9.081 | Fall 2002 | Graduate

Human Memory and Learning


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.


H. Eichenbaum, and N.J. Cohen. From Conditioning to Conscious Recollection. New York: Oxford University Press, 2001.


Badre, D., & Wagner, A. D. “Semantic retrieval, mnemonic control, and prefrontal cortex.” In Behavioral and Cognitive Neuroscience Reviews. 2002, 1, 204-216.

Cabeza, R. “Hemispheric asymmetry reduction in older adults: The HAROLD model.” In Psychology and Aging. 2002, 17, 85-100.

PubMed abstract: A model of the effects of aging on brain activity during cognitive performance is introduced. The model is called HAROLD (hemispheric asymmetry reduction in older adults), and it states that, under similar circumstances, prefrontal activity during cognitive performances tends to be less lateralized in older adults than in younger adults. The model is supported by functional neuroimaging and other evidence in the domains of episodic memory, semantic memory, working memory, perception, and inhibitory control. Age-related hemispheric asymmetry reductions may have a compensatory function or they may reflect a dedifferentiation process. They may have a cognitive or neural origin, and they may reflect regional or network mechanisms. The HAROLD model is a cognitive neuroscience model that integrates ideas and findings from psychology and neuroscience of aging.

Caramazza, A. “Minding the facts: a comment on Thompson-Schill et al.’s ‘A neural basis for category and modality specificity of semantic knowledge’ “. In Neuropsychologia. 38(7), 944-949.

PubMed abstract: In this comment on a recent paper by Thompson-Schill et al. (1999) I argue that the authors failed to consider important empirical facts that are at variance with their favored theory of the causes of semantic category-specific deficits. I also argue that the predictions they make about fusiform gyrus activation on the basis of the interactive modality-specific hypothesis of semantic organization do not obviously follow from that model. I point out that simulations are needed in order to derive predictions from the model. Finally, I argue that the fMRI results they obtained are not obviously relevant to our understanding of the causes of semantic category-specific deficits.

Chein, J. M., & Fiez, J. A. “Dissociation of verbal working memory system components using a delayed serial recall task.” In Cerebral Cortex. 2001, 11, 1003-1014.

PubMed abstract: Functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of component processes in verbal working memory. Based on behavioral research using manipulations of verbal stimulus type to dissociate storage, rehearsal, and executive components of verbal working memory, we designed a delayed serial recall task requiring subjects to encode, maintain, and overtly recall sets of verbal items for which phonological similarity, articulatory length, and lexical status were manipulated. By using a task with temporally extended trials, we were able to exploit the temporal resolution afforded by fMRI to partially isolate neural contributions to encoding, maintenance, and retrieval stages of task performance. Several regions commonly associated with maintenance, including supplementary motor, premotor, and inferior frontal areas, were found to be active across all three trial stages. Additionally, we found that left inferior frontal and supplementary motor regions showed patterns of stimulus and temporal sensitivity implicating them in distinct aspects of articulatory rehearsal, while no regions showed a pattern of sensitivity consistent with a role in phonological storage. Regional modulation by task difficulty was further investigated as a measure of executive processing. We interpret our findings as they relate to notions about the cognitive architecture underlying verbal working memory performance.

Curran, T. “Brain potentials of recollection and familiarity.” In Memory & Cognition. 2000, 28, 923- 938.

PubMed abstract: It is widely hypothesized that separate recollection and familiarity processes contribute to recognition memory. The present research measured event-related brain potentials (ERPs) from 128 head locations to identify patterns of brain activity related to recollection and familiarity. In two experiments, subjects performed a recognition memory task requiring discrimination between previously studied words, similar words that changed plurality between study and test, and new words (following Hintzman & Curran, 1994). The FN400 ERP component (300-500 msec) varied with the familiarity of words (new > studied = similar). The parietal component (400-800 msec) was associated with the recollection of plurality (studied > similar = new). Differences in the timing and spatial topography of the FN400 and parietal effects support the view that familiarity and recollection arise from distinct neurocognitive processes.

Davachi, L., Mitchell, J., & Wagner, A. D. “Multiple routes to memory: Distinct medial temporal lobe processes build item and source memories.” Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2157-62. Epub 2003 Feb 10.

