COGNITION AND BEHAVIOR nito MEC(8) and using neuroimaging rd-base ation learn In addition to the link ism (8). m allows the the onitoring signal (indicating theee detection and ard ased reversal lear of the ntilie n the CN and pre-responseon nd LPFO Anatomic studies in should be emphasized. PMFC and LPFC (37 38).In hum tcionnkCwrdw with ed re n(the indirect finding has beer ated by two recent RCZ)that acro Brodman sin the LPFC and pMF ACC ced cluste reas Little is kno that was c b5 th f activ. 34. sin area all types 35 also show this area for a tions hat ior (36).Whether thes adjust perf lifferent area as der part n diate d by sub tis not ubig 40 for an intimate confict and en in with LPFC e and ativ feedback gh ther contingencies on basis of trial-to-trial and the regulatio e or ck,the feedb with u吗 ticip were continge sally tha foci two structur for futur cnz e ERN d1 h to f prediction signal (8).Also as r gnal the eed hough ou eview the iteratur each stimulus,the with choice errors (provoked thro the ty in this area and subs in In a te ral diffe -lea other brain model that changes in co MFC in imple ERN late gh dies dat e ERN could als serve as contro adjustme nts is the he monkey omolog f the RCZ)are Tn ng-re PMFC nd he and ind ance (8). tha t are needed uppl otor rea 440 ha Conclusions and Future Directions ashion goal-hased action selection We have provide an This nding. ing between of th competing action e monitoring and the MFC and perfor nce monitoring have vith ach of these actions)(43.44).The mp ed ad n b ary fund cate that an e part of the MF ed is hethe moni falling into a region refer red to as the rcz in vithin-trial Refer 296.170 sistently a unfavorable outcomes on.C w.Fong 12 The similaritie nted alr within the ame trial (to tween two brain potentials gen by this nd corre 15 OCTOBER 2004 VOL 306 SCIENCE emag.org monitor, and the LPFC, as a controller, interact in the regulation of goal-directed behavior (18). pMFC activity and reward-based associ￾ation learning. In addition to the link between pMFC activity and immediate adjustments in performance, there also seems to be a close relation between pMFC activity and reward-based association learning. A study of reward-based reversal learning in monkeys identified cells in the CMAr that fired only when two conditions were met: (i) reward was less than anticipated, and (ii) the reduction in reward was followed by changes in the monkeys’ action selection (5). This finding has been corroborated by two recent functional magnetic resonance imaging (fMRI) studies of reversal learning, showing that ACC activity was observed under the same conjunctive condition (34, 35). Rever￾sal learning studies typically also show activation of the LPFC and other structures in association with changes in choice behav￾ior (36). Whether these behavioral adjust￾ments are implemented by or pMFC or whether the pMFC merely signals the LPFC or other structures to implement the adjust￾ments remains to be explored. Finally, there is evidence for an intimate relation between ERN amplitude and associa￾tive learning. In scalp electrophysiological activity, recorded from human participants who were required to learn stimulus-response contingencies on the basis of trial-to-trial positive or negative feedback, the feedback ERN to negative feedback decreased as par￾ticipants were learning the contingencies, which is consistent with the theory dis￾cussed above that the ERN reflects a reward prediction error signal (8). Also, as partici￾pants learned the response associated with each stimulus, the response ERN associated with choice errors (provoked through the use of a stringent reaction time deadline) increased. In a temporal difference-learning model, not only did the ERN correlate with a reward prediction error but the brain activity underlying the ERN could also serve as a reinforcement learning signal for associative learning and hence optimizing task perform￾ance (8). Conclusions and Future Directions We have provided an overview of the evidence suggesting a critical role for the pMFC in performance monitoring and the implementation of associated adjustments in cognitive control. Our meta-analysis indi￾cates that an extensive part of the pMFC— including areas 6, 8, 24, and 32, largely falling into a region referred to as the RCZ in humans—is consistently activated after the detection of response conflict, errors, and unfavorable outcomes. The similarities be￾tween two brain potentials generated by this area, the ERN and feedback ERN, are consistent with the view that the pMFC accommodates a unified functional and neurobiological performance-monitoring mechanism (8). This mechanism allows the pMFC to signal the likelihood of obtaining an anticipated reward (either definitive, as observed in studies of error detection and feedback processing, or probabilistic, as observed in studies of decision uncertainty and pre-response conflict). Three conclusions from the meta-analysis should be