Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder

Abstract

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...

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models

“…Decreased inhibitory tone from the output nuclei of the basal ganglia, namely the substantia nigra reticulata (SNr) and globus pallidus interna (GPi), to the thalamus, appears to have a role in the pathophysiology of SIB in patients with ASD. For example, injections into SNr of muscimol, a GABA receptor agonist, trigger dose-dependent increases in selfbiting behavior (Baumeister and Frye, 1984), and diminished GPi volume has been shown to correlate with the frequency of RRSBs in ASD (Estes et al, 2011). Therefore, one possibility based on expression studies of GABA in rodents after ECS (Ferraro et al, 1990) is that ECT enhances the inhibitory tone of the SNr and GPi, which may mute abnormal motor thalamic spike patterns associated with stereotypy (Lewis and Kim, 2009).…”

Inflectional morphology in high-functioning autism: Evidence for speeded grammatical processing

“…Indeed, repetitive behaviors have been linked to the basal ganglia in autism (Estes et al 2011; Hollander et al 2005; Pina-Camacho et al 2012; Sears et al 1999). Such basal ganglia-based repetitive behaviors are consistent with the Procedural Deficit Hypothesis, which posits that various functions associated with the basal ganglia (not just procedural memory itself) may be problematic in autism.…”

“…Functional and structural neuroimaging studies of these behaviors have implicated the basal ganglia in autism (Estes et al 2011; Hollander et al 2005; Pina-Camacho et al 2012; Sears et al 1999), as well as in Tourette syndrome (Mink 2001; Swerdlow and Young 2001). Moreover, co-morbidity between autism and tic disorders, including Tourette syndrome, appears to be fairly common (Baron-Cohen et al 1999a; Baron-Cohen et al 1999b; Canitano and Vivanti 2007; Gjevik et al 2011; Lugnegård et al 2011; Mattila et al 2010; but see Memari et al 2012; Ringman and Jankovic 2000; Stern and Robertson 1997).…”

Shape of the basal ganglia in preadolescent children is associated with cognitive performance

“…For instance bilateral enlargement of the putamen and the left caudate nucleus was observed in a large group of 3-4 year old autistic children (Estes et al, 2011). Similarly, basal ganglia volume was enlarged in schizophrenics, a group with well documented impaired executive function (Chakos et al, 1994; Hokama et al, 1995; Staal et al, 2000).…”