Neural Circuit Mechanisms Mediating TMS and Oxytocin Effects on Social Cognition

 描述(由申请人提供)：开发安全有效的新疗法来治疗神经精神障碍中受损的社会认知，包括自闭症谱系障碍(ASD)、边缘人格、精神分裂症和社交焦虑，是一个重要的优先事项。在这里，我们建议通过确定药物和磁操作如何影响假定的社会大脑网络中的神经生理动力学来评估和改进受损的社会认知的新治疗方法。鼻内催产素(OT)和经颅磁刺激(TMS)作为社会认知障碍的治疗手段前景广阔，但其神经基础以及安全性和有效性尚不清楚。我们将通过评估局灶性重复TMS(RTMS)和吸入OT对联合注意力、社会奖励/移情和战略社会认知的影响来解决这些问题，同时监测与社会认知有关的功能回路中的同步神经元活动。在人类中，社会认知部分是由包括颞顶交界区(TPJ)和前扣带回(ACCG)在内的回路介导的。然而，很难无创地确定在人类这一回路中调节社会认知的精确神经生理动力学，以及rTMS和OT对局部或跨回路神经元活动的影响。为了应对这一挑战，我们将使用新的复杂社会认知的灵长类动物模型，允许直接、同时研究OT和rTMS对神经回路动力学的影响，以及我们团队设计的新的TMS刺激器，允许同时对猴子进行神经调节和记录。猕猴表现出与人类相似的社会认知能力，这些功能与人类颞上沟(STS)和ACCG中推测的人类TPJ和ACCG同源物的神经元活动有关。首先，我们将记录STS和ACCG中的神经活动，以确定局部神经元放电、局部场电位、振荡神经动力学与社会认知之间的关系。我们将具体探索与社会注意、社会奖励/移情和战略性社会认知相关的神经活动模式。接下来，我们将确定吸入催产素如何影响STS和ACCG的社会注意、社会奖赏/移情、策略性社会认知以及并发神经元尖峰电位、局部场电位和振荡神经动力学。第三，我们将评估rTMS对STS的社会注意、社会奖赏/移情、策略性社会认知以及同时记录在STS和ACCG中的神经元尖峰电位、局部场电位和振荡神经动力学的影响。我们提出的研究承诺了新的知识，可能会改变我们理解和治疗受损的社会认知的方式。

 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.