The ability to remember detailed information is called high-fidelity long-term memory. We use hig... more The ability to remember detailed information is called high-fidelity long-term memory. We use high-fidelity long-term memory to remember the details of our favorite stories and how to track which family member a green pair of socks belongs to. As we age, the ability to remember these details declines as the health of the brain changes. We created a virtual reality video game called Labyrinth-VR, with the aim to restore memory. When playing Labyrinth-VR, participants practice figuring out where they want to go using the shortest route to get there. In Labyrinth-VR, participants learned a virtual neighborhood and then had to find their way around to run errands. In our study, older adults played either h of Labyrinth-VR or h of iPad games. The results of tests of high-fidelity long-term memory showed that playing Labyrinth-VR, but not iPad games, led to improvements in participants' scores.
Recent research has revealed that the presence of irrelevant visual information during retrieval ... more Recent research has revealed that the presence of irrelevant visual information during retrieval of long-term memories diminishes recollection of task-relevant visual details. Here, we explored the impact of irrelevant auditory information on remembering task-relevant visual details by probing recall of the same previously viewed images while participants were in complete silence, exposed to white noise, or exposed to ambient sounds recorded at a busy café. The presence of auditory distraction diminished objective recollection of goal-relevant details, relative to the silence and white noise conditions. Critically, a comparison with results from a previous study using visual distractors showed equivalent effects for auditory and visual distraction. These findings suggest that disruption of recollection by external stimuli is a domain-general phenomenon produced by interference between resourcelimited, top-down mechanisms that guide the selection of mnemonic details and control processes that mediate our interactions with external distractors.
Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (... more Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (VLPFC) and angular gyrus in processes associated with retrieving goal-relevant information, which increases the fidelity and richness of long-term memory (LTM). To further investigate the roles of these cortical regions as nodes in functional networks with memory regions of the medial temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to perturb normal neuronal function. The aim was to test the causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal networks that have been associated with high-fidelity memory retrieval. rTMS treatments were administered immediately before blocks in an old/new recognition test, which was based on a mnemonic similarity task requiring discrimination of previously studied pictures of common objects. Capability for mnemonic discrimination was evaluated after each of three conditions: placebo control (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis) and parietal target (rTMS at left AG). The results showed the effect of rTMS perturbation of mid-VLPFC diminished subsequent discrimination-based memory performance, relative to placebo control, and no significant effect of perturbation of AG. These findings show a causal role for functional networks with left mid-VLPFC in high-fidelity retrieval. Contributions of cognitive control toward the fidelity and richness of long-term memory (LTM) retrieval have been revealed in functional neuroimaging studies that implicate regions of both ventrolateral prefrontal cortex (VLPFC) 1,2 and the angular gyrus region of posterior parietal cortex (PPC) . Consistent with these findings about the anatomical loci of processes associated with retrieval of specific, detailed information, we previously showed that high-fidelity memory is associated with increased functional connectivity of networks between the medial temporal lobe (MTL), VLPFC and PPC 6 . High-fidelity retrieval is based on discrimination of specific details held in memory (i.e., distinctions between target images and related lures). Although fMRI evidence associated with MTL-lateral cortical memory networks has been replicated, and therefore appears compelling, causal evidence of the functional roles fulfilled by the different network nodes remains elusive. One open question is whether top-down control processes associated with VLPFC, which have been implicated in selection of goal-relevant information from memory , are necessary for successful high-fidelity retrieval? Another question is whether top-down processes associated with angular gyrus (AG) regions of PPC serve a necessary role in retrieval of high-fidelity memories? Based on fMRI results, one prominent interpretation holds that AG function is integral to episodic retrieval , while alternative interpretations suggest this region plays a role as a buffer to maintain awareness of different qualities of mnemonic information that might be accessed by other cognitive processes . Most recently, AG activity has been positively correlated with the precision of recollection for spatial cues , and, interestingly, these findings seem to comport with both earlier models for AG function in LTM. The motivation here was to address questions about causality of the cortical nodes in MTL-VLPFC-PPC networks that have been associated with LTM based on discrimination of specific details (i.e., high-fidelity
The detrimental influence of distraction on memory and attention is well established, yet it is n... more The detrimental influence of distraction on memory and attention is well established, yet it is not as clear whether irrelevant information impacts categorization abilities and whether this impact changes in aging. We examined categorization with morphed prototype stimuli in both younger and older adults, using an adaptive staircase approach to assess participants' performance in conditions with and without visual distractors. Results showed that distraction did not affect younger adults, but produced a negative impact on older adults' categorization such that there was an interaction of age and distraction. These results suggest a relationship between the increased susceptibility to visual distraction in normal aging and impairment in categorization.
