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Background The 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. Methods Resting-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. Results We 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. Conclusions The 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. Electronic supplementary material The online version of this article (doi:10.1186/s13229-016-0106-8) contains supplementary material, which is available to authorized users.

Background Previous 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. Methods We 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). Results Compared 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. Conclusions These 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. Electronic supplementary material The online version of this article (doi:10.1186/s13229-015-0026-z) contains supplementary material, which is available to authorized users.

Background Many individuals with autism spectrum disorders (ASD) have difficulty with verbal communication, which might be due to a lack of spontaneous orientation toward social auditory stimuli. Previous studies have shown that a single dose of oxytocin improves speech comprehension in autism. The primary aim of this study was to investigate whether the orientation behaviors toward human sounds are different for neurotypical (NT) adults and adults with ASD and whether oxytocin has an effect on their orientation behaviors toward human sounds. Methods This was a randomized, placebo-controlled, within-subject, crossover design study of intranasal oxytocin versus placebo in 13 NT adults and 16 adults with ASD. Subjects were randomized to 24 IU intranasal oxytocin or placebo on different days, and they were blind to the treatment. The participants then listened passively to human and non-human affective sounds while their skin conductance responses (SCRs) and the changes in peripheral blood vessel constriction were monitored as an indicator of spontaneous orientation. The monitored data were analyzed by a mixed-design ANOVA. Results Oxytocin enhanced the difference between the SCRs to human and non-human sounds in both the NT and ASD groups (F(1,56) = 6.046, p = 0.017). Further correlation coefficient analysis showed significant correlations between this SCR difference and the scores in the autism spectrum quotient ‘attention to detail’ and ‘social skill’ subscales and interpersonal reactivity index and social functioning scale in the ASD group. Oxytocin was well tolerated, and no serious adverse effects were reported. Conclusions The difference in SCRs implies that oxytocin nasal spray may enhance orientation behaviors toward human sounds in the presence of other environmental sounds in both ASD and NT adults. Trial registration UMIN-CTR Clinical Trial, Unique trial number: UMIN000005809