Clinical Research

Autism

Increased motor cortex white matter volume predicts motor impairment in autism

© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Stewart H. Mostofsky^1,2,3, Melanie P. Burgess¹ and Jennifer C. Gidley Larson¹

¹Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205,, Johns Hopkins School of Medicine, Departments of ²Neurology and ³Psychiatry, Baltimore, MD,

Correspondence with Stewart H. Mostofsky, MD, Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205.

Careful consideration of motor impairments, such as those documented in autism, can afford valuable insights into the neurological basis of developmental disorders. Motor signs are highly quantifiable and reproducible and can serve as markers for deficits in parallel systems important for socialization and communication. Correlations of motor signs with anatomic MRI (aMRI) measures therefore offer an important means of investigating brain abnormalities contributing to autism. Prior aMRI studies have revealed increased cerebral volume in young children with autism, particularly in ‘outer zone’ radiate white matter; however functional correlates of these findings have not been reported. In this study, we examined whether radiate white matter within the primary motor cortex would predict impaired motor performance in children with autism. Subjects included children ages 8–12 years: 20 with autism, 36 typically developing (TD) controls and 20 clinical controls with attention-deficit/hyperactivity disorder (ADHD). Regional tissue volumes were measured using an automated tissue classification algorithm followed by a semi-automated parcellation method. Motor performance was assessed using the Physical and Neurologic Examination of Subtle Signs (PANESS), with higher scores indicating poorer performance. Independent linear regression analyses revealed that for TD controls there was a significant negative correlation between total PANESS score and primary motor cortex white matter volume in both the right and left hemispheres, such that increased white matter volume predicted improved motor skill. In contrast, children with autism showed a robust positive correlation between total PANESS score and left hemisphere primary motor and premotor white matter volumes, such that increased white matter volume predicted poorer motor skill. No significant correlations were found for ADHD. Multivariate regression analyses revealed that the correlation between PANESS score and left motor cortex white matter volume in children with autism significantly differed from those in both ADHD and TD children. The correlation in ADHD did not significantly differ from that in TD children. The findings for the first time demonstrate an association between increasing radiate white matter volume and functional impairment in children with autism, in this case basic motor skill impairment. The observed association, which appears specific to autism, may be representative of global patterns of brain abnormality that not only contribute to motor dysfunction in autism, but also deficits in socialization and communication that define the disorder.

Received October 30, 2006. Revised May 9, 2007. Accepted May 10, 2007.

Decreased connectivity and cerebellar activity in autism during motor task performance

Brain Advance Access originally published online on April 23, 2009 Brain 2009 132(9):2413-2425; doi:10.1093/brain/awp088 © The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Stewart H. Mostofsky^1,2,3, Stephanie K. Powell¹, Daniel J. Simmonds¹, Melissa C. Goldberg^1,2, Brian Caffo⁴ and James J. Pekar^1,5,6

¹Kennedy Krieger Institute, Baltimore, MD 21205 | ²Department of Psychiatry Johns Hopkins School of Medicine, Baltimore, MD | ³Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD | ⁴Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD | ⁵Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD | ⁶F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205

Correspondence with Stewart H. Mostofsky, MD, Department of Developmental Cognitive Neurology, Kennedy Krieger Institute/Johns Hopkins University School of Medicine, 707 North Broadway, Baltimore, MD 21205.

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.

Received July 22, 2008. Revised January 30, 2009. Accepted March 2, 2009.