Neural Circuit Mechanisms Mediating TMS and Oxytocin Effects on Social Cognition

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 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.