The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.

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Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine

https://diplopi.files.wordpress.com/2014/04/social-effects-of-oxytocin-in-humans-context-and-person-matter.pdf

Social effects of oxytocin in humans: context and person matter.

The Adaptive Calibration Model of stress responsivity.

Human empathy relies on the ability to share emotions as well as the ability to understand the other’s thoughts, desires, and feelings. Recent evidence points to 2 separate systems for empathy: an emotional system that supports our ability to empathize emotionally and a cognitive system that involves cognitive understanding of the other’s perspective. Converging evidence from neuroimaging and lesion studies shows that a neural network that includes the inferior frontal gyrus and the inferior parietal lobule is necessary for emotion recognition and emotional contagion. On the other hand, the involvement of the ventromedial prefrontal cortex, temporoparietal junction, and the medial temporal lobe in self-reflection and autobiographical memory places these key regions as necessary for cognitive empathy. The proposed dissociation between these systems is supported by recent neurochemical experiments involving administration of oxytocin as well as by ethological, psychiatric, and developmental studies. Finally...

The Neural Bases for Empathy

Given that we live in highly complex social environments, many of our most important decisions are made in the context of social interactions. Simple but sophisticated tasks from a branch of experimental economics known as game theory have been used to study social decision-making in the laboratory setting, and a variety of neuroscience methods have been used to probe the underlying neural systems. This approach is informing our knowledge of the neural mechanisms that support decisions about trust, reciprocity, altruism, fairness, revenge, social punishment, social norm conformity, social learning, and competition. Neural systems involved in reward and reinforcement, pain and punishment, mentalizing, delaying gratification, and emotion regulation are commonly recruited for social decisions. This review also highlights the role of the prefrontal cortex in prudent social decision-making, at least when social environments are relatively stable. In addition, recent progress has been made in understanding the neural bases of individual variation in social decision-making.

The Neuroscience of Social Decision-Making

Oxytocin (OT) is becoming increasingly established as a prosocial neuropeptide in humans with therapeutic potential in treatment of social, cognitive, and mood disorders. However, the potential of OT as a general facilitator of human learning and empathy is unclear. The current double-blind experiments on healthy adult male volunteers investigated first whether treatment with intranasal OT enhanced learning performance on a feedback-guided item-category association task where either social (smiling and angry faces) or nonsocial (green and red lights) reinforcers were used, and second whether it increased either cognitive or emotional empathy measured by the Multifaceted Empathy Test. Further experiments investigated whether OT-sensitive behavioral components required a normal functional amygdala. Results in control groups showed that learning performance was improved when social rather than nonsocial reinforcement was used. Intranasal OT potentiated this social reinforcement advantage and greatly increased emotional, but not cognitive, empathy in response to both positive and negative valence stimuli. Interestingly, after OT treatment, emotional empathy responses in men were raised to levels similar to those found in untreated women. Two patients with selective bilateral damage to the amygdala (monozygotic twins with congenital Urbach-Wiethe disease) were impaired on both OT-sensitive aspects of these learning and empathy tasks, but performed normally on nonsocially reinforced learning and cognitive empathy. Overall these findings provide the first demonstration that OT can facilitate amygdala-dependent, socially reinforced learning and emotional empathy in men.

https://www.jneurosci.org/content/jneuro/30/14/4999.full.pdf

Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans

Background. Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy of a beta-noradrenergic receptor blockade with propranolol in the alleviation of anxiety symptoms and the secondary prevention of post traumatic stress disorder, preclinical evidence for a beta-noradrenergic modulation of BLA activity in humans is missing. Method. We combined functional magnetic resonance imaging in healthy volunteers with probabilistic mapping of intra-amygdalar responses to fearful, neutral and happy facial expressions to test the hypothesis that a beta-noradrenergic receptor blockade with propranolol would inactivate the BLA. Results. Consistent with our a priori hypothesis, propranolol diminished BLA responses to facial expressions, independent of their emotional valence. The absence of activity changes in probabilistically defined visual control regions underscores the specific action of propranolol in the BLA. Conclusions. Our findings provide the missing link between the anxiolytic potential of propranolol and the biological basis of beta-noradrenergic activation in the human BLA as a key target for the pharmacological inhibition of anxiety neurocircuitry. Moreover, our findings add to emerging evidence that NE modulates both the reactivity (sensitivity) and the operating characteristics (specificity) of the BLA via beta-noradrenergic receptors.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/354A02D2D1C325175FE70EBAA5B09C44/S0033291709992376a.pdf/div-class-title-human-amygdala-reactivity-is-diminished-by-the-noradrenergic-antagonist-propranolol-div.pdf

Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol

Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no causative link between elevated NE neurotransmission and BLA hyperresponsiveness to fear signals has been established to date in humans. To determine whether or not increased noradrenergic tone enhances BLA responses to fear signals, we used functional magnetic resonance imaging (fMRI) and a strategy of pharmacologically potentiating NE neurotransmission in healthy volunteers. 18 subjects were scanned two times on a facial emotion paradigm and given either a single-dose placebo or 4 mg of the selective NE reuptake inhibitor reboxetine 2 h prior to an fMRI session. We found that reboxetine induced an amygdala response bias towards fear signals that did not exist at placebo baseline. This pharmacological effect was probabilistically mapped to the BLA. Extrapolation of our data to conditions of traumatic stress suggests that disinhibited endogenous NE signaling could serve as a crucial etiological contributor to post-traumatic stress disorder (PTSD) by eliciting exaggerated BLA responses to fear signals.

/pdf/noradrenergic-enhancement-of-amygdala-responses-to-fear-1zytdz2icl.pdf

Oezguer A. Onur

Papers

Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans

Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol

Noradrenergic enhancement of amygdala responses to fear