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Readings

The readings listed below are the foundation of this course. Where available, journal article abstracts from PubMed (an online database providing access to citations from biomedical literature) are included.

Bontempi, B., C. Laurent-Demir, C. Destrade, and R. Jaffard. "Time-dependent Reorganization of Brain Circuitry Underlying Long-term Memory Storage." Nature 400 (1999): 671-675.

PubMed abstract:  Retrograde amnesia observed following hippocampal lesions in humans and animals is typically temporally graded, with recent memory being impaired while remote memories remain intact, indicating that the hippocampal formation has a time-limited role in memory storage. However, this claim remains controversial because studies involving hippocampal lesions tell us nothing about the contribution of the hippocampus to memory storage if this region was present at the time of memory retrieval. We therefore used non-invasive functional brain imaging using (14C)2-deoxyglucose uptake to examine how the brain circuitry underlying long-term memory storage is reorganized over time in an intact brain. Regional metabolic activity in the brain was mapped in mice tested at different times for retention of a spatial discrimination task. Here we report that increasing the retention interval from 5 days to 25 days resulted in both decreased hippocampal metabolic activity during retention testing and a loss of correlation between hippocampal metabolic activity and memory performance. Concomitantly, a recruitment of certain cortical areas was observed. These results indicate that there is a time-dependent reorganization of the neuronal circuitry underlying long-term memory storage, in which a transitory interaction between the hippocampal formation and the neocortex would mediate the establishment of long-lived cortical memory representations.

Brown, M. W., and J. P. Aggleton. "Recognition Memory: What are the Roles of the perirhinal Cortex and Hippocampus?" Nature Review Neuroscience 2 (2001): 51-61.

PubMed abstract:  The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute--the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome.

Buckner, R. L., and M. E. Wheeler. "The Cognitive Neuroscience of Remembering." Nature Reviews Neuroscience 2 (2001): 624-634.

Burgess, N., E. A. Maguire, H. J. Spiers, and J. O'Keefe. "A Temporoparietal and Prefrontal Network for Retrieving the Spatial Context of Lifelike Events." NeuroImage 14 (2001): 439-453.

PubMed abstract:  Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations in medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events. Copyright 2001 Academic Press.

Davachi, L., J. Mitchell, D. L. Schacter, and A. D. Wagner. "Remember the Source: Evidence for Distinct Rhinal and Hippocampal Encoding Processes." 2001. (Submitted)

Dobbins, I. G., H. J. Rice, D. L. Schacter, and A. D. Wagner. "Isolating Retrieval Orientation from Retrieval Success: fMRI Evidence for Separable Contributions to Episodic Recogntion." 2001. (Submitted)

Eichenbaum, H. "A Cortical-hippocampal System for Declarative Memory." Nature Reviews Neuroscience 1 (2000): 41-50.

PubMed abstract:  Recent neurobiological studies have begun to reveal the cognitive and neural coding mechanisms that underlie declarative memory--our ability to recollect everyday events and factual knowledge. These studies indicate that the critical circuitry involves bidirectional connections between the neocortex, the parahippocampal region and the hippocampus. Each of these areas makes a unique contribution to memory processing. Widespread high-order neocortical areas provide dedicated processors for perceptual, motor or cognitive information that is influenced by other components of the system. The parahippocampal region mediates convergence of this information and extends the persistence of neocortical memory representations. The hippocampus encodes the sequences of places and events that compose episodic memories, and links them together through their common elements. Here I describe how these mechanisms work together to create and re-create fully networked representations of previous experiences and knowledge about the world.

Eldridge, L. L., B. J. Knowlton, C. S. Furmanski, S. Y. Bookheimer, and S. A. Engel. "Remembering Episodes: A Selective Role for the Hippocampus during Retrieval." Nature Neuroscience 3 (2000): 1149-1152.

