Oxytocin specifically enhances valence-dependent parasympathetic responses

The evolutionarily highly conserved neuropeptide oxytocin seems to be involved in the regulation of complex forms of social behavior. It enhances the processing of positive social stimuli, reduces behavioral and neuroendocrine stress responses and modulates amygdala activity in humans. Moreover, it has been proposed that oxytocin dampens sympathetic nervous system activity. This hypothesis was tested in a double-blind, placebo-controlled study with 38 men either receiving 24 IU oxytocin intranasally or a placebo spray. While accomplishing an emotion classification task, electrodermal responses were measured as an index of sympathetic activity. Moreover, heart rate changes were recorded that are additionally mediated by the parasympathetic nervous system. Oxytocin enhanced differential heart rate responses to facial expressions as a function of the emotional valence, but had no effect on electrodermal activity or tonic measures of physiological arousal. These results indicate that oxytocin specifically modulates phasic activity of the parasympathetic nervous system which potentially reflects an increased motivational value of facial expressions following oxytocin treatment. Findings suggest that anxiolytic effects of oxytocin are not reflected in short-term sympathetic responses and may even be a consequence of rather than a prerequisite for improved social information processing.     

Post-learning intranasal oxytocin modulates human memory for facial identity

The nanopeptide oxytocin has physiological functions during labour and lactation. In addition, oxytocin is known to modulate aggression, anxiety, social behaviour and cognition. Little is known about its effects on memory for emotional stimuli. In the present single-blind, placebo-controlled, randomised study we have investigated the short- and long-term effects of a single post-learning dose (20 IU) of intranasal oxytocin on memory for facial identity and expression in 36 healthy young females and males using a face portrait recognition test. In the acquisition phase of the test, 60 different male faces with happy, angry or neutral expressions were presented to the volunteers. Thirty minutes and 24h after oxytocin administration, recognition memory tests were performed using portraits with neutral facial expressions, only. Oxytocin improved identity recognition memory independently of participant's gender, for neutral and angry faces, whereas this effect was not present for happy faces. Oxytocin-treated subjects had a lower bias to judge not previously seen faces as being previously seen. Oxytocin had no effect on facial expression memory. In conclusion, oxytocin has distinct effects on memory performance for facial identity and may contribute to the modulation of social behaviour.     

Gender differences in oxytocin-associated disruption of decision bias during emotion perception

Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin?s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin?s effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocin?s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence women?s performance. These results suggest that oxytocin may impair men?s ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction.     

Oxytocin increases retention of social cognition in autism.

BACKGROUND: Oxytocin dysfunction might contribute to the development of social deficits in autism, a core symptom domain and potential target for intervention. This study explored the effect of intravenous oxytocin administration on the retention of social information in autism. METHODS: Oxytocin and placebo challenges were administered to 15 adult subjects diagnosed with autism or Asperger's disorder, and comprehension of affective speech (happy, indifferent, angry, and sad) in neutral content sentences was tested. RESULTS: All subjects showed improvements in affective speech comprehension from pre- to post-infusion; however, whereas those who received placebo first tended to revert to baseline after a delay, those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task. CONCLUSIONS: These results are consistent with studies linking oxytocin to social recognition in rodents as well as studies linking oxytocin to prosocial behavior in humans and suggest that oxytocin might facilitate social information processing in those with autism. These findings also provide preliminary support for the use of oxytocin in the treatment of autism.     

Oxytocin increases recognition of masked emotional faces

The neuropeptide oxytocin has been shown to improve many aspects of social cognitive functioning, including facial emotion recognition, and to promote social approach behaviour. In the present study, we investigated the modulatory effects of oxytocin on the recognition of briefly presented facial expressions. In order to diversify the degree of visual awareness for the facial stimuli, presentation duration was systematically varied. Fifty-six participants were administered intranasal oxytocin or a placebo in a double-blind, randomized, between-subjects design. Participants viewed angry and happy target faces or neutral distractors for 18, 35, or 53 ms subsequently masked by neutral faces. Participants had to indicate the presence or absence of the briefly presented target face. Discrimination indices (d') showed that oxytocin generally enhanced detection accuracy of emotional stimuli. This effect was more pronounced for the recognition of happy faces. We provide evidence that a single dose of intranasally administered oxytocin enhances detection of briefly presented emotional stimuli. The possible role of stimulus valence and recognition difficulty is discussed.     

