Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates.

To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted amongst patient populations treated with serotonergic drugs. However, those in the field lack a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques (both sexes) to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orienting and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in nonhuman primates and offer translational insights for the role of the serotonergic system in social gaze.SIGNIFICANCE STATEMENT Behavioral changes arising from pharmacological agents that target serotonergic functions are complex and difficult to predict. Here, we examined the causal impacts of administering the direct precursor of serotonin, 5-HTP, on orienting and inhibiting social gaze in nonhuman primates. 5-HTP increased central concentrations of serotonin and selectively impaired the ability of monkeys to inhibit orienting to faces while similarly impairing the ability of monkeys to orient to face and control images. These behavioral gaze impairments were systematically associated with a downregulation of arousal and motivational states, indexed by pupil constriction, increased time to initiate trials, and increased reaction time. These findings provide a causal link between 5-HTP and social gaze behaviors in nonhuman primates and provide translational insights about serotonergic interventions.

Ketamine disrupts gaze patterns during face viewing in the common marmoset.

Faces are stimuli of critical importance for primates. The common marmoset (Callithrix jacchus) is a promising model for investigations of face processing, as this species possesses oculomotor and face-processing networks resembling those of macaques and humans. Face processing is often disrupted in neuropsychiatric conditions such as schizophrenia (SZ), and thus, it is important to recapitulate underlying circuitry dysfunction preclinically. The N-methyl-d-aspartate (NMDA) noncompetitive antagonist ketamine has been used extensively to model the cognitive symptoms of SZ. Here, we investigated the effects of a subanesthetic dose of ketamine on oculomotor behavior in marmosets during face viewing. Four marmosets received systemic ketamine or saline injections while viewing phase-scrambled or intact videos of conspecifics' faces. To evaluate effects of ketamine on scan paths during face viewing, we identified regions of interest in each face video and classified locations of saccade onsets and landing positions within these areas. A preference for the snout over eye regions was observed following ketamine administration. In addition, regions in which saccades landed could be significantly predicted by saccade onset region in the saline but not the ketamine condition. Effects on saccade control were limited to an increase in saccade peak velocity in all conditions and a reduction in saccade amplitudes during viewing of scrambled videos. Thus, ketamine induced a significant disruption of scan paths during viewing of conspecific faces but limited effects on saccade motor control. These findings support the use of ketamine in marmosets for investigating changes in neural circuits underlying social cognition in neuropsychiatric disorders.NEW & NOTEWORTHY Face processing, an important social cognitive ability, is impaired in neuropsychiatric conditions such as schizophrenia. The highly social common marmoset model presents an opportunity to investigate these impairments. We administered subanesthetic doses of ketamine to marmosets to model the cognitive symptoms of schizophrenia. We observed a disruption of scan paths during viewing of conspecifics' faces. These findings support the use of ketamine in marmosets as a model for investigating social cognition in neuropsychiatric disorders.

Intranasal oxytocin enhances the perception of ambiguous averted gaze in women but not in men.

BACKGROUND: Perceiving accurately that others are looking away from us (averted gaze) is as important, for social interactions, as perceiving that others are looking at us (direct gaze). However, previous studies have revealed that when the deflection angle of averted gaze is small, individuals tend to falsely perceive it as direct gaze. Oxytocin (OXT) has been shown to increase orientation to the eye region. Therefore, a critical question is whether and how OXT would facilitate the perception of ambiguous averted gaze. OBJECTIVES: The present study aimed to measure the effects of OXT on the performance of males and females in distinguishing ambiguous averted gaze from direct gaze of different emotional faces. METHODS: In a double-blind placebo-controlled crossover experiment, 48 participants were presented successively two emotional faces with direct gaze (defined as 0, indicating the center of the eye) or averted gaze (defined as ±4, indicating the corner of the eye; +4 means that the iris moves 4 steps to the right; and -4 means that the iris moves 4 steps to the left) following intranasal oxytocin or placebo treatment and asked to make judgments on whether or not the two faces were the same in terms of identity. The interference effect of gaze direction was calculated by subtracting the mean accuracy and reaction time in the congruent gaze condition from those in the incongruent gaze condition. The logic of the measurement was if intranasal OXT would facilitate the detection of ambiguous averted gaze, we would observe a larger interference effect in the gaze incongruent condition compared with the gaze congruent condition, leading to longer RT or/and lower accuracy for identification judgment in the gaze incongruent condition. RESULTS: While there were no OXT effects in accuracy, we found a significant interaction between treatment, sex, and gaze congruency in reaction times. That is, following OXT as compared to placebo, women displayed stronger interference of gaze direction, whereas in men no significant difference was observed. Besides, this interaction did not vary across different emotional expressions. CONCLUSIONS: Our findings provide the first evidence for sex-dependent effects of OXT on the perception of ambiguous averted gaze. Given potential therapeutic applications of OXT to patients with developmental and psychiatric disorders, who are characterized as atypical in encoding gaze features, the findings suggest that rather different treatment outcomes could be anticipated in males and females.

