These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

Brain development in autism follows an abnormal pattern, with accelerated growth in early life that results in brain enlargement in childhood. Brain volume in adolescents and adults with autism is, however, normal, and appears to be due to a slight decrease in brain volume for these individuals at the same time that normal children are experiencing a slight increase.

Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Scientific AbstractWe investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3-4 year old children with autism spectrum disorder (ASD; n=77) and developmental delay without autism (DD; n=34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n=45), DD (n=14) and a group of children with typical development (TD; n=25) were also assessed by magnetic resonance imaging (MRI). Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus. IntroductionAutism spectrum disorders (ASDs) are characterized by impairments in social interaction and communication, and the presence of restricted, repetitive and stereotyped patterns of behavior and interest. The repetitive and stereotyped behavior (RSB) domain encompasses a Send correspondence to Annette Estes, Ph.D., UW Autism Center, Box 357920, University of Washington, Seattle, WA 98195. . This work was conducted at the University of Washington Autism Center, University of Washington, Seattle, WA. (Happe, Ronald, Plomin, 2006;Baron-Cohen & Belmonte, 2005). However, an "insistence on sameness" factor has been identified in several independent samples and genetic linkage in the 15q11-q13 region was found for families with children who scored high on this factor Cuccaro et al., 2003;Szatmari et al., 2006). The variability in severity, type, and even presence or absence of RSB among individuals diagnosed with ASD lends uncertainty as to its diagnostic significance. NIH Public AccessRSB is more often reported in individuals with ASD, as compared to those with developmental delay without autism (DD: Carcani-Rathwell, Rabe-Hasketh & Santosh, 2006;Bodfish, Symons, Parker & Lewis, 2000). Lower cognitive function increases the overall risk for RSB within ASD (Bishop, Richler & Lord, 2006;Estes, Dawson, Sterling, Munson, 2007;Richler, Bishop, Kleink...

Cerebellar histopathological abnormalities have been well documented in autism although findings of structural differences, as determined by magnetic resonance imaging, have been less consistent. This report explores specific cerebellar vermal structures and their relation with symptoms severity and cognitive functioning in young children with autism spectrum disorder (ASD). Children with ASD aged 3 to 4 years were compared with chronological age matched typically developing children (TD) and chronologic and mental age matched children with developmental delay (DD). Volumes of the cerebellum and midsagittal vermal areas were measured from 3-D T1-weighted MR images. Children with ASD had reduced total vermis volumes compared to children with TD after controlling for age, sex, and overall cerebral volume or cerebellum volume. In particular, the vermis lobe VI-VII area was reduced in children with ASD compared to TD children. Children with DD had smaller total vermis areas compared to children with ASD and TD. Within the ASD group, cerebellar measurements were not correlated with symptom severity, or verbal, non-verbal or full scale IQ. Within the DD group, larger cerebellar measurements were correlated with less impairments. The specific relation between altered cerebellar structure and symptom expression in autism remains unclear.

This study assessed midsagittal corpus callosum cross sectional areas in 3-4 year olds with autism spectrum disorder (ASD) compared to typically developing (TD) and developmentally delayed (DD) children. Though not different in absolute size compared to TD, ASD callosums were disproportionately small adjusted for increased ASD cerebral volume. ASD clinical subgroup analysis revealed greater proportional callosum reduction in the more severely affected autistic disorder (AD) than in pervasive developmental disorder-not otherwise specified (PDD-NOS) children. DD children had smaller absolute callosums than ASD and TD. Subregion analysis revealed widely distributed callosum differences between ASD and TD children. Results could reflect decreased inter-hemispheric connectivity or cerebral enlargement due to increase in tissues less represented in the corpus callosum in ASD.

There is disagreement about allowing propofol sedation for research magnetic resonance imaging/spectroscopy (MRI/MRS) in children. Our study is the first to provide relevant safety and efficacy data. With institutional approval, 108 research MRI/MRS procedures under propofol sedation were performed longitudinally on children at ages 3-4 years (N=59) and 6-7 years (N=49). Sedation parameters, physiological values, and outcome data were collected. Success rate for acquisition of satisfactory quality MRI/MRS during propofol sedation was compared with that in typically developing, age-matched sleeping children. Only 5 minor events (2 with need to insert an oral airway, 2 with premature termination of study, 1 with bradycardia not requiring treatment) and no major events occurred. These safety/efficacy data are equal to or better than previously reported with propofol for clinically indicated procedures. A high percentage of parents of children participating in MRI/MRS studies at 3-4 years of age returned with their child at 6-7 years of age, and longitudinal follow-up was not adversely impacted by their child's experience with sedation. The success rate of data acquisition was significantly higher during propofol sedation (98%) than during late-night sleep studies in typically developing children (30%-50%). We conclude that propofol sedation for research MRI/MRS is safe and effective when children of appropriate ASA class are selected, supplemental oxygen is delivered, and sedation and monitoring are done by an experienced anesthesiologist.

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