Cerebral activation related to implicit sequence learning in a Double Serial Reaction Time task

Using functional magnetic resonance imaging (fMRI), we examined the distribution of cerebral activations related to implicitly learning a series of fixed stimulus-response combinations. In a novel - bimanual - variant of the Serial Reaction Time task (SRT), simultaneous finger movements of the two hands were made in response to pairs of visual stimuli that were presented in a fixed order (Double SRT). Paired stimulus presentation prevented explicit sequence knowledge occurring during task practice, which implied that a dual task paradigm could be avoided. Extensive prescanning training on randomly ordered stimulus pairs allowed us to focus on the acquisition of implicit sequence knowledge. Activation specifically related to the acquisition of fixed sequence knowledge was highly significant in the right ventrolateral prefrontal cortex. The medial prefrontal and right ventral premotor cortex were more indirectly related with such procedural learning. We conclude that this set of activations reflects a stage of implicit sequence learning constituted by components of (i) spatial working memory (right ventral prefrontal cortex), (ii) response monitoring and selection (medial prefrontal cortex), and (iii) facilitated linkage of visuospatial cues to compatible responses (right ventral premotor). Comparing the random-order stimulus-response actions with fixed sequences showed activations in dorsal premotor and posterior parietal cortices, consistent with a dorsal pathway dominance in real-time visuomotor control. The relative long time during which performance improves in the DoSRT provides an opportunity for future study of various stages in both general skill and fixed sequence learning. (c) 2006 Elsevier B.V. All rights reserved