Effects of Oxytocin on Emotion Recognition in Schizophrenia: A Randomized Double-Blind Pilot Study.

BACKGROUND: Schizophrenia (SCZ) is a neurodevelopmental disorder that leads to poor social function. Oxytocin (OXT), a neuropeptide involved in social cognition, is a potential therapeutic agent for alleviating social dysfunction. Therefore, we investigated the effects of intranasal oxytocin (IN-OXT) on emotional processes in experimental interactive social contexts in individuals with SCZ. METHODS: In a male-only parallel randomized placebo-controlled double-blind trial, we investigated the effects of IN-OXT (24 IU) on visual fixation on pictures of faces and emotion recognition in an interactive ball-tossing game that probed processing of social and nonsocial stimuli. RESULTS: Intranasal oxytocin enhanced the recognition of emotions during an emotion-based ball-tossing game. This improvement was specific to the game that included social cue processing. Intranasal oxytocin did not affect eye gaze duration or gaze dwell time on faces in these patients. CONCLUSIONS: An acute low dose of IN-OXT had a modest effect on social cue processing and was limited to emotion recognition. Higher doses and long-term trials targeting emotional processing in SCZ may lead to improved social function.

Oxytocin enhances the recovery of eye-contact induced autonomic arousal: A treatment mechanism study with placebo-controlled design.

The neuropeptide oxytocin (OT) is suggested to exert a pivotal role in a variety of complex human behaviors, including trust, attachment, social perception and fear regulation. Previous studies have demonstrated that intranasal administration of OT reduces subjective and neuroendocrine stress responses and dampens amygdala reactivity. OT has also been proposed to modulate activity of the autonomic nervous system. Here, a randomized double-blind, placebo-controlled study (with parallel design) was conducted with 56 healthy adult men to investigate whether a single-dose of OT (24 IU) modulates sympathetic autonomic arousal upon live dyadic gaze interactions. To do so, electrodermal recordings of skin conductance were performed during the engagement of eye contact with a live model in a two-person social context. In accordance to prior research, direct eye gaze elicited a significant enhancement in skin conductance responses, but OT did not specifically enhance or dampen the overall magnitude (amplitude) of the skin conductance response. Administration of OT did facilitate the recovery of skin conductance responses back to baseline (reduced recovery time), indicating a role of OT in restoring homeostatic balance. Notably, the treatment-effect on autonomic recovery was most prominent in participants with low self-reported social responsiveness, indicating that person-dependent factors play an important role in determining OT treatment-responses. Exploratory, it was shown that OT also significantly reduced self-reported feelings of tension and (at trend-level) worrying about how one presents oneself. Together, these observations add further evidence to a role of OT in modulating activity of the autonomic nervous system, primarily by facilitating a restoration of homeostatic balance after stimulus-induced increases in sympathetically-driven autonomic arousal.

Reduced attentional capture by reward following an acute dose of alcohol.

RATIONALE: Previous research has shown that physically salient and reward-related distractors can automatically capture attention and eye gaze in a visual search task, even though participants are motivated to ignore these stimuli. OBJECTIVES: To examine whether an acute, low dose of alcohol would influence involuntary attentional capture by stimuli signalling reward. METHODS: Participants were assigned to the alcohol or placebo group before completing a visual search task. Successful identification of the target earned either a low or high monetary reward but this reward was omitted if any eye gaze was registered on the reward-signalling distractor. RESULTS: Participants who had consumed alcohol were significantly less likely than those in the placebo condition to have their attention captured by a distractor stimulus that signalled the availability of high reward. Analysis of saccade latencies suggested that this difference reflected a reduction in the likelihood of impulsive eye movements following alcohol. CONCLUSIONS: Our findings suggest that alcohol intoxication reduces the capacity to attend to information in the environment that is not directly relevant to the task at hand. In the current task, this led to a performance benefit under alcohol, but in situations that require rapid responding to salient events, the effect on behaviour would be deleterious.

