Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder

Abstract

Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD.

Keywords: autism spectrum disorder; cerebellum; precision grip; sensorimotor.

Figure 1.

Precision grip force experiments. A, Schematic of the experimental setup for both precision grip force tasks. Participants were seated in front of a monitor while resting their arm in a custom device. B, Schematic of a subject pressing on opposing load cells with their index finger and thumb. C, Stimulus presentation showing target (red) and force (white) lines during rest. To begin each trial, the red target line turned green to cue the subject to begin pressing on the load cells. Participants sustained as constant a force level as possible for 15 s. D, Sample force trace showing the subphases of each force trial that were scored, including the RT, the primary response, and the sustained force period.

Figure 2.

The accuracy and peak rate of force increase of primary pulses as a function of target force level for participants with ASD and healthy controls. A, Although both groups showed a transient force overshoot during trials in which the target force level was 5% of their MVC, the degree to which participants exceeded target force levels was greater for participants with ASD compared with healthy controls. B, Peak rate of force increase was greater in participants with ASD at 5% of their MVC but no different from controls at larger force levels. *p < 0.05; **p < 0.01.

Figure 3.

Sustained force performance for participants with ASD and healthy control participants across different force levels. A, Participants with ASD showed increased force variability (SD) compared with healthy controls, especially at larger force levels. B, ApEn of participants with ASD was lower than for healthy control participants, suggesting that they showed less irregularity in the structure of their sustained force output. *p < 0.05.

Figure 4.

Sustained force performance for participants with ASD and healthy control participants across different visual gains. A, Participants with ASD showed increased force variability (SD) compared with healthy controls, especially at smaller and larger visual gains. B, ApEn of participants with ASD was lower than for healthy controls, and this deficit was more severe at larger visual gains. *p < 0.05; **p < 0.01.

Figure 5.

Power spectra across 0–4, 4–8, and 8–12 Hz bandwidths in individuals with ASD and healthy controls. A, Participants with ASD showed elevated power at 0–4 Hz across force levels. They showed reduced 4–8 Hz power (B) and 8–12 Hz power (C) compared with controls at the largest force levels, but these differences were not significant. Participants with ASD showed increases in 0–4 Hz power (D), 4–8 Hz power (E), and 8–12 Hz power (F) across visual gains, but increases in 0–4 Hz power were more severe than those for 4–8 or 8–12 Hz. *p < 0.05; **p < 0.01.

Figure 6.

Relationships between precision force performance and clinical characteristics of individuals with ASD. Increased overshoot of primary pulses at 5% of MVC was associated with more severe clinically rated social-communication abnormalities (A), restricted, repetitive behaviors (C), and handwriting impairments (E) in ASD. Reduced ApEn during sustained precision force was associated with more severe clinically rated social-communication abnormalities (B) and handwriting impairments (D). F, Individuals with ASD with a history of gait abnormalities as rated on the ADI showed reduced ApEn across both force levels and levels of visual gain relative to those individuals with ASD who did not have a history of gait abnormalities.