To identify patterns of memory-related neural activity in the medial temporal lobes (MTL), a quan... more To identify patterns of memory-related neural activity in the medial temporal lobes (MTL), a quantitative meta-analysis of 17 functional magnetic resonance imaging (fMRI) studies was performed. The analysis shows that increased activity in the hippocampus and the parahippocampal cortex predicts subsequent memory strength. During retrieval, activity in the hippocampus increases in association with strong memory. In the perirhinal cortex, increased activity predicts subsequent recognition, whether based on weak or strong memory, whereas during retrieval activity decreases below the level for misses in association with both weak and strong memory. The results are consistent with the claim that the hippocampus selectively subserves recollection, whereas adjacent structures subserve familiarity . The medial temporal lobe and recognition memory. The Annual Review of Neuroscience, 30,. However, this conclusion depends on a specific dual-process theory of recognition memory that has been used to interpret the results. An alternative dual-process model holds that the behavioral methods used to differentiate recollection from familiarity instead separate strong memories from weak memories. When the fMRI data are interpreted in terms of the alternative theory, the fMRI results do not point to selective roles for the hippocampus or the adjacent MTL structures. The fMRI data alone cannot distinguish between these two models, so other methods are needed to resolve the issue.
fMRI studies of recognition memory have often been interpreted to mean that the hippocampus selec... more fMRI studies of recognition memory have often been interpreted to mean that the hippocampus selectively subserves recollection and that adjacent regions selectively subserve familiarity. Yet, many of these studies have confounded recollection and familiarity with strong and weak memories. In a source memory experiment, we compared correct source judgments (which reflect recollection) and incorrect source judgments (often thought to reflect familiarity) while equating for old-new memory strength by including only high-confidence hits in the analysis. Hippocampal activity associated with both correct source judgments and incorrect source judgments exceeded the activity associated with forgotten items and did so to a similar extent. Further, hippocampal activity was greater for high-confidence old decisions relative to forgotten items even when source decisions were at chance. These results identify a recollection signal in the hippocampus and may identify a familiarity signal as well. Similar results were obtained in the parahippocampal gyrus. Unlike in the medial temporal lobe, activation in prefrontal cortex increased differentially in association with source recollection.
Standardized neuropsychological assessments of older adults are important for both clinical diagn... more Standardized neuropsychological assessments of older adults are important for both clinical diagnosis and biobehavioral research. Over decades, in-person testing has been the basis for population normative values that rank cognitive performance by demographic status. Most recently, digital tools have enabled remote data collection for cognitive measures, which offers the significant promise to extend the basis for normative values to be more inclusive of a larger cross section of the older population. We developed a Remote Characterization Module (RCM), using a speechto-text interface, as a novel digital tool to administer an at-home, 25-min cognitive screener that mimics eight standardized neuropsychological measures. Forty cognitively healthy participants were recruited from a longitudinal aging research cohort, and they performed the same measures of memory, attention, verbal fluency and set-shifting in both in-clinic paper-and-pencil (PAP) and at-home RCM versions. The results showed small differences, if any, for how participants performed on in-person and remote versions in five of eight tasks. Critically, robust correlations between their PAP and RCM scores across participants support the finding that remote, digital testing can provide a reliable assessment tool for rapid and remote screening of healthy older adults' cognitive performance in several key domains. The implications for digital cognitive screeners are discussed.
The paired-associate task has been used with functional magnetic resonance imaging (fMRI) in stud... more The paired-associate task has been used with functional magnetic resonance imaging (fMRI) in studies that assessed the role of the medial temporal lobe (MTL) subserving recollection and familiarity. Some researchers have interpreted their results to mean that the hippocampus selectively subserves recollection and not familiarity [cf., Eichenbaum et al., (2007) Annu Rev Neurosci 30:123-152]. Yet many of these results confound recollection and familiarity with strong and weak memories, and it is not clear whether the conclusions represent differences between memory processes or memory strength. In the current study, participants were scanned with fMRI during retrieval in a paired-associate task, and a new approach separated the analysis of memory strength from the analysis of memory processes. The data were sorted by confidence level in an old/new task, and the high-confidence responses were compared in categories when associative memory was highly accurate and when it was not available. The results show that high-confidence memory produced increased activity in the hippocampus, relative to the level for forgotten pairs, both when associative memory was available and when it was not. Two interpretations are discussed for the behavioral results for when associative memory was not available: one account based on familiarity and the other account based on noncriterial recollection. The conclusion is that recognition of the word-pairs was based on familiarity when associative memory was not available. Together with the fMRI results that activity in two regions associated with cognitive control (left ventrolateral prefrontal cortex and left inferior parietal lobule) was greater when responses were based on associative memory than when based on familiarity, the findings suggest that the hippocampus supports strong memory and that cortical regions make an additional contribution to recollection. V V C
Impairment in long-term memory is one of the most salient alterations in cognitive aging. Finding... more Impairment in long-term memory is one of the most salient alterations in cognitive aging. Findings of age-related deficits in source monitoring and recollection have revealed a selective decline in memory for detailed information. The underlying mechanism of this phenomenon is not well understood. We hypothesized that the influence of task-irrelevant visual stimuli present in our environment interferes with retrieval of detailed memories more for older than younger adults. We compared memory performance on a recall test for visual details when older adult participants' eyes were closed versus performance when their eyes were open and irrelevant visual stimuli were presented. The results showed that the presence of irrelevant visual information diminished longterm memory performance based on an objective measure of recollection for visual details. Comparison of the current results to findings from our earlier study using the same experimental paradigm with younger adults revealed that visual distraction disrupted recollection of relevant details to a greater degree in older than younger adults. This result suggests that visual distraction overwhelms older adults' declining cognitive control resources that are instrumental in the retrieval and selection of mnemonic details. More generally, these findings explicate a mechanistic basis for selective impairment of recollection in normal aging.
