Dataset Information

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

ABSTRACT: Background:Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown. Methods:Here, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas. For this, pregnant female mice (C57BL/6J) received valproic acid (450 mg/kg) at embryonic day 12.5 and offspring underwent a battery of behavioral analyses before being killed for histological correlates in motor cortex, nigrostriatal pathway, and cerebellum. Results:We show that while valproic acid male mice show both social and motor impairments, female mice only show motor impairments. Prenatal valproic acid exposure induces specific cell loss within the motor cortex and cerebellum and that is of higher magnitude in males than in females. Finally, we demonstrate that motor dysfunction correlates with reduced social behavior and that motor and social deficits both correlate with a loss of Purkinje cells within the Crus I cerebellar area. Conclusions:Our results suggest that motor dysfunction could contribute to social and communication deficits in autism spectrum disorders and that motor and social deficits may share common neuronal substrates in the cerebellum. A systematic assessment of motor function in autism spectrum disorders may potentially help the quantitative diagnosis of autism spectrum disorders and strategies aimed at improving motor behavior may provide a global therapeutic benefit.

SUBMITTER: Al Sagheer T

PROVIDER: S-EPMC6119291 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

Al Sagheer Tareq T Haida Obelia O Balbous Anais A Francheteau Maureen M Matas Emmanuel E Fernagut Pierre-Olivier PO Jaber Mohamed M

The international journal of neuropsychopharmacology 20180901 9

<h4>Background</h4>Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown.<h4>Methods</h4>Here, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social defici ...[more]

PMID: 29762671

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Project description:Lack of interest in social interaction is a hallmark of autism spectrum disorder. Animal studies have implicated the mesolimbic reward pathway in driving and reinforcing social behaviour, but little is known about the integrity of this pathway and its behavioural consequences in children with autism spectrum disorder. Here we test the hypothesis that the structural and functional integrity of the mesolimbic reward pathway is aberrant in children with autism spectrum disorder, and these aberrancies contribute to the social interaction impairments. We examine structural and functional connectivity of the mesolimbic reward pathway in two independent cohorts totalling 82 children aged 7-13 years with autism spectrum disorder and age-, gender-, and intelligence quotient-matched typically developing children (primary cohort: children with autism spectrum disorder n = 24, typically developing children n = 24; replication cohort: children with autism spectrum disorder n = 17, typically developing children n = 17), using high angular resolution diffusion-weighted imaging and functional MRI data. We reliably identify white matter tracts linking-the nucleus accumbens and the ventral tegmental area-key subcortical nodes of the mesolimbic reward pathway, and provide reproducible evidence for structural aberrations in these tracts in children with autism spectrum disorder. Further, we show that structural aberrations are accompanied by aberrant functional interactions between nucleus accumbens and ventral tegmental area in response to social stimuli. Crucially, we demonstrate that both structural and functional circuit aberrations in the mesolimbic reward pathway are related to parent-report measures of social interaction impairments in affected children. Our findings, replicated across two independent cohorts, reveal that deficits in the mesolimbic reward pathway contribute to impaired social skills in childhood autism, and provide fundamental insights into neurobiological mechanisms underlying reduced social interest in humans.

Project description:ObjectiveMotor impairments are prevalent in children with autism spectrum disorder (ASD) and persistent across age. Our current study was designed to investigate motor deficits in Chinese toddlers with ASD and to explore the relationships between motor deficits and social communication skills.MethodsFor this cross-sectional study, we recruited a total of 210 Chinese toddlers with ASD aged between 18 and 36 months in the study during December 2017 to December 2020. Griffiths Developmental Scales-Chinese (GDS-C), Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Communication and Symbolic Behavior Scales Developmental Profile-Infant-Toddler Checklist (CSBS-DP-ITC) were administered in these toddlers to evaluate their development, social communicative skills, and autism severity. We compared the developmental and social communicational profiles of ASD toddlers in different gross and fine motor subgroups, and explored potential associated factors. The univariate generalized linear model tested the relationship of fine and gross motor skills and social communicative skills.ResultsThe prevalence of gross and fine motor deficits were 59.5 and 82.5%, respectively, which are almost equivalent in boys and girls. The motor impairments tended to be more severe with age in toddlers. After adjusting for age, sex, non-verbal development quotient (DQ) and restricted, repetitive behaviors, severer gross motor impairments were significantly related to higher comparison score of ADOS-2 and higher social composite score of CSBS-DP-ITC, without interactions with other variables. Meanwhile, lower fine motor skills were associated with more deficits of social communication and higher severity of ASD, also depending on non-verbal DQ. In the lower non-verbal DQ subgroup, both fine motor deficits and restricted repetitive behaviors (RRBs) might have effects on autism symptomology.ConclusionMotor impairments are common in Chinese toddlers with ASD. Toddlers with weaker gross and fine motor skills have greater deficits in social communicative skills. Gross motor impairment might be an independent predictor of the severity of autism and social communication skills, while the effect of fine motor deficits might be affected by non-verbal DQ and RRBs of toddlers with ASD. We provide further justification for the inclusion of motor impairments in the early intervention for toddlers with ASD.

Project description:While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery.

Dataset Information

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

Publications

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

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