PubMed abstract: A central function of memory is to permit an organism to distinguish between stimuli that have been previously encountered and those that are novel. Although the medial temporal lobe (which includes the hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortices) is known to be crucial for recognition memory, controversy remains regarding how the specific subregions within the medial temporal lobe contribute to recognition. We used event-related functional MRI to examine the relation between activation in distinct medial temporal lobe subregions during memory formation and the ability (i) to later recognize an item as previously encountered (item recognition) and (ii) to later recollect specific contextual details about the prior encounter (source recollection). Encoding activation in hippocampus and in posterior parahippocampal cortex predicted later source recollection, but was uncorrelated with item recognition. In contrast, encoding activation in perirhinal cortex predicted later item recognition, but not subsequent source recollection. These outcomes suggest that the subregions within the medial temporal lobe subserve distinct, but complementary, learning mechanisms.

Dobbins, I. G., Rice, H. J., Wagner, A. D., & Schacter, D. L. (in press). “Memory orientation and success: Separable neurocognitive components underlying episodic recognition.”  Neuropsychologia. 2003;41(3):318-33.

PubMed abstract: Episodic recognition can be based on recollection of contextual details, on a sense of recent encounter, or some combination of the two. According to several cognitive models, selectively attending to these distinct aspects of memory may require different retrieval orientations and result in different neural responses depending upon whether or not retrieval is successful. Using event-related fMRI, we examined retrieval orientation by having subjects discriminate between two test words in one of two manners. During source recollection, they selected the member of the pair previously associated with a particular encoding task. In contrast, recency judgment required selection of the most recently encountered item of the pair, regardless of how it had been encoded. Furthermore, successful and unsuccessful trials within each retrieval task were contrasted to determine whether retrieval success effects occurred in overlapping or dissimilar neural populations compared to those associated with each retrieval orientation. The results revealed distinct lateral prefrontal and parietal activations that distinguished attempted source recollection from judgments of relative recency; these orientation effects were largely independent of retrieval success. In contrast, medial temporal lobe structures (hippocampus and parahippocampal gyrus) were differentially more active during successful recollection of encoding context, showing similar reduced responses during failed source recollection and judgments of recency. These results indicate that different memory orientations recruit distinct prefrontal and parietal networks and that the recovery of episodic context is associated with the hippocampus and surrounding medial temporal cortices.

Grady, C. L., & Craik, F. I. “Changes in memory processing with age.” In Current Opinion in Neurobiology. 2000, 10, 224-231.

PubMed abstract: Over the years, a large body of literature has shown that humans display losses in memory with age, but that not all types of memory are affected equally. Similarly, recent evidence from functional neuroimaging experiments has revealed that, depending on the task, older adults can display greater or lesser activity in task-relevant brain areas compared with younger adults. Recent behavioral and neurophysiological experiments are furthering our understanding of the effects of aging on cognition. It appears that some brain changes seen with age may be compensatory.

Gupta, P., & Cohen, N. J. “Theoretical and computational analysis of skill learning, repetition priming, and procedural memory.” In Psychological Review. 2002, 109, 401-448.

PubMed abstract: This article analyzes the relationship between skill learning and repetition priming, 2 implicit memory phenomena. A number of reports have suggested that skill learning and repetition priming can be dissociated from each other and are therefore based on different mechanisms. The authors present a theoretical analysis showing that previous results cannot be regarded as evidence of a processing dissociation between skill learning and repetition priming. The authors also present a single-mechanism computational model that simulates a specific experimental task and exhibits both skill learning and repetition priming, as well as a number of apparent dissociations between these measures. These theoretical and computational analyses provide complementary evidence that skill learning and repetition priming are aspects of a single underlying mechanism that has the characteristics of procedural memory.

Haist, F., Bowden Gore, J., & Mao, H. “Consolidation of human memory over decades revealed by functional magnetic resonance imaging.” In Nature Neuroscience. 2001, 4, 1139-1145.

