Takashi Itahashi

Altered Network Topologies and Hub Organization in Adults with Autism: A Resting-State fMRI Study

Recent functional magnetic resonance imaging (fMRI) studies on autism spectrum condition (ASC) have identified dysfunctions in specific brain networks involved in social and non-social cognition that persist into adulthood. Although increasing numbers of fMRI studies have revealed atypical functional connectivity in the adult ASC brain, such functional alterations at the network level have not yet been fully characterized within the recently developed graph-theoretical framework. Here, we applied a graph-theoretical analysis to resting-state fMRI data acquired from 46 adults with ASC and 46 age- and gender-matched controls, to investigate the topological properties and organization of autistic brain network. Analyses of global metrics revealed that, relative to the controls, participants with ASC exhibited significant decreases in clustering coefficient and characteristic path length, indicating a shift towards randomized organization. Furthermore, analyses of local metrics revealed a significantly altered organization of the hub nodes in ASC, as shown by analyses of hub disruption indices using multiple local metrics and by a loss of “hubness” in several nodes (e.g., the bilateral superior temporal sulcus, right dorsolateral prefrontal cortex, and precuneus) that are critical for social and non-social cognitive functions. In particular, local metrics of the anterior cingulate cortex consistently showed significant negative correlations with the Autism-Spectrum Quotient score. Our results demonstrate altered patterns of global and local topological properties that may underlie impaired social and non-social cognition in ASC.

Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: A multimodal brain imaging study

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.

Alterations of local spontaneous brain activity and connectivity in adults with high-functioning autism spectrum disorder

BackgroundPrevious autism research has hypothesized that abnormalities of functional connectivity in autism spectrum disorder (ASD) may vary with the spatial distance between two brain regions. Although several resting-state functional magnetic resonance imaging (rsfMRI) studies have extensively examined long-range (or distant) connectivity in the adult ASD brain, short-range (or local) connectivity has been investigated in less depth. Furthermore, the possible relationship between functional connectivity and brain activity level during the resting state remains unclear.MethodsWe acquired rsfMRI data from 50 adults with high-functioning ASD and 50 matched controls to examine the properties of spontaneous brain activity using measures of local and distant connectivity together with a measure of the amplitude of brain activity, known as fractional amplitude of low-frequency fluctuation (fALFF). The two connectivity measures were calculated using a common graph-theoretic framework. We also examined the spatial overlaps between these measures and possible relationships of these disrupted functional measures with autistic traits assessed by the Autism-Spectrum Quotient (AQ).ResultsCompared to the controls, participants with ASD exhibited local over-connectivity in the right superior frontal gyrus and middle frontal gyrus, accompanied by local under-connectivity in the bilateral fusiform gyri (FG) and right middle temporal gyrus (MTG). On the other hand, we did not find any significant alterations in distant connectivity. Participants with ASD also exhibited reduced fALFF in the right middle occipital gyrus, lingual gyrus, and FG. Further conjunction and spatial overlap analyses confirmed that the spatial pattern of reduced fALFF substantially overlapped with that of local under-connectivity, demonstrating the co-occurrence of disrupted connectivity and spontaneous activity level in the right inferior occipital gyrus, posterior MTG (pMTG), and FG. Finally, within the ASD group, disrupted local connectivity in the right pMTG significantly correlated with the “social interaction” subscale score of the AQ.ConclusionsThese findings revealed local functional disruptions in the occipital and temporal regions, especially the right FG and pMTG, in the form of co-occurrence of spontaneous brain activity level and local connectivity, which may underline social and communicative dysfunctions in adult ASD.

Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation

BackgroundThe insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups.ResultsWe observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain.ConclusionsThe results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD.

Attitudes toward risk and ambiguity in patients with autism spectrum disorder

Although the ability to make optimal decisions under uncertainty is an integral part of everyday life, individuals with autism spectrum disorder (ASD) frequently report that they experience difficulties with this skill. In behavioral economics, researchers distinguish two types of uncertainty to understand decision-making in this setting: risk (known probabilities) and ambiguity (unknown probabilities). However, it remains unclear how individuals with ASD behave under risk and ambiguity, despite growing evidence of their altered decision-making under uncertainty. We therefore extended previous research by studying the attitudes of those with ASD toward risk and ambiguity in both positive and negative contexts (i.e., gain and loss). In gain contexts, no significant difference was observed between the groups in risk attitudes, but ambiguity aversion was attenuated in ASD. In loss contexts, ambiguity attitudes did not significantly differ between the groups, but the ASD participants were less risk-seeking compared with the controls. In addition, insensitivity to the context change under risk and ambiguity in ASD was both significantly associated with poor social skills. These results improve our understanding of altered decision-making under uncertainty by disentangling the attitudes toward risk and ambiguity in ASD individuals. Applying behavioral economic tools may provide insights into the mechanisms underlying behavioral disturbances in ASD.

