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

Abstract

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.

Spinocerebellar Ataxia Type 6: A Disorder of Connectivity?

“…In addition, lower temporal variability was associated with disease severity, but not disease duration. Based on the results of this study, Yacoubi et al (2020) suggest that the degeneration of cerebellar lobule VI may result in a reduced ability to modulate the duration of muscle contraction force. But in light of previous functional connectivity and postmortem studies on individuals with SCA6, several other neuroanatomical regions and processes likely contribute to temporal invariance.…”

“…This disorder arises in adulthood (mean age of onset ;45 years) and is characterized by several behavioral, sensory, and motor impairments (Gierga et al, 2009;Casamento-Moran et al, 2015). One symptom, which is particularly noteworthy, is the inability to perform accurate movements (Yacoubi et al, 2020).…”

“…This finding was in stark contrast with studies involving other populations with cerebellar pathology, which found decreased precision of timing. In a recent study, Yacoubi et al (2020) hypothesized that increased temporal precision in SCA6 results from lower temporal variability of movement. This hypothesis was based on previous research on musicians, which found that reduced temporal variability is associated with a reduced volume of cerebellar lobule VI (a neuroanatomical region impacted by SCA6), thus suggesting that this may be a neural correlate of temporal invariance (i.e., less muscle contraction time variability) in individuals with SCA6 (Baer et al, 2015).…”

“…To determine whether individuals with SCA6 do indeed exhibit temporal invariance of movement, Yacoubi et al (2020) had participants perform tasks involving ankle dorsiflexion (i.e., bending the ankle so the foot moved upward). First, participants performed a task to determine the maximal isometric contraction force they could achieve during voluntary ankle dorsiflexion.…”

“…But in light of previous functional connectivity and postmortem studies on individuals with SCA6, several other neuroanatomical regions and processes likely contribute to temporal invariance. The following paragraph will elaborate on the functional anatomy and connectivity of cerebellar lobule VI to help underscore the importance of other neuroanatomical regions and processes that may play a role in the findings of Yacoubi et al (2020).…”