Age-related abnormalities in white matter microstructure in autism spectrum disorders

Kleinhans, Natalia M.; Pauley, Gregory; Richards, Todd L.; Neuhaus, Emily; Martin, Nathalie; Corrigan, Neva M.; Shaw, Dennis; Estes, Annette; Dager, Stephen R.

doi:10.1016/j.brainres.2012.07.056

Cited by 58 publications

(60 citation statements)

References 85 publications

(125 reference statements)

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“…We did not detect a significant difference in AD between the two groups. These results are compatible with Kleinhans et al's (2012) recent report of widespread WM anomalies in a heterogeneous cohort of adolescents and adults with ASD using TBSS. The results of the group comparison indicate that clinically-significant ASD is associated with a greater degree of WM abnormalities than is found in neurotypical controls.…”

Section: Discussionsupporting

confidence: 92%

“…Evidence shows that age and developmental stage contribute to DTI findings in ASD children and adolescents (Kleinhans et al, 2012). Further, DTI studies of WM maturation show that the majority of FA and MD changes occur prior to 30 years of age, though maturation trajectories differ in each white matter tract (Hasan et al, 2010; Lebel et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…TBSS has been applied to DTI scans of ASD children and adolescents, and WM tract alterations have been reported compared to controls (Ameis et al, 2011; Barnea-Goraly et al, 2010; Bode et al, 2011; Cheng et al, 2010; Jou et al, 2011; Kumar et al, 2010; Noriuchi et al, 2010; Sahyoun et al, 2010; Shukla et al, 2011a; Shukla et al, 2011b; Weinstein et al, 2011). Recently, Kleinhans et al (2012) applied TBSS to a combined adolescent–adult cohort, with findings showing widespread reductions in FA and increases in MD and RD. TBSS has not, to the best of our knowledge, yet been used to study brain structure in a purely adult cohort of ASD.…”

Section: Introductionmentioning

confidence: 99%

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White matter microstructure correlates with autism trait severity in a combined clinical–control sample of high-functioning adults

Gibbard¹,

Ren²,

Seunarine³

et al. 2013

NeuroImage: Clinical

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Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical–neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

White matter microstructure correlates with autism trait severity in a combined clinical–control sample of high-functioning adults

Gibbard¹,

Ren²,

Seunarine³

et al. 2013

NeuroImage: Clinical

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“…In particular, differential age-related white matter changes in ASD have been demonstrated across a broad age range, i.e., infants, children, and adults (Ben Bashat et al, 2007; Cascio et al, 2012; Kleinhans et al, 2012; Mak-Fan et al, 2012; Mengotti et al, 2011; Schumann et al, 2010; Wolff et al, 2012). More specifically, greater FA at 6 months was reportedly followed by slower development, resulting in lower FA at 24 months (Wolff et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Abnormal cingulum bundle development in autism: A probabilistic tractography study

Ikuta

Shafritz

Bregman

et al. 2014

Psychiatry Research: Neuroimaging

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There is now considerable evidence that white matter abnormalities play a role in the neurobiology of autism. Little research has been directed, however, at understanding (a)typical white matter development in autism and how this relates to neurocognitive impairments observed in the disorder. In this study we used probabilistic tractography to identify the cingulum bundle in 21 adolescents and young adults with autism spectrum disorder (ASD), and 21 age- and sex-matched healthy volunteers. We investigated group differences in the relationships between age and fractional anisotropy, a putative measure of white matter integrity, within the cingulum bundle. Moreover, in a preliminary investigation, we examined the relationship between cingulum fractional anisotropy and executive functioning using the Behavior Rating Inventory of Executive Function (BRIEF). The ASD participants demonstrated significantly lower fractional anisotropy within the cingulum bundle compared to the typically developing volunteers. There was a significant group-by-age interaction such that the ASD group did not show the typical age-associated increases in fractional anisotropy observed among healthy individuals. Moreover, lower fractional anisotropy within the cingulum bundle was associated with worse BRIEF behavioral regulation index scores in the ASD group. The current findings implicate a dysregulation in cingulum bundle white matter development occurring in late adolescence and early adulthood in autism spectrum disorder, and suggest that greater disturbances in this trajectory are associated with executive dysfunction in ASD.

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“…The latter study is discussed below. Structural connectivity via white matter tracts are also possible, however, these studies rarely include the brainstem (see Kleinhans, et al (2012) for an exception). To explore the possibility of brainstem involvement in aggression in autism, there is a need for more specific research that includes the brainstem.…”

Section: Discussionmentioning

confidence: 99%

Relationship between brain stem volume and aggression in children diagnosed with autism spectrum disorder

Lundwall

Stephenson

Neeley-Tass

et al. 2017

Research in Autism Spectrum Disorders

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Background Aggressive behaviors are common in individuals diagnosed with autism spectrum disorder (ASD) and may be phenotypic indicators of different subtypes within ASD. In current research literature for non-ASD samples, aggression has been linked to several brain structures associated with emotion and behavioral control. However, few if any studies exist investigating brain volume differences in individuals with ASD who have comorbid aggression as indicated by standardized diagnostic and behavioral measures. Method We examined neuroimaging data from individuals rigorously diagnosed with ASD versus typically developing (TD) controls. We began with data from brain volume regions of interest (ROI) taken from previous literature on aggression including the brainstem, amygdala, orbitofrontal cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex. We defined aggression status using the Irritability subscale of the Aberrant Behavior Checklist and used lasso logistic regression to select among these predictor variables. Brainstem volume was the only variable shown to be a predictor of aggression status. Results We found that smaller brainstem volumes are associated with higher odds of being in the high aggression group. Conclusions Understanding brain differences in individuals with ASD who engage in aggressive behavior from those with ASD who do not can inform treatment approaches. Future research should investigate brainstem structure and function in ASD to identify possible mechanisms related to arousal and aggression.

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Age-related abnormalities in white matter microstructure in autism spectrum disorders

Cited by 58 publications

References 85 publications

White matter microstructure correlates with autism trait severity in a combined clinical–control sample of high-functioning adults

White matter microstructure correlates with autism trait severity in a combined clinical–control sample of high-functioning adults

Abnormal cingulum bundle development in autism: A probabilistic tractography study

Relationship between brain stem volume and aggression in children diagnosed with autism spectrum disorder

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