Neural Circuit Mechanisms Mediating TMS and Oxytocin Effects on Social Cognition

 描述（由申请人提供）：为神经精神障碍（包括自闭症谱系障碍（ASD）、边缘型人格、精神分裂症和社交焦虑）中的社会认知受损开发安全有效的新疗法是一项重要的优先事项。在这里，我们建议评估和完善新的治疗方法受损的社会认知，确定如何药理学和磁操纵影响神经生理学动力学在假定的社会脑网络。鼻内催产素（OT）和经颅磁刺激（TMS）作为社会认知受损的治疗方法有很大的希望，但它们的神经基础以及安全性和有效性却知之甚少。我们将通过评估局灶性重复经颅磁刺激（rTMS）和吸入OT对联合注意力，社会奖励/同理心和战略社会认知的影响来解决这些问题，同时监测在功能上涉及社会认知的电路中的并发神经元活动。在人类中，社会认知部分地由包括颞顶叶连接（TPJ）和前扣带皮层回（ACCg）的回路介导。然而，这是很难确定非侵入性的精确神经生理学动力学介导的社会认知在这个回路中的人类，以及rTMS和OT对神经元活动的影响本地或整个电路。为了应对这一挑战，我们将使用新的复杂的社会认知灵长类动物模型，允许直接，同时调查OT和rTMS对神经回路动力学的影响，以及我们小组设计的一种新的TMS刺激器，允许同时在猴子中进行神经调节和记录。恒河猴显示出与人类相似的社会认知，并且这些功能与上级颞沟（STS）和ACCG中人类TPJ和ACCG的推定同源物中的神经元活性相关。首先，我们将记录STS和ACCG的神经活动，以确定局部神经元尖峰，局部场电位，振荡神经动力学和社会认知之间的关系。我们将专门探讨与社会注意力，社会奖励/同理心和战略社会认知相关的神经活动模式。接下来，我们将确定吸入OT如何影响社会注意力，社会奖励/同理心，战略社会认知以及并发神经元尖峰，局部场电位，振荡神经动力学STS和ACCG。第三，我们将评估rTMS对STS的社会注意力，社会奖励/同情，战略社会认知和神经元尖峰，局部场电位，振荡神经动力学同时记录在STS和ACCG的影响。我们提出的研究承诺新的知识，可能会改变我们如何理解和治疗受损的社会认知。

 DESCRIPTION (provided by applicant): Developing safe and effective new treatments for impaired social cognition in neuropsychiatric disorders, including autism spectrum disorders (ASD), borderline personality, schizophrenia, and social anxiety, is an important priority. Here we propose to evaluate and refine new treatments for impaired social cognition by determining how pharmacological and magnetic manipulations affect neurophysiological dynamics in the putative social brain network. Intranasal oxytocin (OT) and transcranial magnetic stimulation (TMS) hold great promise as therapies for impaired social cognition, yet their neuronal bases, as well as safety and effectiveness, are poorly understood. We will address these questions by assessing the impact of focal repetitive TMS (rTMS) and inhaled OT on joint attention, social reward/empathy, and strategic social cognition, while monitoring concurrent neuronal activity in a circuit functionally implicated in social cognition. In humans, social cognition is mediated, in part, by a circuit including the temporal parietal junction (TPJ) and anterior cingulate cortex gyrus (ACCg). Nevertheless, it is difficult to determine noninvasively the precise neurophysiological dynamics mediating social cognition in this circuit in humans, as well as the impact of rTMS and OT on neuronal activity locally or across the circuit. To address this challenge, we will use new primate models of complex social cognition permitting direct, simultaneous investigation of the effects of OT and rTMS on neural circuit dynamics, and a new TMS stimulator designed by our group that permits simultaneous neuromodulation and recording in monkeys. Rhesus macaques display social cognition similar to that of humans and these functions are linked to neuronal activity in putative homologs of human TPJ and ACCg in the superior temporal sulcus (STS) and ACCg. First, we will record neural activity in STS and ACCg to determine the relationships between local neuronal spiking, local field potentials, oscillatory neural dynamics and social cognition. We will specifically probe neural activity patterns associated with social attention, social reward/empathy, and strategic social cognition. Next, we will determine how inhaled OT affects social attention, social reward/empathy, and strategic social cognition as well as concurrent neuronal spiking, local field potentials, and oscillatory neural dynamics in STS and ACCg. Third, we will assess the effects of rTMS to STS on social attention, social reward/empathy, and strategic social cognition and neuronal spiking, local field potentials, and oscillatory neural dynamics recorded concurrently in STS and in ACCg. Our proposed studies promise new knowledge that may transform how we understand and treat impaired social cognition.