PubMed abstract: Medial temporal lobe (MTL) lesions typically produce retrograde amnesia characterized by the disproportionate loss of recently acquired memories. Temporally graded memory loss is interpreted traditionally as evidence for a consolidation process guided by the MTL. Here, using functional magnetic resonance imaging (fMRI), we show temporally graded changes in MTL activity in healthy older adults taking a famous faces remote memory test. Evidence for temporally graded change in the hippocampal formation was mixed, suggesting it may participate only in consolidation processes lasting a few years. Entorhinal cortex was associated with temporally graded changes extending up to 20 years. These findings support the basic tenets of consolidation theory and suggest that the entorhinal cortex, rather than the hippocampal formation, participates in memory consolidation over decades.

Haxby, J. V., Gobbini, M. I., Furey, M. L., Ishai, A., Schouten, J. L., & Pietrini, P. “Distributed and overlapping representations of faces and objects in ventral temporal cortex.” In Science. 2001, 2425-2430.

PubMed abstract: The functional architecture of the object vision pathway in the human brain was investigated using functional magnetic resonance imaging to measure patterns of response in ventral temporal cortex while subjects viewed faces, cats, five categories of man-made objects, and nonsense pictures. A distinct pattern of response was found for each stimulus category. The distinctiveness of the response to a given category was not due simply to the regions that responded maximally to that category, because the category being viewed also could be identified on the basis of the pattern of response when those regions were excluded from the analysis. Patterns of response that discriminated among all categories were found even within cortical regions that responded maximally to only one category. These results indicate that the representations of faces and objects in ventral temporal cortex are widely distributed and overlapping.

Henson, R., Shallice, T., & Dolan, R. “Neuroimaging evidence for dissociable forms of repetition priming.” In Science. 2000, 287, 1269-1272.

PubMed abstract: Repetition priming has been characterized neurophysiologically as a decreased response following stimulus repetition. The present study used event-related functional magnetic resonance imaging to investigate whether this repetition-related response is sensitive to stimulus familiarity. A right fusiform region exhibited an attenuated response to the repetition of familiar stimuli, both faces and symbols, but exhibited an enhanced response to the repetition of unfamiliar stimuli. Moreover, both repetition effects were modulated by lag between successive presentations. Further experiments replicated the interactions between repetition, familiarity, and lag and demonstrated the persistence of these effects over multiple repetitions. Priming-related responses are therefore not unitary but depend on the presence or absence of preexisting stimulus representations.

Kirchhoff, B. A., Wagner, A. D., Maril, A., & Stern, C. E. “Prefrontal-temporal circuitry for novelty encoding and subsequent memory.” In Journal of Neuroscience. 2000, 20, 6173-6180.

PubMed abstract: Humans encounter and form memories for multiple types of experiences that differ in content, novelty, and memorability. Critical for understanding memory is determining (1) how the brain supports the encoding of events with differing content and (2) whether neural regions that are sensitive to novelty also influence whether stimuli will be subsequently remembered. This event-related functional magnetic resonance imaging (fMRI) study crossed content (picture/word), novelty (novel/repeated), and subsequent memory (remembered/forgotten) to examine prefrontal and temporal lobe contributions to encoding. Results revealed three patterns of encoding-related activation in anatomically connected inferior prefrontal and lateral temporal structures that appeared to vary depending on whether visuospatial/visuo-object, phonological/lexical, or semantic attributes were processed. Event content also modulated medial temporal lobe activity; word encoding predominantly activated the left hemisphere, whereas picture encoding activated both hemispheres. Critically, in prefrontal and temporal regions that were modulated by novelty, the magnitude of encoding activation also predicted whether an event would be subsequently remembered. These results suggest that (1) regions that demonstrate a sensitivity to novelty may actively support encoding processes that impact subsequent explicit memory and (2) multiple content-dependent prefrontal-temporal circuits support event encoding. The similarities between prefrontal and lateral temporal encoding responses raise the possibility that prefrontal modulation of posterior cortical representations is central to encoding.

Logan, J. M., Sanders, A. L., Snyder, A. Z., Morris, J. C., & Buckner, R. L. “Underrecruitment and nonselective recruitment: Dissociable neural mechanisms associated with aging.” In Neuron. 2002, 33, 827-840.

