Background: Eyeblink conditioning is used in many different species to study motor learning and make inferences about cerebellar function. However, considerable discrepancies in performance between different species combined with evidence that awareness of stimulus contingencies affects performance indicates that eyeblink conditioning in part reflects activity in non-cerebellar regions. This questions whether eyeblink conditioning can be used as a pure measure of cerebellar function in humans. Methods: Here we explored two ways to reduce non-cerebellar influences on performance in eyeblink conditioning: (1) using a short interstimulus interval, and (2) having participants do working memory tasks during the conditioning. Data were analyzed, and the influence of the interstimulus interval and working memory tasks was assessed using a linear mixed effects model. Results: Our results show that subjects trained with a short interstimulus interval (150ms and 250ms) produce few conditioned responses after 100 trials. For subjects trained with a longer interstimulus interval (500ms), those who did working memory tasks produced fewer conditioned responses and had a more gradual learning curve, more akin to those reported in the animal literature. Conclusions: Our results suggest that having subjects perform working memory tasks during eyeblink conditioning can be a viable strategy to reduce non-cerebellar interference in the learning.
bioRxiv Subject Collection: Neuroscience