The atypical social brain network in autism: advances in structural and functional MRI studies.

PURPOSE OF REVIEW: To review advances in structural and functional MRI studies regarding the neural underpinnings of social atypicalities in autism spectrum disorder (ASD). RECENT FINDINGS: According to the hypothesis that the social brain network, which includes brain regions, such as the amygdala and superior temporal sulcus, may be atypical in ASD, recent structural MRI studies have identified regional gray matter volume abnormalities in the social brain regions in ASD groups compared with the typically developing groups. Studies evaluating gray matter volume covariance and white matter volume/integrity suggested network-level abnormalities associated with the social brain regions. Recent functional MRI studies assessing resting-state neural activity showed reduced functional connectivity among the social brain regions in individuals with ASD compared with typically developing groups. Similarly, task-based functional MRI studies recently revealed a reduction in regional activity and intraregional functional coupling in the social brain regions during the processing of social stimuli in individuals with ASD. SUMMARY: These structural and functional MRI studies provide supportive evidence for the hypothesis that an atypical social brain network underlies behavioral social problems in ASD.

Widespread and lateralized social brain activity for processing dynamic facial expressions.

Dynamic facial expressions of emotions constitute natural and powerful means of social communication in daily life. A number of previous neuroimaging studies have explored the neural mechanisms underlying the processing of dynamic facial expressions, and indicated the activation of certain social brain regions (e.g., the amygdala) during such tasks. However, the activated brain regions were inconsistent across studies, and their laterality was rarely evaluated. To investigate these issues, we measured brain activity using functional magnetic resonance imaging in a relatively large sample (n = 51) during the observation of dynamic facial expressions of anger and happiness and their corresponding dynamic mosaic images. The observation of dynamic facial expressions, compared with dynamic mosaics, elicited stronger activity in the bilateral posterior cortices, including the inferior occipital gyri, fusiform gyri, and superior temporal sulci. The dynamic facial expressions also activated bilateral limbic regions, including the amygdalae and ventromedial prefrontal cortices, more strongly versus mosaics. In the same manner, activation was found in the right inferior frontal gyrus (IFG) and left cerebellum. Laterality analyses comparing original and flipped images revealed right hemispheric dominance in the superior temporal sulcus and IFG and left hemispheric dominance in the cerebellum. These results indicated that the neural mechanisms underlying processing of dynamic facial expressions include widespread social brain regions associated with perceptual, emotional, and motor functions, and include a clearly lateralized (right cortical and left cerebellar) network like that involved in language processing.

Direction of Amygdala-Neocortex Interaction During Dynamic Facial Expression Processing.

Dynamic facial expressions of emotion strongly elicit multifaceted emotional, perceptual, cognitive, and motor responses. Neuroimaging studies revealed that some subcortical (e.g., amygdala) and neocortical (e.g., superior temporal sulcus and inferior frontal gyrus) brain regions and their functional interaction were involved in processing dynamic facial expressions. However, the direction of the functional interaction between the amygdala and the neocortex remains unknown. To investigate this issue, we re-analyzed functional magnetic resonance imaging (fMRI) data from 2 studies and magnetoencephalography (MEG) data from 1 study. First, a psychophysiological interaction analysis of the fMRI data confirmed the functional interaction between the amygdala and neocortical regions. Then, dynamic causal modeling analysis was used to compare models with forward, backward, or bidirectional effective connectivity between the amygdala and neocortical networks in the fMRI and MEG data. The results consistently supported the model of effective connectivity from the amygdala to the neocortex. Further increasing time-window analysis of the MEG demonstrated that this model was valid after 200 ms from the stimulus onset. These data suggest that emotional processing in the amygdala rapidly modulates some neocortical processing, such as perception, recognition, and motor mimicry, when observing dynamic facial expressions of emotion.

Gray matter volumes of early sensory regions are associated with individual differences in sensory processing.

