Current empirical findings suggest that this creation

process involves the caudal LPFC and premotor cortex along with basal ganglia 23 and 38••]. Newly created task sets driving behavior is initially inferred as being unreliable but through learning (see above), may subsequently become reliable. fMRI results show the latter event Cetuximab in vitro elicits ventral striatal along with premotor and caudal LPFC activations. These activations presumably reflect the consolidation of newly created task sets in long-term memory when they become reliable [38••]. Exploration behaviors thus consist of creating and learning new task sets and perpetuate until the medial PFC infers these new task sets as becoming reliable. Behavioral results suggest that humans can infer the absolute reliability of three or four task sets concurrently 33• and 38••]: the current actor along with two or three alternative task sets. The latter correspond to task sets previously inferred as being reliable and used as actor but no longer reliable. When subjects switch into exploration as described above, the former actor typically remains monitored as an alternative task set (which may be subsequently retrieved, see below). Several fMRI studies have pointed out the role of the lateral frontopolar PFC (FPC) in exploration 46, 47, 48 and 49]. Other fMRI studies show that the FPC is involved in holding on and monitoring alternative courses of action 19, 20 and 50]. Recent

results indicate that consistently, FPC activations more specifically correlate with the absolute reliability Trichostatin A of two concurrent alternative task sets [38••]. The FPC thus appears to keep track and infer the absolute reliability of a few alternative task sets, which notably occur during exploration periods (Figure 2). Such alternative task sets make no contribution to ongoing behavior but may be subsequently retrieved for driving behavior

33• and 38••]: As two task sets cannot be judged as being reliable simultaneously, any HA-1077 order alternative task set becoming reliable is retrieved and replaces the current actor task set. This retrieval process enables the organism to switch out of exploration periods by rejecting newly created task sets. The retrieval process also enables exploration periods to be skipped by directly switching to an alternative task set, when the ongoing actor task set becomes unreliable. fMRI data show that consistent with its critical role in task-switching 12, 24 and 51], the lPFC detects when one alternative task-set become reliable [38••]: the lPFC presumably initiates the retrieval process that propagates from middle to caudal lPFC regions [38••]. Altogether, these recent findings suggest that the PFC comprises two parallel inferential tracks (Figure 2): (1) a medial track from the vmPFC to dmPFC arbitrating between exploiting/adjusting the current task set driving behavior vs. exploring/creating new task sets from long-term memory.