PubMed abstract:  Some memories are linked to a specific time and place, allowing one to re-experience the original event, whereas others are accompanied only by a feeling of familiarity. To uncover the distinct neural bases for these two types of memory, we measured brain activity during memory retrieval using event-related functional magnetic resonance imaging. We show that activity in the hippocampus increased only when retrieval was accompanied by conscious recollection of the learning episode. Hippocampal activity did not increase for items recognized based on familiarity or for unrecognized items. These results indicate that the hippocampus selectively supports the retrieval of episodic memories.

Epstein, R., A. Harris, D. Stanley, and N. Kanwisher. "The Parahippocampal Place area: Recognition, Navigation, or Encoding?" Neuron 23 (1999): 115-125.

PubMed abstract:  The parahippocampal place area (PPA) has been demonstrated to respond more strongly in fMRI to scenes depicting places than to other kinds of visual stimuli. Here, we test several hypotheses about the function of the PPA. We find that PPA activity (1) is not affected by the subjects' familiarity with the place depicted, (2) does not increase when subjects experience a sense of motion through the scene, and (3) is greater when viewing novel versus repeated scenes but not novel versus repeated faces. Thus, we find no evidence that the PPA is involved in matching perceptual information to stored representations in memory, in planning routes, or in monitoring locomotion through the local or distal environment but some evidence that it is involved in encoding new perceptual information about the appearance and layout of scenes.

Fernandez, G., P. Klaver, J. Fell, T. Grunwald, and C. E. Elger. "Human Declarative Memory Formation: Segregating Rhinal and Hippocampal Contributions." Hippocampus. 2002; 12 (4): 514-9.

PubMed abstract:  The medial temporal lobe (MTL) is the core structure of the declarative memory system, but which specific operation is performed by anatomically defined MTL substructures? One hypothesis proposes that the hippocampus carries out an exclusively mnemonic operation during declarative memory formation that is insensitive to content, whereas the rhinal cortex carries out an operation supporting memory formation indirectly. To explore the interaction between a salient item feature and memory formation, we contrasted neural correlates of memory formation of high- and low-frequency words. Event-related potentials (ERPs) were recorded via depth electrodes from within the MTL in nine epilepsy patients while they memorized single words. To assess memory formation, ERPs to words subsequently recalled in a free recall test were contrasted with ERPs to forgotten words. More high- than low-frequency words were remembered. High-frequency words led to distinct ERP subsequent memory effects in rhinal cortex and hippocampus. Low-frequency words, however, were only associated with the hippocampal ERP effect. The anatomically restricted interaction between word frequency and memory formation might indicate a semantically affected operation in the parahippocampal region supporting memory formation indirectly. By contrast, the missing interaction in hippocampal recordings might suggest a direct correlate of declarative memory formation that is insensitive to item properties.

Fuster, J. M. "Executive Frontal Functions." Experimental Brain Research 133 (2000): 66-70.

PubMed abstract:  This chapter presents a conceptual model of the representational and executive functions of the cortex of the frontal lobe derived from empirical evidence obtained principally in the monkey. According to this model, the neuronal networks of the frontal lobe that represent motor or executive memories are probably the same networks that cooperate with other cerebral structures in the temporal organization of behavior. The prefrontal cortex, at the top of the perception-action cycle, plays a critical role in the mediation of contingencies of action across time, an essential aspect of the temporal organization of behavior. That role of cross-temporal mediation is based on the interplay of two short-term cognitive functions: one retrospective, of short-term memory or sensory working memory, and the other prospective, of attentive set (or motor working memory). Both appear represented in the neuronal populations of dorsolateral prefrontal cortex. At least one of the mechanisms for the retention of working memory of either kind seems to be the reentry of excitability through recurrent cortical circuits. With those two complementary and temporally symmetrical cognitive functions of active memory for the sensory past and for the motor future, the prefrontal cortex secures the temporal closure at the top of the perception-action cycle.

