Modulating Temporoparietal Junction Mentalizing-Related Activity in Autism Spectrum Disorder using Transcranial Magnetic Stimulation

使用经颅磁刺激调节自闭症谱系障碍的颞顶交界心智化相关活动

• 批准号: 10735987
• 负责人: Michal Assaf
• 金额: $ 78.69万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735987
• 关键词: Adult; Affect; Age; Area; Behavior; Behavior Therapy; Bilateral; Brain; Brain region; Characteristics; Clinical Research; Data; Diagnosis; Double-Blind Method; Emotions; Functional Magnetic Resonance Imaging; Future; High Prevalence; Impairment; Individual; Investigation; Left; Life; MRI Scans; Medial; Methods; Mind; Modeling; Motivation; Participant; Patient Self-Report; Patients; Prefrontal Cortex; Process; Publishing; Reporting; Research; Rest; Role; Sampling; Scanning; Schedule; Schizophrenia; Social Behavior; Social Interaction; Structure of superior temporal sulcus; Symptoms; Transcranial magnetic stimulation; Treatment Efficacy; adult with autism spectrum disorder; autism spectrum disorder; cingulate cortex; cognitive process; design; effective intervention; effectiveness evaluation; electric field; functional MRI scan; individuals with autism spectrum disorder; mental representation; mentalization; neural; neural circuit; neural network; neuromechanism; noninvasive brain stimulation; recruit; repetitive transcranial magnetic stimulation; side effect; skills; social; social cognition; social communication; social deficits; success; theories; young adult

Deficits in mentalizing, a high-order social cognitive process that allows individuals to build representations of others’ state of mind (e.g. emotions and motivation) and adjust their own behaviors accordingly, are hypothesized to underline the core social communication abnormalities that characterize autism spectrum disorder (ASD). Our pilot data outline a specialized mentalizing neural network that includes the temporo- parietal junction (TPJ, including the posterior superior temporal sulcus, pSTS), that can be modulated with repetitive transcranial magnetic stimulation (rTMS). These data show that the activity in the right TPJ/pSTS is specifically modulated by mentalizing processes, probed with a social-competitive fMRI Domino task, and that young adults diagnosed with either ASD or schizophrenia show decreased mentalizing related activity in this region compared to typically developed (TD) controls. However, this deficit is associated with social communication skills only in ASD. Thus, specifically modulating the underlying neural mechanisms of mentalizing with rTMS could be an effective intervention for this core deficit in ASD. With this proposal, we will delineate the mechanistic effects of inhibitory vs. excitatory rTMS of the right TPJ, specifically in modulating mentalizing task-related (MTR) neural activity in adults diagnosed with ASD (N=40) compared to matched TD (N=40) individuals ages 18-35 with IQ>80. All participants will be scheduled for four study sessions that include a baseline and three subsequent sessions that will each include two functional magnetic resonance imaging (fMRI) scans, one pre and one post an rTMS session. During each fMRI scan, participants will be engaged in intersocial, competitive Domino task that involves mentalizing. Our rTMS manipulation, administered in a double-blind, counterbalanced fashion, includes one session each of excitatory (intermittent theta-burst stimulation, iTBS), inhibitory (continuous TBS, cTBS), and sham sequences. The rTMS will be guided with individualized electric-field modeling calculated from a structural MRI scan collected on the baseline session. This robust design is necessary to identify the optimal rTMS sequence to engage the right TPJ and the mentalizing network in ASD because firm conclusions about how best to modulate this network cannot be drawn from the few known published reports. We expect to replicate our previous findings of a mentalizing network, with a right TPJ node, that will highlight deficits in ASD relative to TD participants. Also, we hypothesize that iTBS will result in increased, while cTBS in decreased MTR neural activity in the mentalizing network, with this being more pronounced in ASD, and sham resulting in no change. Understanding this mechanism will be the first and crucial step in validating rTMS of the right TPJ as a viable neural target to modulate neural circuit, and subsequently to modulate social-communication skills in ASD in future clinical studies. The significance of such a line of research should be considered in the context of the high prevalence of ASD and the dire need of developing effective interventions, especially for adults.

心智化的缺陷，心智化是一种高阶社会认知过程，允许个人建立对事物的表征 他人的心态（例如情绪和动机）并相应地调整自己的行为，是 剥离以强调自闭症谱系特征的核心社交沟通异常 我们的试验数据概述了一个专门的心智化神经网络，其中包括时间- 顶叶交界处（TPJ，包括颞上沟，pSTS），可以通过以下方式调节 重复经颅磁刺激 (rTMS) 这些数据表明右侧 TPJ/pSTS 的活动是 通过心理化过程进行专门调节，并通过社会竞争性功能磁共振成像多米诺任务进行探测，并且 被诊断患有自闭症谱系障碍或精神分裂症的年轻人在这方面表现出与心智化相关的活动减少 然而，这种缺陷与社会相关。 因此，只有在自闭症谱系障碍中，才能专门调节潜在的神经机制。 利用 rTMS 进行心理化可能是针对自闭症谱系障碍这一核心缺陷的有效干预措施。 描述右侧 TPJ 的抑制性与兴奋性 rTMS 的机械效应，特别是在调节方面 与匹配的 TD 相比，被诊断为 ASD 的成人 (N=40) 心智化任务相关 (MTR) 神经活动 (N=40) 18-35 岁且智商>80 的个人 所有参与者将被安排参加四次学习课程，其中包括。 基线和三个后续会话，每个会话将包括两次功能磁共振成像 (fMRI) 扫描，一次 rTMS 扫描前和一次 rTMS 扫描后 在每次 fMRI 扫描期间，参与者将参与其中。 涉及心理化的跨社会、竞争性多米诺骨牌任务。 双盲、平衡方式，包括兴奋性（间歇性 θ 爆发）各一次 rTMS 将由刺激、iTBS）、抑制（连续 TBS、cTBS）和假序列引导。 根据基线会话中收集的结构 MRI 扫描计算出的个性化电场模型。 这种稳健的设计对于确定最佳 rTMS 序列以接合正确的 TPJ 和 自闭症谱系障碍中的心智化网络，因为无法得出关于如何最好地调节该网络的确切结论 我们希望复制我们之前关于心智化的发现。 网络，具有正确的 TPJ 节点，这将突出 ASD 相对于 TD 参与者的缺陷。 iTBS 越来越多地导致心智化中 MTR 神经活动的增加，而 cTBS 则减少 网络，这在自闭症谱系障碍中更为明显，而假动作则不会导致理解这一点的改变。 机制将是验证正确 TPJ 的 rTMS 作为可行的神经目标的第一步也是关键的一步 调节神经回路，并随后在未来的临床中调节 ASD 的社交沟通技能 应在高患病率的背景下考虑此类研究的意义。 自闭症谱系障碍（ASD）的发展以及迫切需要制定有效的干预措施，特别是针对成年人。