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Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation.

Travers BG, Tromp do PM, Adluru N, Lange N, Destiche D, Ennis C, Nielsen JA, Froehlich AL, Prigge MB, Fletcher PT, Anderson JS, Zielinski BA, Bigler ED, Lainhart JE, Alexander AL - Mol Autism (2015)

Bottom Line: In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood.When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger).Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum.

View Article: PubMed Central - PubMed

Affiliation: Occupational Therapy Program, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI USA ; Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA.

ABSTRACT

Background: The corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood.

Methods: The present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age).

Results: The group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum's (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum.

Conclusions: These longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism.

No MeSH data available.


Related in: MedlinePlus

Mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) measures plotted as function of age and group. ASD, autism spectrum disorder; TDC, typically developing controls. Time 1 scatter has been adjusted for the head coil changes, and the overlaid growth models for each group represent the generalized additive mixed model spline curves (with dashed 95% confidence intervals), controlling for head coil changes, total motion index, signal-to-noise ratio, and random effects.
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Fig3: Mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) measures plotted as function of age and group. ASD, autism spectrum disorder; TDC, typically developing controls. Time 1 scatter has been adjusted for the head coil changes, and the overlaid growth models for each group represent the generalized additive mixed model spline curves (with dashed 95% confidence intervals), controlling for head coil changes, total motion index, signal-to-noise ratio, and random effects.

Mentions: Plots of MD, RD, and AD measurements obtained from the corpus callosum subregions are provided in Figure 3. Table 2 demonstrates significant group differences only in MD, RD, and AD of the splenium. However, it should be noted that even though splenium AD had a statistically significant group difference, it corresponded to a very small effect size (that is, on a 0.35% increase in AD in ASD), which means that it might not be a meaningful difference. The only significant age-by-group interaction was found in MD of the splenium. As in the FA follow-up results, linear mixed-effects models suggested that the majority of interaction effects occurred in the youngest age group (that is, participants less than 10 years of age).Figure 3


Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation.

Travers BG, Tromp do PM, Adluru N, Lange N, Destiche D, Ennis C, Nielsen JA, Froehlich AL, Prigge MB, Fletcher PT, Anderson JS, Zielinski BA, Bigler ED, Lainhart JE, Alexander AL - Mol Autism (2015)

Mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) measures plotted as function of age and group. ASD, autism spectrum disorder; TDC, typically developing controls. Time 1 scatter has been adjusted for the head coil changes, and the overlaid growth models for each group represent the generalized additive mixed model spline curves (with dashed 95% confidence intervals), controlling for head coil changes, total motion index, signal-to-noise ratio, and random effects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359536&req=5

Fig3: Mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) measures plotted as function of age and group. ASD, autism spectrum disorder; TDC, typically developing controls. Time 1 scatter has been adjusted for the head coil changes, and the overlaid growth models for each group represent the generalized additive mixed model spline curves (with dashed 95% confidence intervals), controlling for head coil changes, total motion index, signal-to-noise ratio, and random effects.
Mentions: Plots of MD, RD, and AD measurements obtained from the corpus callosum subregions are provided in Figure 3. Table 2 demonstrates significant group differences only in MD, RD, and AD of the splenium. However, it should be noted that even though splenium AD had a statistically significant group difference, it corresponded to a very small effect size (that is, on a 0.35% increase in AD in ASD), which means that it might not be a meaningful difference. The only significant age-by-group interaction was found in MD of the splenium. As in the FA follow-up results, linear mixed-effects models suggested that the majority of interaction effects occurred in the youngest age group (that is, participants less than 10 years of age).Figure 3

Bottom Line: In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood.When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger).Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum.

View Article: PubMed Central - PubMed

Affiliation: Occupational Therapy Program, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI USA ; Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA.

ABSTRACT

Background: The corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood.

Methods: The present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age).

Results: The group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum's (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum.

Conclusions: These longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism.

No MeSH data available.


Related in: MedlinePlus