Peer review information Nature Aging thanks Sara Czaja and the other, anonymous, reviewer(s) for ... more Peer review information Nature Aging thanks Sara Czaja and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
The mere presence of irrelevant external stimuli results in interference with the fidelity of det... more The mere presence of irrelevant external stimuli results in interference with the fidelity of details retrieved from long-term memory (LTM). Recent studies suggest that distractibility during LTM retrieval occurs when the focus of resource-limited, top-down mechanisms that guide the selection of relevant mnemonic details is disrupted by representations of external distractors. We review findings from four studies that reveal distractibility during episodic retrieval. The approach cued participants to recall previously studied visual details when their eyes were closed, or were open and irrelevant visual information was present. The results showed a negative impact of the distractors on the fidelity of details retrieved from LTM. An fMRI experiment using the same paradigm replicated the behavioral results and found that diminished episodic memory was associated with the disruption of functional connectivity in whole-brain networks. Specifically, network connectivity supported recollection of details based on visual imagery when eyes were closed, but connectivity declined in the presence of visual distractors. Another experiment using auditory distractors found equivalent effects for auditory and visual distraction during cued recall, suggesting that the negative impact of distractibility is a domain-general phenomenon in LTM. Comparisons between older and younger adults revealed an aging-related increase in the negative impact of distractibility on retrieval of LTM. Finally, a new study that compared categorization abilities between younger and older adults suggests a cause underlying age-related decline of visual details in LTM. The sum of our findings suggests that cognitive control resources, although limited, have the capability to resolve interference from distractors during tasks of moderate effort, but these resources are overwhelmed when additional processes associated with episodic retrieval, or categorization of complex prototypes, are required.
have not yet been shown to demonstrate restorative effects for declining long-term memory (LTM) t... more have not yet been shown to demonstrate restorative effects for declining long-term memory (LTM) that affects many healthy older adults. We developed a virtual reality (VR) spatial wayfinding game (Labyrinth-VR) as a cognitive intervention with the hypothesis that it could improve detailed, high-fidelity LTM capability. Spatial navigation tasks have been used as a means to achieve environmental enrichment via exposure to and learning about novel and complex information. Engagement has been shown to enhance learning and has been linked to the vitality of the LTM system in the brain. In the current study, 48 older adults (mean age 68.7 ± 6.4 years) with average cognitive abilities for their age were randomly assigned to 12 h of computer game play over four weeks in either the Labyrinth-VR or placebo control game arms. Promptly before and after each participant's treatment regimen, high-fidelity LTM outcome measures were tested to assess mnemonic discrimination and other memory measures. The results showed a post-treatment gain in high-fidelity LTM capability for the Labyrinth-VR arm, relative to placebo, which reached the levels attained by younger adults in another experiment. This novel finding demonstrates generalization of benefits from the VR wayfinding game to important, and untrained, LTM capabilities. These cognitive results are discussed in the light of relevant research for hippocampal-dependent memory functions. Declining long-term memory (LTM) impacts diverse aspects of cognitive performance and overall quality of life for many healthy older adults . Chronic memory loss is typically first apparent as reduced capability for high-fidelity memory 5 , which is the most precise form of LTM. High-fidelity memory depends upon flexible association of diverse bits of information for facts and events that are remembered in distinct and detailed terms 6 , and it can be conceptualized in terms of source , associative 8,9 and autobiographical memory , as well as mnemonic discrimination as a behavioral task to operationalize pattern separation processes . To our knowledge, there has yet to be any cognitive or pharmaceutical interventions that have demonstrated restorative effects for the decline in high-fidelity LTM that occurs with aging. Encoding and retrieval of high-fidelity LTM depend upon hippocampal processes 14 , which are often disrupted in normal aging 15 . These hippocampal memory processes have been examined across the human lifespan with adaptations of a behavioral pattern separation task . The results from a growing literature show a decline in mnemonic discrimination capability for nondemented older adults 1 , as well as associated aging-related changes in functional activity in the hippocampal region . The potential to stimulate plasticity and up-regulate function in the hippocampus has been demonstrated in rodent model studies using spatial exploration of novel, complex environs . Specifically, spatial navigation tasks have been applied to achieve environmental enrichment in animals , which refers to exposure and learning