scholarly journals Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study

2021 ◽  
Author(s):  
Varun Arunachalam Chandran ◽  
Christos Pliatsikas ◽  
Janina Neufeld ◽  
Garret O'Connell ◽  
Anthony Haffey ◽  
...  

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adults (N=91) with and without a clinical diagnosis of autism. We examined regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging). Our findings show widespread grey matter differences, including in the social brain regions, and some evidence for white matter microstructure differences related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

Author(s):  
Claire E Kelly ◽  
Deanne K Thompson ◽  
Alicia J Spittle ◽  
Jian Chen ◽  
Marc L Seal ◽  
...  

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.


2020 ◽  
Vol 15 (4) ◽  
pp. 423-436
Author(s):  
Élodie Cauvet ◽  
Annelies van’t Westeinde ◽  
Roberto Toro ◽  
Ralf Kuja-Halkola ◽  
Janina Neufeld ◽  
...  

Abstract A female advantage in social cognition (SoC) might contribute to women’s underrepresentation in autism spectrum disorder (ASD). The latter could be underpinned by sex differences in social brain structure. This study investigated the relationship between structural social brain networks and SoC in females and males in relation to ASD and autistic traits in twins. We used a co-twin design in 77 twin pairs (39 female) aged 12.5 to 31.0 years. Twin pairs were discordant or concordant for ASD or autistic traits, discordant or concordant for other neurodevelopmental disorders or concordant for neurotypical development. They underwent structural magnetic resonance imaging and were assessed for SoC using the naturalistic Movie for the Assessment of Social Cognition. Autistic traits predicted reduced SoC capacities predominantly in male twins, despite a comparable extent of autistic traits in each sex, although the association between SoC and autistic traits did not differ significantly between the sexes. Consistently, within-pair associations between SoC and social brain structure revealed that lower SoC ability was associated with increased cortical thickness of several brain regions, particularly in males. Our findings confirm the notion that sex differences in SoC in association with ASD are underpinned by sex differences in brain structure.


2017 ◽  
Author(s):  
Kayle S. Sawyer ◽  
Nasim Maleki ◽  
George Papadimitriou ◽  
Nikos Makris ◽  
Marlene Oscar-Berman ◽  
...  

AbstractBackgroundExcessive alcohol consumption is associated with widespread brain damage, including abnormalities in frontal and limbic brain regions. In a prior study of neuronal circuitry connecting the frontal lobes and limbic system structures in abstinent alcoholic men, we demonstrated decreases in white matter fractional anisotropy (FA) on diffusion tensor magnetic resonance imaging (dMRI). In the present study, we examined sex differences in alcoholism-related abnormalities of white matter connectivity.MethodsdMRI scans were acquired from 49 abstinent alcoholic individuals (26 women) and 41 nonalcoholic controls (22 women). Tract-based spatial statistical tools were used to estimate regional FA of white matter tracts and to determine sex differences and their relation to measures of alcoholism history.ResultsSex-related differences in white matter connectivity were observed in association with alcoholism: Compared to nonalcoholic men, alcoholic men had diminished FA in portions of the corpus callosum, the superior longitudinal fasciculi II and III, and the arcuate fasciculus and extreme capsule. In contrast, alcoholic women had higher FA in these regions. Sex differences also were observed for correlations between corpus callosum FA and length of sobriety.ConclusionsSexual dimorphism in white matter microstructure in abstinent alcoholics may implicate underlying differences in the neurobehavioral liabilities for developing alcohol abuse disorders, or for sequelae following abuse.


2020 ◽  
Author(s):  
Carla Esther Meyer Golden ◽  
Victoria X Wang ◽  
Hala Harony-Nicolas ◽  
Patrick R. Hof ◽  
Joseph Buxbaum

Abstract Background: Mutations and deletions in the SHANK3 synaptic gene cause the major neurodevelopmental features of Phelan-McDermid syndrome (PMS). The SHANK3 gene encodes a key structural component of excitatory synapses that is important for synaptogenesis. PMS is characterized by intellectual disability, autism spectrum disorder, cognitive deficits, physical dysmorphic features, sensory hyporeactivity, and alterations in the size of multiple brain regions. Clinical assessments and limited imaging studies have revealed a reduction in volume of multiple brain regions. They have also found white matter thinning and microstructural alterations to be persistent in patients with PMS. While many of these impairments have been replicated in mouse models of PMS, the brain structure of a rat model has not yet been studied. Methods: We assessed the brain structure of haploinsufficient and homozygous Shank3-deficient rats that model the behavioral deficits of PMS with magnetic resonance and diffusion tensor imaging, and compared their brain structure to wild type littermates.Results: Both gray and white matter structures were smaller in Shank3-deficient rats, leading to an overall reduction in brain size compared to wild type littermates. The largest region to be diminished in size was the neocortex. Some regions involved in sensory processing and white matter regions were also reduced in size. Lastly, the microstructure of two white matter tracts, the external capsule and fornix, was abnormal.Conclusions: Shank3-deficient rats replicate the reduced brain volume and altered white matter phenotypes present in individuals with PMS. Therefore, the brain regions that were altered represent potential cross-species structural biomarkers that warrant further study.


2021 ◽  
pp. 102897
Author(s):  
Varun Arunachalam Chandran ◽  
Christos Pliatsikas ◽  
Janina Neufeld ◽  
Garret O'Connell ◽  
Anthony Haffey ◽  
...  