PubMed abstract: Frontal contributions to cognitive decline in aging were explored using functional MRI. Frontal regions active in younger adults during self-initiated (intentional) memory encoding were under-recruited in older adults. Older adults showed less activity in anterior-ventral regions associated with controlled use of semantic information. Under-recruitment was reversed by requiring semantic elaboration suggesting it stemmed from difficulty in spontaneous recruitment of available frontal resources. In addition, older adults recruited multiple frontal regions in a nonselective manner for both verbal and nonverbal materials. Lack of selectivity was not reversed during semantically directed encoding even when under-recruitment was diminished. These findings suggest two separate forms of age-associated change in frontal cortex: under-recruitment and nonselective recruitment. The former is reversible and potentially amenable to cognitive training; the latter may reflect a less malleable change associated with cognitive decline in advanced aging.

MacDonald, A. W., 3rd, Cohen, J. D., Stenger, V. A., & Carter, C. S. “Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control.” In Science. 2000, 288(5472), 1835-1838.

PubMed abstract: Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann’s area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann’s areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.

Martin, A., & Chao, L. L. “Semantic memory and the brain: Structure and processes.” In Current Opinion in Neurobiology. 2001, 11, 194-201.

PubMed abstract: Recent functional brain imaging studies suggest that object concepts may be represented, in part, by distributed networks of discrete cortical regions that parallel the organization of sensory and motor systems. In addition, different regions of the left lateral prefrontal cortex, and perhaps anterior temporal cortex, may have distinct roles in retrieving, maintaining and selecting semantic information.

Milham, M. P., Erickson, K. I., Banich, M. T., Kramer, A. F., Webb, A., Wszalek, T., & Cohen, N. J. “Attentional control in the aging brain: Insights from an fMRI study of the Stroop task.” In Brain & Cognition. 2002, 49, 277-296.

PubMed abstract: Several recent studies of aging and cognition have attributed decreases in the efficiency of working memory processes to possible declines in attentional control, the mechanism(s) by which the brain attempts to limit its processing to that of task-relevant information. Here we used fMRI measures of neural activity during performance of the color-word Stroop task to compare the neural substrates of attentional control in younger (ages: 21-27 years old) and older participants (ages: 60-75 years old) during conditions of both increased competition (incongruent and congruent neutral) and increased conflict (incongruent and congruent neutral). We found evidence of age-related decreases in the responsiveness of structures thought to support attentional control (e.g., dorsolateral prefrontal and parietal cortices), suggesting possible impairments in the implementation of attentional control in older participants. Consistent with this notion, older participants exhibited more extensive activation of ventral visual processing regions (i.e., temporal cortex) and anterior inferior prefrontal cortices, reflecting a decreased ability to inhibit the processing of task-irrelevant information. Also, the anterior cingulate cortex, a region involved in evaluatory processes at the level of response (e.g., detecting potential for error), showed age-related increases in its sensitivity to the presence of competing color information. These findings are discussed in terms of newly emerging models of attentional control in the human brain.

Miller, E. K., & Cohen, J. D. “An integrative theory of prefrontal cortex function.” In Annual Review of Neuroscience. 2001, 24, 167-202.

PubMed abstract: The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed.

Poldrack, R. A., Clark, J., Pare-Blagoev, E. J., Shohamy, D., Creso Moyano, J., Myers, C., & Gluck, M. A. “Interactive memory systems in the human brain.” In Nature. 2001, 414, 546-550.

PubMed abstract: Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates. A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies and neuroimaging, activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning.

Prabhakaran, V., Narayanan, K., Zhao, Z., & Gabrieli, J. D. “Integration of diverse information in working memory within the frontal lobe.” In Nat Neurosci. 2000, 3(1), 85-90.

_PubMed abstract: _ Ability to integrate diverse forms of information in current thought, or working memory, is essential for human reasoning and problem solving. We used functional imaging to identify brain regions preferentially involved in maintaining integrated versus unintegrated information in working memory. For equal amounts of verbal and spatial information, activation of prefrontal cortex was greater for maintaining integrated rather than unintegrated representations. Posterior brain regions showed the opposite pattern. These results demonstrate frontal-lobe specialization in maintaining working-memory representations that integrate verbal and spatial information. The role of prefrontal cortex in integrating multiple forms of information in working memory may underlie its unique contribution to high-level cognition that demands flexible mental representations.

