Symposium Session 1: Neuronal Circuits and Computations Underlying Social Interactions

Friday, October 18, 8:00 - 9:15 am, West Pavilion Auditorium

Chair: Hamidreza Ramezanpour
Speakers: Norihiro sadato, Xiaosi Gu, Hamidreza Ramezanpour and Raymundo Baez-Mendoza


TALK 1: Across-Brain Networks Emerged from Face-to-Face Social Interactions Probed by Hyper-Scanning fMRI: Eye-Contact, Joint Attention, and its Memory.

Norihiro Sadato, MD, PhD, National Institute for Physiological Sciences (Okazaki, Japan)

Eye contact and joint attention (JA) are tightly coupled to generate the state of shared attention across individuals. Hyperscanning fMRI of eye contact that included on-line and delayed off-line conditions showed that recurrent interaction through eye contact activates the cerebellum and the limbic mirror system, including the anterior cingulate cortex and anterior insular cortex (AIC). Hyper-scanning fMRI during JA showed initiating JA related activation of the right AIC of the participant positively correlated with the responsive JA related activation of the homologous regions of the partner. This area was activated by volitional selection of the target during initiating JA. Thus the shared intention of a selection of the target during JA is represented by the inter-individual synchronization of the right AIC. Finally, the experience of JA was shown to leave its memory trace during a subsequent eye-contact condition as pair-specific neural synchronization of the right inferior frontal gyrus adjacent to the right AIC.  These results indicate that both limbic and parieto-premotor mirror systems and the cerebellum are involved in the real-time social interaction through the gaze, and that shared attention is represented and retained by pair-specific neural synchronization during mutual gaze that cannot be reduced to the individual level.

TALK 2: The Social Brain: Norms, Beliefs, and Model Based Influence.

Xiaosi Gu, Ph.D., Director, Computational Psychiatry Unit
Assistant Professor, Psychiatry & Neuroscience
Principal Investigator, Friedman Brain Institute & Addiction Institute, Icahn School of Medicine at Mount Sinai

To maintain the normal functioning of a society, individuals are generally expected to adapt to ‘external’ norms, or the collective behaviors of social others. In some occasions, however, individuals might also be able to influence social others and cause them to change their behaviors. In this talk, I will present our recent neurocomputational work that attempts to model 1) how humans adapt their ‘internal’ norms when others’ behaviors are not changeable and 2) how individuals can manage to influence others through model-based and future-oriented thinking.  Taken together, these findings reveal the dynamic nature of human interactions and the importance of model-based planning in strategic social exchange.

TALK 3: Decoding of the Other's Focus of Attention by a Temporal Cortex Module.

Hamidreza Ramezanpour, Cognitive Neurology Department
Hertie Institute for Clinical Brain Research
University of Tübingen, Germany

Faces attract the observer´s attention towards objects and locations of interest for the other, thereby allowing the two agents to establish joint attention. Previous work has delineated a network of cortical “patches” in the macaque cortex, processing faces, eventually also extracting information on the other´s gaze direction. Yet, the neural mechanism that links information on gaze direction, guiding the observer´s attention to the relevant object has remained elusive. Here we present electrophysiological evidence for the existence of a distinct “gaze-following patch (GFP)” with neurons that establish this linkage in a highly flexible manner. The other´s gaze and the object, singled out by the gaze, are linked only if this linkage is pertinent within the prevailing social context. The properties of these neurons establish the GFP as a key switch in controlling social interactions based on the other´s gaze.

TALK 4: Prefrontal Mechanisms for Tracking Group Behavior, Reputation, Conformity, and Identity in Monkeys and Mice.

Raymundo Baez-Mendoza, Department of Neurosurgery, Massachusetts General Hospital & Harvard Medical School, Boston, MA

Behavior within groups is unique: an individual’s actions can affect other individuals’ fitness directly or indirectly, through reputation and indirect reciprocity, or conformity. To explore the neuronal mechanisms of group behavior, we performed two series of studies. In one, a triad of macaques performed a structured reciprocity-based social task in which one individual could offer a food reward to one of the other two. In the other, a triad of mice foraged for food simultaneously while we surreptitiously introduced confederate mice to induce bias in the focal mice away or towards a food patch. We recorded neuronal activity from the PFC during task performance in both species. Monkeys demonstrated a strategic preference for other individuals. Distinct subpopulations of dACC neurons tracked the identity of the current actor and reward recipient. In contrast, frontopolar neurons correlated with the current actor’s reputation for reciprocity. dmPFC neurons of foraging mice encoded features that defined the animals’ collective behavior. These neurons reflected the group’s joint decisions, the consensus among their members, and shared success. Together, these studies highlight the role of different prefrontal areas in the mammalian brain play in group behavior and lay the groundwork for studying the neuronal mechanisms of group behavior.

