Functional magnetic resonance imaging of proactive interference during spoken cued recall

Though lesions to frontal cortex can increase susceptibility to interference from previously established but irrelevant memories ("proactive interference"), the specific regions underlying this problem are difficult to determine because the lesions are typically large and heterogeneous. We used event-related functional magnetic resonance imaging to investigate proactive interference in healthy volunteers performing an "AB-AC" paired-associate cued-recall paradigm. At Study, participants intentionally encoded semantically related visual word pairs, which were changed three times (high interference), repeated three times (low interference), or presented only once. At Test, participants were presented with the first word of each pair and attempted to recall its most recent associate from the Study phase. To overcome the problem of image artifacts caused by speech-related head motion, we cued speech during a gap between image acquisitions. Regions in left inferior frontal cortex and bilateral frontopolar cortex showed interference effects during both Study and Test. The pattern of responses in these regions differed, however. Left inferior frontal regions showed mainly reduced responses associated with low interference, whereas frontopolar regions showed mainly increased responses associated with high interference. When incorrect as well as correct trials were analyzed at Test, additional activation associated with high interference was observed in right dorsolateral prefrontal cortex. These data suggest that distinct regions within prefrontal cortex subserve different functions in the presence of proactive interference during cued recall.     

Reactivation of visual cortex during memory retrieval: content specificity and emotional modulation

Studies on memory retrieval suggest a reactivation of cortical regions engaged during encoding, such that visual or auditory areas reactivate for visual or auditory memories. The content specificity and any emotion dependency of such reactivations are still unclear. Because distinct visual areas are specialized in processing distinct stimulus categories, we tested for face and word specific reactivations during a memory task using functional magnetic resonance imaging (fMRI). Furthermore, because visual processing and memory are both modulated by emotion, we compared reactivation for stimuli encoded in a neutral or emotionally significant context. In the learning phase, participants studied pairs of stimuli that consisted of either a scene and a face, or a scene and a word. Scenes were either neutral or negative, but did not contain faces or words. In the test phase scenes were presented alone (one in turn), and participants indicated whether it was previously paired with a face, a word, or was new. Results from the test phase showed activation in a functionally defined face-responsive region in the right fusiform gyrus, as well as in a word-responsive region in the left inferior temporal gyrus, for scenes previously paired with faces and words, respectively. Reactivation tended to be larger in both the face- and word-responsive regions when the associated scene was negative as compared to neutral. However, relative to neutral context, the recall of faces and words paired with a negative context produced smaller activations in brain regions associated with social and semantic processing, respectively, as well as poorer memory performance overall. Taken together, these results support the idea of cortical memory reactivations, even at a content-specific level, and further suggest that emotional context may produce opposite effects on reactivations in early sensory areas and more elaborate processing in higher-level cortical areas.     

Memory disorders as a function of traumatic brain injury. Word completion, recall of words and actions

The memory performance of a group with traumatic brain injury and a matched control group was assessed using the following methods (a) word completion, (b) immediate free, final free and final cued recall of words and (c) immediate free and final free recall of subject-performed tasks (SPTs) and SPTs without motor action (SPTs-WA). The brain-injured (BI) group was significantly inferior relative to the control group in all recall tests except immediate free recall of words. No difference was revealed in the word completion test. The BI-group benefitted less by cues presented either at retrieval (final cued recall of words) or at the time of encoding already built-in in the stimulus (SPTs and SPTs-WA). The results were discussed in terms of the neuropathological background of the patients in the BI-group suggesting that frontal dysfunction could play a critical role. When comparing the tests within the BI-group, however, the performance was better when cues were present and especially so for long-term memory. Motor activity also facilitated long-term memory. Finally, an attempt was made to specify conditions for guidance in the construction of training programmes.     

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.     

Content-specific activation during associative long-term memory retrieval

We tested whether visual stimulus material that is assumed to be processed in different cortical networks during perception (i.e., faces and spatial positions) is also topographically dissociable during long-term memory recall. With an extensive overlearning procedure, 12 participants learned paired associates of words and faces and words and spatial positions. Each word was combined with either one or two positions or one or two faces. fMRI was recorded several days later during a cued recall test, in which two words were presented and the participants had to decide whether these were linked to each other via a common mediator, i.e., a face or a position. This paradigm enforces retrieval from long-term memory without confounding recall with perceptual processes. A network of cortical areas was found to be differently activated during recall of positions and faces, including regions along the dorsal and ventral visual pathways, such as the parietal and precentral cortex for positions and the left prefrontal, temporal (including fusiform gyrus) and posterior cingulate cortex for faces. In a subset of these areas, the BOLD response was found to increase monotonically with the number of the to-be-re-activated associations. These results show that material-specific cortical networks are systematically activated during long-term memory retrieval that overlap with areas also activated by positions and faces during perceptual and working memory tasks.     