Rowe, J. B., Toni, I., Josephs, O., Frackowiak, R. S. J., & Passingham, R. E. “The prefrontal cortex: Response selection or maintenance within working memory?” In Science. 2000, 288, 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.

Ryan, L., Nadel, L., Keil, K., Putnam, K., Schnyer, D., Trouard, T., & Moscovitch, M. “The hippocampal complex and retrieval of recent and very remote autobiographical memories: Evidence from functional magnetic resonance imaging in neurologically intact people.” In Hippocampus. 2001, 11, 707- 714.

_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.

Thompson-Schill, S. L., Aguirre, G. K., D’Esposito, M., & Farah, M. J. “A neural basis for category and modality specificity of semantic knowledge.” In Neuropsychologia. 1999a, 37, 671-676.

PubMed abstract: Prevalent theories hold that semantic memory is organized by sensorimotor modality (e.g., visual knowledge, motor knowledge). While some neuroimaging studies support this idea, it cannot account for the category specific (e.g., living things) knowledge impairments seen in some brain damaged patients that cut across modalities. In this article we test an alternative model of how damage to interactive, modality-specific neural regions might give rise to these categorical impairments. Functional MRI was used to examine a cortical area with a known modality-specific function during the retrieval of visual and non-visual knowledge about living and non-living things. The specific predictions of our model regarding the signal observed in this area were confirmed, supporting the notion that semantic memory is functionally segregated into anatomically discrete, but highly interactive, modality-specific regions.

Thompson-Schill, S. L., D’Esposito, M., & Kan, I. P. “Effects of repetition and competition on activity in left prefrontal cortex during word generation.” In Neuron. 1999b, 23, 513-522.

PubMed abstract: Prevalent theories hold that semantic memory is organized by sensorimotor modality (e.g., visual knowledge, motor knowledge). While some neuroimaging studies support this idea, it cannot account for the category specific (e.g., living things) knowledge impairments seen in some brain damaged patients that cut across modalities. In this article we test an alternative model of how damage to interactive, modality-specific neural regions might give rise to these categorical impairments. Functional MRI was used to examine a cortical area with a known modality-specific function during the retrieval of visual and non-visual knowledge about living and non-living things. The specific predictions of our model regarding the signal observed in this area were confirmed, supporting the notion that semantic memory is functionally segregated into anatomically discrete, but highly interactive, modality-specific regions.

Vaina, L. M., Belliveau, J. W., des Roziers, E. B., & Zeffiro, T. A. “Neural systems underlying learning and representation of global motion.” In Proceedings of the National Academy of Sciences. 1998, U.S.A., 95, 12657-12662.

PubMed abstract: We demonstrate performance-related changes in cortical and cerebellar activity. The largest learning-dependent changes were observed in the anterior lateral cerebellum, where the extent and intensity of activation correlated inversely with psychophysical performance. After learning had occurred (a few minutes), the cerebellar activation almost disappeared; however, it was restored when the subjects were presented with a novel, untrained direction of motion for which psychophysical performance also reverted to chance level. Similar reductions in the extent and intensity of brain activations in relation to learning occurred in the superior colliculus, anterior cingulate, and parts of the extrastriate cortex. The motion direction-sensitive middle temporal visual complex was a notable exception, where there was an expansion of the cortical territory activated by the trained stimulus. Together, these results indicate that the learning and representation of visual motion discrimination are mediated by different, but probably interacting, neuronal subsystems.

Wagner, A. D., & Koutstaal, W. “Priming.” Edited by V. S. Ramachandran. In Encyclopedia of the Human Brain. Vol. 4. San Diego: Academic Press, 2002, 27-46).

Wheeler, M. E., Petersen, S. E., & Buckner, R. L. “Memory’s echo: Vivid remembering reactivates sensory-specific cortex.” In Proceedings of the National Academy of Science. 2000, USA, 97, 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.

Yonelinas, A. P. “The nature of recollection and familiarity: A review of 30 years of research.” In Journal of Memory and Language. 2002, 46, 441-517.

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Fall 2002
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