Spinocerebellar Ataxia Type 6: A Disorder of Connectivity?
| Autor: | Max Teaford |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cerebellum business.industry General Neuroscience 05 social sciences Mean age Progressive neurodegenerative disorder medicine.disease Severity of Illness Index 050105 experimental psychology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Severity of illness medicine Humans Spinocerebellar Ataxias Spinocerebellar ataxia type 6 0501 psychology and cognitive sciences business Neuroscience Research Articles 030217 neurology & neurosurgery |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0822-20.2020 |
| Popis: | 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 = 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 < 0.001). Lower temporal variability, which was not associated with disease duration (R(2) = 0.1, p > 0.2), did correlate with both greater ICARS (R(2) = 0.3) and reduced GM volume in cerebellar lobule VI (R(2) = 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. SIGNIFICANCE STATEMENT Variability is an inherent feature of voluntary movement, and traditionally more variability in the targeted output infers impaired performance. For example, cerebellar patients present exacerbated temporal variability during multijoint movements, which is thought to contribute to their motor deficits. In the current work, we show that in a subgroup of spinocerebellar ataxia type 6 individuals, temporal variability is lower than that of healthy controls when performing single-joint fast-goal directed movements. This invariance related to exacerbated atrophy of lobule VI of the cerebellum and exacerbated disease severity. The relation between invariance and disease severity suggests that pathological motor variability can manifest not only as an exacerbation but also as a reduction relative to healthy controls. |
| Databáze: | OpenAIRE |
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