Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction

Abstract

The cerebellar and spinocerebellar dysfunction seen in Friedreich ataxia (FRDA) has known effects on motor function. Recently, it was suggested that people with FRDA may also have impairment in motor planning, either because of cortical pathology or because of cerebello-cortical projections. Fifteen adults with FRDA and 15 matched controls completed a task requiring reciprocating movements between two buttons on a tapping board. Occasionally there was one of three "oddball" stimuli requiring reprogramming of movement. These were change in (1) direction, (2) extent or (3) direction and extent. We hypothesized that people with FRDA would have prolonged movement times due to their movement disorder, and that changes in preparation time would be affected in a way similar to controls, unless there was impairment in motor planning in FRDA. Movement execution and, to a lesser degree, movement preparation were impaired in individuals with FRDA. We argue this points to disturbed cortical function. There was a significant negative correlation between age of onset and all three reprogramming conditions, suggesting an impact of FRDA on developing motor planning. Future studies will be required to establish whether this dysfunction is due to cerebellar impairment interrupting cerebro-ponto-cerebello-thalamo-cerebral loops, primary cortical pathology or a combination of the two.

Utilisation of Advance Motor Information is Impaired in Friedreich Ataxia

“…In the first experiment, the condition that appeared to produce most difficulty for people with FRDA was that of low level of advance information (with significant differences across groups in error data). As with our previous study [20], this condition correlated with age at disease onset. We previously suggested that a deficit of frataxin, a mitochondrial membrane protein involved in iron sulphur protein synthesis [53] and the source of neural dysfunction in FRDA [3,4,54], may influence the pattern of motor cognitive development prior to the onset of overt motor symptoms.…”

“…Not surprisingly, the measure of clinical severity, the FARS, correlated with all conditions indicating in both experiments worse disease was a predictor of dysfunction. The contrasting results from our previous study, which did not reveal a correlation with the FARS [20], highlight perhaps the fact that different task demands are likely to target different functional components of the cerebellum. For example, the cerebellum has been shown to participate in at least three distinct networks targeting specific areas of the prefrontal cortex, including the DLPFC, anterior PFC and medial PFC.…”

“…The response board, consisting of a laminated wooden box measuring 480×100 mm [20,27,36], was used in both experiments. Into the top of the board were set 23 springloaded, circular buttons made from white plastic (Fig.…”

“…In a previously published study, we demonstrated impairment in people with FRDA for reprogramming movement and inhibiting inappropriate automatic responses associated with stimulus-response incompatibility [20]. However, it is still unclear whether this dysfunction is due to known cerebellar impairment interrupting cerebro-pontocerebello-thalamo-cerebral loops, primary cortical pathology and/or a combination of the two.…”

“…However, a pervasive issue in the examination of cognitive function is the confounding effect of the motor impairment associated with FRDA on general reaction time tasks and the challenge of isolating cognitive function in tasks that demand a motoric response. The results of studies to date demonstrate that there are significant and potentially debilitating cognitive changes associated with FRDA that require further investigation [8,16,[19][20][21][22].…”