The Role of the Cerebellum in Repetitive Behavior Across Species: Childhood Stereotypies and Deer Mice

Dean, Shannon L.; Tochen, Laura; Augustine, Farhan; Ali, Syed F.; Crocetti, Deana; Rajendran, Shreenath; Blue, Mary E.; Mahone, E. Mark; Mostofsky, Stewart H.; Singer, Harvey S.

doi:10.1007/s12311-021-01301-3

Cited by 7 publications

(8 citation statements)

References 52 publications

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“…While cerebellar differences in neuroanatomy have previously yielded inconsistent results in autism (Laidi et al, 2022) and associations with social functioning (Elandaloussi et al, 2023), a large body of research also points to the involvement of cerebellar neuroanatomy and neurocircuitry in the etiology of RRBs in autism (Tian et al, 2022). In line with our findings, autistic individuals with high RRBs were found to have increased GM volume in the vermis VIII and left cerebellar lobule VIII (Seng et al, 2022) and children with complex motor stereotypies have been shown to have increased GM volume in the anterior vermis (Dean et al, 2022). Such structural studies are corroborated by functional work showing for example atypical cerebellar-cortical connectivity being related to elevated RRBs in autistic individuals (Lidstone et al, 2021).…”

Section: Discussionsupporting

confidence: 91%

Towards Understanding Autism Heterogeneity: Identifying Clinical Subgroups and Neuroanatomical Deviations

Meijer,

Vieira,

Elleaume

et al. 2023

Preprint

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Autism Spectrum Disorder ('autism') is a neurodevelopmental condition characterized by substantial behavioural and neuroanatomical heterogeneity. This poses significant challenges to understanding its neurobiological mechanisms and developing effective interventions. Identifying phenotypically more homogeneous subgroups and shifting the focus from average group differences to individuals is a promising approach to addressing heterogeneity. In the present study, we aimed to parse clinical and neuroanatomical heterogeneity in autism by combining clustering of clinical features with normative modeling based on neuroanatomical measures (cortical thickness [CT] and subcortical volume) within the ABIDE datasets (N autism=861, N neurotypical=886, age-range 5-64). First, model-based clustering was applied to autistic symptoms as measured by the Autism Diagnostic Observation Schedule to identify clinical subgroups of autism. Next, we examined whether clinical subgrouping resulted in increased neurobiological homogeneity within the subgroups compared to the entire autism group by comparing their spatial overlap of neuroanatomical deviations. We further investigated whether the identified subgroups improved the accuracy of autism classification based on the neuroanatomical deviations using supervised machine learning with cross-validation. Results yielded two clinical subgroups primarily differing in restrictive and repetitive behaviours (RRB). Both subgroups showed increased homogeneity in localized deviations with the high-RRB subgroup showing increased volume deviations in cerebellum and the low-RRB subgroup showing decreased CT deviations predominantly in the postcentral gyrus and fusiform cortex. Nevertheless, substantial within-group heterogeneity remained highlighted by the failure of the classifier to distinguish between the subgroups. Identifying subgroups of autism has substantial clinical implications opening the potential for more tailored behavioural interventions and improving clinical outcomes.

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Section: Discussionsupporting

confidence: 91%

Towards Understanding Autism Heterogeneity: Identifying Clinical Subgroups and Neuroanatomical Deviations

Meijer,

Vieira,

Elleaume

et al. 2023

Preprint

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“…Alterations in cerebellum function had been suggested in Rett patients through MRI [ 39 ], and recent experiments show that deleting Mecp2 from the cerebellum is responsible for the delay in motor learning in mice [ 40 ]. In fact, a parallelism could be established between cerebellar dysfunctions and early-presenting features of the disease such as the movement disorders [ 41 ] or stereotypes [ 42 ]. Despite all this, cerebellum remains understudied in Rett syndrome compared to other brain areas as cortex or hippocampus [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome

