Atypical Lateralization of Motor Circuit Connectivity in Children with High-Functioning Autism Is Associated with Motor Deficits

Thursday, May 14, 2015: 2:52 PM
Grand Ballroom D (Grand America Hotel)
D. L. Floris1,2, A. D. Barber2,3, M. B. Nebel2,3 and S. H. Mostofsky2,3,4, (1)Autism Research Centre, Cambridge, United Kingdom, (2)Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, (3)Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, (4)Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD

Atypical lateralization of language-related functions has repeatedly been shown in individuals with autism. No studies have however investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains such as motor skills. Motor deficits are among the earliest and most prominent symptoms in individuals with autism and precede core social and communicative symptoms. 


We have previously shown that leftward lateralization of motor circuit connectivity is associated with better motor performance in typically developing children. Here we aim to investigate whether motor circuit connectivity is (1) atypically lateralized in children with autism and (2) whether this relates to core autistic symptoms and motor performance.


Participants comprised 45 right-handed children with high-functioning autism (37 boys; 8 girls) and 87 typically developing children (61 boys; 26 girls) matched for age (8-12), performance IQ and sex. Autistic symptoms were assessed by the ADI-R, ADOS and SRS. Motor performance was assessed by the Physical and Neurological Examination for Subtle Signs (PANESS).

Functional images were slice time and motion corrected, co-registered and normalized to a symmetrical age- and gender matched TPM. Six absolute and six differential motion parameters and nuisance variables (CSF and WM) were removed using CompCor and spatial smoothing (6 mm) and temporal filtering (0.01--0.1 Hz band-pass filter) were performed.

Six-millimeters-radius 3D seeds were generated based on peak coordinates of activations previously identified during right-handed finger sequencing. Homotopic seeds were generated by flipping the left hemisphere seeds along the x-axis. Time series from the seeds were extracted and pairwise correlations were conducted in each hemisphere separately. Laterality indices were calculated with the formula: R-L. Statistical analyses were carried out in SPSS.


A univariate ANOVA controlling for sex showed a significant difference in laterality of motor circuit connectivity of the left-hemisphere network (F=5.01; p=0.027) between the two groups. Children with ASD showed rightward lateralization compared to typically developing children. Partial correlations controlling for sex resulted in a significant association between the laterality index and total PANESS Gait scores (r=0.403; p=0.007) and total PANESS scores (r=0.45; p=0.002) with stronger rightward lateralization being related to more motor impairment. There were no significant correlations with autistic symptoms.


Atypical lateralization in autism is not restricted to language functions, but is also present in functional motor circuit connectivity and related to motor deficits. Greater rightward laterality in children with autism may underlie motor deficits.  Future studies should investigate whether atypical lateralization is even more pronounced in left-handed individuals with autism and whether these asymmetries are related to atypical lateralization in the language domain, too.