Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications

Abstract

Background: Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into 'motor-driven' and 'cognitively driven'. RRBI symptomatology depends on the individual's clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures-involving cortical and subcortical areas.

Method: A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n = 152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models.

Results: We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the 'motor-driven' RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the 'cognitively driven' RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p < 0.05). FA1 was negatively associated with the left amygdala (uncorrected p < 0.05), and FA2 was positively associated with the left parietal structure (uncorrected p = 0.001).

Conclusion: Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen's integrative role in RSBI needs to be strengthened in further studies.

Keywords: Cortico-striatal-thalamo-cortical loop; Phenotype; RRB.

Fig. 1

Brain map of linear regression-derived coefficients regarding the relationship between repetitive and restricted behaviors and interests-related factors and neuroanatomic structures. A Representation of the linear regression-derived coefficient obtained for each cortical volume (at left) and subcortical volume (at right) considering Factor 1. Extreme values of the linear regression-derived coefficients are represented in blue (<  − 1) and in red (> + 1). P values < 0.05 before FDR correction were obtained for the left amygdala, left putamen and right putamen volumes; B Representation of the linear regression-derived coefficient obtained for each cortical volume (at left) and subcortical volume (at right) considering Factor 2. Extreme values of the linear regression-derived coefficients are represented in blue (<  − 1) and in red (> + 1). P values < 0.05 before FDR correction were obtained for the left parietal, left putamen and right putamen volumes; C Representation of the linear regression-derived coefficient obtained for each cortical volume (at left) and each subcortical volume (at right) considering Factor 3. Extreme values of the linear regression-derived coefficients are represented in blue (<  − 1) and in red (> + 1). P values < 0.05 before FDR correction were obtained for the left amygdala, left putamen and right putamen volumes