Distributed and interactive brain mechanisms during emotion face perception: evidence from functional neuroimaging

Brain imaging studies in humans have shown that face processing in several areas is modulated by the affective significance of faces, particularly with fearful expressions, but also with other social signals such gaze direction. Here we review haemodynamic and electrical neuroimaging results indicating that activity in the face-selective fusiform cortex may be enhanced by emotional (fearful) expressions, without explicit voluntary control, and presumably through direct feedback connections from the amygdala. fMRI studies show that these increased responses in fusiform cortex to fearful faces are abolished by amygdala damage in the ipsilateral hemisphere, despite preserved effects of voluntary attention on fusiform; whereas emotional increases can still arise despite deficits in attention or awareness following parietal damage, and appear relatively unaffected by pharmacological increases in cholinergic stimulation. Fear-related modulations of face processing driven by amygdala signals may implicate not only fusiform cortex, but also earlier visual areas in occipital cortex (e.g., V1) and other distant regions involved in social, cognitive, or somatic responses (e.g., superior temporal sulcus, cingulate, or parietal areas). In the temporal domain, evoked-potentials show a widespread time-course of emotional face perception, with some increases in the amplitude of responses recorded over both occipital and frontal regions for fearful relative to neutral faces (as well as in the amygdala and orbitofrontal cortex, when using intracranial recordings), but with different latencies post-stimulus onset. Early emotional responses may arise around 120ms, prior to a full visual categorization stage indexed by the face-selective N170 component, possibly reflecting rapid emotion processing based on crude visual cues in faces. Other electrical components arise at later latencies and involve more sustained activities, probably generated in associative or supramodal brain areas, and resulting in part from the modulatory signals received from amygdala. Altogether, these fMRI and ERP results demonstrate that emotion face perception is a complex process that cannot be related to a single neural event taking place in a single brain regions, but rather implicates an interactive network with distributed activity in time and space. Moreover, although traditional models in cognitive neuropsychology have often considered that facial expression and facial identity are processed along two separate pathways, evidence from fMRI and ERPs suggests instead that emotional processing can strongly affect brain systems responsible for face recognition and memory. The functional implications of these interactions remain to be fully explored, but might play an important role in the normal development of face processing skills and in some neuropsychiatric disorders.     

Oxytocin improves "mind-reading" in humans.

BACKGROUND: The ability to "read the mind" of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals. METHODS: In a double-blind, placebo-controlled, within-subject design, 30 healthy male volunteers were tested for their ability to infer the affective mental state of others using the Reading the Mind in the Eyes Test (RMET) after intranasal administration of 24 IU oxytocin. RESULTS: Oxytocin improved performance on the RMET compared with placebo. This effect was pronounced for difficult compared with easy items. CONCLUSIONS: Our data suggest that oxytocin improves the ability to infer the mental state of others from social cues of the eye region. Oxytocin might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.     

ADHD and schizophrenia phenomenology: visual scanpaths to emotional faces as a potential psychophysiological marker?

Commonalities in the clinical phenomenology and psychopharmacology of ADHD and schizophrenia are reviewed. The potential of psychostimulants to produce psychotic symptoms emphasizes the need for objective psychophysiological distinctions between these disorders. Impaired emotion perception in both disorders is discussed. It is proposed that visual scanpaths to facial expressions of emotion might prove a potentially useful psychophysiological distinction between ADHD and schizophrenia. There is consistent evidence that both facial affect recognition and scanpaths to facial expressions are impaired in schizophrenia, with emerging empirical evidence showing that facial affect recognition is impaired in ADHD also. Brain imaging studies show reduced activity in the medial prefrontal and limbic (amygdala) brain regions required to process emotional faces in schizophrenia, but suggest more localized loss of activity in these regions in ADHD. As amygdala activity in particular has been linked to effective visual scanning of face stimuli, it is postulated that condition-specific breakdowns in these brain regions that subserve emotional behavior might manifest as distinct scanpath aberrations to facial expressions of emotion in schizophrenia and ADHD.     