Changes in brain electrical activity during extended continuous word recognition

Twenty healthy subjects (10 men, 10 women) participated in an EEG study with an extended continuous recognition memory task, in which each of 30 words was randomly shown 10 times and subjects were required to make old vs. new decisions. Both event-related brain potentials (ERPs) and induced band power (IBP) were investigated. We hypothesized that repeated presentations affect recollection rather than familiarity. For the 300- to 500-ms time window, an 'old/new' ERP effect was found for the first vs. second word presentations. The correct recognition of an 'old' word was associated with a more positive waveform than the correct identification of a new word. The old/new effect was most pronounced at and around the midline parietal electrode position. For the 500- to 800-ms time window, a linear repetition effect was found for multiple word repetitions. Correct recognition after an increasing number of repetitions was associated with increasing positivity. The multiple repetitions effect was most pronounced at the midline central (Cz) and fronto-central (FCz) electrode positions and reflects a graded recollection process: the stronger the memory trace grows, the more positive the ERP in the 500- to 800-ms time window. The ERP results support a dual-processing model, with familiarity being discernable from a more graded recollection state that depends on memory strengths. For IBP, we found 'old/new' effects for the lower-2 alpha, theta, and delta bands, with higher bandpower during 'old' words. The lower-2 alpha 'old/new' effect most probably reflects attentional processes, whereas the theta and delta effects reflect encoding and retrieval processes. Upon repeated word presentations, the magnitude of induced delta power in the 375- to 750-ms time window diminished linearly. Correlation analysis suggests that decreased delta power is moderately associated with faster decision speed and higher accuracy.     

The effect of word concreteness on recognition memory

Concrete words that are readily imagined are better remembered than abstract words. Theoretical explanations for this effect either claim a dual coding of concrete words in the form of both a verbal and a sensory code (dual-coding theory), or a more accessible semantic network for concrete words than for abstract words (context-availability theory). However, the neural mechanisms of improved memory for concrete versus abstract words are poorly understood. Here, we investigated the processing of concrete and abstract words during encoding and retrieval in a recognition memory task using event-related functional magnetic resonance imaging (fMRI). As predicted, memory performance was significantly better for concrete words than for abstract words. Abstract words elicited stronger activations of the left inferior frontal cortex both during encoding and recognition than did concrete words. Stronger activation of this area was also associated with successful encoding for both abstract and concrete words. Concrete words elicited stronger activations bilaterally in the posterior inferior parietal lobe during recognition. The left parietal activation was associated with correct identification of old stimuli. The anterior precuneus, left cerebellar hemisphere and the posterior and anterior cingulate cortex showed activations both for successful recognition of concrete words and for online processing of concrete words during encoding. Additionally, we observed a correlation across subjects between brain activity in the left anterior fusiform gyrus and hippocampus during recognition of learned words and the strength of the concreteness effect. These findings support the idea of specific brain processes for concrete words, which are reactivated during successful recognition.     

Retrieving autobiographical memories of painful events activates the anterior cingulate cortex and inferior frontal gyrus.

Patients will often reflect on the meaning of a painful episode, as, for example, when completing questionnaire measures of subjective pain experience or in clinical interviews. Neuroimaging studies of the human cortical and subcortical physical pain response have identified a neural network consistently referred to as the "pain matrix." We used functional magnetic resonance imaging to investigate whether the pain matrix could be activated through the retrieval of memories relating to previously painful events, in the absence of any direct peripheral noxious input. Fourteen pain-free participants were explicitly instructed to recall autobiographical memories of painful episodes in response to pain-related words and non-painful episodes in response to equally salient but non-pain words. Memories triggered by pain-related words produced significantly greater activation of left caudal anterior cingulate cortex (BA32'), and left inferior frontal gyrus (BA44, extending to BA47/45) more than memories triggered by equally salient but non-pain words. We suggest that these activations demonstrate a semantic retrieval process for pain-related memories, which may provide a means of cognitively reappraising the memory of the painful episode, thus allowing the person to elaborate on the circumstances surrounding the event, without physically re-experiencing it. PERSPECTIVE: The present study reveals a putative neural mechanism for the retrieval of autobiographical memories of previously painful events, which may provide a means of cognitively reappraising a painful episode, without physically re-experiencing it. This finding has implications for understanding disease mechanisms of chronic pain and their impact on subsequent treatment.     

