Oral cortisol impairs implicit sequence learning

Abstract

Glucocorticoids have been shown to affect declarative memory, an explicit form of memory for facts and events operated by medial temporal lobe structures. Recent neuroimaging data suggest that the medial temporal lobe (including the hippocampus) is also active in implicit sequence learning. The aim of the present study was to investigate whether implicit sequence learning may also be affected by glucocorticoid administration. Oral cortisol (30 mg) was given to 29 healthy subjects whereas 31 control subjects received placebo. One hour after treatment all volunteers performed five consecutive blocks of a five-choice serial reaction time task by responding to colored lights by pressing buttons of the same color. The subjects responded without knowing to a quasi-randomized stimulus sequence, including higher-order sequential regularities (a combination of two colors that predicted the following target color). The reaction speed of every button-press (100 per block) was determined and difference scores were calculated as a proof of learning. Both groups showed significant implicit sequence learning throughout the experiment. However, we found an impaired learning performance of the cortisol group compared with the placebo group. Further analysis revealed that a delayed learning in the cortisol group occurred at the very beginning of the task. This study is the first human investigation indicating impaired implicit memory function after exogenous administration of the stress hormone cortisol. This effect may depend on hippocampus engagement in implicit sequence learning, but the involvement of other brain structures is also discussed.