Sensory processing (i.e., the manner in which the nervous system receives, modulates, integrates, and organizes sensory stimuli) is critical when humans are deciding how to react to environmental demands. Although behavioral studies have shown that there are stable individual differences in sensory processing, the neural substrates that implement such differences remain unknown. To investigate this issue, structural magnetic resonance imaging scans were acquired from 51 healthy adults and individual differences in sensory processing were assessed using the Sensory Profile questionnaire (Brown et al.: Am J Occup Ther 55 (2001) 75-82). There were positive relationships between the Sensory Profile modality-specific subscales and gray matter volumes in the primary or secondary sensory areas for the visual, auditory, touch, and taste/smell modalities. Thus, the present results suggest that individual differences in sensory processing are implemented by the early sensory regions. Hum Brain Mapp 38:6206-6217, 2017. © 2017 Wiley Periodicals, Inc.

Time course of gamma-band oscillation associated with face processing in the inferior occipital gyrus and fusiform gyrus: A combined fMRI and MEG study.

Debate continues over whether the inferior occipital gyrus (IOG) or the fusiform gyrus (FG) represents the first stage of face processing and what role these brain regions play. We investigated this issue by combining functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in normal adults. Participants passively observed upright and inverted faces and houses. First, we identified the IOG and FG as face-specific regions using fMRI. We applied beamforming source reconstruction and time-frequency analysis to MEG source signals to reveal the time course of gamma-band activations in these regions. The results revealed that the right IOG showed higher gamma-band activation in response to upright faces than to upright houses at 100 ms from the stimulus onset. Subsequently, the right FG showed greater gamma-band response to upright faces versus upright houses at around 170 ms. The gamma-band activation in the right IOG and right FG was larger in response to inverted faces than to upright faces at the later time window. These results suggest that (1) the gamma-band activities occurs rapidly first in the IOG and next in the FG and (2) the gamma-band activity in the right IOG at later time stages is involved in configuration processing for faces. Hum Brain Mapp 38:2067-2079, 2017. © 2017 Wiley Periodicals, Inc.

Bidirectional electric communication between the inferior occipital gyrus and the amygdala during face processing.

Faces contain multifaceted information that is important for human communication. Neuroimaging studies have revealed face-specific activation in multiple brain regions, including the inferior occipital gyrus (IOG) and amygdala; it is often assumed that these regions constitute the neural network responsible for the processing of faces. However, it remains unknown whether and how these brain regions transmit information during face processing. This study investigated these questions by applying dynamic causal modeling of induced responses to human intracranial electroencephalography data recorded from the IOG and amygdala during the observation of faces, mosaics, and houses in upright and inverted orientations. Model comparisons assessing the experimental effects of upright faces versus upright houses and upright faces versus upright mosaics consistently indicated that the model having face-specific bidirectional modulatory effects between the IOG and amygdala was the most probable. The experimental effect between upright versus inverted faces also favored the model with bidirectional modulatory effects between the IOG and amygdala. The spectral profiles of modulatory effects revealed both same-frequency (e.g., gamma-gamma) and cross-frequency (e.g., theta-gamma) couplings. These results suggest that the IOG and amygdala communicate rapidly with each other using various types of oscillations for the efficient processing of faces. Hum Brain Mapp 38:4511-4524, 2017. © 2017 Wiley Periodicals, Inc.

Putamen Volume is Negatively Correlated with the Ability to Recognize Fearful Facial Expressions.

Findings of previous functional magnetic resonance imaging (MRI) and neuropsychological studies have suggested that specific aspects of the basal ganglia, particularly the putamen, are involved in the recognition of emotional facial expressions. However, it remains unknown whether variations in putamen structure reflect individual differences in the ability to recognize facial expressions. Thus, the present study assessed the putamen volumes and shapes of 50 healthy Japanese adults using structural MRI scans and evaluated the ability of participants to recognize facial expressions associated with six basic emotions: anger, disgust, fear, happiness, sadness, and surprise. The volume of the bilateral putamen was negatively associated with the recognition of fearful faces, and the local shapes of both the anterior and posterior subregions of the bilateral putamen, which are thought to support cognitive/affective and motor processing, respectively, exhibited similar negative relationships with the recognition of fearful expressions. These results suggest that individual differences in putamen structure can predict the ability to recognize fearful facial expressions in others. Additionally, these findings indicate that cognitive/affective and motor processing underlie this process.

Neural mechanisms underlying conscious and unconscious attentional shifts triggered by eye gaze.

