Biopsychological correlates of repetitive and restricted behaviors in autism spectrum disorders

Abstract

Background: Autism Spectrum Disorder (ASD) is considered a neurodevelopmental condition that is characterized by alterations in social interaction and communication, as well as patterns of restrictive and repetitive behaviors (RRBs). RRBs are defined as broad behaviors that comprise stereotypies, insistence on sameness, and attachment to objects or routines. RRBs can be divided into lower-level behaviors (motor, sensory, and object-manipulation behaviors) and higher-level behaviors (restrictive interests, insistence on sameness, and repetitive language). According to the DSM-5, the grade of severity in ASD partially depends on the frequency of RRBs and their consequences for disrupting the life of patients, affecting their adaptive skills, and increasing the need for parental support.

Methods: We conducted a systematic review to examine the biopsychological correlates of the symptomatic domains of RRBs according to the type of RRBs (lower- or higher-level). We searched for articles from the National Library of Medicine (PubMed) using the terms: autism spectrum disorders, ASD, and autism-related to executive functions, inhibitory control, inflexibility, cognitive flexibility, hyper or hypo connectivity, and behavioral approaches. For describing the pathophysiological mechanism of ASD, we also included animal models and followed PRISMA guidelines.

Results: One hundred and thirty-one articles were analyzed to explain the etiology, continuance, and clinical evolution of these behaviors observed in ASD patients throughout life.

Conclusions: Biopsychological correlates involved in the origin of RRBs include alterations in a) neurotransmission system, b) brain volume, c) inadequate levels of growth factors, d) hypo- or hyper-neural connectivity, e) impairments in behavioral inhibition, cognitive flexibility, and monitoring and f) non-stimulating environments. Understanding these lower- and higher-level of RRBs can help professionals to improve or design novel therapeutic strategies.

Keywords: autism spectrum disorder; neurodevelopmental disorders; repetitive behaviors; restricted behaviors; stereotypes.

FIGURE 1

Timeline showing the type of RRBs found in ASD and the brain regions affected according to age. Dotted lines represent the increased (+) or decreased (−) volume of cortical and subcortical structures by age group. B, bilateral; L, left; R, right

FIGURE 2

Brain schemes showing patterns of functional hypo‐ and hyperconnectivity between cortical and subcortical regions associated with RRBs at different developmental stages in patients with ASD. (a) In childhood and adolescence, hypoconnectivity among the precentral gyrus, postcentral gyrus, left posterior insula, and left posterior putamen is associated with stereotypies (a lower‐level RRB) and compulsive‐restrictive behaviors (higher‐level RRBs), whereas hypoconnectivity among the left precentral gyrus, left postcentral gyrus, left posterior insula, and left posterior putamen is associated with ritualistic behaviors (higher‐level RRBs). Otherwise, hyperconnectivity between the left NAcc and right PMC is associated with not‐specified RBBs. In childhood, adolescence, and adulthood, hyperconnectivity between the left pVC and right IFGpo is associated with not‐specified RRBs, whereas hyperconnectivity between the right IPL and right IFGpt is related to higher‐level RRBs. In adolescence and adulthood, hyperconnectivity between the right MFG and right caudate nucleus is associated with unstipulated RRBs. In adulthood, hyperconnectivity between the PCC and right pHG is associated with not‐specified RRBs. (b) Patterns of hypo‐ and hyperconnectivity intra and/or inter functional networks. In children, hyperconnectivity in the SN is associated with no specified RRBs, whereas, in adolescents, hypoconnectivity in the DMN is associated with undetermined RRBs. In childhood, adolescence, and adulthood, hypoconnectivity in the VN and in the VAN, and hyperconnectivity between the SCN and SMN are associated with ritualism, maintenance of sameness, repetitive language, circumscribed interests, and compulsions (higher‐levels RRBs) and stereotypies, mannerism, and self‐injurious behavior (lower‐level RRBs) (Abbott et al., ; Akkermans et al., ; Delmonte et al., ; Monk et al., ; S. Tang et al., ; Traynor et al., ; Uddin et al., ; Weng et al., 2010). Blue color represents hypoconnectivity and red color indicates hyperconnectivity. Violet circles and dotted lines represent the SMN. Green circles and dotted lines represent the VN. Brown circles and dotted lines in brown represent the VAN. Gray circle and dotted lines represent the DMN. Dark red circle and dotted lines represent the SN. Dark blue circle and dotted lines represent the SCN. Black solid lines indicate connectivity among cerebral networks. Brain regions: AC, auditory cortex; ACC, anterior cingulate cortex; IFGpo, inferior frontal gyrus pars orbitalis; IFGpt, inferior frontal gyrus pars triangularis; Ins, insula; IPL, inferior parietal lobule; MFG, middle frontal gyrus; MPC, medial prefrontal cortex; NAcc, nucleus accumbens; PCC, posterior cingulate cortex; pHG, parahippocampal gyrus; PMC, premotor cortex; pVC, primary visual cortex; Pre‐Post CG, pre and post central gyrus; SFG, superior frontal gyrus; TL, temporal lobe; TPJ, temporoparietal junction; VC, visual cortices; VFC, ventral frontal cortex. Brain networks: DMN, default mode network; SCN, subcortical network; SMN, somatomotor network; SN, salient network; VAN, ventral attention network; VN, visual network

FIGURE 3

Schematic summary of the psychobiological correlates according to the type of RRBs. B, bilateral; L, left; R, right; ↑, high levels of expression; ↓, low levels of expression. Figure references: (Aida et al., ; Ashwood et al., ; Burrows et al., ; Chao et al., ; Ciaranello, ; Durand & Crimmins, ; Estes et al., ; Gould et al., ; Gover et al., ; Hardan et al., ; Lanovaz et al., ; Miller et al., ; Nakamura et al., ; Presti et al., ; Rehfeldt & Chambers, ; Rojas et al., ; Russo, , 2014; Schauer, ; Schmitt et al., ; Sears et al., ; J. Tang et al., 2002)