State-dependent changes of connectivity patterns and functional brain network topology in Autism Spectrum Disorder

Anatomical and functional brain studies have converged to the hypothesis that Autism Spectrum Disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that functional connectivity changes in opposite ways in ASD and typicals as attention shifts from external world towards one's body generated information. Furthermore, ASD subject alter more markedly than typicals their connectivity across cognitive states. Using differences in brain connectivity across conditions, we classified ASD subjects at a performance around 80% while classification based on the connectivity patterns in any given cognitive state were close to chance. Connectivity between the Anterior Insula and dorsal-anterior Cingulate Cortex showed the highest classification accuracy and its strength increased with ASD severity. These results pave the path for diagnosis of mental pathologies based on functional brain networks obtained from a library of mental states

Tract-based statistical analyzes in dMRI in autism spectrum disorder

International audienceIntroduction Recent studies show an atypical perceptive behavior on face processing in autism. Functional studies show that the fusiform gyrus is involved in face perception and is not or less activated in autistic subjects [1]. These face processing is believed to affect social interaction, which can be quantified by ADOS scores and related to the functionality of the prefrontal cortex. The aim of this study is to quantify anatomical changes in autistic subjects on the white matter tracts that traverse the fusiform gyrus, the prefrontal cortex and the superior temporal gyrus and correlate them with ADOS scores to complete. In this study, we first verified the connectivity difference between the fusiform gyrus, the prefrontal cortex and the superiotemporal gyrus through fMRI. Then, we used Diffusion Tensor MRI (DT) images to assess the integrity of automatically segmented white matter bundles connecting these girii. Finally, we perform statistical analysis on these fiber bundles using diffusivity measures calculated from DT to characterize tissue microstructure changes and correlate these changes with ADOS scores. Materials and methods Data acquisition. We acquired dMRI of eight adults with high-functioning autism or Asperger syndrome and eleven healthy adults at the University of Buenos Aires on a GE Signa Hdxt 3.0T scanner. The acquisition consisted in 80 directions with b=1000s/mm2 and 1 image with b=0s/mm2 with 1×1×1.3mm voxel size. Data preparation. We started by generating an unbiased template of the DT images and registering linearly and non-linearly all of the images to it. Then, we computed DT-based full brain tractography for every subject. Finally, we used the tools developed by Wassermann et al [2] to cluster fiber bundles and select the bundles traversing the fusiform gyrus. This gyrus was identified through the girii parcelation of the JHU atlas. We clustered these bundles across subjects extracting a set of population-obtained bundles (see for Fig 1 for an example). Data analysis. We applied the statistical analysis of Wassermann et al [3] for each population-obtained bundle, we calculated its tract-probability map (TPM) (see Fig.3 for an example) and skeletonized this map to obtain a bidimensional representation of each bundle. For each patient, we projected the measure of diffusivity (FA, axial or radial diffusivity) around the tract to their closest point on the skeleton and we average them with a weight according to the TPM. This produces two populations (one for autists and one for controls) of projected functions on the skeleton. For each tract and each measure, we used a cluster-based permutation hypothesis testing approach [4] to detect dissimilarities between both populations. For significant clusters, we calculated correlation between the mean diffusivity measure and ADOS scores. Results We found different clusters (Fig 1, red voxels) where there were dissimilarities between autistic and healthy subjects in FA measures on tracts traversing the fusiform gyrus in both hemispheres of the brain. We observed a reduction of FA values in a cluster (Fig 2, red voxels) on a bundle joined the superior temporal gyrus to the prefrontal cortex. In this cluster, the mean FA on the autistic subjects was strongly correlated with their scores to ADOS social interaction with a correlation coefficient lower than -0.96 a p-value lower than 0.004 (Fig3). Discussion First, results revealing difference between controls and autists in clusters on fiber bundle traversing the fusiform gyrus are in agreement with current literature giving this area as a classical area of face perception. Agreement reinforced by functional study of autists showing a drop of connectivity between the fusiform gyrus and the superior temporal cortex in comparison with controls (Fig 4). The localisation of the cluster where we founded a correlation with ADOS social interaction scores (Fig3) is in agreement with current anatomical literature, the superior temporal gyrus being a classical area of face perception and emotion and the prefrontal cortex a classical area of social interaction. This is reinforced by the strong inverse correlation showing that in this linking cluster a drop of FA value is strongly correlated by a rise of the intensity of autism. Our fMRI study (Fig 4) corroborates these statistical results, showing a drop of connectivity between the prefrontal cortex and the superior temporal gyrus. Disruption of white matter tracts between regions implicated in social functioning and face perception may contribute to increase the severity of autism