Haxby, J. V., L. Petit, L. G. Ungerleider, and S. M. Courtney. "Distinguishing the Functional Roles of Multiple Regions in Distributed Neural Systems for Visual Working Memory." NeuroImage 11 (2000): 380-391.

PubMed abstract:  We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules. Copyright 2000 Academic Press.

Johnson, M. K., J. Kounios, and S. F. Nolde. "Electrophysiological Brain Activity and Memory Source Monitoring." NeuroReport 8 (1997): 1317-1320.

PubMed abstract:  To investigate brain mechanisms involved in identifying the origin of memories, event-related potentials (ERPs) were recorded as participants discriminated previously presented (old) from new items or identified their earlier source (picture, word, or new). Differences in ERPs between old-new recognition and source identification were focused at frontal sites. For source identification, prominent negative deflections at occipital or frontal sites occurred depending on encoding task. These results support a model in which memory attributes are distributed neocortically and the frontal lobes are critical for source monitoring.

Maguire, E. A. "Neuroimaging Studies of Autobiographical Event Memory." Philosophical Transactions of the Royal Society of London (Biology). 2001 Sep 29; 356 (1413): 1441-51.

PubMed abstract:  Commonalities and differences in findings across neuroimaging studies of autobiographical event memory are reviewed. In general terms, the overall pattern across studies is of medial and left-lateralized activations associated with retrieval of autobiographical event memories. It seems that the medial frontal cortex and left hippocampus in particular are responsive to such memories. However, there are also inconsistencies across studies, for example in the activation of the hippocampus and dorsolateral prefrontal cortex. It is likely that methodological differences between studies contribute to the disparate findings. Quantifying and assessing autobiographical event memories presents a challenge in many domains, including neuroimaging. Methodological factors that may be pertinent to the interpretation of the neuroimaging data and the design of future experiments are discussed. Consideration is also given to aspects of memory that functional neuroimaging might be uniquely disposed to examine. These include assessing the functionality of damaged tissue in patients and the estimation of inter-regional communication (effective connectivity) between relevant brain regions.

Maguire, E. A., N. Burgess, J. G. Donnett, R. S. Frackowiak, C. D. Frith, and J. O'Keefe. "Knowing Where and Getting There: A Human Navigation Network." Science 280 (1998): 921-924.

PubMed abstract:  The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.

Maguire, E. A., R. N. Henson, C. J. Mummery, and C. D. Frith. "Activity in Prefrontal Cortex, not Hippocampus, Varies Parametrically with the Increasing Remoteness of Memories." NeuroReport 12 (2001): 441- 444.

PubMed abstract:  The time-scale of hippocampal and neocortical involvement in memory retrieval is keenly debated. Using event-related fMRI we examined whether recollecting autobiographical and public event memories, ranging from the recent to the very remote, was associated with parametric changes in brain activity. A ventrolateral prefrontal region was sensitive to memory age, showing increased activation during retrieval of recent autobiographical events and subsequent parametric decrease with remoteness. While we observed modulation of hippocampal activity in relation to memory type (autobiographical events in particular), there was no evidence for sensitivity of this region to memory age. These findings are concordant with a view of hippocampal involvement in autobiographical memory retrieval throughout the lifetime.

Muller, R. "A Quarter of a Century of Place Cells." Neuron 17 (1996): 813-822.

Mummery, C. J., T. Shallice, and C. J. Price. "Dual-Process Model in Semantic Priming: A Functional Imaging Perspective." NeuroImage 9 (1999): 516-525.

