Aberrant prefrontal cortical–striatal functional connectivity in children with primary complex motor stereotypies

Augustine, Farhan; Nebel, Mary Beth; Mostofsky, Stewart H.; Mahone, E. Mark; Singer, Harvey S.

doi:10.1016/j.cortex.2021.05.022

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…Augustine et al showed the reduced functional connectivity between the prefrontal and striatal regions (i.e., regions associated with goal-directed behaviors). However, the functional connectivity between motor/premotor cortex and striatal regions (i.e., regions critical for developing and regulating habitual behaviors) had no difference in children with motor stereotypies (a type of RRBs) compared to TD children (Augustine et al, 2021). A speculative contention was decreased prefrontal -striatal connectivity altered the balance between habitual and goal-directed action control, which resulted in enduring motor stereotypies.…”

Section: Reinforcement and Habitmentioning

confidence: 99%

“…Moreover, complex motor stereotypies (CMS) were rhythmic, repetitive, fixed, and purposeless movements (Oakley et al, 2015). Augustine et al (2021) found reduced functional connectivity between the prefrontal cortex and striatal regions in children with CMS. However, functional connectivity between motor/premotor cortex and striatal regions was no different from the control group.…”

Section: Neuroimaging Of Cortico-striatal-thalamo-cortical Circuitmentioning

confidence: 99%

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Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics

2022

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social communication, social interaction, and repetitive restricted behaviors (RRBs). It is usually detected in early childhood. RRBs are behavioral patterns characterized by repetition, inflexibility, invariance, inappropriateness, and frequent lack of obvious function or specific purpose. To date, the classification of RRBs is contentious. Understanding the potential mechanisms of RRBs in children with ASD, such as neural connectivity disorders and abnormal immune functions, will contribute to finding new therapeutic targets. Although behavioral intervention remains the most effective and safe strategy for RRBs treatment, some promising drugs and new treatment options (e.g., supplementary and cell therapy) have shown positive effects on RRBs in recent studies. In this review, we summarize the latest advances of RRBs from mechanistic to therapeutic approaches and propose potential future directions in research on RRBs.

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Section: Reinforcement and Habitmentioning

confidence: 99%

Section: Neuroimaging Of Cortico-striatal-thalamo-cortical Circuitmentioning

confidence: 99%

Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics

2022

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“…The precise pathophysiological mechanism for motor stereotypies remains obscure [ 31 ], though investigators have hypothesized abnormalities within cortico-striatal-thalamo-cortical pathways [ 32 – 38 ] and several neurotransmitter systems [ 33 , 39 – 41 ]. A recent study reported reduced functional connectivity between prefrontal cortical and striatal regions in pCMS [ 42 ]. A genetic etiology for stereotypies has been suggested in primary and secondary categories, although the specific gene(s) contributing to this movement disorder remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene

Fernandez,

Williams,

Kline

et al. 2023

PLoS ONE

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Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children (“primary” stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.

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Motor Stereotypies

Singer¹,

Mink²,

Gilbert³

et al. 2022

Movement Disorders in Childhood

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Aberrant prefrontal cortical–striatal functional connectivity in children with primary complex motor stereotypies

Cited by 5 publications

References 54 publications

Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics

Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics

Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene

Motor Stereotypies

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