Cortico-Cerebellar Dysfunctions Associated with Visuomotor Abnormalities in Autism Spectrum Disorder Vary According to the Quality of Visual Feedback
Objectives: To characterize cortico-cerebellar alterations associated with increased visuomotor variability in ASD, and to determine whether brain alterations vary in relation to the gain of visual feedback.
Twenty individuals with ASD and 23 healthy controls matched on age, nonverbal IQ and handedness performed an fMRI test of visually guided precision grip force (Figure 1). During the test, participants pressed with their thumb and index finger on a force transducer while viewing a white FORCE bar on a screen that moved upwards with increased force toward a fixed green TARGET bar. Participants were instructed to maintain the FORCE bar at the level of the TARGET bar which was set to 15% of each individual’s maximum force. Subjects also completed a rest condition in which they viewed the two bars on the screen. Both conditions lasted 26 s and they were alternated 3 times during each run. To assess the impact of changes in visual feedback on force control and brain activation, separate runs were completed at three different visual gains. Visual gain was manipulated by varying the vertical distance the FORCE bar moved per Newton of grip force. Visual gain was increased by moving the FORCE bar a greater distance for every Newton of force generated.
Subjects with ASD showed increased force variability relative to controls that was most severe at the lowest and highest gain levels compared to the medium gain level. At low visual gain, individuals with ASD showed reduced activation in contralateral primary motor cortex, thalamus, bilateral anterior cerebellum (lobules I-IV) and ipsilateral cerebellar lobules V/VI. At the medium visual gain level, reduced activity in ASD was seen in primary motor cortex, inferior parietal lobule and middle occipital gyrus. Individuals with ASD showed increased activity in lingual gyrus and superior temporal gyrus. When visual gain was high, individuals with ASD showed increased activation in right cuneus and precuneus, supplementary motor area, middle frontal gyri, right superior temporal gyrus, and right superior parietal lobule.
Our results indicate that increases in force variability at high and low visual gains reflect different underlying cortico-cerebellar dysfunctions in ASD. At low visual gain, individuals with ASD show reduced activation in parietal cortex, cerebellum, thalamus and primary motor cortex indicating that failure to minimize motor variability may reflect under-responsiveness throughout the visuomotor circuit. When visual gain was high, individuals with ASD showed over-activity of extrastriate and parietal cortices suggesting increases in motor variability may reflect hyperactivity during visual processing. These findings provide new insights into the brain mechanisms underlying sensorimotor abnormalities in ASD, and suggest that multiple distinct cortico-cerebellar systems are involved in the neurodevelopmental alterations that cause this disorder.