Motor stereotypies and volumetric brain alterations in children with Autistic Disorder
Highlights
► Quantitative rating of motor stereotypies from videotaped play sessions. ► Lack of correlation between basal ganglia volumes and presence of stereotypies. ► Number of stereotypies is uncorrelated with volumetric measures of basal ganglia. ► Persistence of stereotypies does not affect these volumetric measures.
Introduction
Motor stereotypies are patterned repetitive purposeless movements such as hand flapping, finger twisting, pacing, or rocking. They constitute a subcategory of “restricted repetitive and stereotyped patterns of behavior, interests and activities” which is the third core criterion required for an Autistic Disorder (AD) diagnosis as defined in the Diagnostic and Statistical Manual of Mental Disorders ([DSM IV-TR]; American Psychiatric Association, 2000). These stigmatizing repetitive motor manifestations are receiving increased attention as potential early markers suggestive of an autism diagnosis (Watt, Wetherby, Barber, & Morgan, 2008). Furthermore, given the limited advances made toward unraveling the neurobiology of autism through the study of the cardinal non-motor manifestations such as language disorder and social impairments, a growing number of researchers have turned their attention to motor impairments and stereotypies as a potential source of additional insights into the pathophysiology of autism (Lewis & Kim, 2009).
To pursue these investigations, a variety of functional and structural imaging modalities have been used in children with autism (Amaral et al., 2008, Schumann et al., 2010, Stigler et al., 2011) with few motor studies focusing on stereotypies (Estes et al., 2011, Hardan et al., 2003, Thakkar et al., 2008). None of these studies has revealed a consistent pattern of neuronatomical characteristics in children with autism and stereotypies. Some investigators (Hollander et al., 2005, Rojas et al., 2006, Sears et al., 1999) report an increase in caudate nucleus volume, when total brain volume is taken into account. Other magnetic resonance imaging (MRI)-based brain volumetric investigations yielded no consensus between repetitive behaviors and the size of orbitofrontal cortex, anterior cingulate cortex, the basal ganglia, or thalamus, the brain structures most commonly thought to be implicated in repetitive behaviors (Langen et al., 2007, Langen et al., 2009).
There are at least four possible reasons for this lack of correspondence. First, size or structure may not correlate systematically with function or, if there are volumetric alterations, they may be too slight to be resolved with current low resolution morphometric technology. Second, methodologic differences in image acquisition or analysis may mask subtle disparities, given the challenges of recording optimal images from individuals with autism, especially from younger children in whom stereotypies may be particularly prominent. Third, heterogeneity in age, cognitive abilities, and autism severity, together with small sample sizes (Kates, Lanham, & Singer, 2005), jeopardize the likelihood of gathering optimally representative data (Toal et al., 2010). Finally, a lack of comparable measures of stereotypies likely contributes to between-study inconsistencies. There are several validated instruments such as questionnaires and observational scales like the Repetitive Behavior Scale-Revised ([RBS-R]; Lam & Aman, 2007) to measures stereotypies. However, none of these provides standardized measures for the videocoding of stereotypies and thus far no systematic attempt has been made to examine consistency of results across different types of measures such as observations, interviews, and questionnaires (Honey, Rodgers, & McConachie, 2012). Some investigations emphasize behavioral features whereas others focus on motor components (DiGennaro Reed, Hirst, & Hyman, 2012). Rating scales and questionnaires yield less objective and accurate data than scoring of videos which provide the opportunity for repeated detailed examination by several observers (Goldman et al., 2009). A major limitation of video studies is limited sampling time and the rarity of records obtained under standardized circumstances ideally suited to enhancing the expression and characterization of stereotypies in all or most subjects. These considerations have limited the utility to date of video recordings.
Here we report an analysis of motor stereotypies videoscored using a rigorous approach and correlated with volumetric measures of selected basal ganglia and other relevant brain regions. Subjects were a subset of a larger population of children with a uniformly documented preschool Autistic Disorder (AD) diagnosis ([DSM III-R]; American Psychiatric Association, 1987, Rapin, 1996) in whom MRI data were obtained at school age. In this cohort we had carried out video data analysis of stereotypies in a standardized play setting at preschool (Goldman et al., 2009) and again at school age. Previous studies from school age MRIs in an overlapping subset of children eligible for the present study had yielded brain volumetric data showing significant differences between AD and control subjects in language regions (Herbert et al., 2002), total and regional brain volumes (Herbert et al., 2003), localization of white matter enlargement (Herbert et al., 2004), and brain asymmetries (Herbert et al., 2002, Herbert et al., 2005). These studies demonstrated sufficient quality of the morphometric data to justify our exploring the relationship between brain volumes and the presence and severity of motor stereotypies.
Herein, we compared brain volumetric measures in the AD school age sample group with available videocoded stereotypy data to corresponding volumes in a control group of typically developing (TD) children free of stereotypies. We hypothesized that in children with AD, stereotypies scored from videotapes would be associated with volumetric alterations in basal ganglia circuitry, most likely the striatum, as compared with controls.
Section snippets
Participants
Participants included 61 school age children (M = 9.12 years, SD = 1.27); 31 children with a preschool diagnosis of AD who were matched on chronological age with 30 TD (Table 1). All of the TD subjects were recruited specifically for imaging purposes; they all had normal birth weights, normal developmental histories without seizures or significant head injury. Their screening neurological examination was normal and school performance had never required special help. IQ was not measured. English was
Analysis of demographic variables
To investigate possible demographic differences when making group comparisons, we performed a series of a priori analyses. First, in regard to ethnicity, based on previous reports published about this cohort the two AD and TD groups did not differ in ethnicity distribution. The available data about the ethnicity of the AD group shows that 70% of the participants were Caucasian (Rapin, 1996). Since so far no published data on ethnicity has suggested difference in brain volume we did not covary
Discussion
This study examines the relationship of neuroanatomical volumes to stereotypies in autism. We found that the total brain volumes of children with AD were larger than those of typically developing children with neither autism nor stereotypies. We also found that in AD, lower PIQ was marginally associated with more stereotypies. However, in contrast with previous brain imaging studies of subjects from the same cohort which had reported significant morphometric differences in brain regions
Financial disclosure
Sylvie Goldman was supported by the Einstein/Montefiore Autism Center and a LEND grant – Leadership Education in Neurodevelopmental and Related Disabilities from the Bureau of Maternal and Child Health in the Department of Health and Human Services. Liam O’Brien was supported by a grant from the Division of Natural Sciences at Colby College. The original study, including collection of all historical, neurologic, neuropsychologic, and play data, MRI acquisition and preliminary analyses, was
Conflict of interest
None declared.
Acknowledgments
We thank the children and their parents for their participation and all the investigators and research assistants for their participation in the original project. We thank Dr Lucy Brown for her insightful comments on an earlier version of this manuscript.
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