Reprint of: The amygdala and FFA track both social and non-social face dimensions

The amygdala is thought to perform a number of social functions, and has received much attention for its role in processing social properties of faces. In particular, it has been shown to respond more to facial expressions than to neutral faces, and more to positively valenced and negatively valenced faces than faces in the middle of the continuum. However, when these findings are viewed in the context of a multidimensional face space, an important question emerges. Face space is a vector space where every face can be represented as a point in the space. The origin of the space represents the average face. In this context, positively valenced and negatively valenced faces are further away from the average face than faces in the middle of the continuum. It is therefore unclear if the amygdala response to positively valenced and negatively valenced faces is due to their social properties or to their general distance from the average face. Here, we compared the amygdala response to a set of faces that varied along two dimensions centered around the average face but differing in social content. In both the amygdala and much of the posterior face network, we observed a similar response to both dimensions, with stronger responses to the extremes of the dimensions than to faces near the average face. These findings suggest that the responses in these regions to socially relevant faces may be partially due to general distance from the average face.     

The amygdala and FFA track both social and non-social face dimensions

The amygdala is thought to perform a number of social functions, and has received much attention for its role in processing social properties of faces. In particular, it has been shown to respond more to facial expressions than to neutral faces, and more to positively valenced and negatively valenced faces than faces in the middle of the continuum. However, when these findings are viewed in the context of a multidimensional face space, an important question emerges. Face space is a vector space where every face can be represented as a point in the space. The origin of the space represents the average face. In this context, positively valenced and negatively valenced faces are further away from the average face than faces in the middle of the continuum. It is therefore unclear if the amygdala response to positively valenced and negatively valenced faces is due to their social properties or to their general distance from the average face. Here, we compared the amygdala response to a set of faces that varied along two dimensions centered around the average face but differing in social content. In both the amygdala and much of the posterior face network, we observed a similar response to both dimensions, with stronger responses to the extremes of the dimensions than to faces near the average face. These findings suggest that the responses in these regions to socially relevant faces may be partially due to general distance from the average face.     

Individual differences in social behavior predict amygdala response to fearful facial expressions in Williams syndrome

Williams syndrome (WS) is a genetic condition often paired with abnormal social functioning and behavior. In particular, those with WS are characterized as being relatively hypersocial, overly emotional/empathic, and socially uninhibited or fearless. In addition, WS is associated with abnormal amygdala structure and function. Very little is known however about the relationship between specific social behaviors and altered amygdala function in WS. This study was designed to compare three models that relate abnormal social behavior with amygdala function in WS (indiscriminate sociability, emotional and empathic sociability and social fearlessness). We used a social behavior assessment procedure (Salk Institute Sociability Questionnaire), functional magnetic resonance imaging and an implicit emotion face processing task to test these models. Our findings provide support for a model of abnormal social fearlessness by showing that in WS, abnormal amygdala response to fear is paired with an increased tendency to approach strangers. Specifically, individuals with WS that exhibited less amygdala response to fearful facial expressions (compared to neutral) also exhibited an increased tendency to approach strangers. These findings contribute to our understanding of social and emotional functioning in neurodevelopmental conditions and provide evidence that in WS, amygdala response to fear modulates social behavior.     

Roles of oxytocin neurones in the control of stress, energy metabolism, and social behaviour

Oxytocin neurones are activated by stressful stimuli, food intake and social attachment. Activation of oxytocin neurones in response to stressful stimuli or food intake is mediated, at least in part, by noradrenaline/prolactin-releasing peptide (PrRP) neurones in the nucleus tractus solitarius, whereas oxytocin neurones are activated after social stimuli via medial amygdala neurones. Activation of oxytocin neurones induces the release of oxytocin not only from their axon terminals, but also from their dendrites. Oxytocin acts locally where released or diffuses and acts on remote oxytocin receptors widely distributed within the brain, resulting in anxiolytic, anorexic and pro-social actions. The action sites of oxytocin appear to be multiple. Oxytocin shows anxiolytic actions, at least in part, via serotoninergic neurones in the median raphe nucleus, has anorexic actions via pro-opiomelanocortin neurones in the nucleus tractus solitarius and facilitates social recognition via the medial amygdala. Stress, obesity and social isolation are major risk factors for mortality in humans. Thus, the oxytocin-oxytocin receptor system is a therapeutic target for the promotion of human health.     