Sleep Loss Produces False Memories

People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a) as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b) as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., “night”, “dark”, “coal”,…), lacking the strongest common associate or theme word (here: “black”). Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.     

Recognition memory for studied words is determined by cortical activation differences at encoding but not during retrieval

Prior work has shown that when responses to incidentally encoded words are sorted, subsequently remembered words elicit greater left prefrontal BOLD signal change relative to forgotten words. Similarly, low-frequency words elicit greater activation than high-frequency words in the same left prefrontal regions, contributing to their better subsequent memorability. This study examined the relative contribution of encoding and retrieval processes to the correct recognition of target words. A mixture of high- and low-frequency words was incidentally encoded. Scanning was performed at encoding as well as during retrieval. During encoding, greater activation in the left prefrontal and anterior cingulate regions predicted a higher proportion of hits for low-frequency words. However, data acquired during recognition showed that word frequency did not modulate activation in any of the areas tracking successful recognition. This result demonstrates that under some circumstances, the recognition of studied words is determined purely by processes that are active during encoding. In contrast to the finding for hits, activation associated with correctly rejected foils was modulated by word frequency, being higher for high-frequency words in the left lateral parietal and anterior prefrontal regions. These findings were replicated in two further experiments, one in which the number of test items at recognition was doubled and another where encoding strength for high-frequency words was varied (once vs. 10 times). These results indicate that word frequency modulates activity in the left lateral parietal and anterior prefrontal regions contingent on whether the item involved is correctly recognized as a target or a foil. This observation is consistent with a dual process account of episodic memory.     

fMRI BOLD response to increasing task difficulty during successful paired associates learning

We used functional magnetic resonance imaging (fMRI) to assess cortical activations associated with increasing task difficulty (TD) in a visuospatial paired associates learning task. Encoding and retrieval were examined when 100% successful retrieval of three, four, or six object-location pairs had been attained (thus ensuring that performance was matched across subjects). As memory load increased, in general, the number of attempts taken to achieve 100% successful retrieval increased, while the number of trials correctly completed on the first attempt decreased. By modelling parametric variations in working memory load with BOLD signal changes we were able to identify brain regions displaying linear and nonlinear responses to increasing load. During encoding, load-independent activations were found in occipitoparietal cortices (excluding the precuneus for which linear load dependency was demonstrated), anterior cingulate, and cerebellum, while linear load-dependent activations in these same regions were found during retrieval. Nonlinear load-dependent responses, as identified by categorical contrasts between levels of load, were found in the right DLPFC and left inferior frontal gyrus. The cortical response to increasing cognitive demands or TD appears to involve the same, rather than an additional, network of brain regions "working harder."     

The effect of encoding strategies on medial temporal lobe activations during the recognition of words: an event-related fMRI study

It is known that manipulation of the encoding strategy affects behavioral and activation data during later retrieval. In the present fMRI study, we examined brain activity during the recognition of words encoded using three different strategies formed by the combination of two factors of relational and self-performed processes. The first encoding strategy involved subjects learning words using both relational and self-performed processes (R+S+). In the second, subjects learned words using only a relational process (R+S-). In the third, subjects learned words without using either process (R-S-). During fMRI after encoding, subjects were randomly presented with words encoded previously and with new words (New) and were required to judge whether or not the word presented had been previously encoded. The fMRI experiment was performed with the event-related design. Compared to New, activation of the left medial temporal lobe (MTL) occurred during the recognition of words encoded using R+S+ and R+S-, whereas right MTL activations only occurred with the R+S+ strategy. ROI analysis for the bilateral hippocampus and parahippocampal gyrus showed a linear increase in left MTL activity (hippocampus and parahippocampal gyrus) during the recognition of words encoded with the R-S-, R+S-, to R+S+, whereas right MTL activity (parahippocampal gyrus) was only increased with the R+S+ strategy. The findings suggest that the left and right MTL structures may contribute differentially to the processes involved in the recognition of stimuli and that these differential activities may depend on the encoding strategies formed by the two factors of relational and self-performed processes.     

Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4 T

Animal studies suggest an involvement of CA3 and dentate gyrus (CA3&DG) in memory encoding and early retrieval and an involvement of CA1 in late retrieval, consolidation and recognition. The aim of this study was to test if similar associations could be found between hippocampal subfield volumes measured in vivo using a manual parcellation scheme and selected scores of the California Verbal Learning Test II (CVLTII): total immediate free recall discriminability (IFRD), short free recall discriminability (SFRD), and delayed recall discriminability (DRD). 50 elderly subjects (25 controls and 25 cognitively impaired subjects) had CVLTII and high resolution hippocampal MRI at 4T. Entorhinal cortex, subiculum, CA1, CA1-CA2 transition zone, and CA3&DG were manually marked on five slices in the anterior hippocampal body on the MRI. Pearson correlations followed by stepwise regression analysis were used to test for associations between subfield volumes and CVLTII. IFRD and SFRD, which are measures of encoding/early retrieval, were associated with CA3&DG, and DRD, which measures consolidation/late retrieval, with CA1. These preliminary findings demonstrate that subfield volumetry has the potential to study non invasively subfield specific memory functions.     

Encoding the future: Successful processing of intentions engages predictive brain networks

Evidence from cognitive, patient and neuroimaging research indicates that “remembering to remember” intentions, i.e., prospective memory (PM) retrieval, requires both general memory systems involving the medial temporal lobes and an executive system involving rostral PFC (BA 10). However, it is not known how prospective memories are initially formed. Using fMRI, we investigated whether brain activity during encoding of future intentions and present actions differentially predicted later memory for those same intentions (PM) and actions (retrospective memory). We identified two significant patterns of neural activity: a network linked to overall memory and another linked specifically to PM. While overall memory success was predicted by temporal lobe activations that included the hippocampus, PM success was also uniquely predicted by activations in additional regions, including left rostrolateral PFC and the right parahippocampal gyrus. This finding extends the role of these structures to the formation of individual intentions. It also provides the first evidence that PM encoding, like PM retrieval, is supported by both a common episodic memory network and an executive network specifically recruited by future-oriented processing.     

Re-experiencing old memories via hippocampus: a PET study of autobiographical memory

The time-scale of medial temporal lobe (MTL) involvement in storage and retrieval of episodic memory is keenly debated. To test competitive theories of long-term memory consolidation, the present work aimed at characterizing which cerebral regions are involved during retrieval of recent and remote strictly episodic autobiographical memory. Using positron emission tomography (PET), we examined mental retrieval of recent (0-1 year) and remote (5-10 years) autobiographical memories, controlling for the nature of the autobiographical memories (i.e., specificity, state of consciousness, vividness of mental visual imagery, emotion) retrieved during scanning by behavioral measures assessed at debriefing for each event recalled. Cognitive results showed that specificity and emotion did not change with time interval although both autonoetic consciousness and mental image quality were significantly higher for recent memories, suggesting an underlying shift in the phenomenal experience of remembering with the passage of time. The SPM analysis revealed common activations during the recollection of recent and remote memories that involved a widespread but mainly left-sided cerebral network, consistent with previous studies. Subtraction analysis demonstrated that the retrieval of recent (relative to remote) autobiographical memories principally activated the left dorsolateral prefrontal cortex whereas the retrieval of remote (relative to recent) autobiographical memories activated the inferior parietal cortex bilaterally. ROIs analysis revealed more hippocampal activity for remote memories than for recent ones and a preferentially right-sided involvement of the hippocampal responses whatever the remoteness of autobiographical memories. New insights based on higher hippocampal response to the remoteness of episodic autobiographical memories challenge the standard model and are less discrepant with the multiple trace theory.     