Symposium Session 2: Neural Mechanisms Underlying Social Decision-Making Across Species

Friday, October 18, 9:20 - 10:30 am, West Pavilion Auditorium

Chair: Patricia Lockwood
Speakers: Gül Dölen, Olga Dal Monte, Patricia Lockwood
and Marco Wittmann.


TALK 1: Social Reward: Developmental Mechanisms and Therapeutic Opportunities.

Gül Dölen, M.D., Ph.D., Assistant Professor in the Department of Neuroscience and Brain Science Institute, Wendy Klag Center

A critical period is a developmental epoch during which the nervous system is expressly sensitive to specific environmental stimuli that are required for proper circuit organization and learning. Recently we have discovered a novel critical period for social reward learning and demonstrated that a single dose of (+/-)-3,4-methylendioxymethamphetamine (MDMA) reopens this critical period. Moreover, our studies demonstrate that these effects are blocked by oxytocin receptor antagonists and recapitulated by optogenetic stimulation of oxytocinergic terminals in the nucleus accumbens (Nardou, et al. Nature, 2019). These studies have important implications for understanding the pathogenesis of disorders that respond to social influence or are the result of social injury, as well as reveal mechanisms underlying the therapeutic efficacy of psychedelics. 

TALK 2: Neural Circuits of Dynamic and Interactive Social Behaviors.

Olga Dal Monte, Department of Psychology, Yale University, New Haven, CT, US, Department of Psychology, University of Turin, Turin, Italy

Social behaviors are characterized by a series of dynamic decisions and actions involving at least two individuals. Accumulating evidence suggests that oscillatory coordination between cortical and subcortical brain regions regulate a wide range of social functions. However, it remains unknown whether and how cells from distinct nodes in the social brain network coordinate activity in specialized manners during real-life social behaviors. I will discuss the progress made from two lines of research focusing on the neuronal coordination between the prefrontal cortex and the amygdala involved in social decisionmaking and social gaze interaction between pairs of rhesus macaques. During social decision-making, prosocial and antisocial decision preferences were differentiated by frequency-specific and direction-selective synchronization of spikes and local field potential activity between the rostral anterior cingulate gyrus (ACCg) and the basolateral amygdala (BLA). During social gaze interaction, in which many cells from multiple prefrontal areas and BLA signaled various social gaze events, distinct inter-areal synchrony patterns relating spiking and local field potential activity were also observed across the prefrontal areas and the BLA. Together, these findings support the notion that specialized coordination between the primate amygdala and the prefrontal areas shape complex social behaviors.

TALK 3: Neural signatures of model-free learning when avoiding harm to self and other 

Patricia Lockwood, Medical Research Council Fellow, Junior Research Fellow, Christ Church College, Lecturer in Psychology, Corpus Christi College, Wellcome Centre for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford

Moral behaviour requires learning how our actions help or harm others. Theoretical accounts of learning propose a key division between ‘model-free’ algorithms that efficiently cache outcome values in actions and ‘model-based’ algorithms that prospectively map actions to outcomes, a distinction that may be critical for moral learning. Here, we tested the engagement of these learning mechanisms and their neural basis as participants learned to avoid painful electric shocks for themselves and a stranger. We found that model-free learning was prioritized when avoiding harm to others compared to oneself. Model-free prediction errors for others relative to self were tracked in the thalamus/caudate at the time of the outcome. At the time of choice, a signature of model-free moral learning was associated with responses in subgenual anterior cingulate cortex (sgACC), and resisting this model-free influence was predicted by stronger connectivity between sgACC and dorsolateral prefrontal cortex. Finally, multiple behavioural and neural correlates of model-free moral learning varied with individual differences in moral judgment. Our findings suggest moral learning favours efficiency over flexibility and is underpinned by specific neural mechanisms. 

TALK 4: Social Influences on Performance Learning in Medial Prefrontal Cortex.

