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.

Public Health Relevance

Individuals with autism spectrum disorders (ASD) share core deficits in social interaction. These deficits could be further characterized in difficulties associated with social perception, social reward, and social skill. Here we propose to study how two promising therapeutic interventions aimed to enhance social functions in ASD - intranasal oxytocin therapy and noninvasive brain stimulation - influence neuronal dynamics in the brain. We will use our animal models of social perception, social reward, and social skill to discover how these therapies affect neuronal signals from key brain areas to enhance overall and specific social functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH109728-05
Application #
9883645
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Simmons, Janine M
Project Start
2016-04-20
Project End
2021-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Neurosciences
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Jiang, Yaoguang; Platt, Michael L (2018) Oxytocin and vasopressin increase male-directed threats and vocalizations in female macaques. Sci Rep 8:18011
Jiang, Yaoguang; Platt, Michael L (2018) Oxytocin and vasopressin flatten dominance hierarchy and enhance behavioral synchrony in part via anterior cingulate cortex. Sci Rep 8:8201
Tremblay, S├ębastien; Sharika, K M; Platt, Michael L (2017) Social Decision-Making and the Brain: A Comparative Perspective. Trends Cogn Sci 21:265-276
Rosati, Alexandra G; Arre, Alyssa M; Platt, Michael L et al. (2016) Rhesus monkeys show human-like changes in gaze following across the lifespan. Proc Biol Sci 283:
Platt, Michael L; Seyfarth, Robert M; Cheney, Dorothy L (2016) Adaptations for social cognition in the primate brain. Philos Trans R Soc Lond B Biol Sci 371:20150096
Delgado, Mauricio R; Beer, Jennifer S; Fellows, Lesley K et al. (2016) Viewpoints: Dialogues on the functional role of the ventromedial prefrontal cortex. Nat Neurosci 19:1545-1552
Watson, Karli K; Miller, Stephanie; Hannah, Eleanor et al. (2015) Increased reward value of non-social stimuli in children and adolescents with autism. Front Psychol 6:1026
Chang, Steve W C; Fagan, Nicholas A; Toda, Koji et al. (2015) Neural mechanisms of social decision-making in the primate amygdala. Proc Natl Acad Sci U S A 112:16012-7
Drucker, Caroline B; Carlson, Monica L; Toda, Koji et al. (2015) Non-invasive primate head restraint using thermoplastic masks. J Neurosci Methods 253:90-100