Memory retrieval under the control of the prefrontal cortex

Memory retrieval is a process wherein a distributed neural network reactivates the brain's representation of past experiences. Sensory long-term memory is represented among a population of neurones in the modality-specific posterior association cortex. The coded representation of memory can be retrieved by interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. We examined the function of the prefrontal cortex in memory retrieval by two different approaches. Firstly, a meta-analysis of brain imaging studies revealed that the prefrontal cortex is reliably activated by memory retrieval in humans. Secondly, in order to determine the causal relationship between the prefrontal activations and memory retrieval, we designed a new experimental paradigm using posterior-split-brain monkeys. Following section of the splenium of the corpus callosum and the anterior commissure, visual stimulus-stimulus association learning within one hemisphere did not transfer to the other. Nevertheless, when a visual cue was presented to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These findings suggest that the prefrontal cortex can regulate the recall of long-term memory in the absence of bottom-up sensory inputs.     

Is Multivariate Analysis of PET Data More Revealing Than the Univariate Approach? Evidence from a Study of Episodic Memory Retrieval

In a functional imaging study of cued paired associate retrieval, in which the strength of association between pair members was systematically varied, we predicted increased right frontal activity as a function of weakening semantic linkage. An initial univariate analysis found the opposite effect, with greater right frontal activity during recall of strongly linked paired associates. This unexpected result led us to perform a multivariate analysis of covariance (MANCOVA), an approach which proved more informative. This analysis showed that the most significant source of task-related variance was accounted for by a nonlinear relationship not predicted by the prior hypothesis and not revealed by the standard univariate approach. This application of the MANCOVA supports the assertion that multivariate analysis can provide an important adjunct to univariate approaches like statistical parametric mapping (SPM). New perspectives engendered by the MANCOVA still allow for statistical inference but are not constrained by explicit hypotheses about specific task-dependent effects.     

Distributed self in episodic memory: neural correlates of successful retrieval of self-encoded positive and negative personality traits

Words processed with reference to the self are generally better remembered than words processed in semantic terms. An account of this phenomenon, labeled the Self Reference Effect (SRE), is that the self promotes elaboration and organization of encoded information. Although a few neuroimaging studies associated self-referential encoding with activations of the medial prefrontal cortex, no previous study has investigated the neural correlates of remembering emotional words encoded in an SRE paradigm. The main goal of this study was to define with fMRI the neural correlates of the successful retrieval of negative and positive personality traits encoded in a self-referential mode. Functional MRI scans were acquired for 11 subjects as they recognized positive and negative emotional personality traits adjectives encoded in a self-referential condition, a semantic condition and in a phonemic condition. The correct recognition of self-encoded personality traits engaged dorso-medial prefrontal cortex and lateral prefrontal regions, premotor cortex, parietal and occipital cortex, caudate and cerebellum. The specific recognition of self-encoded negative personality traits involved greater neural activation in the right extra-striate region than the recognition of positive personality traits. Our fMRI findings suggest that specific processes may operate at both encoding and retrieval to subserve the SRE. Unlike self-encoding, the retrieval of personality traits is modulated by the valence of the stimuli with greater activation for negative words. Our results indicate that personally relevant words may signal important emotional clues and support the notion of a widely distributed set of brain regions involved in maintaining the concepts of self.     

II. PET Studies of Memory: Novel versus Practiced Free Recall of Word Lists

Positron emission tomography (PET) with the tracer Ha₂¹⁵O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or task-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.     

Two brain pathways for attended and ignored words

The dependency of word processing on spare attentional resources has been debated for several decades. Recent research in the study of selective attention has emphasized the role of task load in determining the fate of ignored information. In parallel to behavioral evidence, neuroimaging data show that the activation generated by unattended stimuli is eliminated in task-relevant brain regions during high attentional load tasks. We conducted an fMRI experiment to explore how word encoding proceeds in a high load situation. Participants saw a rapid series of stimuli consisting of overlapping drawings and letter strings (words or nonwords). In different blocks, task instructions directed attention to either the drawings or the letters, and subjects responded to immediate repetition of items in the attended dimension. To look at the effect of attention on word processing, we compared brain activations for words and nonwords under the two attentional conditions. As compared to nonwords, word stimuli drove responses in left frontal, left temporal and parietal areas when letters were attended. However, although the behavioral measures suggested that ignored words were not analyzed when drawings were attended, a comparison of ignored words to ignored nonwords indicated the involvement of several regions including left insula, right cerebellum and bilateral pulvinar. Interestingly, word-specific activations found when attended and ignored words were compared showed no anatomical overlap, suggesting a change in processing pathways for attended and ignored words presented in a high attentional load task.