Marco Wittmann, University of Oxford

Humans have to track the success of their actions for survival. However, in a social world, we not only have to monitor our own performance, but also the performance of other people. Here we show using functional magnetic resonance imaging, that dorsomedial prefrontal area 9, an area typically involved in mentalizing, tracks the performance of others. In addition, it encodes information about the relationship between oneself and others (cooperation or competition), and also one’s own performance success. Importantly, the presence of self-related signals in area 9 was crucial for how area 9 monitored other’s performance. Knowledge about one’s own performance spread to how well participants judged others. This resulted in estimating other people as more similar to oneself in cooperative relationships, but more dissimilar to oneself in competitive relationships. In a second study we show that transcranial magnetic stimulation to area 9 enhances this bias, causing judgements of other’s performance to me even more merged with knowledge about one’s own. These findings highlight a key role for area 9 in monitoring other’s performance and suggest it operates in an implicit self-centred frame of reference.

Symposium Session 3: Role of Contextual and Individual Factors in Modulating Stress Reactivity Across Species.

Friday, October 18, 12:15 - 1:25 pm, West Pavilion Auditorium

Chair: Janelle Beadle
Speakers: Stuart White, Adam Smith, Janelle Beadle
and Rosemary Strasser.

White, Stuart.jpg

TALK 1: Testosterone Reactivity Following a Social Challenge Influences the Neural Correlates of Emotion Regulation in Healthy Adolescents.

Stuart White, Ph.D., Assistant Professor, Boys Town National Research Hospital

Hormonal changes assist an organism in adapting to contexts. With respect to behavior, hormones accomplish this by modulating neural activity. This is true both with respect to both basal levels of hormones, but also with respect to moment-to-moment changes in hormones. The role of moment-to-moment hormone changes in modulating behavior remain under-studied. The first study investigates how acute testosterone change modulates the neural systems underpinning emotion regulation in typically developing adolescents. Greater moment-to-moment testosterone reactivity following a social challenge paradigm was associated with increased activation within posterior cingulate and parietal cortices in response to emotional versus neutral stimuli. In other words, greater increases in testosterone response to social challenge was associated with increased response to salient (emotional) relative to neutral stimuli within attentional control regions. This is consistent with the putative role of testosterone in boosting the salience for short-term, immediate information at the expense of more future-oriented information.

TALK 2: Oxytocin Induces Reverse Susceptibility to Social Defeat Stress in a Sex-Specific Manner.

Adam Smith, Ph.D., Assistant Professor, Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, Kansas, USA

While there are advantages to social living, social conflict represents a form of encounters which can produce negative outcomes. People who repeatedly experience bullying, rejection, or abuse are more prone to developing social anxiety and aversion to common social situations. Social defeat stress is an animal model of social conflict that reliably induces a social avoidance phenotype and offers an opportunity to explore the neurobiology underlying social anxiety. Here, we demonstrated that social defeat in male and female prairie voles (Microtus ochrogaster) cultivated a social aversion that persisted for at least eight weeks. Receptor autoradiography in limbic regions illustrated restricted oxytocin receptor binding in defeated females which was not observed in males. By contrast, serotonin 1a receptor binding was reduced in defeated males in amygdala and raphe nuclei, implicating 5-HT1a heteroreceptor and autoreceptor sensitivity. Oxytocin and paroxetine were used to alleviate social anxiety in defeated males and females. Intranasal oxytocin treatment reversed susceptibility in females, promoting oxytocin receptor expression and social interactions during novel encounters. Neither treatment was successful in fully eliminating defeat effects in males. These data indicate that oxytocin and serotonin systems, two neurochemical systems which regulate social behavior, are sensitive to defeat experience, divergently in females and males.

TALK 3: Cortisol Reactivity and Prosocial Decision Making in Older Caregivers.

Janelle Beadle, Ph.D., Assistant Professor, Department of Gerontology, University of Nebraska at Omaha

It is well-established that providing care to older adults with chronic conditions can be highly stressful due to the many emotional and physical challenges experienced by caregivers. However, it is not known how the social context of caregiving can affect older adults’ hormones, emotion, and decision making in response to acute emotional situations. We examine how the caregiving context affects older adults’ hormonal, emotional, and decision making responses to an emotionally relevant situation; specifically, an empathy induction in which participants’ learn about the suffering of another person. We find that in response to the empathic context, older caregivers show a negative relationship between acute cortisol reactivity and prosocial decision making, such that greater monetary donation in response to the empathic context is associated with a decrease in cortisol levels. Therefore, the findings suggest that the caregiving context is associated with differences in stress reactivity and prosocial behavior that have broader implications for our understanding of the hormonal mechanisms of stress and social decision making in older adults.

TALK 4: Cortisol Synchrony and Stress Buffering in Dog-Owner Dyads.