PubMed abstract:  In this positron emission tomography study, we investigated the neural correlates of semantic priming, where response to a word is facilitated when preceded by a semantically related word. Nine normal subjects were scanned while performing a lexical decision task. Within this condition, the proportion of related prime-target word pairs was varied across scans from 0 to 100%. The control task involved letter decision on consonant letter strings, controlling orthographic processing and response selection. First, lexical decision (relative to letter decision) activated regions previously observed in lexicosemantic tasks, i.e., the left anterior and inferior temporal lobe and left inferior frontal gyrus. Behavioral analysis confirmed significant facilitation of lexical decision to related targets (mean priming effect 68 ms). It also suggested the contribution of both automatic and strategic processes, consistent with theoretical accounts of priming. Automatic priming was indicated by consistent RTs to related targets irrespective of the proportion of related word pairs per scan. Strategic processing was indicated by decreases in RTs to nonwords as the proportion of related targets increased. Nonlinear correlational analysis of cerebral activity during lexical decision revealed a neurophysiological correlate of these behavioral effects in (i) the left anterior temporal lobe (BA 38), a region involved in lexicosemantic processing; (ii) the anterior cingulate cortex, right premotor region (BA 6), and right superior parietal lobe (BA 7), regions associated with attentional processes. We conclude that in this experimental context, semantic priming involves both automatic and strategic processing.

Nadel, L., and M. Moscovitch. "Memory Consolidation, Retrograde Amnesia and the Hippocampal Complex." Current Opinion in Neurobiology 7 (1997): 217-227.

PubMed abstract:  Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject's lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.

Nadel, L., A. Samsonovich, L. Ryan, and M. Moscovitch. "Multiple Trace Theory of Human Memory: Computational, Neuroimaging, and Neuropsychological Results." Hippocampus 10 (2000): 352-368.

PubMed abstract:  Hippocampal-neocortical interactions in memory have typically been characterized within the "standard model" of memory consolidation. In this view, memory storage initially requires hippocampal linking of dispersed neocortical storage sites, but over time this need dissipates, and the hippocampal component is rendered unnecessary. This change in function over time is held to account for the retrograde amnesia (RA) gradients often seen in patients with hippocampal damage. Recent evidence, however, calls this standard model into question, and we have recently proposed a new approach, the "multiple memory trace" (MMT) theory. In this view, hippocampal ensembles are always involved in storage and retrieval of episodic information, but semantic (gist) information can be established in neocortex, and will survive damage to the hippocampal system if enough time has elapsed. This approach accounts more readily for the very long RA gradients often observed in amnesia. We report the results of analytic and connectionist simulations that demonstrate the feasibility of MMT. We also report a neuroimaging study showing that retrieval of very remote (25-year-old) memories elicits as much activation in hippocampus as retrieval of quite recent memories. Finally, we report new data from the study of patients with temporal lobe damage, using more sensitive measures than previously the case, showing that deficits in both episodic and spatial detail can be observed even for very remote memories. Overall, these findings indicate that the standard model of memory consolidation, which views the hippocampus as having only a temporary role in memory, is wrong. Instead, the data support the view that for episodic and spatial detail the hippocampal system is always necessary.

Nyberg, L., R. Habib, A. R. McIntosh, and E. Tulving. "Reactivation of Encoding-Related Brain Activity During Memory Retrieval." Proceedings of the National Academy of Science, USA 97 (2000): 11120-11124.

PubMed abstract:  Neuronal models predict that retrieval of specific event information reactivates brain regions that were active during encoding of this information. Consistent with this prediction, this positron-emission tomography study showed that remembering that visual words had been paired with sounds at encoding activated some of the auditory brain regions that were engaged during encoding. After word-sound encoding, activation of auditory brain regions was also observed during visual word recognition when there was no demand to retrieve auditory information. Collectively, these observations suggest that information about the auditory components of multisensory event information is stored in auditory responsive cortex and reactivated at retrieval, in keeping with classical ideas about "redintegration, " that is, the power of part of an encoded stimulus complex to evoke the whole experience.

Passingham, R. E., I. Toni, and M. F. Rushworth. "Specialisation within the Prefrontal Cortex: The Ventral Prefrontal Cortex and Associative Learning." Experimental Brain Research 133 (2000): 103-113.