emphasized. First, performance monitoring is associated with pMFC activa￾tions in a functionally integrated region (the RCZ) that cuts across various Brodmann areas beyond the ‘‘traditionally’’ reported ACC. Second, the most pronounced cluster of activations is in area 32 for all types of monitored events, suggesting the importance of this area for a unified performance monitoring function. Thus, the conclusion that error monitoring and conflict monitoring are performed by different areas, as derived from initial studies that were designed to identify differential involvement, is not ubiq￾uitously confirmed by the meta-analysis. Third, activations related to pre-response conflict and uncertainty occur more often in area 8 and less often in area 24 than do activations associated with errors and neg￾ative feedback. Thus, although there is considerable overlap, there are some appar￾ent differences as well, with activation foci associated with reduced probabilities of obtaining reward clustering slightly more dorsally than foci associated with errors and failures to obtain anticipated reward. This generic monitoring function endows the pMFC with the capacity to signal the need for performance adjustment. Indeed, further evidence indicates a tight link between activ￾ity in this area and subsequent adjustments in performance, suggesting that the pMFC sig￾nals other brain regions that changes in cog￾nitive control are needed. Although direct evidence is sparse, a likely candidate structure for effecting these control adjustments is the LPFC. Thus, monitoring-related pMFC activ￾ity may serve as a signal that engages con￾trol processes in the LPFC that are needed to regulate task performance in an adaptive fashion. This conclusion notwithstanding, several questions remain. First, most studies of the pMFC and performance monitoring have tried to relate pMFC activity to control adjustments on the subsequent trial. An unresolved issue is whether the monitoring signal from the pMFC can also be used to resolve response conflicts on a within-trial basis (34). There is in principle no reason why such adjustments could not be imple￾mented already within the same trial (to resolve conflict and correct the activation of inappropriate responses before they eventu￾ate in an overt error). It is hard to tackle this question empirically using neuroimaging studies, because it requires disentangling the monitoring signal (indicating the need for control) and the answer to this signal (control implementation), which may be partly overlapping in time. Another unresolved issue concerns the nature of the connection between the pMFC and LPFC. Anatomical studies in monkeys show dense reciprocal connections of the pMFC and LPFC (37, 38). In humans, evidence for such connections is more indirect. Neuroimaging studies show con￾comitant activations in the LPFC and pMFC (39), suggesting close functional connectiv￾ity between these two areas. Little is known, however, about differential or selective reciprocal projections between various por￾tions of the pMFC on the one hand and various subdivisions of the LPFC on the other. Possibly, this functional interplay is in part mediated by subcortical structures such as the basal ganglia and mesencephalic nuclei (7, 8) or by the supplementary motor area (SMA) or pre-SMA (29, 40). Electrophysiological studies of patients with LPFC lesions have reported abnormal pMFC activity in response to errors (41). Such studies argue against the possibility of unidirectional information flow between the pMFC and LPFC, and instead suggest that performance monitoring and the regulation of cognitive control may be realized through intricate reciprocal projections between these two structures. It is a challenge for future research to further identify and characterize these interactions. Although our review of the literature capitalizes on the role of the pMFC in performance monitoring, leading to perform￾ance adjustments on subsequent trials, other studies have suggested a more executive role for the pMFC in implementing control directly (42). Studies in nonhuman primates have shown that cells in the pMFC (especially in the monkey homolog of the RCZ) are well situated for this role, because this area has direct and indirect projections to primary and supplementary motor areas (43, 44). It has been argued that some of these cells are involved in ‘‘goal-based action selection’’ (that is, selecting between competing actions in view of the anticipated reward associated with each of these actions) (43, 44). The relation between these complementary func￾tions remains to be further explored. References and Notes 1. M. Shidara, B. Richmond, Science 296, 1709 (2002). 2. B. Knutson, G. W. Fong, C. M. Adams, J. L. Varner, D. Hommer, Neuroreport 12, 3683 (2001). 3. V. Stuphorn, T. L. Taylor, J. D. Schall, Nature 408, 857 (2000). CCOGNITION AND OGNITION ANDBBEHAVIOR EHAVIOR 446 15 OCTOBER 2004 VOL 306 SCIENCE www.sciencemag.org S PECIAL S ECTION