Cerebellar Volumes and Sensorimotor Behavior in Autism Spectrum Disorder

Abstract

Background: Sensorimotor issues are common in autism spectrum disorder (ASD), though their neural bases are not well understood. The cerebellum is vital to sensorimotor control and reduced cerebellar volumes in ASD have been documented. Our study examined the extent to which cerebellar volumes are associated with multiple sensorimotor behaviors in ASD.

Materials and methods: Fifty-eight participants with ASD and 34 typically developing (TD) controls (8-30 years) completed a structural MRI scan and precision grip testing, oculomotor testing, or both. Force variability during precision gripping as well as absolute error and trial-to-trial error variability of visually guided saccades were examined. Volumes of cerebellar lobules, vermis, and white matter were quantified. The relationships between each cerebellar region of interest (ROI) and force variability, saccade error, and saccade error variability were examined.

Results: Relative to TD controls, individuals with ASD showed increased force variability. Individuals with ASD showed a reduced volume of cerebellar vermis VI-VII relative to TD controls. Relative to TD females, females with ASD showed a reduced volume of bilateral cerebellar Crus II/lobule VIIB. Increased volume of Crus I was associated with increased force variability. Increased volume of vermal lobules VI-VII was associated with reduced saccade error for TD controls but not individuals with ASD. Increased right lobule VIII and cerebellar white matter volumes as well as reduced right lobule VI and right lobule X volumes were associated with greater ASD symptom severity. Reduced volumes of right Crus II/lobule VIIB were associated with greater ASD symptom severity in only males, while reduced volumes of right Crus I were associated with more severe restricted and repetitive behaviors only in females.

Conclusion: Our finding that increased force variability in ASD is associated with greater cerebellar Crus I volumes indicates that disruption of sensory feedback processing supported by Crus I may contribute to skeletomotor differences in ASD. Results showing that volumes of vermal lobules VI-VII are associated with saccade precision in TD but not ASD implicates atypical organization of the brain systems supporting oculomotor control in ASD. Associations between volumes of cerebellar subregions and ASD symptom severity suggest cerebellar pathological processes may contribute to multiple developmental challenges in ASD.

Keywords: Crus I; MRI; autism spectrum disorder (ASD); cerebellum; oculomotor; sensorimotor; structure; volumetry.

FIGURE 1

(A) Grip configuration and load cells for precision grip testing. Participants pressed with their thumb and forefinger against two precision load cells. Participants pressed the load cells as quickly as possible when the red target bar (B) turned green (C) and continued pressing to maintain the force bar steady at the level of the green target bar. (D) During visually guided saccade testing, participants fixed their gaze on a centrally located crosshair at the start of each trial, then looked quickly toward (E) peripheral targets (i.e., white circles) which appeared pseudorandomly at ± 12° or 24° of visual angle.

FIGURE 2

Representative segmentation from a single subject depicting 18 cerebellar ROIs obtained from automated segmentation procedures (ACAPULCO; Han et al., 2020) and an accompanying pediatric template (Carass et al., 2018).

FIGURE 3

Sex-dependent group differences in Crus II/lobule VIIB volume. Error bars reflect mean ± 1 SD. * denotes p < 0.05.

FIGURE 4

Volumes for 18 cerebellar ROIs for typically developing controls (black circles) and individuals with ASD (empty triangles). Error bars reflect mean ± 1 SD. * denotes p < 0.05.

FIGURE 5

Relationship between the volume of vermal lobules VI-VII and saccade error, averaged across target direction and amplitude. Greater volumes of vermal lobules VI-VII were associated with reduced saccade error in TD controls (r = –0.438, p = 0.007), but not individuals with ASD (r = –0.060, p = 0.671). Shaded regions reflect the 95% confidence interval of a group-level linear fit.

FIGURE 6

Associations between cerebellar volume and ASD symptom severity. Increased volume of cerebellar white matter (A) and right lobule VIII (B) were associated with increased ASD symptom severity as measured using the ADOS-2 Calibrated Severity Score. Increased volume of right lobule X (C) was associated with reduced ASD symptom severity. Increased volume of right lobule VI (D) was associated with reduced severity of RRBs as measured using the Repetitive Behaviors Scale—Revised. The shaded region reflects the 95% confidence interval of a linear fit. R² values reflect the proportion of variance in clinical symptoms accounted for by the cerebellar volume in a one-term model. ADOS CSS, Autism Diagnostic Observation Schedule Calibrated Severity Score; RBS-R, Repetitive Behaviors Scale—Revised.

FIGURE 7

Associations between cerebellar volumes and ASD symptom severity which vary across males and females. Increased volume of cerebellar right Crus II/lobule VIIB (A) was associated with reduced ASD symptom severity in males, but not females. Increased volume of cerebellar right Crus I (B) was associated with reduced severity of RRBs in females, but not males. The shaded region reflects the 95% confidence interval of a linear fit. R² values reflect the proportion of variance in clinical symptoms accounted for by cerebellar ROI volume in a one-term model. ADOS CSS, Autism Diagnostic Observation Schedule Calibrated Severity Score; RBS-R, Repetitive Behaviors Scale—Revised.