology; Outcome; Patients; Performance; Placebos; Prefrontal Cortex; Primary Progressive Aphasia; Progressive Nonfluent Aphasias; Research; Resources; Rest; Sample Size; Sampling; Semantics; Site; Strategic Planning; Symptoms; Syndrome; System; Techniques; Testing; Time; Training; Variant; Work; analytical method; brain volume; career; cognitive ability; cognitive task; efficacy evaluation; experimental study; follow-up; gray matter; improved; improved outcome; insight; language impairment; medical schools; neural; neuromechanism; neuroregulation; novel; predictive marker; programs; repetitive transcranial magnetic stimulation; stroke-induced aphasia; tool; treatment optimization; treatment response; white matter

SUMMARY The proposed research examines the potential benefits of non-invasive repetitive transcranial magnetic stimulation (rTMS) to behavior and language neurocircuit in patients with Primary Progressive Aphasia (PPA), usually an aphasic variant of Alzheimer's disease and related disorders (ADRD). A long-term goal of the research program is to deploy rTMS interventions for treatment of PPA. The proposal builds upon preliminary evidence showing that rTMS to dorsolateral prefrontal cortex improves language abilities in patients with PPA. The first aim is to replicate and extend the effects of rTMS on language in PPA. The second aim is to assess these effects in different subtypes of PPA and determine which subtype or subtypes are more likely to benefit from rTMS to dorsolateral prefrontal cortex. Training for these aims will develop the candidate's expertise in using rTMS and neuropsychological tools for clinical research in patients with PPA. Short-term goals include obtaining expertise in language assessments and longitudinal analytic methods that will further the candidate's long-term goal of assessing the efficacy of rTMS to induce durable effects in PPA. The third aim is to examine the neural mechanism of action of rTMS by measuring the effects of rTMS on functional connectivity of the brain's language network. Training for this aim will extend the candidate's expertise beyond imaging brain networks into modulating them for clinical benefits in PPA. Training for this aim will additionally develop the candidate's expertise in morphometric analyses to quantify and control for the effect of gray and white matter loss in PPA. All aims will be obtained by new data collected in the proposed project. Training available at Massachusetts General Hospital and Harvard Medical School community allows access to resources and mentors and advisors in the many techniques necessary to the aims of the candidate's training and career goals. rTMS over the dorsolateral prefrontal cortex will be administered in a single session and in consecutive 10 sessions. Language and other cognitive abilities will be measured with neuropsychological assessments. The language network functional connectivity will be measured using resting-state functional magnetic resonance imaging (rsfMRI). The brain volume and white matter integrity will be measured with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Using longitudinal data, the transient and durable effects of TMS on behavior and language network over time will be assessed. The relationship of rTMS-induced changes in language with changes in brain functional connectivity will be examined. If rsfMRI proves to be a reliable measure of neural change, it may prove to be a biomarker for predicting TMS treatment responsiveness. Completion of the aims will enhance our understanding of the behavioral and neuromodulatory mechanisms of rTMS and inform future trials that optimize treatments for PPA, in line with the NIDCD strategic plans on developing novel intervention strategies to improve outcomes in PPA.

总结 拟议的研究探讨了非侵入性重复经颅磁共振成像的潜在好处。 目的：观察经颅磁刺激（rTMS）对原发性进行性失语（PPA）患者行为和语言神经回路的影响， 通常是阿尔茨海默病和相关疾病（ADRD）的失语症变体。一个长期的目标， 研究计划是部署rTMS干预治疗PPA。该提案建立在初步 有证据表明，对背外侧前额叶皮层进行rTMS可以改善PPA患者的语言能力。 第一个目标是复制和扩展rTMS对PPA语言的影响。第二个目标是评估 这些影响在不同亚型的PPA，并确定哪些亚型或亚型更有可能受益 从rTMS到背外侧前额叶皮层针对这些目标的培训将培养候选人在以下方面的专门知识： 使用rTMS和神经心理学工具对PPA患者进行临床研究。短期目标包括 获得语言评估和纵向分析方法的专业知识，这将进一步提高候选人的 长期目标是评估rTMS在PPA中诱导持久效应的有效性。第三个目的是检查 通过测量rTMS对神经元功能连接的影响， 大脑的语言网络为这一目标进行的培训将使候选人的专业知识超越大脑成像 网络来调节它们以获得PPA的临床益处。为此目的进行的培训还将发展 候选人在量化和控制灰色和白色物质影响的形态分析方面的专业知识 PPA的损失。所有目标都将通过拟议项目中收集的新数据来实现。培训地点： 马萨诸塞州总医院和哈佛医学院社区允许访问资源， 导师和顾问在许多技术必要的候选人的培训和职业生涯的目标 目标.将在单次和连续治疗中对背外侧前额叶皮质进行rTMS 10个疗程。语言和其他认知能力将通过神经心理学评估进行测量。 语言网络的功能连接将使用静息态功能磁 共振成像（rsfMRI）。脑体积和白色物质完整性将通过结构性测量 磁共振成像（MRI）和扩散张量成像（DTI）。使用纵向数据， 将评估TMS对行为和语言网络随时间的持久影响。的关系 将检查rTMS诱导的语言变化与脑功能连接的变化。如果rsfMRI 被证明是神经变化的可靠测量，它可能被证明是预测TMS治疗的生物标志物 响应能力。完成这些目标将增强我们对行为和 rTMS的神经调节机制，并为未来优化PPA治疗的试验提供信息， NIDCD战略计划制定新的干预战略，以改善PPA的结果。

项目成果

Cingulate-centered large-scale networks: Normal functions, aging, and neurodegenerative disease.

• DOI: 10.1016/b978-0-444-64196-0.00008-x
• 发表时间: 2019
• 期刊: Handbook of clinical neurology
• 作者: Alexandra Touroutoglou;B. Dickerson

Topography of cortical thinning in the Lewy body diseases.

路易体疾病中皮质变薄的地形。

• DOI: 10.1016/j.nicl.2020.102196
• 发表时间: 2020
• 期刊: NeuroImage. Clinical
• 作者: Ye,Rong;Touroutoglou,Alexandra;Brickhouse,Michael;Katz,Samantha;Growdon,JohnH;Johnson,KeithA;Dickerson,BradfordC;Gomperts,StephenN
• 通讯作者: Gomperts,StephenN