Family Studies of Sensorimotor Disturbances in Autism Spectrum Disorder
Sensorimotor impairments are prevalent in individuals with autism spectrum disorder (ASD) and among the earliest emerging features, yet the pathophysiological mechanisms underlying these deficits remain poorly understood. Family studies are one approach to better understand these pathophysiological mechanisms by identifying sensorimotor impairments that are present in both individuals with ASD (probands) and their unaffected biological family members. Previous studies have identified reduced saccade accuracy and increased variability of saccade in probands as well as analogous deficits in unaffected relatives. We also have recently demonstrated reduced accuracy and increased variability of precision gripping in ASD. Accuracy of ocular and manual motor behaviors is controlled by feedforward motor control processes responsible for guiding initial motor output prior to available visual feedback as well as feedback processes that use visual feedback information to compensate for any systematic error. Thus, previous findings implicated disruptions of feedforward and feedback mechanisms in ASD. Here, we characterized saccade and precision gripping abnormalities in probands and their unaffected biological parents, and determined the extent to which these abnormalities are familial by studying family trios (proband, biological mother, biological father). Our results demonstrated that probands show reduced accuracy of rapid ocular and manual motor responses as well as increased variability of sustained manual motor behaviors, suggesting that cerebellar-mediated feedforward and feedback motor control processes are disrupted in ASD. Biological parents demonstrated a similar pattern of sensorimotor abnormalities to individuals with ASD. Further, impaired saccade dynamics and variability of sustained gripping inter-correlated among probands and their parents indicating that these deficits may be familial. Oculomotor and manual motor abilities were relatively independent in controls, whereas these abilities were correlated in both probands and parents suggesting reduced differentiation of these motor control systems in ASD. Sensorimotor deficits also were related to core diagnostic features in probands as well as to sub-clinical phenotypic features in parents, suggesting that deficits in sensorimotor behaviors may share pathogenic mechanisms with core symptoms. Overall, our findings provide support that sensorimotor impairments are highly prevalent in ASD, and that they may be familial, suggesting their use as intermediate phenotypes and potential biological markers of risk in ASD.
Autism Spectrum Disorder, Cerebellum, Child Development Disorders, Pervasive, Feedback, Physiological, Motor Activity, Psychomotor Performance
University of Texas Southwestern Medical Center
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