The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals

Users of ±3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) report prosocial effects such as sociability and empathy. Supporting these apparently unique social effects, data from controlled laboratory studies indicate that MDMA alters social feelings, information processing, and behavior in humans, and social behavior in rodents. Here, we review this growing body of evidence. In rodents, MDMA increases passive prosocial behavior (adjacent lying) and social reward while decreasing aggression, effects that may involve serotonin 1A receptor mediated oxytocin release interacting with vasopressin receptor 1A. In humans, MDMA increases plasma oxytocin and produces feelings of social affiliation. It decreases identification of negative facial expressions (cognitive empathy) and blunts responses to social rejection, while enhancing responses to others’ positive emotions (emotional empathy) and increasing social approach. Thus, consistent with drug folklore, laboratory administration of MDMA robustly alters social processing in humans and increases social approach in humans and animals. Effects are consistent with increased sociability, with mixed evidence about enhanced empathy. These neurobiologically-complex prosocial effects likely motivate recreational ecstasy use.     

The role of the cannabinoid receptor in adolescents′ processing of facial expressions

The processing of emotional faces is an important prerequisite for adequate social interactions in daily life, and might thus specifically be altered in adolescence, a period marked by significant changes in social emotional processing. Previous research has shown that the cannabinoid receptor CB1R is associated with longer gaze duration and increased brain responses in the striatum to happy faces in adults, yet, for adolescents, it is not clear whether an association between CBR1 and face processing exists. In the present study we investigated genetic effects of the two CB1R polymorphisms, rs1049353 and rs806377, on the processing of emotional faces in healthy adolescents. They participated in functional magnetic resonance imaging during a Faces Task, watching blocks of video clips with angry and neutral facial expressions, and completed a Morphed Faces Task in the laboratory where they looked at different facial expressions that switched from anger to fear or sadness or from happiness to fear or sadness, and labelled them according to these four emotional expressions. A‐allele versus GG‐carriers in rs1049353 displayed earlier recognition of facial expressions changing from anger to sadness or fear, but not for expressions changing from happiness to sadness or fear, and higher brain responses to angry, but not neutral, faces in the amygdala and insula. For rs806377 no significant effects emerged. This suggests that rs1049353 is involved in the processing of negative facial expressions with relation to anger in adolescence. These findings add to our understanding of social emotion‐related mechanisms in this life period.     

Antidepressant drug treatment modifies the neural processing of nonconscious threat cues.

BACKGROUND: The amygdala is believed to play a key role in processing emotionally salient, threat-relevant, events that require further online processing by cortical regions. Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala, but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information. METHODS: The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging. A double-blind, between-groups design was used with volunteers randomized to 20 mg/day citalopram versus placebo. RESULTS: Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo. Citalopram also reduced responses within the hippocampus and medial prefrontal cortex (mPFC) specifically during the fear-relevant stimuli. These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan. By contrast, there was no effect of citalopram on the neural or behavioral response to the happy facial expressions. CONCLUSIONS: These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans. Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety.     

Neural correlates of social approach and withdrawal in patients with major depression

Successful human interaction is based on correct recognition, interpretation, and appropriate reaction to facial affect. In depression, social skill deficits are among the most restraining symptoms leading to social withdrawal, thereby aggravating social isolation and depressive affect. Dysfunctional approach and withdrawal tendencies to emotional stimuli have been documented, but the investigation of their neural underpinnings has received limited attention. We performed an fMRI study including 15 depressive patients and 15 matched, healthy controls. All subjects performed two tasks, an implicit joystick task as well as an explicit rating task, both using happy, neutral, and angry facial expressions. Behavioral data analysis indicated a significant group effect, with depressed patients showing more withdrawal than controls. Analysis of the functional data revealed significant group effects for both tasks. Among other regions, we observed significant group differences in amygdala activation, with patients showing less response particularly during approach to happy faces. Additionally, significant correlations of amygdala activation with psychopathology emerged, suggesting that more pronounced symptoms are accompanied by stronger decreases of amygdala activation. Hence, our results demonstrate that depressed patients show dysfunctional social approach and withdrawal behavior, which in turn may aggravate the disorder by negative social interactions contributing to isolation and reinforcing cognitive biases.     

Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids

Oxytocin has been linked to social behavior, including social recognition, pair bonding and parenting, but its potential role in promoting neuronal growth has not been investigated. We show here that oxytocin, but not vasopressin, stimulates both cell proliferation and adult neurogenesis in the hippocampus of rats. Oxytocin is also capable of stimulating adult neurogenesis in rats subjected to glucocorticoid administration or cold water swim stress. These findings suggest that oxytocin stimulates neuronal growth and may protect against the suppressive effects of stress hormones on hippocampal plasticity.     

The face of rejection: rejection sensitivity moderates dorsal anterior cingulate activity to disapproving facial expressions

Previous research has examined neural responses to threatening facial expressions such as those displaying anger, fear, and disgust. Here, we examined neural responses to a different type of threatening facial expression that primarily signifies a threat to social connection, namely a "disapproving" facial expression. We hypothesized that neural responses to disapproving facial expressions would be moderated by individual differences in rejection sensitivity. Using functional magnetic resonance imaging (fMRI), we scanned participants while they viewed brief video clips of facial expressions depicting disapproval, anger, and disgust. As expected, all three expressions yielded bilateral amygdala activation relative to a resting baseline. Additionally, individuals who scored higher on a measure of rejection sensitivity exhibited greater dorsal anterior cingulate cortex activity in response to disapproving facial expressions, but not in response to anger or disgust facial expressions. Results suggest that, at the neural level, individuals high in rejection sensitivity may be more sensitive to facial expressions signaling potential rejection, but not to threatening facial expressions in general. Results also suggest that disapproving facial expressions convey a distinct type of threat and should be considered in future studies of socially threatening facial expressions.     

Evidence for altered amygdala activation in schizophrenia in an adaptive emotion recognition task

Deficits in social cognition seem to present an intermediate phenotype for schizophrenia, and are known to be associated with an altered amygdala response to faces. However, current results are heterogeneous with respect to whether this altered amygdala response in schizophrenia is hypoactive or hyperactive in nature. The present study used functional magnetic resonance imaging to investigate emotion-specific amygdala activation in schizophrenia using a novel adaptive emotion recognition paradigm. Participants comprised 11 schizophrenia outpatients and 16 healthy controls who viewed face stimuli expressing emotions of anger, fear, happiness, and disgust, as well as neutral expressions. The adaptive emotion recognition approach allows the assessment of group differences in both emotion recognition performance and associated neuronal activity while also ensuring a comparable number of correctly recognized emotions between groups. Schizophrenia participants were slower and had a negative bias in emotion recognition. In addition, they showed reduced differential activation during recognition of emotional compared with neutral expressions. Correlation analyses revealed an association of a negative bias with amygdala activation for neutral facial expressions that was specific to the patient group. We replicated previous findings of affected emotion recognition in schizophrenia. Furthermore, we demonstrated that altered amygdala activation in the patient group was associated with the occurrence of a negative bias. These results provide further evidence for impaired social cognition in schizophrenia and point to a central role of the amygdala in negative misperceptions of facial stimuli in schizophrenia.     

Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress

Background

The presence of social support has been associated with decreased stress responsiveness. Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress. This study was designed to determine the effects of social support and oxytocin on cortisol, mood, and anxiety responses to psychosocial stress in humans.

Methods

In a placebo-controlled, double-blind study, 37 healthy men were exposed to the Trier Social Stress Test. All participants were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either social support from their best friend during the preparation period or no social support.

Results

Salivary free cortisol levels were suppressed by social support in response to stress. Comparisons of pre- and poststress anxiety levels revealed an anxiolytic effect of oxytocin. More importantly, the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress.

Conclusions

Oxytocin seems to enhance the buffering effect of social support on stress responsiveness. These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions.