Evaluation of bidirectional interstimulus interval (ISI) shift in auditory delay eye-blink conditioning in healthy humans

Delay eye-blink conditioning is an associative learning task that can be utilized to probe the functional integrity of the cerebellum and related neural circuits. Typically, a single interstimulus interval (ISI) is utilized, and the amplitude of the conditioned response (CR) is the primary dependent variable. To study the timing of the CR, an ISI shift can be introduced (e.g., shifting the ISI from 350 to 850 ms). In each phase, a conditioned stimulus (e.g., a 400- or 900-ms tone) coterminates with a 50-ms corneal air puff unconditioned stimulus. The ability of a subject to adjust the CR to the changing ISI constitutes a critical timing shift. The feasibility of this procedure was examined in healthy human participants (N = 58) using a bidirectional ISI shift procedure while cortical event-related brain potentials were measured. CR acquisition was faster and the responses better timed when a short ISI was used. After the ISI shift, additional training was necessary to allow asymptotic responding at the new ISI. Interestingly, auditory event-related potentials to the CR were not associated with conditioning measures at either ISI.