Inflexible daily behaviour is associated with the ability to control an automatic reaction in autism spectrum disorder

Inflexible behaviours in people with autism spectrum disorder (ASD) broadly obstruct social communication. Meanwhile, flexibility implicates cognitive control to resolve socially conflicting situations; however, it remains unclear how people with ASD behave in the face of these conflicts in this respect. We used the ultimatum game (UG) and the implicit-association test (IAT) to examine goal-directed/economic flexibility, both of which involve conflict and cognitive control. In addition, we used the Detail and Flexibility Questionnaire (DFlex) to measure inflexible everyday behaviour with diminished cognitive control and attention shifting. We observed the decreased flexibility in participants with ASD (DFlex and IAT); further, their IAT scores positively correlated with DFlex. However, in the UG, contrary to our prediction, participants with ASD accepted unfair offers more frequently than TD. These results suggest that assessing the automatic/attention processing level with the IAT could be a useful approach to study behavioural flexibility among ASD compared with the UG, which might comprise multiple response strategies besides economic rationality. Overall, the severity of inflexible daily behaviours in people with ASD may be associated with a reduced flexible attitude at an automatic level, altered attention processing and decreased cognitive control.

The effect of visual cues on performance in the ultimatum game in individuals with autism spectrum disorder

The Ultimatum Game (UG) allows for the assessment of altruistic behavior as well as the perception of fairness. We examined the effects of visual social cues (gaze of others), factors associated with autism, and trust on UG performance in typical adults (TAs) and individuals with autism spectrum disorder (ASD). We hypothesized that individuals with ASD would be less affected by visual social cues than TAs. We recruited 30 TAs and 30 individuals with ASD. Participants completed 30 trials of the UG, during which the visual background was altered to include either stylized eyespots, flowers, or a neutral background. Reaction times and money distributed in each condition were recorded. Reaction times did not vary among background conditions in either group, although individuals with ASD responded more slowly overall. TAs distributed less money in the neutral background and flowers conditions than in the eyespots condition, while no significant differences in the amount of money distributed were observed among background conditions for individuals with ASD, who also distributed more money overall than TAs. Such findings may be due to decreased susceptibility to social cues among individuals with ASD.

Social Skills in Autism Spectrum Disorders

Autism spectrum disorders children with (ASD), having core problems associated with social deficits, have recently attracted significant attention because the number of ASD is increasing in these days. Clarifying the difference between ASD and typically developing (TD) children in earlier developmental stages is difficult. The core difficulties of ASD are mainly manifest in social interaction and social skills development, verbal and nonverbal communication, and behavioral issues (e.g., stereotyped behaviors). Studies show that social skills development strongly involves learning to execute complex movements. One part of this chapter emphasizes the importance of sensory and motor development and their role to enhance social skills development in individuals with ASD. The more physical (motor learning and motor skills) and social interaction is used during the early years of development, the more fundamental social skills (e.g., eye gaze, joint attention, imitation, gestures, etc.) can be developed and encouraged.

White matter endophenotypes and correlates for the clinical diagnosis of autism spectrum disorder

Abstract Since prior diffusion tensor imaging (DTI) studies reported no significant differences in white matter organizations between individuals with autism spectrum disorder (ASD) and their unaffected siblings, the neural correlates for developing a clinical diagnosis among people with endophenotypes remain undetermined. We obtained DTI data from a total of 60 participants consisting of 30 people with endophenotypes and 30 people without. We first followed a conventional approach by comparing individuals with ASD and their unaffected siblings. Using region-of-interest approach, we then performed bootstrapping to examine whether the differences in white matter organizations between individuals with ASD and their unaffected siblings were substantially large, considering the distribution of differences between typically developing (TD) siblings. Conventional approaches revealed no significant differences in white matter organizations between individuals with ASD and their unaffected siblings. Bootstrapping revealed a significantly large difference in axial diffusivity in the left stria terminalis between individuals with ASD and their unaffected siblings after accounting for the distribution of differences in axial diffusivity among TD siblings (99.998 percentile). The results remained significant after controlling for multiple comparisons with Bonferroni method. We assumed that one aspect of this tract was associated with the development of a clinical diagnosis.

Sunk Cost Effect in Individuals with Autism Spectrum Disorder

The sunk cost effect, an interesting and well-known decision bias, is pervasive in real life and has been studied in various disciplines. In this study, we modified a task exemplifying the sunk cost effect and used it to evaluate this behavior in individuals with autism spectrum disorder (ASD). The control group exhibited a typical sunk cost effect in our task. We found that the sunk cost effect was lower in the ASD group than in the control group. The results agree with previous evidence of reduced sensitivity to context stimuli in individuals with ASD and extend this finding to the context of the sunk cost effect. Our findings are useful in addressing the practical implications on their socioeconomic behavior.