Tract-based statistical analyzes in dMRI in autism spectrum disorder

International audienceIntroduction Recent studies show an atypical perceptive behavior on face processing in autism. Functional studies show that the fusiform gyrus is involved in face perception and is not or less activated in autistic subjects [1]. These face processing is believed to affect social interaction, which can be quantified by ADOS scores and related to the functionality of the prefrontal cortex. The aim of this study is to quantify anatomical changes in autistic subjects on the white matter tracts that traverse the fusiform gyrus, the prefrontal cortex and the superior temporal gyrus and correlate them with ADOS scores to complete. In this study, we first verified the connectivity difference between the fusiform gyrus, the prefrontal cortex and the superiotemporal gyrus through fMRI. Then, we used Diffusion Tensor MRI (DT) images to assess the integrity of automatically segmented white matter bundles connecting these girii. Finally, we perform statistical analysis on these fiber bundles using diffusivity measures calculated from DT to characterize tissue microstructure changes and correlate these changes with ADOS scores. Materials and methods Data acquisition. We acquired dMRI of eight adults with high-functioning autism or Asperger syndrome and eleven healthy adults at the University of Buenos Aires on a GE Signa Hdxt 3.0T scanner. The acquisition consisted in 80 directions with b=1000s/mm2 and 1 image with b=0s/mm2 with 1×1×1.3mm voxel size. Data preparation. We started by generating an unbiased template of the DT images and registering linearly and non-linearly all of the images to it. Then, we computed DT-based full brain tractography for every subject. Finally, we used the tools developed by Wassermann et al [2] to cluster fiber bundles and select the bundles traversing the fusiform gyrus. This gyrus was identified through the girii parcelation of the JHU atlas. We clustered these bundles across subjects extracting a set of population-obtained bundles (see for Fig 1 for an example). Data analysis. We applied the statistical analysis of Wassermann et al [3] for each population-obtained bundle, we calculated its tract-probability map (TPM) (see Fig.3 for an example) and skeletonized this map to obtain a bidimensional representation of each bundle. For each patient, we projected the measure of diffusivity (FA, axial or radial diffusivity) around the tract to their closest point on the skeleton and we average them with a weight according to the TPM. This produces two populations (one for autists and one for controls) of projected functions on the skeleton. For each tract and each measure, we used a cluster-based permutation hypothesis testing approach [4] to detect dissimilarities between both populations. For significant clusters, we calculated correlation between the mean diffusivity measure and ADOS scores. Results We found different clusters (Fig 1, red voxels) where there were dissimilarities between autistic and healthy subjects in FA measures on tracts traversing the fusiform gyrus in both hemispheres of the brain. We observed a reduction of FA values in a cluster (Fig 2, red voxels) on a bundle joined the superior temporal gyrus to the prefrontal cortex. In this cluster, the mean FA on the autistic subjects was strongly correlated with their scores to ADOS social interaction with a correlation coefficient lower than -0.96 a p-value lower than 0.004 (Fig3). Discussion First, results revealing difference between controls and autists in clusters on fiber bundle traversing the fusiform gyrus are in agreement with current literature giving this area as a classical area of face perception. Agreement reinforced by functional study of autists showing a drop of connectivity between the fusiform gyrus and the superior temporal cortex in comparison with controls (Fig 4). The localisation of the cluster where we founded a correlation with ADOS social interaction scores (Fig3) is in agreement with current anatomical literature, the superior temporal gyrus being a classical area of face perception and emotion and the prefrontal cortex a classical area of social interaction. This is reinforced by the strong inverse correlation showing that in this linking cluster a drop of FA value is strongly correlated by a rise of the intensity of autism. Our fMRI study (Fig 4) corroborates these statistical results, showing a drop of connectivity between the prefrontal cortex and the superior temporal gyrus. Disruption of white matter tracts between regions implicated in social functioning and face perception may contribute to increase the severity of autism

