Automatic Imitation in Comorbid PTSD & Alcohol Use Disorder and Controls: an RCT of Intranasal Oxytocin.

INTRODUCTION: Mimicking movements of others makes both the imitating and imitated partners feel closer. Oxytocin may increase focus on others and has been shown to increase automatic imitation in healthy controls (HC). However, this has not been replicated, and oxytocin's effects on automatic imitation have not been demonstrated in clinical populations. This study attempts to replicate effects on HC and examine effects on people with comorbid posttraumatic stress disorder and alcohol use disorder (PTSD-AUD). METHODS: Fifty-four males with PTSD-AUD and 43 male HC received three intranasal treatment conditions (placebo, oxytocin 20 International Units (IU), and oxytocin 40 IU) in a randomized order, across three separate testing days, as part of a double-blind, crossover parent study. At 135 min post-administration, each performed the imitation-inhibition task, which quantifies automatic imitation as the congruency effect (CE). After exclusions, the final analyzed data set included 49 participants with PTSD-AUD and 38 HC. RESULTS: In HC, oxytocin 20 IU demonstrated a statistically significant increase in CE, and 40 IU showed a trend-level increase. In PTSD-AUD, oxytocin did not significantly increase CE. Post-hoc analysis showed the PTSD-AUD group had higher CE than HC on placebo visits. DISCUSSION: Our data suggest PTSD-AUD is associated with higher automatic imitation than HC in the absence of oxytocin administration. We successfully replicated findings that oxytocin increases automatic imitation in HC. This demonstrates an unconscious motor effect induced by oxytocin, likely relevant to more complex forms of imitative movements, which have the potential to improve social connection. We did not find a significant effect of oxytocin on automatic imitation in PTSD-AUD. Future research should examine imitation in both sexes, at peak oxytocin levels, and on increasingly complex forms of imitation.

Sniff and mimic - Intranasal oxytocin increases facial mimicry in a sample of men.

The neuropeptide oxytocin (OT) has many potential social benefits. For example, intranasal administration of OT appears to trigger caregiving behavior and to improve the recognition of emotional facial expressions. But the mechanism for these effects is not yet clear. Recent findings relating OT to action imitation and to the visual processing of the eye region of faces point to mimicry as a mechanism through which OT improves processing of emotional expression. To test the hypothesis that increased levels of OT in the brain enhance facial mimicry, 60 healthy male participants were administered, in a double-blind between-subjects design, 24 international units (IUs) of OT or placebo (PLA) through nasal spray. Facial mimicry and emotion judgments were recorded in response to movie clips depicting changing facial expressions. As expected, facial mimicry was increased in the OT group, but effects were strongest for angry infant faces. These findings provide further evidence for the importance of OT in social cognitive skills, and suggest that facial mimicry mediates the effects of OT on improved emotion recognition.

Disruption of Epithalamic Left-Right Asymmetry Increases Anxiety in Zebrafish.

Differences between the left and right sides of the brain are found throughout the animal kingdom, but the consequences of altered neural asymmetry are not well understood. In the zebrafish epithalamus, the parapineal is located on the left side of the brain where it influences development of the adjacent dorsal habenular (dHb) nucleus, causing the left and right dHb to differ in their organization, gene expression, and connectivity. Left-right (L-R) reversal of parapineal position and dHb asymmetry occurs spontaneously in a small percentage of the population, whereas the dHb develop symmetrically following experimental ablation of the parapineal. The habenular region was previously implicated in modulating fear in both mice and zebrafish, but the relevance of its L-R asymmetry is unclear. We now demonstrate that disrupting directionality of the zebrafish epithalamus causes reduced exploratory behavior and increased cortisol levels, indicative of enhanced anxiety. Accordingly, exposure to buspirone, an anxiolytic agent, significantly suppresses atypical behavior. Axonal projections from the parapineal to the dHb are more variable when it is located on the right side of the brain, revealing that L-R reversals do not necessarily represent a neuroanatomical mirror image. The results highlight the importance of directional asymmetry of the epithalamus in the regulation of stress responses in zebrafish.

The influence of Oxytocin on automatic motor simulation.

Motor simulation is important for imitation, action understanding, and a wide range of social cognitive skills. Furthermore, the neuropeptide hormone Oxytocin (OT) has also been related to social information processing in humans, improving perception of social stimuli and increasing altruism and trust. Surprisingly, however, a direct link between OT and motor simulation has never been systematically investigated. The current study examined this question using the imitation-inhibition task, a paradigm used to investigate automatic imitation behaviour and motor simulation. In this task, participants carry out simple finger movements while observing irrelevant movements that either match (congruent condition) or do not match (incongruent condition) the instructed movements. In a double-blind, placebo-controlled design, male participants were administered either OT (N=24) or placebo (N=24), and subsequently performed the imitation-inhibition task. To ensure specificity of OT effects to imitative behaviour, participants additionally performed a Stroop colour-word interference task (adapted to optimize similarities with the imitation inhibition task) to rule out general effects on cognitive control. As predicted, OT selectively influenced the congruency effect in the imitation-inhibition task but not the congruency effect in the Stroop task. This effect showed that OT led to a larger congruency effect by slowing down reaction times on incongruent trials when observed and own actions did not match. The findings suggest that OT leads to a decrease of control over automatic imitative behaviour mediated by increased self-other merging. Thus, for the first time, a link between OT and motor simulation is demonstrated, providing a window into the role of OT in motoric aspects of social cognition.

