Brain Advance Access published online on June 15, 2007
Brain, doi:10.1093/brain/awm129
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Increased motor cortex white matter volume predicts motor impairment in autism
1Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA, Johns Hopkins School of Medicine, Departments of 2Neurology and 3Psychiatry, Baltimore, MD, USA
Correspondence to:
Stewart H. Mostofsky, MD, Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA E-mail: mostofsky{at}kennedykrieger.org
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.
Key Words: autism; white matter; imaging; motor; central coherence
Abbreviations: ADHD, attention deficit hyperactivity disorder; PANESS, Physical and Neurologic Examination of Subtle Signs; TD, typically developing
Received October 30, 2006. Revised May 9, 2007. Accepted May 10, 2007.