Prefrontal activity associated with working memory and episodic long-term memory
Introduction
Recent neuroimaging findings have prompted intense interest in the role of prefrontal cortex (PFC) in human memory processes. For example, numerous studies of episodic long-term memory (LTM) for events have reported activation in ventrolateral (BA 44, 45, 47, and parts of 6), dorsolateral (at or near Brodmann’s Areas [BA] 9 and parts of 46), and anterior (BA 10 and parts of 46) PFC. Ventrolateral prefrontal activation has been observed during both LTM encoding and retrieval tasks, whereas dorsolateral and anterior prefrontal activation has been primarily observed during LTM retrieval tasks [9], [23], [53], [67]. Working memory (WM) studies have also reported ventrolateral and dorsolateral prefrontal activation associated with maintenance and manipulation of information across short delays [15], [18], [29], [46], [71], with some suggestions that these regions may play differing roles in WM [27], [47].
These findings raise two important questions: (1) are the PFC regions that subserve episodic LTM distinct from those that subserve WM? and (2) within LTM or WM, do distinct PFC regions exhibit patterns of activity associated with different task phases (e.g. encoding, maintenance, or retrieval)? Such specificity would argue for characterizing memory systems in terms of familiar task distinctions such as LTM, WM, encoding, and retrieval [58], [66]. An alternative approach is to characterize memory systems in terms of component processes—for example, in terms of perceptual (bottom-up or stimulus-driven) and reflective (top-down or internally-generated) processes [30], [32]. Within such a framework, reflective processes (e.g. rehearsing information, retrieving information, shifting between task-related features or between tasks, etc.) are the sorts of executive control processes typically linked to prefrontal cortex [40], [41], [59], [63]. These component reflective processes may be flexibly recruited in the service of task goals and not uniquely dedicated to WM or LTM.
Some support for the component process view comes from neuropsychological studies showing that the effect of prefrontal lesions on WM and LTM task performance depends on the reflective complexity of the test. Patients with prefrontal lesions can exhibit intact performance on simple WM span tasks, but impaired performance on WM tasks that tax attentional inhibition or selection processes [17]. Similarly, they can exhibit intact performance on simple LTM tests such as recognition or cued recall, but impaired performance on more complex free recall and source memory tests [53], [60]. Thus, prefrontal regions may implement reflective processes that are relevant to both WM and LTM [23], [30], [41], [53], [61].
Consistent with these findings, results from recent meta-analyses of neuroimaging data also suggest that the same dorsolateral and ventrolateral regions are active during both WM and LTM tasks [9], [22]. In contrast, these reviews suggest that anterior regions of PFC may be uniquely activated during LTM retrieval tasks. Based on these results, interpretations of anterior prefrontal activation have largely focused on processes specific to episodic memory retrieval [35], [36], [67] (but see [11]).
In summary, although recent findings converge on the idea that PFC contributes to memory, it remains unclear whether different regions play roles specific to WM or LTM. This question was recently addressed by four studies, with conflicting results [6], [8], [43], [44]. In one fMRI study by Braver et al. [6], ventrolateral PFC was active during performance of a “2-back” task (used to assess WM), and during blocks of intentional encoding and yes–no recognition trials (used to assess LTM). In contrast, dorsolateral and anterior PFC were selectively active during WM, but not LTM task performance. In another study by Cabeza et al. [8], event-related fMRI was used to compare activity between a delay task requiring memory for the spatial locations of words (used to assess WM) and a “remember-know-new” recognition memory task (used to assess LTM) that was matched for behavioral performance. Contrary to Braver et al., these investigators found that activity in anterior (BA10), dorsolateral (BA 9), and parts of ventrolateral (BA 45,47) PFC was greater during LTM retrieval than during WM trials. Finally, across two experiments, Nyberg et al. [43], [44] used positron emission tomography (PET) to examine activity across three separate WM and LTM measures. Across these studies, Nyberg et al. identified areas in left fronto-polar and left ventrolateral PFC that were active during all the memory conditions relative to a non-memory baseline task.
One difficulty in comparing results from previous imaging studies of WM and LTM involves differences in stimulus sets. Most previous imaging studies of WM used small stimulus sets, such that stimuli were repeated from trial-to-trial, whereas most previous LTM studies used large stimulus sets with minimal overlap among items to be remembered. Using a small set of items in the WM but not the LTM task could confound effects related to interference with effects intrinsic to WM and LTM. For example, accumulating proactive interference could increase the degree to which subjects need to evaluate the specific attributes of each item [31], which, in turn, could modulate prefrontal activation [19], [28], [52], [56], [57]. Consistent with this view, regions in lateral PFC exhibited greater activation during a 2-back WM task with familiar, repeated scenes than during a 2-back task with novel scenes in another recent study [62].
Here, using event-related functional magnetic resonance imaging (fMRI) methods to identify temporal patterns of brain activity within a trial [20], [48], [70], we compared prefrontal activation during WM and LTM tasks. In the present experiment, the stimuli presented during WM trials were novel (i.e. each stimulus was only used on one trial, such that there was no repetition of stimuli across trials), as were the stimuli in the LTM encoding trials. Furthermore, the temporal parameters of each task were matched (see Fig. 1), and the specific stimuli were counterbalanced across WM and LTM trials so that the topography of prefrontal activity associated with encoding and retrieval and WM and LTM could be assessed in the same group of subjects for the same materials.
Section snippets
Subjects
Five male and three female healthy, right-handed volunteers ranging in age from 19 to 40 were recruited from the University of Pennsylvania student community. All gave full informed consent before participating.
Procedure
Historically, distinctions between short-term/working memory and episodic long-term memory have focused on the amount of information and the duration for which the information is to be remembered [2], [3], [21]. For example, many WM tasks assess the active maintenance of information that
Behavioral results
An ANOVA revealed that participants were significantly more accurate at identifying same (M=97.7%, S.D.=2.8%) and different (M=97.2%, S.D.=2.6%) faces on WM trials than for studied (M=88.9%, S.D.=7.9%) and unstudied (M=85.6%, S.D.=9.9%) faces on LTM recognition trials [F(1,7)=13.89, P<0.01]. Similarly, mean response times were significantly faster for same (M=825.9 ms, S.D.=266.9) and different (M=785.8 ms, S.D.=199.8) faces on WM trials than for studied (M=1433.3 ms, S.D.=395.3) and unstudied (M
Discussion
In the present study, we used event-related fMRI to identify the degree to which distinct prefrontal regions support performance during different phases of WM and LTM tasks. Our results revealed a remarkable degree of overlap between activated prefrontal regions during WM and LTM trials. Thus, the present findings cast doubt on the idea that any of these prefrontal regions is uniquely recruited to support either WM or LTM. Instead, the present results converge with neuropsychological [53], [61]
Acknowledgements
We thank Jeff Berger, Dan Caggiano, Mike Cohen, Alexander Taich, and Sabrina Tom for their assistance. This research was supported by grants from the American Federation for Aging Research (MD), the McDonnell-Pew Program in Cognitive Neuroscience (CR), and National Institute on Aging grants AG05863, AG15793, and AG09253.
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