Paroxysmal tonic upgaze: A heterogeneous clinical condition responsive to carbonic anhydrase inhibition.

BACKGROUND: Paroxysmal tonic upgaze (PTU), defined as an involuntary upward movement of the eyes, has been considered as a benign phenomenon but may also be associated with ataxia and developmental delay. METHODS: We report eight children with PTU; six of them also exhibiting symptoms of ataxia and/or developmental delay. Treatment with carbonic anhydrase inhibition was offered to children with persisting and/or severe forms. RESULTS: Whole-exome sequencing and genome-wide array analysis (n = 7) did not reveal mutations in the three known genes associated with PTU (CACNA1A, GRID2, SEPSECS), whereas by MLPA a heterozygous deletion of exon 31 of the CACNA1A gene could be detected in one patient, her mother and two further family members. Further exome and array analysis showed no recurrent variants in potentially novel PTU-related genes in more than one patient. A de novo variant at a highly conserved position in the SIM1 gene was detected in one patient, for which a pathogenic effect could be speculated. Carbonic anhydrase inhibition was started in five children and proved at least partially effective in all of them. CONCLUSION: Irrespective of the clinical background and the molecular basic mechanism of PTU, therapeutic carbonic anhydrase inhibition was effective in all five children (acetazolamide, n = 3; sultiame, n = 2) who received this treatment.

Opposing sex-dependent effects of oxytocin on the perception of gaze direction.

BACKGROUND: Gaze direction is an important cue of the eye region. Previous studies have revealed that oxytocin (OXT) increases orienting to the eye region of face. However, little has been known about the effect of OXT in men and women on the perception of gaze direction particularly when associated with different emotions. OBJECTIVES: We investigated how oxytocin would affect gaze direction judgments for threatening, angry, and neutral facial expressions and whether this effect would be modulated by observers' sex. METHODS: We used the cone of direct gaze (CoDG) task. Participants were required to judge the gaze direction of face between directed and averted gaze. RESULTS: Results showed opposing sex-dependent effects of OXT such that OXT, as compared with placebo, tended to decrease the CoDG in men but increase it in women. The CoDG was marginally wider in men than in women in the placebo condition, and however, this difference was abolished following OXT treatment. We also found that the perception of gaze direction varied as a function of emotional expression such that the CoDG for angry and neutral faces was wider than that for fearful faces and the CoDG for angry faces was marginally wider than that for neutral ones. However, there was no significant interaction between treatment and facial expression. CONCLUSIONS: Our findings provide the first evidence for sex-dependent effects of OXT on gaze direction perception, suggesting that OXT attenuates the self-referential judgment of gaze directions of others in men and enhances it in women despite differentiated emotions of faces.

Oxytocin increases eye gaze in schizophrenia.

Abnormal eye gaze is common in schizophrenia and linked to functional impairment. The hypothalamic neuropeptide oxytocin modulates visual attention to social stimuli, but its effects on eye gaze in schizophrenia are unknown. We examined visual scanning of faces in men with schizophrenia and neurotypical controls to quantify oxytocin effects on eye gaze. In a randomized, double-blind, crossover study, 33 men with schizophrenia and 39 matched controls received one dose of intranasal oxytocin (40 IU) and placebo on separate testing days. Participants viewed 20 color photographs of faces while their gaze patterns were recorded. We tested for differences in fixation time on the eyes between patients and controls as well as oxytocin effects using linear mixed-effects models. We also tested whether attachment style, symptom severity, and anti-dopaminergic medication dosage moderated oxytocin effects. In the placebo condition, patients showed reduced fixation time on the eyes compared to controls. Oxytocin was associated with an increase in fixation time among patients, but a decrease among controls. Higher attachment anxiety and greater symptom severity predicted increased fixation time on the eyes on oxytocin versus placebo. Anti-dopaminergic medication dosage and attachment avoidance did not impact response to oxytocin. Consistent with findings that oxytocin optimizes processing of social stimuli, intranasal oxytocin enhanced eye gaze in men with schizophrenia. Further work is needed to determine whether changes in eye gaze impact social cognition and functional outcomes. Both attachment anxiety and symptom severity predicted oxytocin response, highlighting the importance of examining potential moderators of oxytocin effects in future studies.

Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome.

