Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder

Abstract

Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical-cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical-cerebellar networks and visuomotor impairments in ASD have not yet been clarified. Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined. Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex. Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar-cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.

Keywords: amplitude of low-frequency fluctuations; autism spectrum disorder; cortical–cerebellar connectivity; functional connectivity; precision grip; resting-state functional MRI; visuomotor control.

Figure 1

(A) Individuals pressed against the Bragg grating fiber optic force transducer during a test of precision grip. (B) Visual information individuals received during task-based fMRI (tb-fMRI). Participants viewed two horizontal bars presented against a black background (Rest/Release). The TARGET bar (red/green) was stationary during each trial. The TARGET bar turned from red to green at the beginning of each trial to cue participants to begin pressing the force transducer. The white FORCE bar moved upward with increased force. The discrepancy between the TARGET and FORCE bars provided online visual feedback to the participants about their motor performance.

Figure 2

Significant correlations between the whole brain amplitude of low-frequency fluctuations (ALFFs) and sustained force standard deviation in individuals with ASD and TD controls. The red areas depict voxels presenting positive correlations, whereas the blue areas depict voxels showing negative correlations with sustained force standard deviation. IFG.L, left inferior frontal gyrus; PreCG.R, right precentral gyrus; PoCG.L, left postcentral gyrus; SMG.R, right supramarginal gyrus; ANG.L, left angular gyrus; PCUN.L, left precuneus; HES.L, left Heschl's gyrus; STG.L, left superior temporal gyrus; MT/V5. R, right middle temporal gyrus including visual area 5; CAL.R, right calcarine cortex; CBL.Vermis VI, cerebellar vermis VI; CBL.Crus I. L, left cerebellar crus I; CBL.Crus I. R, right cerebellar crus I; CBL. VIII. L, left cerebellar lobule VIII.

Figure 3

Between-group functional connectivity (FC) maps (ASD vs. TD). Green lines depict FC reductions in individuals with ASD relative to TD controls, while yellow lines represent FC elevations in ASD relative to TD controls. SFG.R, right superior frontal gyrus; MFG.L, left middle frontal gyrus; SPG.L, left superior parietal gyrus; SPG.R, right superior parietal gyrus; SMG.R, right supramarginal gyrus; ANG.L, left angular gyrus; PCUN.L, left precuneus; HES.L, left Heschl's gyrus; STG.L, left superior temporal gyrus; SOG.L, left superior occipital gyrus; SOG.R, right superior occipital gyrus; MOG.L, left middle occipital gyrus; DCG.L, left median cingulate gyrus; CBL.Vermis VI, cerebellar vermis VI; CBL.Crus I.L, left cerebellar crus I; CBL.Crus I.R, right cerebellar crus I; CBL.Crus II.L, left cerebellar crus II; CBL.Crus II.R, right cerebellar crus II; CBL.VIII.L, left cerebellar lobule VIII. All clusters were AlphaSim corrected and statistically significant at p < 0.05.