The final blink: intact eyeblink conditioning in isolated dystonia

Abstract

Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia. However, the results from individual studies are conflicting and underpowered. This collaborative project collated all published data and systematically re-examined the contribution of the predictors dystonia and its subtypes within a statistical model which controlled for the co-variates age and sex. Original neurophysiological data were shared and a sex and age matched control group were collected (dystonia n=52, controls n=50). Two raters blinded to participant identity rescored all recordings (6732 trials). After high inter-rater agreement was confirmed, mean conditioning per block was entered into a mixed repetitive measures model to evaluate the influence of sex, age, dystonia subtype (focal hand dystonia, cervical dystonia, DYT-TOR1A and DYT-THAP1) and clinical features such as tremor. There was a wide range of conditioning behavior across individuals in both groups. Young age (p=0.031) was associated with higher conditioning. All dystonia versus controls showed no difference in conditioning (p=0.517). Analysis of dystonia subgroup, with age and sex as co-variates, showed that conditioning in cervical dystonia, focal hand dystonia and DYT-TOR1A was comparable to controls. DYT-THAP1 was characterized by high levels of conditioning. Clinical features such as tremor did not significantly influence conditioning. Sample size estimates for future work are provided based on the variance observed. Eyeblink conditioning, a proxy for cerebellar function, appears intact in the subtypes of isolated dystonia examined. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains elusive.