PubMed abstract:  This paper provides evidence that the ventral prefrontal cortex plays a role in the learning of tasks in which subjects must learn to associate visual cues and responses. Imaging with both positron-emission tomography (PET) and functional magnetic-resonance imaging (fMRI) reveals learning-related increases in activity when normal subjects learn visual associative tasks. Evidence is also presented from an event-related fMRI study that activity in this area is time-locked both to the presentation of the visual stimuli and also to the time of the motor response. Finally, it is shown in a study of monkeys that removal of the ventral prefrontal area 12 (including 45 A) impairs the ability of monkeys to relearn a visual associative task (visual matching), even though there were no demands on working memory. It is, therefore, proposed that the ventral prefrontal cortex constitutes part of the circuitry via which associations are formed between visual cues and the actions or choices that they specify. On the basis of the existing anatomical and electrophysiological data, it is argued that the prefrontal cortex is the only area that can represent cues, responses and outcomes.

Postle, B. R., and M. D'Esposito. "'What'--then--'Where' in Visual Working Memory: An Eventrelated fMRI Study." Journal of Cognitive Neuroscience 11 (1999): 585-597.

PubMed abstract:  Behavioral studies indicate that spatial and object working memory are computed by dissociable subsystems. We investigated the neural bases of this dissociation with a whole-brain fMRI design and analysis technique that permitted direct assessment of delay-period activity, uncontaminated by other components of the trial. The task employed a "what"-then-"where" design, with an object and a spatial delay period incorporated in each trial; within-trial order of delay conditions was balanced across each scan. Our experiment failed to find evidence, at the single-subject level and at the group level, for anatomical segregation of spatial and object working memory function in the frontal cortex. Delay-period activity in the caudate nucleus revealed a sensitivity to position in the trial in the spatial, but not the object, condition. In posterior regions, spatial delay-period activity was associated with preferential recruitment of extrastriate areas falling within Brodmann's area 19 and, less reliably, the superior parietal lobule. Object-specific delay-period activity was found predominantly in ventral regions of the posterior cortex and demonstrated more topographic variability across subjects than did spatial working memory activity.

Pylkkänen, L., A. Stringfellow, and A. Marantz. "Neural Mechanisms of Spoken Word Recognition: MEG Evidence for Distinct Sources of Inhibitory Effects." (Submitted)

Rao, S. C., G. Rainer, and E. K. Miller. "Integration of What and Where in the Primate Prefrontal Cortex." Science 276 (1997): 821-824.

PubMed abstract:  The visual system separates processing of an object's form and color ("what") from its spatial location ("where"). In order to direct action to objects, the identity and location of those objects must somehow be integrated. To examine whether this process occurs within the prefrontal (PF) cortex, the activity of 195 PF neurons was recorded during a task that engaged both what and where working memory. Some neurons showed either object-tuned (what) or location-tuned (where) delay activity. However, over half (52 percent, or 64/123) of the PF neurons with delay activity showed both what and where tuning. These neurons may contribute to the linking of object information with the spatial information needed to guide behavior.

Rees, G., C. Russell, C. D. Frith, and J. Driver. "Inattentional Blindness Versus Inattentional Amnesia for Fixated but Ignored Words." Science 286 (1999): 2504-2507.

PubMed abstract:  People often are unable to report the content of ignored information, but it is unknown whether this reflects a complete failure to perceive it (inattentional blindness) or merely that it is rapidly forgotten (inattentional amnesia). Here functional imaging is used to address this issue by measuring brain activity for unattended words. When attention is fully engaged with other material, the brain no longer differentiates between meaningful words and random letters, even when they are looked at directly. These results demonstrate true inattentional blindness for words and show that visual recognition wholly depends on attention even for highly familiar and meaningful stimuli at the center of gaze.

Rowe, J. B., I. Toni, O. Josephs, R. S. J. Frackowiak, and R. E. Passingham. "The Prefrontal Cortex: Response Selection or Maintenance within Working Memory?" Science 288 (2000): 1656-1660.

