Decreased connectivity and cerebellar activity in autism during motor task performance - PubMed (original) (raw)

Decreased connectivity and cerebellar activity in autism during motor task performance

Stewart H Mostofsky et al. Brain. 2009 Sep.

Abstract

Although motor deficits are common in autism, the neural correlates underlying the disruption of even basic motor execution are unknown. Motor deficits may be some of the earliest identifiable signs of abnormal development and increased understanding of their neural underpinnings may provide insight into autism-associated differences in parallel systems critical for control of more complex behaviour necessary for social and communicative development. Functional magnetic resonance imaging was used to examine neural activation and connectivity during sequential, appositional finger tapping in 13 children, ages 8-12 years, with high-functioning autism (HFA) and 13 typically developing (TD), age- and sex-matched peers. Both groups showed expected primary activations in cortical and subcortical regions associated with motor execution [contralateral primary sensorimotor cortex, contralateral thalamus, ipsilateral cerebellum, supplementary motor area (SMA)]; however, the TD group showed greater activation in the ipsilateral anterior cerebellum, while the HFA group showed greater activation in the SMA. Although activation differences were limited to a subset of regions, children with HFA demonstrated diffusely decreased connectivity across the motor execution network relative to control children. The between-group dissociation of cerebral and cerebellar motor activation represents the first neuroimaging data of motor dysfunction in children with autism, providing insight into potentially abnormal circuits impacting development. Decreased cerebellar activation in the HFA group may reflect difficulty shifting motor execution from cortical regions associated with effortful control to regions associated with habitual execution. Additionally, diffusely decreased connectivity may reflect poor coordination within the circuit necessary for automating patterned motor behaviour. The findings might explain impairments in motor development in autism, as well as abnormal and delayed acquisition of gestures important for socialization and communication.

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Figures

Figure 1

Glass brain and sectional maps showing regions where fMRI activation was significantly associated with LHFS (left images) and RHFS (right images), each contrasted with rest, for TD children (upper images) and children with autism (lower images). All maps were thresholded at P = 0.05 corrected for multiple comparisons. Neurologic convention is used (i.e. right = right hemisphere; projections looking rightward or into the page).

Figure 2

Charts showing results of RHFS (upper chart) and LHFS (lower chart) with bar graphs representing mean percent signal change (± SEM) compared with rest for children with autism (blue) and TD controls (red) in ROIs derived from the individual group maps (Fig. 1). **P < 0.05, Bonferroni-corrected for multiple comparisons; *P < 0.1, Bonferroni-corrected for multiple comparisons.

Figure 3

Sectional maps showing localization of differences in fMRI activation between children with autism and TD children during RHFS (red), LHFS (blue), and the overlap between RHFS and LHFS (pink). The upper maps show regions where TD children showed greater activation than did those with autism; the lower maps show regions where children with autism showed greater activation than did TD children. The results are based on a Gaussian random effects analysis of each group of 13 participants; all maps were thresholded at P = 0.05 uncorrected for multiple comparisons. Representative slices are shown in the sagittal (left hemisphere), coronal and axial planes. Neurologic convention is used (i.e. right = right hemisphere; projections looking rightward or into the page).

Figure 4

Bar graphs demonstrating differences in functional connectivity between HFA and TD children. The legend in the grey box explains how information is presented. Within the triangle as a whole, the six boxes in the top-left portion represent connectivity between region-pairs in left-handed (L) motor circuits (e.g. right motor cortex, left cerebellum), the six boxes in the bottom-right portion represent connectivity between region-pairs in right-handed (R) motor circuits (e.g. left motor cortex, right cerebellum), and the nine boxes in the top-right represent connectivity between region-pairs in hand-neutral (N) motor circuits (e.g. right motor cortex, left motor cortex). Within each box, the three plots, from left to right, represent connectivity between the region pair during rest (left), RHFS (middle) and LHFS (right), respectively; children with HFA are shown in red and TD children are show in blue. Also within each box, the _y_-axis represents normalized _r_-values, and the axis ranges from 0 to 2; standard deviation bars are shown. Labels at the top and left of the figure demonstrated the region-pairs examined in each box (R = right; L = left; M1 = primary motor cortex; cer = anterior cerebellum; thal = thalamus).

Figure 5

Sectional maps and illustration demonstrating differences in functional connectivity between HFA and TD children. The thickness of the lines represents the magnitude of the difference in standard errors (differences of < 1 SEM are not shown).

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Decreased connectivity and cerebellar activity in autism during motor task performance - PubMed (original) (raw)