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.

心理化的缺陷，这是一个高阶的社会认知过程，允许个人建立代表 他人的心态（例如情感和动机）并相应地调整自己的行为，是 假设强调自闭症谱系的核心社会交流异常 疾病（ASD）。我们的飞行员数据概述了一个专门的心理神经网络，其中包括模板 - 顶交界处（TPJ，包括后临时沟，PSTS），可以通过 重复的thrancranial磁刺激（RTMS）。这些数据表明，右TPJ/PST中的活动是 特别是通过心理过程调节的，并通过社会竞争力的fMRI多米诺骨牌任务证明 被诊断为ASD或精神分裂症的年轻人在这方面表现出与心理相关活动的减少 与通常开发的（TD）对照相比。但是，这种辩护与社会有关 仅在ASD中进行沟通技巧。这是专门调节的 对RTM的心理可能是对ASD核心防御的有效干预。有了这个建议，我们将 描述右TPJ的抑制性与兴奋性RTM的机械效应，特别是调节 与匹配的TD相比 （n = 40）年龄在18-35岁的个人，智商> 80。所有参与者将安排四个学习课程，包括 基线和三个随后的会话，每个会话将包括两个功能性磁共振成像 （fMRI）扫描，一个预先和一个后RTMS会话。在每次fMRI扫描中，参与者将参与 社交间，竞争性的多米诺骨牌任务，涉及心理化。我们的RTMS操纵，以A 双盲，平衡的时尚，包括一次兴奋性（间歇性theta-burst） 刺激，ITB），抑制（连续TBS，CTB）和假序列。 RTM将被引导 根据基线会话收集的结构MRI扫描计算得出的个性化电场建模。 这种可靠的设计对于确定最佳RTMS序列是必要的，以参与正确的TPJ和 ASD中的心理化网络是因为关于如何最好地调节该网络的固件结论不能是 从少数已知的已发表报告中得出。我们希望复制我们先前关于心理化的发现 网络具有正确的TPJ节点，将突出显示相对于TD参与者的ASD定义。另外，我们 假设ITB会导致增加，而CTB的MTR神经活动降低 网络，这在ASD中更为明显，而假手术没有改变。了解这一点 机制将是验证右TPJ的RTM的第一步，作为可行的神经目标 调节神经元电路，然后在未来的临床上调节ASD的社会通信技能 研究。在高流行率的背景下，应考虑这种研究的重要性 ASD的直接需求，需要制定有效的干预措施，尤其是对于成年人。