Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: a multimodal brain imaging study.
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ABSTRACT:
SUBMITTER: Itahashi T
PROVIDER: S-EPMC4299973 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with autism spectrum disorder (ASD). METHODS:We acquired pulsed arterial spin labeling magnetic resonance imaging data in 44 generally high-functioning participants with ASD simplex and 66 typically developing control subjects with comparable mean full-scale IQs. We compared rCBF values voxelwise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with N-acetylaspartate metabolite levels. RESULTS:We detected significantly higher rCBF values throughout frontal white matter and subcortical gray matter in participants with ASD. rCBF correlated positively with socialization deficits in participants with ASD in regions where hyperperfusion was greatest. rCBF declined with increasing IQ in the typically developing group, a correlation that was absent in participants with ASD, whose rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with N-acetylaspartate metabolite levels throughout the frontal white matter, with greater rCBF accompanying lower and increasingly abnormal N-acetylaspartate levels relative to those of typically developing control subjects. CONCLUSIONS:These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.
| S-EPMC6420395 | biostudies-literature
Project description:Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multimodal imaging to better inform on the neural characteristics most relevant to the disorder.
| S-EPMC4782775 | biostudies-other
Project description:BackgroundDespite decades of research, there is continued uncertainty regarding whether autism is associated with a specific profile of gray matter (GM) structure. This inconsistency may stem from the widespread use of voxel-based morphometry (VBM) methods that combine indices of GM density and GM volume. If GM density or volume, but not both, prove different in autism, the traditional VBM approach of combining the two indices may obscure the difference. The present study measures GM density and volume separately to examine whether autism is associated with alterations in GM volume, density, or both.MethodsDifferences in MRI-based GM density and volume were examined in 6-25 year-olds with a diagnosis of autism spectrum disorder (n = 213, 80.8% male, IQ 47-154) and a typically developing (TD) sample (n = 190, 71.6% male, IQ 67-155). High-resolution T1-weighted anatomical images were collected on a single MRI scanner. Regional density and volume were estimated via whole-brain parcellation comprised of 1625 parcels. Parcel-wise analyses were conducted using generalized additive models while controlling the false discovery rate (FDR, q < 0.05). Volume differences in the 68-region Desikan-Killiany atlas derived from Freesurfer were also examined, to establish the generalizability of findings across methods.ResultsNo density differences were observed between the autistic and TD groups, either in individual parcels or whole brain mean density. Increased volume was observed in autism compared to the TD group when controlling for Age, Sex, and IQ, both at the level of the whole brain (total volume) and in 45 parcels (2.8% of total parcels). Parcels with greater volume included inferior, middle, and superior temporal gyrus, inferior and superior frontal gyrus, precuneus, and fusiform gyrus. Converging evidence from a standard Freesurfer pipeline also identified greater volume in a number of overlapping regions.LimitationsThe method for determining "density" is not a direct measure of neuronal density, and this study cannot reveal underlying cellular differences. While this study represents possibly the largest single-site sample of its kind, it is underpowered to detect very small differences.ConclusionsThese results provide compelling evidence that autism is associated with regional GM volumetric differences, which are more prominent than density differences. This underscores the importance of examining volume and density separately, and suggests that direct measures of volume (e.g. region-of-interest or tensor-based morphometry approaches) may be more sensitive to autism-relevant differences in neuroanatomy than concentration/density-based approaches.
| S-EPMC8633367 | biostudies-literature
Project description:There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients.
| S-EPMC6869166 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is currently viewed as a disorder of cortical systems connectivity, with a heavy emphasis being on the structural integrity of white matter tracts. However, the majority of the literature to date has focused on children with ASD. Understanding the integrity of white matter tracts in adults may help reveal the nature of ASD pathology in adulthood and the potential contributors to cognitive impairment. This study examined white matter water diffusion using diffusion tensor imaging in relation to neuropsychological measures of cognition in a sample of 45 adults with ASD compared to 20 age, gender, and full-scale-IQ-matched healthy volunteers. Tract-based spatial statistics were used to assess differences in diffusion along white matter tracts between groups using permutation testing. The following neuropsychological measures of cognition were assessed: processing speed, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Results indicated that fractional anisotropy (FA) was significantly reduced in adults with ASD in the anterior thalamic radiation (P = 0.022) and the right cingulum (P = 0.008). All neuropsychological measures were worse in the ASD group, but none of the measures significantly correlated with reduced FA in either tract in the adults with ASD or in the healthy volunteers. Together, this indicates that the tracts that are the most impacted in autism may not be (at least directly) responsible for the behavioral deficits in ASD. Autism Res 2020, 13: 702-714. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long-range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.
| S-EPMC8237714 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is a highly complex neurodevelopmental condition that is accompanied by neuroanatomical differences on the macroscopic and microscopic level. Findings from histological, genetic, and more recently in vivo neuroimaging studies converge in suggesting that neuroanatomical abnormalities, specifically around the gray-white matter (GWM) boundary, represent a crucial feature of ASD. However, no research has yet characterized the GWM boundary in ASD based on measures of diffusion. Here, we registered diffusion tensor imaging data to the structural T1-weighted images of 92 adults with ASD and 92 matched neurotypical controls in order to examine between-group differences and group-by-sex interactions in fractional anisotropy and mean diffusivity sampled at the GWM boundary, and at different sampling depths within the superficial white and into the gray matter. As hypothesized, we observed atypical diffusion at and around the GWM boundary in ASD, with between-group differences and group-by-sex interactions depending on tissue class and sampling depth. Furthermore, we identified that altered diffusion at the GWM boundary partially (i.e., ~50%) overlapped with atypical gray-white matter tissue contrast in ASD. Our study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.
| S-EPMC7775996 | biostudies-literature
Project description:Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies.
| S-EPMC6093436 | biostudies-literature
Project description:BackgroundRecent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.Materials and methodsWe used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3).ResultsASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.LimitationsOur study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples.ConclusionThese preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.
| S-EPMC8248433 | biostudies-literature
Project description:Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression.
| S-EPMC4827723 | biostudies-literature
Project description:Background Brain gray matter alterations in patients with trigeminal neuralgia (TN) have been detected in prior neuroimaging studies, but the results are heterogeneous. The current study conducted coordinate-based meta-analyses across neuroimaging studies, aiming to find the pattern of brain anatomic and functional alterations in patients with TN. Methods We performed a systematic literature search of PubMed, Embase, and Web of Science to identify relevant publications. A multimodal meta-analysis for whole-brain voxel-based morphometry (VBM) studies and functional imaging studies in TN was performed using anisotropic effect size-based signed differential mapping. Results The meta-analysis comprised 10 VBM studies with 398 TN patients and 275 healthy controls, and 13 functional magnetic resonance imaging studies with 307 TN patients and 264 healthy controls. The multimodal meta-analysis showed conjoint structural and functional brain alterations in the right fusiform gyrus and inferior temporal gyrus, bilateral thalamus, left superior temporal gyrus, left insula, and inferior frontal gyrus. The unimodal meta-analysis showed decreased gray matter volume alone in the left putamen, left postcentral gyrus, and right amygdala as well as only functional abnormalities in the left cerebellum, bilateral precuneus, and left middle temporal gyrus. Conclusion This meta-analysis revealed overlapping anatomic and functional gray matter abnormalities in patients with TN, which may help provide new insights into the neuropathology and potential treatment biomarkers of TN.
| S-EPMC10436096 | biostudies-literature