Autism spectrum disorder (ASD) is proposed to reflect atypical connectivity between higher-order association areas. Using diffusion imaging, Catani et al. reveal associations between ASD and white matter abnormalities of the frontal lobe, and suggest that the condition is linked to aberrant developmental trajectories of frontal networks that persist in adulthood.

BackgroundFine motor skill impairments are common in autism spectrum disorder (ASD), significantly affecting quality of life. Sensory inputs reaching the primary motor cortex (M1) from the somatosensory cortex (S1) are likely involved in fine motor skill and specifically motor learning. However, the role of these connections has not been directly investigated in humans. This study aimed to investigate, for the first time, the role of the S1-M1 connections in healthy subjects in vivo and whether microstructural alterations are associated with motor impairment in ASD.MethodsSixty right-handed neurotypical adult men aged 18 to 45 years, and 60 right-handed age- and sex-matched subjects diagnosed with ASD underwent fine motor skill assessment and scanning with diffusion tensor imaging (DTI). The streamlines of the hand region connecting S1-M1 of the motor-sensory homunculus were virtually dissected using TrackVis, and diffusion properties were extracted. The face/tongue region connections were used as control tracts.ResultsThe ASD group displayed lower motor performances and altered DTI measurements of the hand-region connection. Behavioral performance correlated with hand-region DTI measures in both groups, but not with the face/tongue connections, indicating anatomical specificity. There was a left-hemisphere association of motor ability in the control group and an atypical rightward shift in the ASD group.ConclusionsThese findings suggest that direct interaction between S1 and M1 may contribute to the human ability to precisely interact with and manipulate the environment. Because electrophysiological evidence indicates that these connections may underpin long-term potentiation in M1, our findings may lead to novel therapeutic treatments for motor skill disorders.

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Highlights This is the first study to investigate the development of response inhibition focussing on variability. We examined intraindividual variability both in stopping latencies and the underlying neural circuitry. There were no developmental differences in mean response inhibition, yet clear differences in performance variability. This, in turn, was associated with developmental differences in brain signal variability. Behavioral and neural variability indices might be a more sensitive measure of developmental differences in inhibition.

Background: Autism spectrum condition (ASC) is accompanied by developmental differences in brain anatomy and connectivity. White matter differences in ASC have been widely studied with diffusion imaging but results are heterogeneous and vary across the age range of study participants and varying methodological approaches. To characterize the neurodevelopmental trajectory of white matter maturation, it is necessary to examine a broad age range of individuals on the autism spectrum and typically developing controls, and investigate age × group interactions. Methods: Here, we employed a spatially unbiased tract-based spatial statistics (TBSS) approach to examine age-related differences in white matter connectivity in a sample of 41 individuals with ASC, and 41 matched controls between 7-17 years of age. Results: We found significant age-related differences between the ASC and control group in widespread brain regions. This included age-related differences in the uncinate fasciculus, corticospinal tract, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior longitudinal fasciculus and forceps major. Measures of fractional anisotropy (FA) were significantly positively associated with age in both groups. However, this relationship was significantly stronger in the ASC group relative to controls. Measures of radial diffusivity (RD) were significantly negatively associated with age in both groups, but this relationship was significantly stronger in the ASC group relative to controls. Limitations: The generalisability of our findings is limited by the restriction of the sample to right-handed males with an IQ > 70. Furthermore, a longitudinal design would be required to fully investigate maturational processes across this age group. Conclusions: Taken together, our findings suggest that autistic males have an altered trajectory of white matter maturation relative to controls. Future longitudinal analyses are required to further characterize the extent and time course of these differences.