Longitudinal Microstructure of the Thalamus and Anterior Limb of the Internal Capsule in Individuals with Autism Spectrum Disorder

Background:  The thalamus is a highly connected brain area, and white matter connections related to the thalamus have been shown to be atypical in adolescents with autism spectrum disorder (ASD) and related to motor impairments in this population (Nair et al., 2013). What is not known is how thalamic white and gray matter microstructure develops and changes from childhood through adulthood in ASD. In other populations, gray matter microstructure has been shown to be a sensitive marker of age-related changes (Manna et al., 2015). Given that the thalamus is a key sensorimotor relay area, it is essential to examine microstructural changes in thalamic gray and white matter and surrounding white matter tracts as a function of age and motor ability in ASD.

Objectives:  (1) To compare the longitudinal development of white and gray matter microstructure of the bilateral thalamus and the anterior limb of the internal capsule (ALIC) between the ASD and typically developing groups. (2) To examine if microstructure in these areas are related to finger tapping speed.  

Methods: Fifty-six males with typical development and 100 males with ASD (ages 3.3 to 41 years old) underwent longitudinal DTI scanning on Siemens 3T scanner at four points across a 10-year period of time (DW, single-shot, spin-echo EPI, b=1000, 12 non-collinear directions, 4 averages). At the time of each scan, participants completed a neuropsychological battery of tasks, including finger tapping speed.  Groups were matched on age (p= .46). Anatomical regions of interest were defined, including the left and right thalamus and left and right ALIC, a white matter tract connecting thalamus to frontal cortices. Linear mixed-effects analyses examined age-related changes in thalamic microstructure as a function of group, accounting for repeated measures over time. For aim 2, linear mixed-effects analyses examined finger tapping speed changes as a function of thalamic microstructure and age.  

Results: In the ALIC, the group with ASD had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) (p < .05). However, developmental trajectories in the ASD and typically developing groups did not differ. In the thalamus, the group with ASD had significantly different developmental trajectories from the group with typical development in FA, RD, and mean diffusivity (MD) (all p’s < .02) but not axial diffusivity. After accounting for age, the thalamus predicted finger tapping speed (p = .009), but the anterior limb of the internal capsule did not (p > .28).   

 Conclusions:  DTI studies in ASD have traditionally focused on white matter tracts. However, DTI in gray matter has been used to examine aging and learning-related brain changes (Sagi et al., 2012) in non-ASD populations. In applying DTI to the thalamus and ALIC, we found that the microstructure of the thalamus demonstrated a different pattern of results than the microstructure of the ALIC. Specifically, the thalamic metrics had distinct developmental trajectories in ASD compared to the ALIC metrics. Further, the thalamic microstructure related to finger tapping speed, whereas the ALIC microstructure did not.