Evaluation of a novel event-related parametric fMRI paradigm investigating prefrontal function.

While prefrontal pathology is considered to be a core feature in schizophrenia, evidence from functional magnetic resonance imaging (fMRI) studies using cognitive activation tasks is less reliable in terms of demonstrating 'functional hypofrontality'. Here we present a new event-related fMRI paradigm specifically developed to assess the gradual recruitment of brain areas during verbal working memory (WM) by taking into account theoretical and pragmatic limitations of activation tools used in clinical cognitive neuroscience. We studied 15 healthy subjects during the performance of a WM task that required the manipulation of verbal information. We observed a robust recruitment of frontoparietal areas with increasing load. Comparing the two highest loads, we found further bilateral striatal activation. A median split into good and poor performers revealed significant positive correlations of prefrontal activation in the group of good performers and correlations with striato-thalamic activation in the poor-performance group, thus emphasizing a crucial role of subcortical structures for performance in highly demanding WM tasks. Because it induces a robust bilateral frontoparietal activation pattern along with performance-related effects of cerebral activation, we consider this paradigm to be suitable to test prefrontal function in schizophrenic patients during the manipulation of items held in WM.