PubMed abstract:  It is controversial whether the dorsolateral prefrontal cortex is involved in the maintenance of items in working memory or in the selection of responses. We used event-related functional magnetic resonance imaging to study the performance of a spatial working memory task by humans. We distinguished the maintenance of spatial items from the selection of an item from memory to guide a response. Selection, but not maintenance, was associated with activation of prefrontal area 46 of the dorsal lateral prefrontal cortex. In contrast, maintenance was associated with activation of prefrontal area 8 and the intraparietal cortex. The results support a role for the dorsal prefrontal cortex in the selection of representations. This accounts for the fact that this area is activated both when subjects select between items on working memory tasks and when they freely select between movements on tasks of willed action.

Rugg, M. D., K. Allan, and C. S. Birch. "Electrophysiological Evidence for the Modulation of Retrieval Orientation by Depth of Study Processing." Journal of Cognitive Neuroscience 12 (2000): 664-678.

PubMed abstract:  Event-related potentials (ERPs) were employed to investigate whether brain activity elicited by retrieval cues in a memory test varies according to the encoding task undertaken at study. Two recognition memory test blocks were administered, preceded, in one case, by a "shallow" study task (alphabetic judgement) and, in the other case, by a "deep" task (sentence generation). ERPs elicited by the new words in each test block differed, the ERPs elicited in the block following the shallow study task exhibiting the more positive-going waveforms. This finding was taken as evidence that subjects adopt different "retrieval sets" when attempting to retrieve items that had been encoded in terms of alphabetic versus semantic attributes. Differences between the ERPs elicited by correctly classified old and new words (old/new effects) also varied with encoding task. The effects for deeply studied words resembled those found in previous ERP studies of recognition memory, whereas old/new effects for shallowly studied words were confined to a late-onsetting, right frontal positivity. Together, the findings indicate that the depth of study processing influences two kinds of memory-related neural activity, associated with memory search operations, and the processing of retrieved information, respectively.

Rugg, M. D., and E. L. Wilding. "Retrieval Processing and Episodic Memory." Trends in Cognitive Science 4 (2000): 108-115.

PubMed abstract:  The emergence of brain imaging has had a major impact on research into the cognitive and neural bases of human memory. An area in which this impact has been particularly strong is retrieval processing - the processes engaged when attempting to retrieve information during a memory test. Several different classes of retrieval process - such as 'mode', 'effort' and 'success' - have been invoked to account for findings from neuroimaging studies of episodic retrieval. In this article we discuss how these different kinds of process, along with a fourth kind associated with 'retrieval orientation', can be investigated in brain imaging experiments. We then review studies of retrieval processing, and assess how well their designs match up to our proposed criteria for dissociating the neural correlates of different classes of retrieval process. We conclude that few studies have used designs that permit these different kinds of process to be independently identified, and that presently there is little evidence to indicate which kinds of processing can be fractionated in terms of their neural correlates.

Ryan, L., L. Nadel, K. Keil, K. Putnam, D. Schnyer, T. Trouard, and M. Moscovitch. "The Hippocampal Complex and Retrieval of Recent and Very Remote Autobiographical Memories: Evidence from Functional Magnetic Resonance Imaging in Neurologically Intact People." Hippocampus. 2001; 11 (6): 707-14.

PubMed abstract:  It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation.

Rympa, B., and M. D'Esposito. "The Roles of Prefrontal Brain Regions in Components of Working Memory: Effects of Memory Load and Individual Differences." Proceedings of the National Academy of Sciences, USA 96 (1999): 6558-6563.

PubMed abstract:  Using an event-related functional MRI design, we explored the relative roles of dorsal and ventral prefrontal cortex (PFC) regions during specific components (Encoding, Delay, Response) of a working memory task under different memory-load conditions. In a group analysis, effects of increased memory load were observed only in dorsal PFC in the encoding period. Activity was lateralized to the right hemisphere in the high but not the low memory-load condition. Individual analyses revealed variability in activation patterns across subjects. Regression analyses indicated that one source of variability was subjects' memory retrieval rate. It was observed that dorsal PFC plays a differentially greater role in information retrieval for slower subjects, possibly because of inefficient retrieval processes or a reduced quality of mnemonic representations. This study supports the idea that dorsal and ventral PFC play different roles in component processes of working memory.

