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

心智化缺陷，一种高阶社会认知过程，允许个人建立对 他人的心理状态（如情绪和动机），并相应地调整自己的行为， 假设强调了自闭症谱系特征的核心社会沟通异常， 自闭症（ASD）我们的试验数据概述了一个专门的心智化神经网络，包括时间- 顶骨交界处（TPJ，包括后上级颞沟，pSTS），可以用 重复经颅磁刺激（rTMS）。这些数据表明，右TPJ/pSTS中的活性是 特别是由心理化过程调制，用社会竞争性功能磁共振成像多米诺骨牌任务探测， 被诊断为ASD或精神分裂症的年轻人在这一过程中表现出与心理化相关的活动减少。 与典型开发的（TD）对照相比。然而，这一赤字与社会 只有在ASD的沟通技巧。因此，特异性地调节 用rTMS进行心理治疗可能是对ASD核心缺陷的有效干预。根据这项建议，我们将 描述右TPJ的抑制性与兴奋性rTMS的机制效应，特别是在调节 与匹配的TD相比，诊断为ASD的成人（N=40）的心理化任务相关（MTR）神经活动 （N=40）年龄18-35岁且IQ>80的个体。所有参与者将被安排参加四个学习课程，包括 一个基线和三个后续会议，每个会议将包括两个功能磁共振成像 （fMRI）扫描，一个在rTMS会话之前，一个在rTMS会话之后。在每次fMRI扫描期间，参与者将参与 一种涉及心智化的社会间竞争性多米诺骨牌任务。我们的rTMS操作，在一个 双盲、平衡方式，包括兴奋性（间歇性θ-爆发） 刺激，iTBS）、抑制（连续TBS，cTBS）和假序列。rTMS将遵循以下指导原则： 根据基线阶段收集的结构MRI扫描计算的个体化电场建模。 这种稳健的设计对于识别最佳rTMS序列以接合正确的TPJ和合适的TPJ是必要的。 在ASD中将网络精神化，因为关于如何最好地调节该网络的确定结论无法 从已知的几份已发表的报告中提取。我们希望复制我们之前的发现， 网络，具有右TPJ节点，其将突出ASD相对于TD参与者的不足。另外我们 假设iTBS会导致MTR神经活动的增加，而cTBS则会导致MTR神经活动的减少 网络，这在ASD中更加明显，而假的则没有变化。理解这一 这一机制将是验证右TPJ的rTMS作为可行的神经靶点的第一步，也是关键的一步。 调节神经回路，并随后在未来的临床上调节ASD的社交技能 问题研究这一系列研究的意义应在高患病率的背景下考虑 ASD的发病率以及开发有效干预措施的迫切需要，特别是针对成年人。

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.