Constrained spherical deconvolution-based tractography and tract-based spatial statistics show abnormal microstructural organization in Asperger syndrome

Peer reviewe

Abnormal wiring of the connectome in adults with high-functioning autism spectrum disorder

Background: Recent brain imaging findings suggest that there are widely distributed abnormalities affecting the brain connectivity in individuals with autism spectrum disorder (ASD). Using graph theoretical analysis, it is possible to investigate both global and local properties of brain's wiring diagram, i.e., the connectome. Methods: We acquired diffusion-weighted magnetic resonance imaging data from 14 adult males with high-functioning ASD and 19 age-, gender-, and IQ-matched controls. As with diffusion tensor imaging-based tractography, it is not possible to detect complex (e.g., crossing) fiber configurations, present in 60-90 % of white matter voxels; we performed constrained spherical deconvolution-based whole brain tractography. Unweighted and weighted structural brain networks were then reconstructed from these tractography data and analyzed with graph theoretical measures. Results: In subjects with ASD, global efficiency was significantly decreased both in the unweighted and the weighted networks, normalized characteristic path length was significantly increased in the unweighted networks, and strength was significantly decreased in the weighted networks. In the local analyses, betweenness centrality of the right caudate was significantly increased in the weighted networks, and the strength of the right superior temporal pole was significantly decreased in the unweighted networks in subjects with ASD. Conclusions: Our findings provide new insights into understanding ASD by showing that the integration of structural brain networks is decreased and that there are abnormalities in the connectivity of the right caudate and right superior temporal pole in subjects with ASD.Peer reviewe

Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised

Tämä artikkeli ei ole avattavissa lehden sivuilta, koska linkit ja DOI vievät väärään artikkeliin samoin PDF sen ohessa. Kustantajalle ilmoitettu ja pyydetty korjausta.Abstract Background: Twin and family studies have indicated a strong genetic component in autism spectrum disorders, and genetic studies have revealed highly heterogeneous risk factors. The range and severity of the symptom presentation also vary in the spectrum. Thus, symptom-based phenotypes are putatively more closely related to the underlying biology of autism than the end-state diagnosis. Methods: We performed principal component analysis on Autism Diagnostic Interview-Revised algorithm for 117 Finnish families and 594 families from the Autism Genetic Research Exchange (AGRE). The resulting continuous component scores were used as quantitative phenotypes in family-based association analysis. In addition, K-means clustering was performed to cluster and visualize the results of the PCA. Unaffected siblings were included in the study. Results: The components were interpreted as Social Component (SC), communication component and Restricted and Stereotyped Behavior Component (RSBC). K-means clustering showed that, especially in SC, the range of the symptom severity was increased by the siblings. The association of neuroligin 1 with SC was increased, compared to a previous study where only the end-state diagnosis was used. In RSBC, the range of the symptom severity of siblings overlapped greatly with that of patients, which could explain why no association of reelin was found in previous studies in which only the end-state diagnosis was used, but a significant association of reelin with RSBC was now found in the Finnish families (Bonferroni-corrected p=0.029 for rs362644). Although, the Finnish sample is isolated and genetically very homogeneous, compared to the heterogeneous background of AGRE families, many single-nucleotide polymorphisms in reelin, showed modest association with RSBC in the AGRE sample, too. Conclusions: This study demonstrates how the quantitative phenotypes can affect the association analyses, and yields further support to the use of siblings in the study of complex neuropsychiatric disorders.Peer reviewe

Topological Structural Brain Connectivity Alterations in Aspartylglucosaminuria: A Case-Control Study

BACKGROUND AND PURPOSE: We investigated global and local properties of the structural brain connectivity networks in aspartylglucosaminuria, an autosomal recessive and progressive neurodegenerative lysosomal storage disease. Brain connectivity in aspartylglucosaminuria has not been investigated before, but previous structural MR imaging studies have shown brain atrophy, delayed myelination, and decreased thalamic and increased periventricular WM T2 signal intensity. MATERIALS AND METHODS: We acquired diffusion MR imaging and T1-weighted data from 12 patients with aspartylglucosaminuria (mean age, 23 [SD, 8] years; 5 men), and 30 healthy controls (mean age, 25 [SD, 10] years; 13 men). We performed whole-brain constrained spherical deconvolution tractography, which enables the reconstruction of neural tracts through regions with complex fiber configurations, and used graph-theoretical analysis to investigate the structural brain connectivity networks. RESULTS: The integration of the networks was decreased, as demonstrated by a decreased normalized global efficiency and an increased normalized characteristic path length. In addition, the average strength of the networks was decreased. In the local analyses, we found decreased strength in 11 nodes, including, for example, the right thalamus, right putamen, and, bilaterally, several occipital and temporal regions. CONCLUSIONS: We found global and local structural connectivity alterations in aspartylglucosaminuria. Biomarkers related to the treatment efficacy are needed, and brain network properties may provide the means for long term follow-up.Peer reviewe

Additional file 1: Table S1. of Abnormal wiring of the connectome in adults with high-functioning autism spectrum disorder

p values for the local network properties. p values <0.05 are emphasized

The brains of high functioning autistic individuals do not synchronize with those of others

Multifaceted and idiosyncratic aberrancies in social cognition characterize autism spectrum disorders (ASDs). To advance understanding of underlying neural mechanisms, we measured brain hemodynamic activity with functional magnetic resonance imaging (fMRI) in individuals with ASD and matched-pair neurotypical (NT) controls while they were viewing a feature film portraying social interactions. Pearson's correlation coefficient was used as a measure of voxelwise similarity of brain activity (InterSubject Correlations—ISCs). Individuals with ASD showed lower ISC than NT controls in brain regions implicated in processing social information including the insula, posterior and anterior cingulate cortex, caudate nucleus, precuneus, lateral occipital cortex, and supramarginal gyrus. Curiously, also within NT group, autism-quotient scores predicted ISC in overlapping areas, including, e.g., supramarginal gyrus and precuneus. In ASD participants, functional connectivity was decreased between the frontal pole and the superior frontal gyrus, angular gyrus, superior parietal lobule, precentral gyrus, precuneus, and anterior/posterior cingulate gyrus. Taken together these results suggest that ISC and functional connectivity measure distinct features of atypical brain function in high-functioning autistic individuals during free viewing of acted social interactions. Our ISC results suggest that the minds of ASD individuals do not ‘tick together’ with others while perceiving identical dynamic social interactions.Peer reviewe