Prefrontal activity associated with working memory and episodic long-term memory

https://doi.org/10.1016/S0028-3932(02)00169-0Get rights and content

Abstract

Many recent neuroimaging studies have highlighted the role of prefrontal regions in the sustained maintenance and manipulation of information over short delays, or working memory (WM). In addition, neuroimaging findings have highlighted the role of prefrontal regions in the formation and retrieval of memories for events, or episodic long-term memory (LTM), but it remains unclear whether these regions are distinct from those that support WM. We used event-related functional magnetic resonance imaging (fMRI) to identify patterns of prefrontal activity associated with encoding and recognition during WM and LTM tasks performed by the same subjects. Results showed that the same bilateral ventrolateral prefrontal regions (at or near Brodmann’s Areas [BA] 6, 44, 45, and 47) and dorsolateral prefrontal regions (BA 9/46) were engaged during encoding and recognition within the context of WM and LTM tasks. In addition, a region situated in the left anterior middle frontal gyrus (BA 10/46) was engaged during the recognition phases of the WM and LTM tasks. These results support the view that the same prefrontal regions implement reflective processes that support both WM and LTM.

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.

References (71)

  • A.R. McIntosh

    Towards a network theory of cognition

    Neural Networks

    (2000)
  • L. Nyberg et al.

    Brain imaging of human memory systems: between-systems similarities and within-system differences

    Brain Research. Cognitive Brain Research

    (2002)
  • B.R. Postle et al.

    Using event-related fMRI to assess delay-period activity during performance of spatial and nonspatial working memory tasks

    Brain Research. Brain Research Protocols

    (2000)
  • C. Ranganath et al.

    Medial temporal lobe activity associated with active maintenance of novel information

    Neuron

    (2001)
  • C. Ranganath et al.

    Frontal brain potentials during recognition are modulated by requirements to retrieve perceptual detail

    Neuron

    (1999)
  • C. Ranganath et al.

    Neural correlates of memory retrieval and evaluation

    Brain Research. Cognitive Brain Research

    (2000)
  • M.D. Rugg et al.

    The role of the prefrontal cortex in recognition memory and memory for source: an fMRI study

    NeuroImage

    (1999)
  • A.D. Wagner

    Working memory contributions to human learning and remembering

    Neuron

    (1999)
  • E. Zarahn et al.

    Empirical analyses of BOLD fMRI statistics. Part I. Spatially unsmoothed data collected under null-hypothesis conditions

    NeuroImage

    (1997)
  • E. Zarahn et al.

    A trial-based experimental design for functional MRI

    NeuroImage

    (1997)
  • E. Zarahn et al.

    Temporal isolation of the neural correlates of spatial mnemonic processing with fMRI

    Brain Research. Cognitive Brain Research

    (1999)
  • R.C. Atkinson et al.

    The control of short-term memory

    Scientific American

    (1971)
  • Baddeley A. Working Memory. New York: Oxford University Press;...
  • P. Barcelo et al.

    Prefrontal modulation of visual processing in humans

    Nature Neuroscience

    (2000)
  • M. Brett et al.

    The problem of functional localization in the human brain

    Nature Review of Neuroscience

    (2002)
  • R. Cabeza et al.

    Imaging cognition. Part II. An empirical review of 275 PET and fMRI studies

    Journal of Cognitive Neuroscience

    (2000)
  • C.B. Cave et al.

    Intact verbal and nonverbal short-term memory following damage to the human hippocampus

    Hippocampus

    (1992)
  • K. Christoff et al.

    The frontopolar cortex and human cognition: evidence for a rostrocaudal hierarchical organization within the human prefrontal cortex

    Psychobiology

    (2000)
  • C. Cocosco et al.

    Brainweb: online interface to a 3D MRI simulated brain database

    NeuroImage

    (1997)
  • M. Corbetta et al.

    Neural systems for visual orienting and their relationships to spatial working memory

    Journal of Cognitive Neuroscience

    (2002)
  • S.M. Courtney et al.

    Transient and sustained activity in a distributed neural system for human working memory

    Nature

    (1997)
  • R. Desimone

    Neural mechanisms for visual memory and their role in attention

    Proceedings of the National Academy of Science of the United States of America

    (1996)
  • M. D’Esposito et al.

    The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI

    Proceedings of the National Academy of Science of the United States of America

    (1999)
  • M. D’Esposito et al.

    Event-related functional MRI: implications for cognitive psychology

    Psychological Bulletin

    (1999)
  • D.A. Drachman et al.

    Memory and the hippocampal complex II. Is memory a multiple process

    Archives of Neurology

    (1966)
  • Cited by (344)

    View all citing articles on Scopus
    View full text