Functional–Anatomic Study of Episodic Retrieval

In a companion paper (R. L. Buckner et al., 1998, NeuroImage 7, 151–162) we used fMRI to identify brain areas activated by episodic memory retrieval. Prefrontal areas were shown to differentiate component processes related to retrieval success and retrieval effort in block-designed paradigms. Importantly, a right anterior prefrontal area was most active during task blocks involving greatest retrieval success, consistent with an earlier PET study by M. D. Rugg et al. (1996, Brain 119, 2073–2083). However, manipulation of these variables within the context of blocked trials confounds differences related to varying levels of retrieval success with potential shifts in subjects’ strategies due to changes in the probability of target events across blocks. To test more rigorously the hypothesis that certain areas are directly related to retrieval success, we adopted recently developed procedures for eventrelated fMRI. Fourteen subjects studied words under deep encoding and were then tested in a mixed trial paradigm where old and new words were randomly presented. This recognition testing procedure activated similar areas to the blocked trial paradigm, with all areas showing similar levels of activation across old and new items. Of critical importance, significant activation was detected in right anterior prefrontal cortex for new items when subjects correctly indicated they were new (correct rejections). These findings go against the retrieval success hypothesis as formally proposed and provide an important constraint for interpretation of this region’s role in episodic retrieval. Furthermore, anterior prefrontal activation was found to occur late, relative to other brain areas, suggesting that it may be involved in retrieval verification or monitoring processes or perhaps even in anticipation of subsequent trial events (although an alternative possibility, that the late onset is mediated by a late vascular response, cannot be ruled out). These findings and their relation to the results obtained in the companion blocked-trial paradigm are discussed. r 1998 Academic Press In a companion paper (Buckner et al., 1998a), we identified brain areas involved in episodic memory retrieval using a blocked fMRI recognition paradigm where trials of a similar type were presented sequentially, in sets or ‘‘blocks’’ of items. Across recognition task blocks, we varied the manner in which the target items had been previously studied (either under deep or shallow encoding conditions). The main finding was that blocks of recognition trials composed of items that were earlier presented under deep encoding conditions, and where retrieval success was high, were correlated with greater activation in right anterior prefrontal cortex as contrasted with low retrieval success (left anterior prefrontal cortex also showed a tendency for such an effect but was not included in targeted regional hypotheses). Rugg et al. (1996) and Tulving et al. (1994) have observed a similar effect in PET experiments examining recognition of visual words and auditory sentences, respectively. Thus, our companion study and these two previous studies all point to the possibility that anterior prefrontal cortex, particularly on the right, is differentially involved in processes related to retrieval success. However, these studies are all characterized by a possible complicating factor—groups of trials of the same type were presented in blocks, thereby allowing the more general task context within which the individual trials occurred to change across task blocks of different types. Blocks with lower or higher percentages of successfully retrieved items may have served to modify how subjects engaged in the recognition task, and/or the manner in which they arrived at their recognition decisions, and thereby have indirectly contributed to modulation of anterior prefrontal cortex, activation. Thus, for these three recognition studies we do not know whether differential right anterior prefrontal activation was due directly to retrieval success at an item-specific level or to shifts in subject-initiated strategies that might ensue when NEUROIMAGE 7, 163–175 (1998) ARTICLE NO. NI980328