2019 ◽  
Author(s):  
Justin C. Hayes ◽  
Katherine L Alfred ◽  
Rachel Pizzie ◽  
Joshua S. Cetron ◽  
David J. M. Kraemer

Modality specific encoding habits account for a significant portion of individual differences reflected in functional activation during cognitive processing. Yet, little is known about how these habits of thought influence long-term structural changes in the brain. Traditionally, habits of thought have been assessed using self-report questionnaires such as the visualizer-verbalizer questionnaire. Here, rather than relying on subjective reports, we measured habits of thought using a novel behavioral task assessing attentional biases toward picture and word stimuli. Hypothesizing that verbal habits of thought are reflected in the structural integrity of white matter tracts and cortical regions of interest, we used diffusion tensor imaging and volumetric analyses to assess this prediction. Using a whole-brain approach, we show that word bias is associated with increased volume in several bilateral language regions, in both white and grey matter parcels. Additionally, connectivity within white matter tracts within an a priori speech production network increased as a function of word bias. These results demonstrate long-term structural and morphological differences associated with verbal habits of thought.


Author(s):  
Shawn D’Souza ◽  
Lisa Hirt ◽  
David R Ormond ◽  
John A Thompson

Abstract Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.


2017 ◽  
Vol 30 (5) ◽  
pp. 454-460
Author(s):  
Dana M Middleton ◽  
Jonathan Y Li ◽  
Steven D Chen ◽  
Leonard E White ◽  
Patricia I Dickson ◽  
...  

Purpose We compared fractional anisotropy and radial diffusivity measurements between pediatric canines affected with mucopolysaccharidosis I and pediatric control canines. We hypothesized that lower fractional anisotropy and higher radial diffusivity values, consistent with dysmyelination, would be present in the mucopolysaccharidosis I cohort. Methods Six canine brains, three affected with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and imaged using a 7T small-animal magnetic resonance imaging system. Average fractional anisotropy and radial diffusivity values were calculated for four white-matter regions based on 100 regions of interest per region per specimen. A 95% confidence interval was calculated for each mean value. Results No difference was seen in fractional anisotropy or radial diffusivity values between mucopolysaccharidosis affected and unaffected brains in any region. In particular, the 95% confidence intervals for mucopolysaccharidosis affected and unaffected canines frequently overlapped for both fractional anisotropy and radial diffusivity measurements. In addition, in some brain regions a large range of fractional anisotropy and radial diffusivity values were seen within the same cohort. Conclusion The fractional anisotropy and radial diffusivity values of white matter did not differ between pediatric mucopolysaccharidosis affected canines and pediatric control canines. Possible explanations include: (a) a lack of white matter tissue differences between mucopolysaccharidosis affected and unaffected brains at early disease stages; (b) diffusion tensor imaging does not detect any existing differences; (c) inflammatory processes such as astrogliosis produce changes that offset the decreased fractional anisotropy values and increased radial diffusivity values that are expected in dysmyelination; and (d) our sample size was insufficient to detect differences. Further studies correlating diffusion tensor imaging findings to histology are warranted.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinfeng Yu ◽  
Xinzhen Yin ◽  
Hui Hong ◽  
Shuyue Wang ◽  
Yeerfan Jiaerken ◽  
...  

Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Sussanne Reyes ◽  
Patricio Peirano ◽  
Betsy Lozoff ◽  
Cecilia Algarin

Abstract IntroductionObesity has been associated with lower white matter integrity (WMI) in limbic brain regions, including the fornix. Both early decrease of WMI in the fornix (WMIf) and midlife obesity have been related to dementia incidence with advancing age. No studies have explored early cognitive predictors of WMIf in overweight-obese (OO) adults. Aim of this study was to compare OO and normal-weight (NW) participants with respect to (a) WMIf in adulthood and (b) the relationship between cognitive performance at school-age and in adolescence with WMIf in adulthood.MethodsParticipants were part of a cohort followed since infancy who underwent magnetic resonance imaging studies in adulthood (22.3 ± 1.3 years). Diffusion tensor imaging was performed and Tract Based Spatial Statistics (TBSS) was used to obtain fractional anisotropy (FA) skeleton; increased FA relates to greater WMI. A mask for the fornix was created (JHU-ICBM DTI-81 Atlas) and then used to extract the average FA for each individual. Participants also performed neurocognitive tasks: (a) school-age (10.3 ± 1.0 years): the trail making test comprises two conditions and time difference between conditions reflects cognitive flexibility; (b) adolescence (15.6 ± 0.5 years): incentive task that test the effect of incentives (reward, loss avoidance or neutral) on inhibitory control performance (correct responses latency). In adulthood, BMI was categorized as NW (≥ 18.5 to < 25.0 kg/m2) and OO (≥ 25.0 kg/m2) groups. A t-test and univariate GLM were conducted. Analysis were adjusted by sex and age-specific BMI z-scores.ResultsParticipants were 27 NW (41% female) and 41 OO (49% female). Compared to NW, OO participants showed decreased FA in the fornix (0.585 vs. 0.618, p < 0.05), i.e. lower WMIf. Differences were apparent in the relationship between cognitive flexibility at school-age (F = 2.9, p = 0.06) and loss avoidance latency in adolescence (F = 3.5, p < 0.05) with FA in the fornix in adulthood. Increased cognitive flexibility at school-age (β = 0.335, p < 0.05) and decreased loss avoidance latency in adolescence (β = -0.581, p < 0.001) were related to higher FA in the fornix in OO adults. No relationship resulted significant in NW adults.DiscussionPerformance in neurocognitive tasks at earlier developmental stages were related with WMIf only in OO adults, group characterized by decreased WMIf. Our results provide evidence regarding specific neurocognitive tasks with predictive value for WMIf alterations. Further, they could contribute to the understanding of neural mechanisms underlying obesity and also provide insight relative to neurodegenerative risk with advancing age.SupportFondecyt 11160671 and NIH HD33487.


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