Accelerated Decline of Motor Tracts and Links with Symptom Severity in Older Adults with ASDs

Background: Motor function often declines in healthy aging, with negative consequences for quality of life. In autism spectrum disorders (ASDs), motor deficits are common and can be detected even before core diagnostic symptoms (e.g. socio-communicative deficits) become evident. Much less is known about motor functions in older adults with ASDs. A few studies have suggested impaired motor function and a possible increased risk for Parkinsonism, but little is known about brain changes in the motor system in adults with ASDs past the age of 40 years.

Objectives: To characterize the microstructure of motor and premotor tracts in older adults with ASDs compared with a matched neurotypical group (NT), and identify the relationship between path structure, age, and behavior.

Methods: Diffusion weighted MRI data were collected from older adults (40-65 years): 19 with ASDs (mean age 50.5 years, 2 female, 1 left-handed) and 24 neurotypical (mean age 51.3 years, 3 female, 3 left-handed). Diagnostic groups were matched for gender, age, handedness and head motion. Motor function was assessed with the Bruininks motor ability test (BMAT). The primary motor, dorsal pre-motor, ventral pre-motor, supplementary motor and pre-supplementary motor cortices of the Human Motor Area Template were warped to individual diffusion space and used as seed regions for probabilistic tractography (FSL). Only ipsilateral streamlines passing through the posterior limb of the internal capsule and cerebral peduncles were retained. Left and right tracts were recoded to dominant and non-dominant based on hand dominance. To study group, age and group by age interactions, ANCOVAs were run on tract measures (fractional anisotropy [FA], mean diffusivity [MD], volume) for dominant and non-dominant hemispheres, covarying for head motion and protocol. To investigate relationships between structure and behavior, partial correlations were run between tract measures and BMAT and ADOS-2 scores controlling for age, head motion and protocol.

Results: Only 3 out of 5 tracts were reliably identified (Fig. 1A). We found a significant group by age interaction for MD of the dominant dorsal premotor tract (Fig. 1B, p=.006) using a Bonferroni-corrected threshold. Follow-up partial correlations showed a positive relationship with age for MD in the ASD, but not the TD, group. Behavioral partial correlations revealed a significant positive association between volume of the dominant primary motor tract and ADOS-2 comparison score in ASD (partial r=.814, p<.001), using an FDR-corrected threshold (Fig. 1C). Additional correlations with medium effect size (|r|≥.5) were found between structural measures and the BMAT (summary score, manual dexterity) and ADOS-2 (social affect, restricted and repetitive behavior), in ASDs but did not survive FDR correction.

Conclusions: In older adults with autism, we found atypical decline of the dominant dorsal premotor tract, which may reflect disruption of learning associations between sensory input and action, and could reflect accelerated decline in ASDs. The association between motor tract structural measures and both motor performance and autism symptoms found in older adults with ASDs suggests possible decline beyond the motor system or an at-risk subgroup among those with higher ASD severity.