BACKGROUND: Numerous preclinical studies have supported the theory that enhanced activation of mGluR5 signaling, due to the absence or reduction of the FMR1 protein, contributes to cognitive and behavioral deficits in patients with fragile X syndrome (FXS). However multiple phase 2 controlled trials in patients with FXS have failed to demonstrate efficacy of compounds that negatively modulate mGluR5, including two phase 2b randomized controlled trials (RCT) of mavoglurant (AFQ056, Novartis Pharma AG), when the primary measures of interest were behavioral ratings. This has cast some doubt onto the translation of the mGluR5 theory from animal models to humans with the disorder. METHODS: We evaluated social gaze behavior-a key phenotypic feature of the disorder-and sympathetic nervous system influence on pupil size using a previously-validated eye tracking paradigm as a biobehavioral probe, in 57 adolescent or adult patients with FXS at baseline and following three months of blinded treatment with one of three doses of mavoglurant or placebo, within the context of the AFQ056 RCTs. RESULTS: Patients with FXS treated with mavoglurant demonstrated increased total absolute looking time and number of fixations to the eye region while viewing human faces relative to baseline, and compared to those treated with placebo. In addition, patients had greater pupil reactivity to faces relative to baseline following mavoglurant treatment compared to placebo. DISCUSSION: The study shows that negative modulation of mGluR5 activity improves eye gaze behavior and alters sympathetically-driven reactivity to faces in patients with FXS, providing preliminary evidence of this drug's impact on behavior in humans with the disorder.

Intranasal oxytocin does not alter initial perceptions of facial trustworthiness in younger or older adults.

BACKGROUND: Oxytocin is a neuropeptide involved in a range of social processes, and prior research has shown that intranasal oxytocin (iOT) may enhance trusting behaviors. However, it is unclear whether iOT influences perceptions of whether a face is trustworthy. In addition, no studies in this literature have investigated whether the participant's age may play a moderating role in the effects of iOT on trust. AIMS: We aimed to examine for the first time whether iOT influences perceptions of facial trustworthiness and eye-gaze patterns and, if so, whether age moderates these iOT effects. METHODS: One hundred and eighteen participants took part in a randomized, double-blind, placebo-controlled, within-groups study. Participants made judgments about the perceived trustworthiness of a series of faces while their eye movements were monitored. RESULTS: Younger and older adults differed in their judgments of facial trustworthiness. However, most critically, iOT had no effect on these judgments for either age group. For the eye-tracking data, prior age effects in attending to the stimuli were replicated, with older adults gazing less at the eye region and more at the mouth region relative to younger adults. However, iOT had no effect on eye gaze. CONCLUSIONS: These findings are discussed in relation to the growing body of literature that suggests that the effect of iOT on social processing is complex and may not be as robust as first thought.

Oxytocin increases eye-gaze towards novel social and non-social stimuli.

Research on oxytocin (OT) has revealed a substantial involvement of this neuropeptide in social cognition processes and attachment behavior. The rationale of the present project was to decipher the differential role of OT in basic social cognition processes towards non-erotic attachment stimuli vs. reproduction-related stimuli in human subjects. In a randomized double-blind repeated-measures cross-over design, N = 82 participants were investigated twice and received either intranasal OT or placebo at the first assessment followed by placebo or OT at second assessment. Participants were presented with standardized pictures of parent-child dyads, romantic couples engaging in non-erotic or explicit sexual activities, and non-social pictures while we assessed pupil dilation and eye focus on specific pre-defined areas of interest. Multilevel analyses suggest that during the initial presentation, OT increased pupil dilation towards all categories of stimuli and led the eye focus towards the eyes and body regions, followed by a strong decrease in pupil dilation and fixations at the second session. These carry-over effects indicate that hormonal treatment at an initial contact to social stimuli can determine how these stimuli are processed later. These results might have implications for OT as a treatment in interventions with repeated exposure to social material.

Androstadienone, a putative chemosignal of dominance, increases gaze avoidance among men with high social anxiety.