Inhaled oxytocin increases positive social behaviors in newborn macaques.

Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults--including expression recognition and affiliation--it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors--lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver--suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder.

From facial mimicry to emotional empathy: a role for norepinephrine?

Tendency to mimic others' emotional facial expressions predicts empathy and may represent a physiological marker of psychopathy. Anatomical connectivity between amygdala, cingulate motor cortex (M3, M4), and facial nucleus demonstrates a potential neuroanatomical substrate for mimicry, though pharmacological influences are largely unknown. Norepinephrine modulation selectively impairs negative emotion recognition, reflecting a potential role in processing empathy-eliciting facial expressions. We examined effects of single doses of propranolol (beta-adrenoceptor blocker) and reboxetine (selective norepinephrine reuptake inhibitor) on automatic facial mimicry of sadness, anger, and happiness, and the relationship between mimicry and empathy. Forty-five healthy volunteers were randomized to 40 mg propranolol or 4 mg reboxetine. Two hours after drug subjects viewed and rated facial expressions of sadness, anger, and happiness, while corrugator, zygomatic, and mentalis EMG were recorded. Trait emotional empathy was measured using the Balanced Emotional Empathy Scale. EMG confirmed emotion-specific mimicry and the relationship between corrugator mimicry and empathy. Norepinephrine modulation did not alter mimicry to any expression or influence the relationship between mimicry and empathy. Corrugator but not zygomaticus mimicry predicts trait empathy, consistent with greater anatomical connectivity between amygdala and M3 coding upper facial muscle representations. Although influencing emotion perception, norepinephrine does not influence emotional facial mimicry or its relationship with trait empathy.

Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference.

Previous findings demonstrate the involvement of the cholinergic NBM in the acquisition of the social transmission of food preference (STFP), a relational associative odor-guided learning task. There is also evidence that muscarinic receptors in the medial prefrontal cortex, an important NBM target area, may modulate olfactory associative memory. The present experiment determined the consequences of blocking muscarinic cholinergic receptors in a component of the medial prefrontal region (the prelimbic cortex) on the STFP task. Adult male Wistar rats were bilaterally infused with scopolamine (20 microg/site) prior to training and showed a severe impairment in the expression of the task measured in two retention sessions, both immediately and 24h after training. Local scopolamine injections in the prelimbic cortex did not affect other behavioral measures such as olfactory perception, social interaction, motivation to eat, neophobia, or exploration. Results suggest that muscarinic transmission in the prelimbic cortex is essential for the STFP, supporting the hypothesis that ACh in a specific prefrontal area is important for this naturalistic form of olfactory relational memory. Current data are discussed in the context of disruption of learning as a result of interferences in PLC functions such as behavioral flexibility, attention, and strategic planning.

Correlations between orbitofrontal dysfunction and tobacco smoking.

Orbitofrontal cortex is involved in various reward and reinforcement processes in the human brain. There is both anatomical and functional evidence for a dysfunction of orbitofrontal cortex in substance abusers, and nicotine has been shown to activate reward-related structures in the brain similarly to other abused drugs. This study shows positive correlations between smoking parameters (smoking status and packs smoked per day) and impairment on putative measures of orbitofrontal dysfunction (go/no-go, antisaccades, delayed alternation and impulsivity ratings). While causality could not be determined, other research suggests that an orbitofrontal dysfunction predisposes one toward tobacco abuse.

Imitation, social facilitation, and the effects of ACTH 4-10 on rats' bar-pressing behavior.

The effects of ACTH 4-10 on rats' imitation learning was examined during the acquisition and extinction of a bar-press response for water reinforcement. Rats were exposed to either a bar-pressing conspecific (OB), an experimentally naive conspecific (ON), or an empty box (OE) during bar-press acquisition. In a factorial design, each rat was then exposed to one of the same three conditions during extinction. An 80 mcg dose of ACTH 4-10 was administered to half of the rats in each group prior to observation. Performance differences during acquisition were generally small, but significant performance differences during extinction were found. Social facilitation was indicated by the finding that rats extinguished in the presence of a conspecific exhibited significantly greater resistance to extinction than rats extinguished in the presence of an empty box. An imitation effect was also found. Rats that observed a bar-pressing conspecific during both acquisition and extinction (group OB-OB) showed significantly greater resistance top extinction than did groups OB-ON, CB-OE, or OE-OE. There were no significant effects of the hormone, however, relative to saline controls.