Rosemary Strasser, Ph.D., Associate Professor, Department of Psychology, University of Nebraska at Omaha

Social bonds play an important role in regulating the physiological processes involved in stress coping. Formation and maintenance of social bonds in many species are essential for normal social development, and are inherently tied to physiological processes. Attachments are a special type of affectional relationship that emerge as a means of maintaining security and reducing arousal. The dog-owner relationship exhibits many of the behavioral features unique to an attachment bond: proximity maintenance and contact-seeking with the attachment figure, thus making them a good model species for understanding the physiological basis for social bond formation. We have found evidence that dogs show cortisol synchrony with their owners and that these social interactions can have a stress buffering effect. Further, physiological responsiveness in dogs can be impacted by the quality of the attachment bond, the level of engagement (pet, therapy dogs, and performance dogs), and well as owner personality. Therefore, the findings support the idea that dogs form interspecific social bonds with humans which could provide a valid model for studying social bond formation and maintenance due to shared environment.

Symposium Session 4: New Perspectives on the Neurochemical Bases of Social and Non-Social Stress Relief.

Friday, October 18, 3:35 - 4:20 pm, West Pavilion Auditorium

Chair: Siri Leknes
Speakers: James Burkett, Leah Mayo, Matt Hill
and Siri Leknes


TALK 1: Vicarious Distress and Consolation in Prairie Voles as a Model of Empathy.

James Burkett, Emory University, USA

The scientific study of empathy is an emerging topic of great interest, and animal models of empathy hold significant promise as outcome measures relevant to autism research. Empathy for the pain and suffering of others is widespread among social animals and can provide a motivation for prosocial behaviors, including consolation. Oxytocin, which plays a significant role in social buffering of pain and distress, may also act in social observers to promote these prosocial behaviors. Here, we describe a definition-free approach to studying empathy using consoling behavior in the prairie vole (Microtus ochrogaster). Prairie voles respond consistently and selectively to stressed cagemates with an increase in pro-social grooming that provides social buffering. Prairie voles observing a stressed cagemate also match their anxiety-related behaviors, fear response, and stress hormone release, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused directly into this region abolishes the consoling response. Additionally, oxytocin receptor density in this region predicts the magnitude of the consoling response. Finally, we demonstrate how empathy-related behaviors in rodents can be used to assess autism phenotypes by discussing our experiments looking at behavioral and neurological effects of developmental toxin exposure in mice.

TALK 2: The Endocannabinoid System as a Novel Target for the Treatment of Stress-Related Psychopathologies: Evidence from Healthy and Clinical Human Populations.

Leah Mayo, Linköping University, Sweden

The endocannabinoid system is a neuromodulatory system regulating stress, emotion, and social behavior and has recently garnered interest as a potential therapeutic target. In particular, accumulating preclinical animal research suggests that enhancing endogenous cannabinoid signaling may serve as a novel pharmacotherapeutic treatment for stress- and affect-related psychiatric disorders. For the first time in humans, we show that pharmacologically enhancing the endocannabinoid ligand anandamide (AEA) via inhibition of its main degradative enzyme, fatty acid amide hydrolase (FAAH), produces advantageous effects in stress reactivity, emotion regulation, and social processing. Moreover, in a unique sample of adult patients with prospective assessment of childhood trauma exposure, we find that deficits in social and emotion processing are the mirror opposite of the advantages conferred via enhanced AEA signaling in healthy adults. Together, our data suggest that enhancing endogenous cannabinoid signaling may be ideally suited to treat trauma-related psychopathologies that are hallmarked by deficits in social and emotional processing.

TALK 3: Opioid Drug Relief of Social and Non-Social Stress in Humans: Implications for Addiction.

Siri Leknes, University of Oslo, Norway

Acute administration of opioid drugs relieves pain and physiological stress responses such as cortisol release. Opioid dependence is also closely associated with stress; laboratory or real-life stressors increase drug craving, and opioid drugs relieve the stress of impending or actual withdrawal symptoms. Opioid dependence often also leads to increased life stressors due to illicit drug use and related life style factors. Emerging clinical data from chronic pain patients suggests that opioid misuse is driven by a desire to relieve stress rather than pain relief. Somewhat surprisingly, little systematic data exists to support the notion that acute opioid drug administration relieves subjective stress in humans. I will review this literature, including new unpublished data on acute effects of pre-surgery opioid administration. Finally, I will discuss parallels and differences between the effects of acute and chronic opioid administration.