14 Apr 2015
April 14, 2015. Among the symptoms of schizophrenia, impairments in social cognition—that special set of skills that helps us interact with others—may cause the most disability and loss of quality of life. In this meeting report on the topic from the International Congress on Schizophrenia Research, we combine a plenary talk summary from ICOSR Young Investigator travel awardee Urvakhsh Mehta of the National Institute of Mental Health and Neurosciences in Bangalore, India, with a related symposium report from SRF reporter Michele Solis.
The systems that make us social
In his Sunday, March 29, plenary talk, Michael Green of the University of California, Los Angeles, provided a synthesis of the last decade in social neuroscience research, which has arrived at four possible neural subsystems within the social brain that drive a range of social cognitive processes. He discussed various empirical studies employing neuroimaging and electroencephalography techniques that support the existence of these neural systems and also highlighted emerging evidence of their disruption in schizophrenia. He also deliberated on potential implications of studying these social brain neural systems in other brain disorders and translating this information to develop novel treatment strategies targeting social cognition deficits.
The social cue identification system subserves the processing of biological motion, facial emotions, affective prosody, and gestures. Neural regions include the fusiform gyrus (face identification), amygdala (emotional valence), and the posterior superior temporal sulcus (biological motion). Green presented fairly robust evidence of dysfunctional task-related brain activation in these regions in patients with schizophrenia. The experience sharing system comprises shared neural circuits that are active while observing as well as engaging in social situations. These include the motor resonance system (mirror neuron regions of the premotor cortex and inferior parietal lobule) and the affect sharing system (dorsal cingulate and anterior insula). Given the limited number of studies exploring these systems, it was noted that even though there was evidence indicating a dysfunction in these neural regions in schizophrenia, the data were inconsistent.
The mentalizing system, which plays a role in reflective thinking, involves the medial prefrontal cortex, temporoparietal junction, precuneus, and temporal pole—regions that clearly overlap with the default-mode network seen on resting-state functional brain imaging. Studies in schizophrenia have demonstrated either reduced or delayed activations in these networks during theory of mind tasks. The emotion regulation system influences expression of emotions within appropriate social contexts and includes brain regions that overlap with the amygdala and the ventral and dorsal lateral prefrontal cortices. Dysfunctional neural activity in these brain regions has regularly been demonstrated in schizophrenia.
A synchronized functioning of these four systems is considered to be necessary for empathic and adaptive pro-social behaviors, according to Green. He then discussed newer tasks to tap into coordinated functioning of these neural systems (e.g., the empathic accuracy task by Zaki and colleagues; Zaki et al., 2009) and their application in schizophrenia (Harvey et al., 2013). Social brain aberrations in varying degrees have been described in other disorders such as bipolar disorder, autism, frontotemporal dementia, personality disorders, and even traumatic brain injury and post-traumatic stress disorder. This overarching dimensional strategy not only provides an organizational framework to support future studies in schizophrenia, but also lends itself to a transdiagnostic Research Domain Criteria (RDoC)-like investigational approach. Lastly, the potential translational applications of utilizing these social brain systems as targets for novel treatment strategies were discussed. These go beyond conventional cognitive remediation strategies, to include intranasal oxytocin, novel pharmacotherapy, and neuromodulatory strategies.—Urvaksh Mehta.
Targeting social cognition deficits
Deficits in social cognition currently go largely untreated, and an afternoon symposium on Tuesday, March 31, was devoted to finding ways to boost social cognition. Stephen Marder of UCLA began with his recent results showing how combining social cognition training with a dose of oxytocin, a hormone that boosts affiliative feelings, leads to lasting gains in empathic accuracy, meaning how well a person gauges how another person feels, compared to training with placebo (Davis et al., 2014). Marder also presented new data suggesting that oxytocin influences specific neural systems, which gives some insight into how it works. For example, while watching biological motion, oxytocin led to more mu suppression, which is an EEG measure of the engagement of the mirror neuron system thought to mediate empathy. Oxytocin also led to less pupil dilation while viewing fearful images, suggesting that the hormone affected attention-allocating brain systems.
Mercedes Perez-Rodriguez of the Icahn School of Medicine at Mount Sinai, New York City, also found evidence for drug-induced facilitation of cognitive remediation training for mentalizing, which refers to deciphering the mental states of others. Missing social cues and focusing on the literal aspects of a conversation, people with schizophrenia and the milder schizotypal personality disorder (SPD) are impaired at mentalizing. Focusing on people with SPD because their social cognition impairments are not mixed up with effects of antipsychotic medications or negative symptoms, Perez-Rodriguez reported that the alpha2-adrenergic receptor agonist guanfacine combined with cognitive remediation training led to greater gains in mentalizing, as measured by their reactions to the Movie for the Assessment of Social Cognition (MASC), than those who had received a placebo plus training. Perez-Rodriguez also suggested that mentalizing could be taken too far—that distorted overinterpretations of another person's behavior could be just as impairing to social cognition and may affect those with borderline personality disorder. She is currently testing oxytocin to see if it may help normalize both surfeits and deficits in mentalizing.
Training up neural systems for social cognition may also help those at risk of psychosis, according to a presentation by Christine Hooker of Harvard University, Cambridge, Massachusetts. Building on previous work in schizophrenia (Hooker et al., 2013), Hooker showed that a 40-hour regimen of computerized training of both cognitive and social skills over four to eight weeks improved these skills in people at risk of developing psychosis. Brain scanning revealed discrete changes in the brain network subserving emotion recognition, including decreased activity in the amygdala and superior temporal sulcus (STS). This was accompanied by increases in correlated activity between the STS and the anterior cingulate cortex and medial prefrontal cortex—a measure of functional connectivity. An intervention's effect on functional connectivity may ultimately matter the most, she suggested, based on results from another study designed to train a person's ability to understand the mental states of others (Theory of Mind). This resulted in enhanced functional connectivity between the amygdala and other cortical regions, indicating that non-pharmacological interventions can rework brain circuits important for social cognition.
Dawn Velligan of the University of Texas Health and Science Center at San Antonio, Texas, presented results from a pilot study of a negative symptom intervention called MOtiVation Enhancement (MOVE) treatment. This is a home-based therapy designed to comprehensively address every aspect of negative symptoms. For example, therapists cued behavior at a person's home by using alarms or other reminders; reminded people of the pleasure they had at an outing; practiced skills in the neighborhood, such as going to a store; role played to practice social interactions; and delivered cognitive behavior therapy to address self-defeatist thinking. "We wanted to throw the kitchen sink at these negative symptoms to see if we would get some kind of effect," Velligan said. They did, but it took nine months: among people with persistent negative symptoms (who were, maybe not surprisingly, difficult to recruit), consisting of 26 receiving MOVE and 25 treatment as usual, those receiving MOVE showed a small improvement in motivation and social engagement. Velligan called it a small effect for a lot of effort and suggested that something such as oxytocin may prime the brain for larger improvements.—Michele Solis.