Musokhranova,

Grau,

Vergara

et al. 2023

J Transl Med

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Background Rett syndrome is a neuropediatric disease occurring due to mutations in MECP2 and characterized by a regression in the neuronal development following a normal postnatal growth, which results in the loss of acquired capabilities such as speech or purposeful usage of hands. While altered neurotransmission and brain development are the center of its pathophysiology, alterations in mitochondrial performance have been previously outlined, shaping it as an attractive target for the disease treatment. Methods We have thoroughly described mitochondrial performance in two Rett models, patients’ primary fibroblasts and female Mecp2tm1.1Bird−/+ mice brain, discriminating between different brain areas. The characterization was made according to their bioenergetics function, oxidative stress, network dynamics or ultrastructure. Building on that, we have studied the effect of leriglitazone, a PPARγ agonist, in the modulation of mitochondrial performance. For that, we treated Rett female mice with 75 mg/kg/day leriglitazone from weaning until sacrifice at 7 months, studying both the mitochondrial performance changes and their consequences on the mice phenotype. Finally, we studied its effect on neuroinflammation based on the presence of reactive glia by immunohistochemistry and through a cytokine panel. Results We have described mitochondrial alterations in Rett fibroblasts regarding both shape and bioenergetic functions, as they displayed less interconnected and shorter mitochondria and reduced ATP production along with increased oxidative stress. The bioenergetic alterations were recalled in Rett mice models, being especially significant in cerebellum, already detectable in pre-symptomatic stages. Treatment with leriglitazone recovered the bioenergetic alterations both in Rett fibroblasts and female mice and exerted an anti-inflammatory effect in the latest, resulting in the amelioration of the mice phenotype both in general condition and exploratory activity. Conclusions Our studies confirm the mitochondrial dysfunction in Rett syndrome, setting the differences through brain areas and disease stages. Its modulation through leriglitazone is a potential treatment for this disorder, along with other diseases with mitochondrial involvement. This work constitutes the preclinical necessary evidence to lead to a clinical trial.

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“…Sagledavanjem ovog istraživanja prilazi se korak bliže uzroku problema primarnih motoričkih stereotipija. U tome je od pomoći i istraživanje iz 2022. godine (Dean et al, 2022), koje je za razliku od puteva prenosa signala ispitivalo samu funkciju malog mozga (cerebeluma). Pronađeno je da su zadnji deo i određeni regioni malog mozga koji su zaduženi za posturalnu ravnotežu, skradične pokrete očiju, koordinaciju i motoričku adaptaciju (Stoodley & Schmanhmann, 2010) deficitarni kod osoba sa PMSt (Dean et al, 2022), tj.…”

Section: Koren Problema Motoričkih Stereotipijaunclassified

Primary motor stereotypies

Zrnić

2024

Spec eduk i rehabilitacija

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Introduction. Motor stereotypies are almost always associated with developmental disorders, such as autism spectrum disorder, intellectual disability, etc. Although they most often occur together with sensory deprivation, they are also recognized as isolated. They occur in children with normal, typical development. These isolated stereotypies are called primary motor stereotypies. Aim. The aim of this paper is to provide a better insight into the specificity of this disorder and to show how it affects people (children), as well as to provide insight into the cause of primary motor stereotypies and possible approaches to treatment. Method. Descriptive method with a review of the literature published in the previous ten years, with a critical review. Inclusion and exclusion criteria were defined. Research on the cause of primary motor stereotypies, primary motor stereotypies themselves, and the treatment of primary motor stereotypies was reviewed. Results. Primary motor stereotypies in children with typical development negatively affect daily activities and disrupt social development, which leads to social stigmatization. Many interventions have been found in children with autism spectrum disorder (stereotypies are one of the main features of autism), but there is very little published research on interventions and treatments for primary motor stereotypies. The root of the problem of primary motor stereotypies is complex and involves certain parts of the cortex and pathways of information transmission. The problem is also the identification of this problem, which further affects the interventions themselves. Conclusion. The cause of primary motor stereotypies is still unknown, and behavioral therapies are the possible treatments for primary motor stereotypies. Based on the available research, there is not much literature on this topic, which provides us with exceptional potential and space for discovering new information and knowledge. With new information, there are many ways to work with these people.

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The Role of the Cerebellum in Repetitive Behavior Across Species: Childhood Stereotypies and Deer Mice

Cited by 7 publications

References 52 publications

Towards Understanding Autism Heterogeneity: Identifying Clinical Subgroups and Neuroanatomical Deviations

Towards Understanding Autism Heterogeneity: Identifying Clinical Subgroups and Neuroanatomical Deviations

Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome

Primary motor stereotypies

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