Exploration of cerebellar-dependent associative learning in schizophrenia: Effects of varying and shifting interstimulus interval on eyeblink conditioning

Abstract

Eyeblink conditioning abnormalities have been reported in schizophrenia, but the extent to which these anomalies are evident across a range of delay intervals (i.e., interstimulus intervals; ISIs) is unknown. In addition, the effects of ISI shifts on learning are unknown, though such manipulations can be informative about the plasticity of cerebellar timing functions. Therefore, the primary purpose of the present study was to investigate the interactions between ISI manipulations and learning in schizophrenia. A standard delay eyeblink conditioning procedure with four different interstimulus intervals (ISIs; 250, 350, 550, 850 ms) was employed. Each eyeblink conditioning experiment was immediately followed by another with a different ISI, thus permitting the characterization of conditioned response (CR) learning at one ISI and the extent to which CRs could be generated at a different latency following an ISI shift. Collapsing across all conditions, the schizophrenia group (n = 55) had significantly fewer conditioned responses and longer onset latencies than age-matched controls (n = 55). Surprisingly, shifting to a new ISI had negligible effects on conditioned response rates in both groups. These findings contribute to evidence of robust eyeblink conditioning abnormalities in schizophrenia and suggest impaired cerebellar function, but underscore the need for more research to clarify the source of these abnormalities and their relationship to clinical manifestations of schizophrenia.