LTR Retrotransposons in Fungi

Transposable elements with long terminal direct repeats (LTR TEs) are one of the best studied groups of mobile elements. They are ubiquitous elements present in almost all eukaryotic genomes. Their number and state of conservation can be a highlight of genome dynamics. We searched all published fungal genomes for LTR-containing retrotransposons, including both complete, functional elements and remnant copies. We identified a total of over 66,000 elements, all of which belong to the Ty1/Copia or Ty3/Gypsy superfamilies. Most of the detected Gypsy elements represent Chromoviridae, i.e. they carry a chromodomain in the pol ORF. We analyzed our data from a genome-ecology perspective, looking at the abundance of various types of LTR TEs in individual genomes and at the highest-copy element from each genome. The TE content is very variable among the analyzed genomes. Some genomes are very scarce in LTR TEs (<50 elements), others demonstrate huge expansions (>8000 elements). The data shows that transposon expansions in fungi usually involve an increase both in the copy number of individual elements and in the number of element types. The majority of the highest-copy TEs from all genomes are Ty3/Gypsy transposons. Phylogenetic analysis of these elements suggests that TE expansions have appeared independently of each other, in distant genomes and at different taxonomical levels. We also analyzed the evolutionary relationships between protein domains encoded by the transposon pol ORF and we found that the protease is the fastest evolving domain whereas reverse transcriptase and RNase H evolve much slower and in correlation with each other

The feeling of me feeling for you: Interoception, alexithymia and empathy in autism.

Following recent evidence for a link between interoception, emotion and empathy, we investigated relationships between these factors in Autism Spectrum Disorder (ASD). 26 adults with ASD and 26 healthy participants completed tasks measuring interoception, alexithymia and empathy. ASD participants with alexithymia demonstrated lower cognitive and affective empathy than ASD participants without alexithymia. ASD participants showed reduced interoceptive sensitivity (IS), and also reduced interoceptive awareness (IA). IA was correlated with empathy and alexithymia, but IS was related to neither. Alexithymia fulfilled a mediating role between IA and empathy. Our findings are suggestive of an alexithymic subgroup in ASD, with distinct interoceptive processing abilities, and have implications for diagnosis and interventions

Atypical Time Course of Object Recognition in Autism Spectrum Disorder

International audienceIn neurotypical observers, it is widely believed that the visual system samples the world in a coarse-to-fine fashion. Past studies on Autism Spectrum Disorder (ASD) have identified atypical responses to fine visual information but did not investigate the time course of the sampling of information at different levels of granularity (i.e. Spatial Frequencies, SF). Here, we examined this question during an object recognition task in ASD and neurotypical observers using a novel experimental paradigm. Our results confirm and characterize with unprecedented precision a coarse-to-fine sampling of SF information in neurotypical observers. In ASD observers, we discovered a different pattern of SF sampling across time: in the first 80 ms, high SFs lead ASD observers to a higher accuracy than neurotypical observers, and these SFs are sampled differently across time in the two subject groups. Our results might be related to the absence of a mandatory precedence of global information, and to top-down processing abnormalities in ASD

Real-world expectations and their affective value modulate object processing

International audienceIt is well known that expectations influence how we perceive the world. Yet the neural mechanisms underlying this process remain unclear. Studies about the effects of prior expectations have focused so far on artificial contingencies between simple neutral cues and events. Real-world expectations are however often generated from complex associations between contexts and objects learned over a lifetime. Additionally, these expectations may contain some affective value and recent proposals present conflicting hypotheses about the mechanisms underlying affect in predictions. In this study, we used fMRI to investigate how object processing is influenced by realistic context-based expectations, and how affect impacts these expectations. First, we show that the precuneus, the inferotemporal cortex and the frontal cortex are more active during object recognition when expectations have been elicited a priori, irrespectively of their validity or their affective intensity. This result supports previous hypotheses according to which these brain areas integrate contextual expectations with object sensory information. Notably, these brain areas are different from those responsible for simultaneous context-object interactions , dissociating the two processes. Then, we show that early visual areas, on the contrary, are more active during object recognition when no prior expectation has been elicited by a context. Lastly, BOLD activity was shown to be enhanced in early visual areas when objects are less expected, but only when contexts are neutral; the reverse effect is observed when contexts are affective. This result supports the proposal that affect modulates the weighting of sensory information during predictions. Together, our results help elucidate the neural mechanisms of real-world expectations

Explicit processing of everyday social scenes in ASD.

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