Stark, C. E., and L. R. Squire. "fMRI Activity in the Medial Temporal Lobe During Recognition Memory as a Function of Study-test Interval." Hippocampus 10 (2000): 329-337.

PubMed abstract:  The phenomenon of temporally graded retrograde amnesia (loss of information acquired before the onset of amnesia) suggests that the hippocampus, and possibly other medial temporal lobe (MTL) structures, have a time-limited role in memory. In three experiments, we made a first attempt to use fMRI to assess activity in the hippocampal region (the CA fields of the hippocampus, the dentate gyrus, and the subiculum) and the adjacent parahippocampal gyrus (parahippocampal, entorhinal, and perirhinal cortices) during recognition memory testing as a function of study-test interval. Experiment 1 (n = 5) demonstrated activity in the hippocampal region and parahippocampal gyrus for targets relative to foils during recognition memory performance following a single study-test delay of about one-half hour. In Experiment 2, 15 participants studied line drawings at each of three different times prior to scanning: one-half hour, 1 day, and 1 week. fMRI data were then collected during recognition memory testing, using targets from all three delays and foils. While an overall effect of targets vs. foils was found in both the hippocampal region and the parahippocampal gyrus, there was no effect of study-test interval on target activity. In Experiment 3 (n = 13), behavioral performance (reaction time and accuracy) was equated across the three delays. Again, no effect of study-test interval was observed. It is possible that the time span sampled in our study (one-half hour to 1 week) was too short to observe changes in activity. Alternatively, activity in the MTL during memory testing may occur even when these structures are not necessary for retrieval.

Thompson-Schill, S. L., M. D'Esposito, and I. P. Kan. "Effects of Repetition and Competition on Activity in Left Prefrontal Cortex During Word Generation." Neuron 23 (1999): 513-522.

PubMed abstract:  Neuroimaging studies have revealed an association between word generation and activity in the left inferior frontal gyrus (IFG) that is attentuated with item repetition. The experiment reported here examined the effects of repeated word generation, under conditions in which completion was either decreased or increased, on activity measured during whole-brain echoplanar functional magnetic resonance imaging. Activity in left IFG decreased during repetition conditions that reduced competition but increased during repetition conditions that increased competition; this pattern was contrasted to repetition effects observed in other cortical areas, specifically regions of left temporal cortex. The increase in left IFG activity, which is not predicted by a simple semantic retrieval account of prefrontal function, is consistent with the hypothesis that left IFG subserves the selection of semantic knowledge among competing alternatives.

Wagner, A. D., A. Maril, R. A. Bjork, and D. L. Schacter. "Prefrontal Contributions to Executive Control: fMRI Evidence for Functional Distinctions within Lateral Prefrontal Cortex." NeuroImage. (In press)

PubMed abstract:  The prefrontal cortex (PFC) plays a fundamental role in internally guided behavior. Although it is generally accepted that PFC subserves working memory and executive control operations, it remains unclear whether the subregions within lateral PFC support distinct executive control processes. An event-related fMRI study was implemented to test the hypothesis that ventrolateral and dorsolateral PFC are functionally distinct, as well as to assess whether functional specialization exists within ventrolateral PFC. Participants performed two executive control tasks that differed in the types of control processes required. During rote rehearsal, participants covertly rehearsed three words in the order presented, thus requiring phonological access and maintenance. During elaborative rehearsal, participants made semantic comparisons between three words held in working memory, reordering them from least to most desirable. Thus, in addition to maintenance, elaborative rehearsal required goal-relevant coding of items in working memory ("monitoring") and selection from among the items to implement their reordering. Results revealed that left posterior ventrolateral PFC was active during performance of both tasks, whereas right dorsolateral PFC was differentially engaged during elaborative rehearsal. The temporal characteristics of the hemodynamic responses further suggested that dorsolateral activation lagged ventrolateral activation. Finally, differential activation patterns were observed within left ventrolateral PFC, distinguishing between posterior and anterior regions. These data suggest that anatomically separable subregions within lateral PFC may be functionally distinct and are consistent with models that posit a hierarchical relationship between dorsolateral and ventrolateral regions such that the former monitors and selects goal-relevant representations being maintained by the latter. Copyright 2001 Academic Press.