Behavioral studies have shown that eye gaze triggers attentional shifts both with and without conscious awareness. However, the neural substrates of conscious and unconscious attentional shifts triggered by eye gaze remain unclear. To investigate this issue, we measured brain activity using event-related functional magnetic resonance imaging while participants observed averted or straight eye-gaze cues presented supraliminally or subliminally in the central visual field and then localized a subsequent target in the peripheral visual field. Reaction times for localizing the targets were shorter under both supraliminal and subliminal conditions when eye-gaze cues were directionally congruent with the target locations than when they were directionally neutral. Conjunction analyses revealed that a bilateral cortical network, including the middle temporal gyri, inferior parietal lobules, anterior cingulate cortices, and superior and middle frontal gyri, was activated more in response to averted eyes than to straight eyes under both supraliminal and subliminal conditions. Interaction analyses revealed that the right inferior parietal lobule was specifically active when participants viewed averted eyes relative to straight eyes under the supraliminal condition; the bilateral subcortical regions, including the superior colliculus and amygdala, and the middle temporal and inferior frontal gyri in the right hemisphere were activated in response to averted versus straight eyes under the subliminal condition. These results suggest commonalities and differences in the neural mechanisms underlying conscious and unconscious attentional shifts triggered by eye gaze.

Self-referential and social saliency information influences memory following attention orienting.

Self-referential information is a processing priority in individuals. Whether or how self-referential information plays a role in attention orienting by modulating memory encoding during attention orienting is presently unknown. First, we investigated this role with self-referential processing for words. Participants were trained to associate two cues (red and green arrows) with social labels (the words "self" and "other" in Experiment 1). Then, participants performed a cueing task to determine whether various targets were presented at a right or left location. Finally, a recognition task of target items was implemented to examine the influence of arrow cues on memory. Second, given that the difference in social salience also exists between self-and other-referential processing, we investigate whether the same effect as the self-referential processing of words exists for emotional faces with high social salience and regardless of emotional valence (a high and a low social salience in Experiment 2A; and a positive and a negative emotional face in Experiment 2B). The results showed that self-referential and emotional cues, irrespective of their emotional valence, enhance memory for the indicated target objects across experiments. This suggests that automatic prioritization of social salience for self-referential words or emotional faces plays an important role in subsequent cognitive processing through attention orienting to influence memory.

Reduced gaze-cueing effect with neutral and emotional faces in adults with attention deficit/hyperactivity disorder.

This study examined whether gaze shift of neutral and emotional faces triggers reflexive attention orienting in 45 adults with attention deficit/hyperactivity disorder (ADHD) and 45 age-, sex-, and intelligence quotient-matched typically developing (TD) adults. The cues changed from neutral to anger, fearful, or happy expressions under the emotional face condition. Participants were asked to detect a target that appeared to the left or right of the cue stimuli, as rapidly and accurately as possible. The results revealed a gaze-cueing effect, where the reaction time to the target was shorter under the "gaze-at-target" condition than under the "non-gaze-at-target" condition in both groups. Facial expressions did not modulate the gaze-cueing effect in either group. However, the magnitude of the gaze-cueing effect was smaller in the ADHD group than in the TD group. Contrary to our expectations, a larger gaze-cueing effect was observed in individuals with ADHD who exhibited more severe inattention. Our results suggest that adults with ADHD ineffectively orient their attention toward another's gaze. Moreover, difficulty with sustained and selective attention may be associated with a larger influence of gaze direction; this difficulty may play a role in social interaction problems.

Temporal profile of amygdala γ oscillations in response to faces.

Neuroimaging studies have reported greater activation of the human amygdala in response to faces than to nonfacial stimuli, yet little is known about the temporal profile of this activation. We investigated this issue by recording the intracranial field potentials of the amygdala in participants undergoing preneurosurgical assessment (n = 6). Participants observed faces, mosaics, and houses in upright and inverted orientations using a dummy target detection task. Time-frequency statistical parametric mapping analyses revealed that the amygdala showed greater gamma-band activity in response to faces than to mosaics at 200-300 msec, with a peak at 255 msec. Gamma-band activation with a similar temporal profile was also found in response to faces versus houses. Activation patterns did not differ between upright and inverted presentations of stimuli. These results suggest that the human amygdala is involved in the early stages of face processing, including the modulation of subjective perception of faces.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

BACKGROUND: Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). RESULT: Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. CONCLUSIONS: These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

No Influence of Emotional Faces or Autistic Traits on Gaze-Cueing in General Population.

