Motor Stereotypies: A Pathophysiological Review

Péter, Zsanett; Oliphant, Melody; Fernandez, Thomas

doi:10.3389/fnins.2017.00171

Cited by 65 publications

(52 citation statements)

References 36 publications

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“…This property reflects that side-choice behavior derives from a stable internal representation that lasted many months for our mice. Maybe not surprisingly, the propensity to develop motor stereotypies depends on genomic factors ( Peter et al, 2017 ). Some innate behaviors, such as exploring or avoiding predators, could be sculpted by evolution into stereotyped modules that encode coherent and adaptive patterns of action ( Wiltschko et al, 2015 ; Abrahamyan et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Adaptive Choice Biases in Mice and Humans

Treviño

León

Haro

2020

Front. Behav. Neurosci.

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The contribution of non-sensory information processing to perceptual decision making is not fully understood. Choice biases have been described for mice and humans and are highly prevalent even if they decrease rewarding outcomes. Choice biases are usually reduced by discriminability because stimulus strength directly enables the adjustments in the decision strategies used by decision-makers. However, choice biases could also derive from functional asymmetries in sensory processing, decision making, or both. Here, we tested how particular experimental contingencies influenced the production of choice biases in mice and humans. Our main goal was to establish the tasks and methods to jointly characterize psychometric performance and innate side-choice behavior in mice and humans. We implemented forced and un-forced visual tasks and found that both species displayed stable levels of side-choice biases, forming continuous distributions from low to high levels of choice stereotypy. Interestingly, stimulus discriminability reduced the side-choice biases in forced-choice, but not in free-choice tasks. Choice biases were stable in appearance and intensity across experimental days and could be employed to identify mice and human participants. Additionally, side- and alternating choices could be reinforced for both mice and humans, implying that choice biases were adaptable to non-visual manipulations. Our results highlight the fact that internal and external elements can influence the production of choice biases. Adaptations of our tasks could become a helpful diagnostic tool to detect aberrant levels of choice variability.

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Section: Discussionmentioning

confidence: 99%

Adaptive Choice Biases in Mice and Humans

Treviño

León

Haro

2020

Front. Behav. Neurosci.

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“…Stereotypy and rigidity of behavior are considered core features of ASD 60 , 61 . Moreover, the involvement of the brain histaminergic neurotransmission in the pathophysiology of Tourette syndrome, a condition commonly comorbid among ASD patients and featured by stereotypies, has been proposed and has been associated with a premature termination codon (W317X) responsible for the L-histidine decarboxylase (HDC) gene, the rate-limiting enzyme in biosynthesis of brain histamine.…”

Section: Discussionmentioning

confidence: 99%

The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism

Eissa

Jayaprakash

Azimullah

et al. 2018

Sci Rep

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Autistic spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social communication and restricted/repetitive behavior patterns or interests. Antagonists targeting histamine H3 receptor (H3R) are considered potential therapeutic agents for the therapeutic management of different brain disorders, e.g., cognitive impairments. Therefore, the effects of subchronic treatment with the potent and selective H3R antagonist DL77 (5, 10, or 15 mg/kg, i.p.) on sociability, social novelty, anxiety, and aggressive/repetitive behavior in male Tuck-Ordinary (TO) mice with ASD-like behaviors induced by prenatal exposure to valproic acid (VPA, 500 mg/kg, i.p.) were evaluated using the three-chamber test (TCT), marble burying test (MBT), nestlet shredding test (NST), and elevated plus maze (EPM) test. The results showed that VPA-exposed mice exhibited significantly lower sociability and social novelty preference compared to VPA-exposed mice that were pretreated with DL77 (10 or 15 mg/kg, i.p.). VPA-exposed mice presented a significantly higher percentage of buried marbles in MBT and shredded nestlet significantly more in NST compared to the control groups. However, VPA-exposed animals pretreated with DL77 (10 or 15 mg/kg, i.p.) buried a reduced percentage of marbles in MBT and presented a significantly lower percentage of shredding behavior in NST. On the other hand, pretreatment with DL77 (5, 10, or 15 mg/kg, i.p.) failed to restore the disturbed anxiety levels and hyperactivity observed in VPA-exposed animals in EPM, whereas the reference drug donepezil (DOZ, 1 mg/kg, i.p.) significantly palliated the anxiety and reduced the hyperactivity measures of VPA-exposed mice. Furthermore, pretreatment with DL77 (10 or 15 mg/kg, i.p.) modulated oxidative stress status by increasing GSH and decreasing MDA, and it attenuated the proinflammatory cytokines IL-1β, IL-6 and TNF-α exacerbated by lipopolysaccharide (LPS) challenge, in VPA-exposed mouse brain tissue. Taken together, these results provide evidence that modulation of brain histaminergic neurotransmission, such as by subchronic administration of the H3R antagonist DL77, may serve as an effective pharmacological therapeutic target to rescue ASD-like behaviors in VPA-exposed animals, although further investigations are necessary to corroborate and expand these initial data.

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“…First, temporal invariance should not be confused with motor stereotypy. Motor stereotypies (also called stereotypic movement disorder), are rhythmic, fixed, but purposeless movements (Péter et al, 2017), which occur in many disorders including autism and down syndrome (Sanders et al, 2015). Rather, temporal invariance appears to be a limitation of the CNS in planning muscle contraction.…”

Section: Time Invariance In Sca6: a Distinct Phenotypementioning

confidence: 99%

Temporal Invariance in SCA6 Is Related to Smaller Cerebellar Lobule VI and Greater Disease Severity

Yacoubi¹,

Casamento‐Moran²,

Burciu³

et al. 2020

J. Neurosci.

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Regulating muscle force and timing are fundamental for accurate motor performance. In spinocerebellar ataxia type 6 (SCA6), there is evidence that individuals have greater force dysmetria but display better temporal accuracy during fast goal directed contractions. Here, we test whether greater temporal accuracy occurs in all individuals with SCA6, and can be explained by lesser temporal variability. Further we examine whether it is linked to disease severity and specific degenerative changes in the cerebellum. Nineteen human participants with SCA6 (13 woman) and 18 healthy controls performed fast goal-directed ankle dorsiflexion contractions aiming at a spatiotemporal target. We quantified the endpoint control of these contractions, gray matter (GM) integrity of the cerebellum, and disease severity using the International Cooperative Ataxia Rating Scale (ICARS). SCA6 individuals exhibited lower temporal endpoint error and variability than the healthy controls (p ϭ 0.008). Statistically, SCA6 clustered into two distinct groups for temporal variability. A group with low temporal variability ranging from 10 to 19% (SCA6a) and a group with temporal variability similar to healthy controls (SCA6b; 19-40%).SCA6a exhibited greater disease severity than SCA6b, as assessed with ICARS (p Ͻ 0.001). Lower temporal variability, which was not associated with disease duration (R 2 ϭ 0.1, p Ͼ 0.2), did correlate with both greater ICARS (R 2 ϭ 0.3) and reduced GM volume in cerebellar lobule VI (R 2 ϭ 0.35). Other cerebellar lobules did not relate to temporal variability. We provide new evidence that a subset of SCA6 with greater loss of GM in cerebellum lobule VI exhibit temporal invariance and more severe ataxia than other SCA6 individuals.

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Motor Stereotypies: A Pathophysiological Review

Cited by 65 publications

References 36 publications

Adaptive Choice Biases in Mice and Humans

Adaptive Choice Biases in Mice and Humans

The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism

Temporal Invariance in SCA6 Is Related to Smaller Cerebellar Lobule VI and Greater Disease Severity

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