The final blink: intact eyeblink conditioning in isolated dystonia

Background: Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered.

Objective: To systematically examine the influence of dystonia, dystonia subtype and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex.

Methods: Original neurophysiological data from all published studies were shared to an age and sex matched control group. Two raters blinded to participant identity scored all recordings (6732 trials). After higher inter-rater agreement was confirmed, mean conditioning per block was entered into a mixed repetitive measures model.

Results: Much variability of eyeblink conditioning was seen in both groups. All dystonia versus controls showed no difference in conditioning (p=0.517). Analysis of dystonia subgroup, with age and sex as covariates did not reveal evidence that eyeblink conditioning is impaired in specific subtypes (cervical dystonia, DYT-TOR1A, DYT-THAP1 or focal hand dystonia). The presence of tremor did not significantly influence levels of eyeblink conditioning.

Conclusions: Collaborative efforts such as this article allow larger number of patients to be evaluated and provide more balanced estimates of disease effects over experimental outcomes. Intact eyeblink conditioning is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question.