The present study addressed the controversial issue of whether autistic traits in the general population are associated with the automatic and fundamental aspects of joint attention through eye gaze. Specifically, we examined whether the degree of autistic traits is associated with the magnitude of reflexive attention orienting in the direction of another's eye gaze embedded in neutral and emotional (angry, fearful, and happy) faces. The cue stimuli changed gaze direction and facial expressions simultaneously. Participants were asked to detect a target that appeared at the left or right of the cue stimuli. The results revealed a robust gaze-cueing effect, such that the reaction time to the target was shorter under the gazed-at-target condition than under the non-gazed-at-target condition. However, emotional expressions did not modulate the gaze-cueing effect. Furthermore, individual differences in autistic traits and emotional characteristics (social anxiety, alexithymia, and emotional disturbances) did not influence the magnitude of the gaze-cueing effect. Although the ability to orient attention in the direction of another's gaze is a fundamental function of social development, the gaze-cueing effect measured in a controlled experiment might not be an elaborate representation of the current social cognitive function, at least in typically developing adults.

The structural neural correlates of atypical facial expression recognition in autism spectrum disorder.

Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) are worse at recognizing facial expressions than are typically developing (TD) individuals. The present study investigated the differences in structural neural correlates of emotion recognition between individuals with and without ASD using voxel-based morphometry (VBM). We acquired structural MRI data from 27 high-functioning adults with ASD and 27 age- and sex-matched TD individuals. The ability to recognize facial expressions was measured using a label-matching paradigm featuring six basic emotions (anger, disgust, fear, happiness, sadness, and surprise). The behavioural task did not find deficits of emotion recognition in ASD after controlling for intellectual ability. However, the VBM analysis for the region of interest showed a positive correlation between the averaged percent accuracy across six basic emotions and the grey matter volume of the right inferior frontal gyrus in TD individuals, but not in individuals with ASD. The VBM for the whole brain region under each emotion condition revealed a positive correlation between the percent accuracy for disgusted faces and the grey matter volume of the left dorsomedial prefrontal cortex in individuals with ASD, but not in TD individuals. The different pattern of correlations suggests that individuals with and without ASD use different processing mechanisms for recognizing others' facial expressions.

Beauty in everyday motion: Electrophysiological correlates of aesthetic preference for human walking.

Aesthetic preference occurs in everyday experience. Studies have suggested that aesthetic preference (such as observing other's motion) affects social interaction via enhanced neural processing. This study investigated the effect of aesthetic preference on neural activities, in response to walking motion. Twenty participants observed biological motion (BM) representing three walking types (model-posture, good-posture, and bad-posture) and their scrambled motion (SM) during the event-related potentials measurement. The N200 and N300 amplitudes, reflecting the early sensory and the later integrational processes, were analyzed. The results revealed that the N200 amplitude of BM was greater than that of SM in the good- and bad-posture conditions. The N300 amplitude was larger in BM than SM regardless of the walking type. Exploratory regression analyses indicated that the N300 for BM, but not for SM or N200, was more negatively deflected with the increase of aesthetic preference scores. Our findings suggest that aesthetic preference enhances the later integrational process of BM represented in the N300 amplitude, whereas the early perceptual process (reflected by the N200 amplitude) is potentially modulated by familiarity rather than aesthetic preference in other's motion.

Cognitive adaptations for gathering-related navigation in humans.

Current research increasingly suggests that spatial cognition in humans is accomplished by many specialized mechanisms, each designed to solve a particular adaptive problem. A major adaptive problem for our hominin ancestors, particularly females, was the need to efficiently gather immobile foods which could vary greatly in quality, quantity, spatial location and temporal availability. We propose a cognitive model of a navigational gathering adaptation in humans and test its predictions in samples from the US and Japan. Our results are uniformly supportive: the human mind appears equipped with a navigational gathering adaptation that encodes the location of gatherable foods into spatial memory. This mechanism appears to be chronically active in women and activated under explicit motivation in men.

Eye contact perception in high-functioning adults with autism spectrum disorder.