Wagner, A. D., E. J. Paré-Blagoev, J. Clark, and R. A. Poldrack. "Recovering Meaning: Left Prefrontal Cortex Guides Controlled Semantic Retrieval." Neuron 31 (2001): 329-338.

PubMed abstract:  Prefrontal cortex plays a central role in mnemonic control, with left inferior prefrontal cortex (LIPC) mediating control of semantic knowledge. One prominent theory posits that LIPC does not mediate semantic retrieval per se, but rather subserves the selection of task-relevant knowledge from amidst competing knowledge. The present event-related fMRI study provides evidence for an alternative hypothesis: LIPC guides controlled semantic retrieval irrespective of whether retrieval requires selection against competing representations. With selection demands held constant, LIPC activation increased with semantic retrieval demands and with the level of control required during retrieval. LIPC mediates a top-down bias signal that is recruited to the extent that the recovery of meaning demands controlled retrieval. Selection may reflect a specific instantiation of this mechanism.

Wheeler, M. E., S. E. Petersen, and R. L. Buckner. "Memory's Echo: Vivid Remembering Reactivates Sensory-specific Cortex." Proceedings of the National Academy of Science, USA 97 (2000): 11125-11129.

PubMed abstract:  A fundamental question in human memory is how the brain represents sensory-specific information during the process of retrieval. One hypothesis is that regions of sensory cortex are reactivated during retrieval of sensory-specific information (1). Here we report findings from a study in which subjects learned a set of picture and sound items and were then given a recall test during which they vividly remembered the items while imaged by using event-related functional MRI. Regions of visual and auditory cortex were activated differentially during retrieval of pictures and sounds, respectively. Furthermore, the regions activated during the recall test comprised a subset of those activated during a separate perception task in which subjects actually viewed pictures and heard sounds. Regions activated during the recall test were found to be represented more in late than in early visual and auditory cortex. Therefore, results indicate that retrieval of vivid visual and auditory information can be associated with a reactivation of some of the same sensory regions that were activated during perception of those items.

Wilding, E. L. "Separating Retrieval Strategies from Retrieval Success: An Event-related Potential Study of Source Memory." Neuropsychologia 37 (1999): 441-454.

PubMed abstract:  Event-related potentials (ERPs) were recorded while subjects performed two different source memory retrieval tasks. Each task was preceded by a study phase in which subjects heard an equal number of words spoken in a male or a female voice. A cue preceding each word indicated whether the subjects should make an active/passive (action) or a pleasant/unpleasant (liking) judgment to the word. In one retrieval task (the voice condition), subjects made a three-way distinction between new (unstudied) words, and words that had been spoken by the male or the female voice at study. In the second retrieval task (the task condition), subjects distinguished between new words, and words to which they had made an action or a liking judgment. All test words were presented visually. In keeping with previous findings, the differences between the ERPs to correct memory judgments for old and new items were characterised by two temporally and topographically dissociable modulations, with right-frontal and left-parietal maxima respectively. These 'old/new effects' displayed different sensitivities to successful retrieval of either voice or task information, providing further evidence that they index functionally dissociable processes. The direct comparison of the ERPs to correct rejections in the voice and task retrieval conditions revealed reliable differences over frontal scalp, suggesting that, irrespective of whether retrieval is successful, neural processing differs according to the source retrieval demands of the task.