We studied changes in brain activity related to visuospatial procedural learning in a mirror-reading (MR) task using event-related functional magnetic resonance imaging (fMRI). Eight healthy subjects were investigated during an early (naïve) and a late (after the procedure was well-learned) stage of skill learning. Between the two scan sessions subjects performed training in mirror reading twice a day over the period of almost 3 weeks. We were addressing following question: How are cortical and subcortical components of fronto-striatal pathways implicated in initial and late learning stages during mirror reading? The condition Χ session interaction contrast for MR compared to normal reading (NR) during the initial learning stage was associated with a broad activation in frontal, temporal, parietal, occipital and striatal activation. Well-learned MR revealed frontal and parietal brain activation during the second scan session, but no striatal activity occurred. In particular, over-learned MR exhibited increased activation in the left middle and superior frontal cortex (DLPFC), in the left medial frontal cortex (VLPFC), right cingulum (Posterior cingulate cortex), the right precuneus and activation in left inferior and superior parietal cortex. Changes in brain activity related to initial procedural learning exhibited thus the significance of striatofrontal loops whereas the extensive practice of the MR task resulted in less activity in these regions and a shift to more posterior cortical areas. The results suggest the requirement of recruitment of a fronto-parietal network for automatic mirror reading. As for learning this procedure, our results support the evidence that fronto-striatal loops seem to be involved in this very early phase of procedural learning, acting as an effective network for acquisition of mirror reading. According to our data and previous studies of skill learning, we postulate that there is no learning-specific distinct neural network associated with the processing of mirror-reversed words before and after extensive training. We rather postulate a common network in cognitive skill acquisition with a critical role in the prefrontal cortex and the caudate nucleus.
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