LAY ABSTRACT: The detection of a self-directed gaze is often the starting point for social interactions and a person who feels as if they are being watched can prepare to respond to others' actions irrespective of the real gaze direction because the other person may likely be motivated to approach. Although many studies demonstrated that individuals with autism spectrum disorder have difficulty discriminating gaze direction, it remains unclear how the perception of self-directed gaze by individuals with autism spectrum disorder differs from that of age-, sex-, and IQ-matched typically developing individuals. Participants observed faces with various gaze directions and answered whether the person in the photograph was looking at them or not. Individuals with and without autism spectrum disorder were just as likely to perceive subtle averted gazes as self-directed gazes. The frequency of perceiving a self-directed gaze decreased as gaze aversion increased in both groups and, in general, individuals with autism spectrum disorder showed a comparable ability to perceive a self-directed gaze as that of typically developing individuals. Interestingly, considering face membership of photographs (ingroup or outgroup faces), typically developing individuals, but not individuals with autism spectrum disorder, were more likely to perceive self-directed gazes from ingroup faces than from outgroup faces. However, individuals with autism spectrum disorder had different affective experiences in response to ingroup and outgroup faces. These results suggest that individuals with autism spectrum disorder did not show an ingroup bias for the perception of a self-directed gaze, and raise a possibility that an atypical emotional experience contributes to the diminished ingroup bias.

Schizotypy is associated with difficulties detecting emotional facial expressions.

People with schizophrenia or subclinical schizotypal traits exhibit impaired recognition of facial expressions. However, it remains unclear whether the detection of emotional facial expressions is impaired in people with schizophrenia or high levels of schizotypy. The present study examined whether the detection of emotional facial expressions would be associated with schizotypy in a non-clinical population after controlling for the effects of IQ, age, and sex. Participants were asked to respond to whether all faces were the same as quickly and as accurately as possible following the presentation of angry or happy faces or their anti-expressions among crowds of neutral faces. Anti-expressions contain a degree of visual change that is equivalent to that of normal emotional facial expressions relative to neutral facial expressions and are recognized as neutral expressions. Normal expressions of anger and happiness were detected more rapidly and accurately than their anti-expressions. Additionally, the degree of overall schizotypy was negatively correlated with the effectiveness of detecting normal expressions versus anti-expressions. An emotion-recognition task revealed that the degree of positive schizotypy was negatively correlated with the accuracy of facial expression recognition. These results suggest that people with high levels of schizotypy experienced difficulties detecting and recognizing emotional facial expressions.

Amygdala integrates emotional expression and gaze direction in response to dynamic facial expressions.

Neuroimaging studies suggest that the amygdala integrates emotional expression and gaze direction, but the findings are inconsistent. We hypothesized that the dynamic facial expressions, which are more salient stimuli than static facial expressions are, would reveal the integration of emotional expression and gaze direction in amygdala activity. To test this hypothesis, we presented dynamic and static facial expressions of anger and happiness looking toward and away from the subject, and we visualized brain activity during these presentations using functional magnetic resonance imaging (fMRI). After the image acquisition phase of the study, the subject's experienced emotion in response to each stimulus was investigated. The left amygdala showed an interaction between presentation condition and gaze direction, indicating higher activity in response to dynamic, but not static, expressions looking toward the subjects than to expressions looking away from them. This was true for both angry and happy expressions. This pattern corresponded with the intensity of emotional arousal. These results suggest that the amygdala integrates emotional expression and gaze direction in dynamic facial expressions and modulates emotional arousal.

Neurocognitive Mechanisms Underlying Social Atypicalities in Autism: Weak Amygdala's Emotional Modulation Hypothesis.

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with atypicalities in social interaction. Although psychological and neuroimaging studies have revealed divergent impairments in psychological processes (e.g., emotion and perception) and neural activity (e.g., amygdala, superior temporal sulcus, and inferior frontal gyrus) related to the processing of social stimuli, it remains difficult to integrate these findings. In an effort to resolve this issue, we review our psychological and functional magnetic resonance imaging (fMRI) findings and present a hypothetical neurocognitive model. Our psychological study showed that emotional modulation of reflexive joint attention is impaired in individuals with ASD. Our fMRI study showed that modulation from the amygdala to the neocortex during observation of dynamic facial expressions is reduced in the ASD group. Based on these findings and other evidence, we hypothesize that weak modulation from the amygdala to the neocortex-through which emotion rapidly modulates various types of perceptual, cognitive, and motor processing functions-underlies the social atypicalities in individuals with ASD.