Age-related differences in autism: The case of white matter microstructure

Abstract

Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: DTI; adults; autism; interference control; intra-individual variability; underconnectivity; white matter.

Figure 1

Group‐by‐age interactions for mean (MD) and radial diffusivity (RD). Figure 1 displays the significant group‐by‐age interactions, taking TMI into account, reported in Table II. Abbreviations: MD, mean diffusivity; RD, radial diffusion; ATR, Anterior Thalamic Radiation; ILF, Inferior Longitudinal Fasciculus; SLFT, Superior Longitudinal Fasciculus Temporal. [Color figure can be viewed at http://wileyonlinelibrary.com.]

Figure 2

Difference scores of partial correlations between intra‐individual variability and white matter microstructure for ASD and controls. Values represent ΔZ‐scores, controlled for TMI. Upper diagonal: all ΔZ‐scores between ASD and CTRL for DTI parameters and Flanker measures. Lower diagonal: significant ΔZ‐scores ΔZ > |1.96|); non‐significant values in black. Warm colors indicate more positive partial‐correlation in ASD than in controls (e.g. rho‐ASD= −0.15 and rho‐CTRL = −0.44; or rho‐ASD = 0.44 and rho‐CTRL = 0.15; both result in positive ΔZ‐scores). Cool colors indicate more positive partial‐correlation in controls than in ASD (e.g. rho‐ASD = −0.44 and rho‐CTRL = −0.15; or rho‐ASD = 0.15 and rho‐CTRL = 0.44; both result in negative ΔZ‐scores). See Table 3 for exact values, also in‐text explanation and original partial‐correlations in Supporting Information Fig. 4. For denotation of rows/columns see Supporting Information Table VI. [Color figure can be viewed at http://wileyonlinelibrary.com.]