Socially anxious individuals show increased sensitivity toward social threat signals, including cues of dominance. This sensitivity may account for the hypervigilance and gaze avoidance commonly reported in individuals with social anxiety. This study examines visual scanning behavior in response to androstadienone (androsta-4,16,-dien-3-one), a putative chemosignal of dominance. We tested whether exposure to androstadienone would increase hypervigilance and gaze avoidance among individuals with high social anxiety. In a double-blind, placebo-controlled, within-subject design, 26 participants with high social anxiety and 26 with low social anxiety were exposed to androstadienone and a control solution on two separate days. On each day, an eye-tracker recorded their spontaneous scanning behavior while they viewed facial images of men depicting dominant and neutral poses. The results indicate that among participants with high social anxiety, androstadienone increased gaze avoidance by reducing the percentage of fixations made to the eye-region and the total amount of time spent gazing at the eye-region of the faces. Participants with low social anxiety did not show this effect. These findings indicate that androstadienone serves as a threatening chemosignal of dominance, further supporting the link between hypersensitivity toward social threat cues and the perpetuation of social anxiety.

Alcohol-related attentional bias in a gaze contingency task: Comparing appetitive and non-appetitive cues.

BACKGROUND: Non-problem drinkers attend automatically to alcohol-related cues compared to non-alcohol related cues on tests of inhibitory control. Moreover, attentional bias for alcohol-related cues varies between problem and non-problem drinkers. AIM: To examine attentional bias towards alcoholic and non-alcoholic appetitive cues between problem and non-problem drinkers. METHOD: Forty-one university students (9 male, 32 female; Mage = 21.50) completed an eye-tracking gaze contingency paradigm, measuring the number of times participants looked at peripherally and centrally located stimuli (break frequency) when instructed to maintain focus on a target object. Stimuli consisted of appetitive alcohol-related (e.g., wine), appetitive non-alcohol-related (e.g., cola) and non-appetitive (e.g., fabric softener) stimuli. Participants were split using the Alcohol Use Disorders Identification Test (AUDIT) into non-problem (M AUDIT = 3.86) and problematic drinkers (M AUDIT = 11.59). RESULTS: Problematic drinkers had higher break frequencies towards peripheral appetitive stimuli than towards non-appetitive stimuli, while break frequency was equivalent between appetitive cues presented centrally (alcohol and non-alcohol-related). In contrast, there were no differences in break frequency across stimuli type or cue presentation location (central or peripheral) for non-problem drinkers. CONCLUSION: In contrast to non-problem drinkers, people displaying more problematic consumption practices may find it more difficult to inhibit eye movements towards appetitive stimuli, particularly when in peripheral vision. This may suggest that attentional biases, as measured in terms of overt eye movements, in problem drinkers may be most powerful when the alcoholic and appetitive stimuli are not directly in field of view. An uncertainty reduction process in the allocation of attention to appetitive cues may help explain the patterns of results observed.

Conjugate Eye Deviation Caused by Upper Medial Medullary Infarction: A Case Report.

Conjugate eye deviation (CED) is defined as a sustained shift in horizontal gaze toward 1 side, together with gaze failure to the other side, caused by lesions in the brainstem, basal ganglia, or cortical frontal eye fields. To date, very few reports have described CED in patients with medullary infarction. A 76-year-old woman presented with sudden onset of vertigo and right hemiparesis, accompanied by CED to the right with gaze palsy to the left. Her brain magnetic resonance imaging showed left upper medial medullary infarction involving the left nucleus prepositus hypoglossi (NPH) and adjacent to the left inferior olivary nucleus (ION). After treatments with 200 mg of aspirin and 60 mg of edaravone daily, symptoms gradually improved. The NPH and ION constitute NPH-ION-floccus-vestibular nucleus loop and contribute to the inhibitory mechanisms for horizontal eye movements. In addition, NPH projects excitatory neurons to the contralateral vestibular nucleus. In our case, disorders of the NPH and ION might have dysregulated inhibitory and excitatory projections, and thereby cause CED to the right with gaze palsy to the left. This represents a rare case showing CED to the contralesional side in upper medial medullary infarction.

To mirror or not to mirror upon mutual gaze, oxytocin can pave the way: A cross-over randomized placebo-controlled trial.

The eyes constitute a highly salient cue to communicate social intent. Previous research showed that direct eye contact between two individuals can readily evoke an increased propensity to 'mirror' other peoples' actions. Considering the implicated role of the prosocial neuropeptide oxytocin (OXT) in enhancing the saliency of social cues and modulating approach/avoidance motivational tendencies, the current study adopted the non-invasive brain stimulation technique transcranial magnetic stimulation (TMS) to explore whether a single dose of intranasal OXT (24 IU) modulated (enhanced) a person's propensity to show heightened mirroring or motor resonance upon salient social cues, such as eye contact. The study involved a double-blind, placebo-controlled, cross-over trial with twenty-seven healthy adult men (19-32 y). By applying single-pulse TMS over the primary motor cortex during movement observation, it was shown that motor resonance was significantly higher when movement observation was accompanied by direct, compared to averted gaze, but that a single dose of OXT did not uniformly enhance this effect. Significant moderations of the treatment effect were noted however, indicating that participants with high self-reports of attachment avoidance displayed a stronger OXT-treatment effect (enhancement of motor resonance upon direct eye contact), compared to participants with low attachment avoidance. Particularly, while participants with high attachment avoidance initially displayed a reduced propensity to increase their motor resonance upon direct eye contact, a single dose of OXT was able to promote an otherwise avoidant individual's propensity to engage in motor resonance upon a salient social cue such as eye contact.

Bumetanide for autism: more eye contact, less amygdala activation.

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism.

Intranasal oxytocin does not reduce age-related difficulties in social cognition.

Oxytocin is a neuropeptide that plays a key role in social processing and there are several studies suggesting that intranasally administered oxytocin may enhance social cognitive abilities and visual attention in healthy and clinical groups. However, there are very few studies to date that have investigated the potential benefits of intranasal oxytocin (iOT) on older adults' social cognitive abilities. This is a surprising omission, because relative to their younger counterparts, older adults also exhibit a range of social cognitive difficulties and also show differences in the way they visually attend to social information. Therefore, we tested the effect of iOT (24 IU) versus a placebo spray on 59 older and 61 younger adults' social cognitive abilities and visual attention using a double-blind placebo-controlled within-groups design. While iOT provided no overall age-related benefit on social cognitive abilities, the key finding to emerge was that iOT improved ToM ability in both age-groups when the task had minimal contextual information, but not when the task had enriched contextual information. Interestingly, iOT had gender specific effects during a ToM task with minimal context. For males in both age-groups, iOT reduced gazing to the social aspects of the scenes (i.e., faces & bodies), and for females, iOT eliminated age differences in gaze patterns that were observed in the placebo condition. These effects on eye-gaze were not observed in a very similar ToM task that included more enriched contextual information. Overall, these findings highlight the interactive nature of iOT with task related factors (e.g., context), and are discussed in relation to the social salience hypothesis of oxytocin.

Botulinum Toxin for the Treatment of Cyclic Strabismus in Children: Three Case Reports.

Cyclic strabismus is a rare disease of unknown origin. If untreated, it leads to manifest strabismus with the risk of amblyopia in children. Treatment is generally surgical. Here we report on three children in whom cyclic esotropia was successfully treated with one bimedial injection of 5 IU Botox®. All patients remained orthotropic with good stereo functions at the last follow-ups at 16, 11, and 8 months. Botulinum toxin offered a minimally invasive treatment option in these patients.

The effects of 5-hydroxytryptophan on attention and central serotonin neurochemistry in the rhesus macaque.

Psychiatric disorders, particularly depression and anxiety, are often associated with impaired serotonergic function. However, serotonergic interventions yield inconsistent effects on behavioral impairments. To better understand serotonin's role in these pathologies, we investigated the role of serotonin in a behavior frequently impaired in depression and anxiety, attention. In this study, we used a quantitative, repeated, within-subject, design to test how L-5-hydroxytryptophan (5-HTP), the immediate serotonin precursor, modulates central serotoninergic function and attention in macaques. We observed that intramuscular 5-HTP administration increased cisternal cerebrospinal fluid (CSF) 5-HTP and serotonin. In addition, individuals' baseline looking duration, during saline sessions, predicted the direction and magnitude in which 5-HTP modulated attention. We found that 5-HTP decreased looking duration in animals with high baseline attention, but increased looking duration in low baseline attention animals. Furthermore, individual differences in 5-HTP's effects were also reflected in how engaged individuals were in the task and how they allocated attention to salient facial features-the eyes and mouth-of stimulus animals. However, 5-HTP constricted pupil size in all animals, suggesting that the bi-directional effects of 5-HTP cannot be explained by serotonin-mediated changes in autonomic arousal. Critically, high and low baseline attention animals exhibited different baseline CSF concentrations of 5-HTP and serotonin, an index of extracellular functionally active serotonin. Thus, our results suggest that baseline central serotonergic functioning may underlie and predict variation in serotonin's effects on cognitive operation. Our findings may help inform serotonin's role in psychopathology and help clinicians predict how serotonergic interventions will influence pathologies.