Brent C. Vander Wyk

Neural signatures of autism

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Oxytocin enhances brain function in children with autism

Significance This article presents our discovery that intranasal administration of oxytocin enhances activity in the brain for socially meaningful stimuli and attenuates its response to nonsocially meaningful stimuli in children with autism spectrum disorder (ASD) as measured via functional MRI. We also identified a relationship between changes in salivary oxytocin following administration and enhancements in brain function. These discoveries are particularly important given the urgent need for treatments that target the core social dysfunction in ASD. The functional neural attunement we demonstrated might facilitate social learning, thus potentially bringing about long-term change in neural systems and subsequent behavioral improvements. Our results illustrate the power of a translational neuroscience approach to facilitate the development of pharmacological interventions for neurodevelopmental disorders like ASD. Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.

Action Understanding in the Superior Temporal Sulcus Region

The posterior superior temporal sulcus (STS) region plays an important role in the perception of social acts, although its full role has not been completely clarified. This functional magnetic resonance imaging experiment examined activity in the STS region as participants viewed actions that were congruent or incongruent with intentions established by a previous emotional context. Participants viewed an actress express either a positive or a negative emotion toward one of two objects and then subsequently pick up one of them. If the object that was picked up had received positive regard, or if the object that was not picked up had received negative regard, the action was congruent; otherwise, the action was incongruent. Activity in the right posterior STS region was sensitive to the congruency between the action and the actresss emotional expression (i.e., STS activity was greater on incongruent than on congruent trials). These findings suggest that the posterior STS represents not only biological motion, but also how another persons motion is related to his or her intentions.

Brain mechanisms for processing direct and averted gaze in individuals with autism

Prior studies have indicated brain abnormalities underlying social processing in autism, but no fMRI study has specifically addressed the differential processing of direct and averted gaze, a critical social cue. Fifteen adolescents and adults with autism and 14 typically developing comparison participants viewed dynamic virtual-reality videos depicting a simple but realistic social scenario, in which an approaching male figure maintained either direct or averted gaze. Significant group by condition interactions reflecting differential responses to direct versus averted gaze in people with autism relative to typically developing individuals were identified in the right temporoparietal junction, right anterior insula, left lateral occipital cortex, and left dorsolateral prefrontal cortex. Our results provide initial evidence regarding brain mechanisms underlying the processing of gaze direction during simple social encounters, providing new insight into the social deficits in individuals with autism.

Individual differences in personality predict how people look at faces.

Background Determining the ways in which personality traits interact with contextual determinants to shape social behavior remains an important area of empirical investigation. The specific personality trait of neuroticism has been related to characteristic negative emotionality and associated with heightened attention to negative, emotionally arousing environmental signals. However, the mechanisms by which this personality trait may shape social behavior remain largely unspecified. Methodology/Principal Findings We employed eye tracking to investigate the relationship between characteristics of visual scanpaths in response to emotional facial expressions and individual differences in personality. We discovered that the amount of time spent looking at the eyes of fearful faces was positively related to neuroticism. Conclusions/Significance This finding is discussed in relation to previous behavioral research relating personality to selective attention for trait-congruent emotional information, neuroimaging studies relating differences in personality to amygdala reactivity to socially relevant stimuli, and genetic studies suggesting linkages between the serotonin transporter gene and neuroticism. We conclude that personality may be related to interpersonal interaction by shaping aspects of social cognition as basic as eye contact. In this way, eye gaze represents a possible behavioral link in a complex relationship between genes, brain function, and personality.

Enhanced neural responses to rule violation in children with autism: A comparison to social exclusion

The present study aimed to explore the neural correlates of two characteristic deficits in autism spectrum disorders (ASD); social impairment and restricted, repetitive behavior patterns. To this end, we used comparable experiences of social exclusion and rule violation to probe potentially atypical neural networks in ASD. In children and adolescents with and without ASD, we used the interactive ball-toss game (Cyberball) to elicit social exclusion and a comparable game (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic resonance imaging (fMRI), we identified group differences in brain responses to social exclusion and rule violation. Though both groups reported equal distress following exclusion, the right insula and ventral anterior cingulate cortex were hypoactive during exclusion in children with ASD. In rule violation, right insula and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a dissociation in activation; it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were modulated in each game, highlighting differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity. These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD.

Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: Initial findings

Prepulse inhibition (PPI) of the startle reflex is disrupted in a number of developmental neuropsychiatric disorders, including Tourette syndrome (TS). This disruption is hypothesized to reflect abnormalities in sensorimotor gating. We applied whole-brain functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of PPI in adult TS subjects using airpuff stimuli to the throat to elicit a tactile startle response. We used a cross-sectional, case-control study design and a blocked-design fMRI paradigm. There were 33 participants: 17 with TS and 16 healthy individuals. As a measure of PPI-related brain activity, we looked for differential cerebral activation to prepulse-plus-pulse stimuli versus activation to pulse-alone stimuli. In healthy subjects, PPI was associated with increased activity in multiple brain regions, of which activation in the left middle frontal gyrus in the healthy controls showed a significant linear correlation with the degree of PPI measured outside of the magnet. Group comparisons identified nine regions where brain activity during PPI differed significantly between TS and healthy subjects. Among the TS subjects, activation in the left caudate was significantly correlated with current tic severity as measured by the total score on the Yale Global Tic Severity Scale. Differential activation of the caudate nucleus associated with current tic severity is consistent with neuropathological data and suggests that portions of cortical-striatal circuits may modulate the severity of tic symptoms in adulthood.

Social, reward, and attention brain networks are involved when online bids for joint attention are met with congruent versus incongruent responses.

Joint attention (JA) is a cornerstone of adaptive human social functioning. Little functional magnetic resonance imaging (fMRI) research has examined, in interactive paradigms, neural activation underlying bids for JA, met with a congruent or an incongruent social response. We developed a highly naturalistic fMRI paradigm utilizing eye-tracking to create real-time, contingent social responses to participant-initiated JA. During congruent responses to JA bids, we observed increased activation in the right amygdala, the right fusiform gyrus, anterior and dorsal anterior cingulate cortices, striatum, ventral tegmental area, and posterior parietal cortices. Incongruent responses to JA bids elicited increased activity localized to the right temporoparietal junction (TPJ) and bilateral cerebellum. No differences in eye-gaze patterns were observed during congruent or incongruent trials. Our results highlight the importance of utilizing interactive fMRI paradigms in social neuroscience and the impact of congruency in recruiting integrated social, reward, and attention circuits for processing JA.

Action representation in the superior temporal sulcus in children and adults: an fMRI study

The superior temporal sulcus (STS) plays an important role in the perception of biological motion and in the representation of higher order information about others goals and intentions. Using a rapid event related functional magnetic resonance imaging paradigm (fMRI), children (n=37, mean age 11.0) and adults (n=17, mean age 25.3) viewed congruent or incongruent actions. Congruency (and incongruency) of a reach toward an object was a function of whether the object had just previously received positive or negative regard. Relative to congruent trials, both children and adults showed an increase in activation in the posterior STS bilaterally, in response to incongruent trials. In children, these STS regions exhibited developmental changes. Specifically, the differential response to incongruent trials relative to congruent trials was larger in older children in both hemispheres.

Intranasal Oxytocin Enhances Connectivity in the Neural Circuitry Supporting Social Motivation and Social Perception in Children with Autism.

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain’s reward and socioemotional processing systems, and does so preferentially for social (versus nonsocial) stimuli. This effect is observed both while viewing coherent versus scrambled biological motion, and while listening to happy versus angry voices. Our findings suggest a mechanism by which intranasal OT may bolster social motivation—one that could, in future, be harnessed to augment behavioral treatments for ASD.