Facial mimicry is not modulated by dopamine D2/3 and opioid receptor antagonism

Abstract Rationale According to theories of embodied cognition, facial mimicry — the spontaneous, low-intensity imitation of a perceived emotional facial expression — is first an automatic motor response, whose accompanying proprioceptive feedback contributes to emotion recognition. Alternative theoretical accounts, however, view facial mimicry as an emotional response to a rewarding stimulus, and/or an affiliative signal, and thus reject the view of an automatic motor copy. Objectives To contribute to this debate and further investigate the neural basis of facial mimicry, as well as its relation to reward processing, we measured facial reactions to dynamic happy and angry faces after pharmacologically manipulating the opioid and dopamine systems — respectively, thought to subserve ‘liking’ and ‘wanting’ of rewards. Methods In a placebo-controlled, double-blind experiment, 130 volunteers received in a between-subjects design 50 mg of the opioidergic antagonist naltrexone, 400 mg of the dopaminergic antagonist amisulpride, or placebo. Results Clear occurrence of facial mimicry, measured 4 h after drug intake with electromyography (EMG) of the zygomaticus major and corrugator supercilii muscles, was found. However, facial mimicry was not affected by either compound, as shown with both frequentist statistics, and a Bayesian asymptotic regression model. Conclusions This null finding does not support the hypothesis that facial mimicry (of happiness) reflects an emotional response to a rewarding stimulus, leaving open the possibility of facial mimicry being an automatic motor copy. The results are relevant to the discussion about the psychological nature and the neural basis of facial mimicry, although they should be considered preliminary, given the challenges of interpreting null findings when targeting a novel effect of unknown size. </jats:sec

Aberrant Effective Connectivity in Schizophrenia Patients during Appetitive Conditioning

It has recently been suggested that schizophrenia involves dysfunction in brain connectivity at a neural level, and a dysfunction in reward processing at a behavioral level. The purpose of the present study was to link these two levels of analyses by examining effective connectivity patterns between brain regions mediating reward learning in patients with schizophrenia and healthy, age-matched controls. To this aim, we used functional magnetic resonance imaging and galvanic skin recordings (GSR) while patients and controls performed an appetitive conditioning experiment with visual cues as the conditioned (CS) stimuli, and monetary reward as the appetitive unconditioned stimulus (US). Based on explicit stimulus contingency ratings, conditioning occurred in both groups; however, based on implicit, physiological GSR measures, patients failed to show differences between CS+ and CS− conditions. Healthy controls exhibited increased blood-oxygen-level dependent (BOLD) activity across striatal, hippocampal, and prefrontal regions and increased effective connectivity from the ventral striatum to the orbitofrontal cortex (OFC BA 11) in the CS+ compared to the CS− condition. Compared to controls, patients showed increased BOLD activity across a similar network of brain regions, and increased effective connectivity from the striatum to hippocampus and prefrontal regions in the CS− compared to the CS+ condition. The findings of increased BOLD activity and effective connectivity in response to the CS− in patients with schizophrenia offer insight into the aberrant assignment of motivational salience to non-reinforced stimuli during conditioning that is thought to accompany schizophrenia

Dopaminergic and opioidergic regulation during anticipation and consumption of social and nonsocial rewards

The observation of animal orofacial and behavioral reactions has played a fundamental role in research on reward but is seldom assessed in humans. Healthy volunteers (N = 131) received 400 mg of the dopaminergic antagonist amisulpride, 50 mg of the opioidergic antagonist naltrexone, or placebo. Subjective ratings, physical effort, and facial reactions to matched primary social (affective touch) and nonsocial (food) rewards were assessed. Both drugs resulted in lower physical effort and greater negative facial reactions during reward anticipation, especially of food rewards. Only opioidergic manipulation through naltrexone led to a reduction in positive facial reactions to liked rewards during reward consumption. Subjective ratings of wanting and liking were not modulated by either drug. Results suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, and also that the neurochemical bases for food and touch rewards are not identical

On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study.

Schizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of "endogenous" sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and positron emission tomography. Healthy volunteers (n = 28, 14 female) underwent a baseline and then a post-amphetamine scan before and after a mildly sensitizing regimen of repeated oral amphetamine. Unmedicated patients with first-episode psychosis (n = 21; 6 female) underwent a single pair of baseline and then post-amphetamine scans. Furthermore, T1 weighted magnetic resonance imaging of the prefrontal cortex was performed. Patients with first-episode psychosis showed larger release of dopamine compared to healthy volunteers. After sensitization of healthy volunteers their dopamine release was significantly amplified and no longer different from that seen in patients. Healthy volunteers showed a negative correlation between prefrontal cortical volume and dopamine release. There was no such relationship after sensitization or in patients. Our data in patients with untreated first-episode psychosis confirm the "endogenous sensitization" hypothesis and support the notion of impaired prefrontal control of the dopamine system in schizophrenia

Effect of morphine administration on human social motivation during stress

Physical social contact, such as grooming in primates or touch in humans, is fundamental to create and maintain social bonds. The Brain Opioid Theory of Social Attachment postulates that µ-opioids play a central role in social connection. Accordingly, pharmacological studies in isolated animals indicate that µ-opioid agonists reduce, and µ-opioid antagonists increase distress responses and motivation for social contact. Despite the abundance of animal studies, human evidence is still lacking. Here, we investigated the neurochemical basis of social motivation under stress in healthy human volunteers, following morphine (µ-opioid agonist) or placebo administration. By adopting a translational approach, real physical effort and facial hedonic reactions, together with self-reports of wanting and liking for social touch, were assessed. Preliminary results revealed increased adverse response to stress following morphine administration. In line with animal models and previous evidence in humans, this enhanced stress response led to increased motivation to obtain social touch

Making Sense of : Sensitization in Schizophrenia

Sensitization is defined as a process whereby repeated intermittent exposure to a given stimulus results in an enhanced response at subsequent exposures. Next to robust findings of an increased dopamine synthesis capacity in schizophrenia, empirical data and neuroimaging studies support the notion that the mesolimbic dopamine system of patients with schizophrenia is more reactive compared with healthy controls. These studies led to the conceptualization of schizophrenia as a state of endogenous sensitization, as stronger behavioral response and increased dopamine release after amphetamine administration or exposure to stress have been observed in patients with schizophrenia. These findings have also been integrated into the neurodevelopmental model of the disorder, which assumes that vulnerable neuronal circuits undergo progressive changes during puberty and young adulthood that lead to manifest psychosis. Rodent and human studies have made an attempt to identify the exact mechanisms of sensitization of the dopaminergic system and its association with psychosis. Doing so, several epigenetic and molecular alterations associated with dopamine release, neuroplasticity, and cellular energy metabolism have been discovered. Future research aims at targeting these key proteins associated with sensitization in schizophrenia to enhance the knowledge of the pathophysiology of the illness and pave the way for an improved treatment or even prevention of this severe psychiatric disorder.(VLID)458200