Cortico-basal ganglia white matter microstructure is linked to restricted repetitive behavior in autism spectrum disorder.

BACKGROUND: Restricted repetitive behavior (RRB) is one of two behavioral domains required for the diagnosis of autism spectrum disorder (ASD). Neuroimaging is widely used to study brain alterations associated with ASD and the domain of social and communication deficits, but there has been less work regarding brain alterations linked to RRB. METHODS: We utilized neuroimaging data from the National Institute of Mental Health Data Archive to assess basal ganglia and cerebellum structure in a cohort of children and adolescents with ASD compared to typically developing (TD) controls. We evaluated regional gray matter volumes from T1-weighted anatomical scans and assessed diffusion-weighted scans to quantify white matter microstructure with free-water imaging. We also investigated the interaction of biological sex and ASD diagnosis on these measures, and their correlation with clinical scales of RRB. RESULTS: Individuals with ASD had significantly lower free-water corrected fractional anisotropy (FAT) and higher free-water (FW) in cortico-basal ganglia white matter tracts. These microstructural differences did not interact with biological sex. Moreover, both FAT and FW in basal ganglia white matter tracts significantly correlated with measures of RRB. In contrast, we found no significant difference in basal ganglia or cerebellar gray matter volumes. LIMITATIONS: The basal ganglia and cerebellar regions in this study were selected due to their hypothesized relevance to RRB. Differences between ASD and TD individuals that may occur outside the basal ganglia and cerebellum, and their potential relationship to RRB, were not evaluated. CONCLUSIONS: These new findings demonstrate that cortico-basal ganglia white matter microstructure is altered in ASD and linked to RRB. FW in cortico-basal ganglia and intra-basal ganglia white matter was more sensitive to group differences in ASD, whereas cortico-basal ganglia FAT was more closely linked to RRB. In contrast, basal ganglia and cerebellar volumes did not differ in ASD. There was no interaction between ASD diagnosis and sex-related differences in brain structure. Future diffusion imaging investigations in ASD may benefit from free-water estimation and correction in order to better understand how white matter is affected in ASD, and how such measures are linked to RRB.

Reduction of restricted repetitive behavior by environmental enrichment: Potential neurobiological mechanisms.

Restricted repetitive behaviors (RRB) are one of two diagnostic criteria for autism spectrum disorder and common in other neurodevelopmental and psychiatric disorders. The term restricted repetitive behavior refers to a wide variety of inflexible patterns of behavior including stereotypy, self-injury, restricted interests, insistence on sameness, and ritualistic and compulsive behavior. However, despite their prevalence in clinical populations, their underlying causes remain poorly understood hampering the development of effective treatments. Intriguingly, numerous animal studies have demonstrated that these behaviors are reduced by rearing in enriched environments (EE). Understanding the processes responsible for the attenuation of repetitive behaviors by EE should offer insights into potential therapeutic approaches, as well as shed light on the underlying neurobiology of repetitive behaviors. This review summarizes the current knowledge of the relationship between EE and RRB and discusses potential mechanisms for EE's attenuation of RRB based on the broader EE literature. Existing gaps in the literature and future directions are also discussed.