of novel and complex information that have been linked to the vitality of the memory system in the brain . Moreover, in a study with younger adults, who played five-hours in a visually complex video game, participants improved their capability for high-fidelity LTM, relative to placebo control 28 . We developed a virtual reality (VR) spatial wayfinding game as a cognitive intervention aimed to mimic environmental enrichment approaches used in the study of animals with the goal of improving, and potentially restoring, memory abilities in healthy older adults. Using a head-mounted VR display (i.e., HMD VR), the Labyrinth game immerses participants in entirely novel, visually elaborate environments (Fig. ). Applying video games as cognitive interventions to impact behavior and brain function is an emerging method in translational neuroscience research 29 , and early results suggest mixed findings. Successful interventions have depended upon how effectively this demanding technology was targeted to engage and sustain the attention of participants during
My research interests pursue a more complete understanding of the cognitive neuroscience of decla... more My research interests pursue a more complete understanding of the cognitive neuroscience of declarative memory, the functional roles of the hippocampus and the medial temporal lobe, and how affect modulates memory. Innovative Research Grant awarded by the Kavli Institute for Brain and Mind (2007). Publications Wais, P., Squire, L. & Wixted, J. ( ). The hippocampus subserves recollection of word pairs and strong memory associated with item recognition. in preparation Mickes, L., Wais, P. & Wixted, J. ( ). Recollection is a continuous process: implications for dual process theories of recognition memory. in review Wais, P., Squire, L. & Wixted, J. ( ). An fMRI signal for both familiarity and recollection in the hippocampus. in review . Recognition memory processes in the medial temporal lobe: a quantitative meta-analysis of fMRI results. in review ix VITA (continued) Wais, P., . Remember/Know judgments probe degrees of recollection.
Dual-process theory, which holds that recognition decisions can be based on recollection or famil... more Dual-process theory, which holds that recognition decisions can be based on recollection or familiarity, has long seemed incompatible with signal detection theory, which holds that recognition decisions are based on a singular, continuous memory-strength variable. Formal dual-process models typically regard familiarity as a continuous process (i.e., familiarity comes in degrees), but they construe recollection as a categorical process (i.e., recollection either occurs or does not occur). A continuous process is characterized by a graded relationship between confidence and accuracy, whereas a categorical process is characterized by a binary relationship such that high confidence is associated with high accuracy but all lower degrees of confidence are associated with chance accuracy. Using a source-memory procedure, we found that the relationship between confidence and source-recollection accuracy was graded. Because recollection, like familiarity, is a continuous process, dual-process theory is more compatible with signal detection theory than previously thought.
The presence of irrelevant external stimuli during the retrieval of long-term memory (LTM) has a ... more The presence of irrelevant external stimuli during the retrieval of long-term memory (LTM) has a negative impact on the fidelity of recollected details. Top-down control processes that both guide the selection of internal information relevant to LTM goals and resolve interference on retrieval from irrelevant external information have been associated with the same region in left ventrolateral prefrontal cortex (VLPFC). The current study examined a causal role of the left VLPFC in memory performance when external distraction (i.e., visual stimuli irrelevant to the current task goals) was presented during retrieval of LTM. Immediately after functional perturbation of the left VLPFC with 1-Hz repetitive transcranial magnetic stimulation, participants' memory was tested when their eyes were closed and when their eyes were open and irrelevant visual stimuli were presented. The results showed that visual distraction diminished LTM performance based on an objective measure of recollection and that perturbation of left VLPFC exacerbated the disruptive effect. This is the first evidence of a direct role of the left VLPFC in diminishing the impact of distraction on recollection, elucidating neural mechanisms that are critically involved in how we reconstruct the past while navigating the external environment.
People are generally skilled at using a confidence scale to rate the strength of their memories o... more People are generally skilled at using a confidence scale to rate the strength of their memories over a wide range. Specifically, low-confidence recognition decisions are often associated with close-to-chance accuracy, whereas high-confidence recognition decisions can be associated with close-to-perfect accuracy. However, using a 20-point rating scale, the authors found that the ability to scale memory strength had its limitations in that a high proportion of list items received the highest rating of 20. Efforts to induce participants to differentiate between these strong memories using emphatic instructions and alternative scales were not successful. Remember/know judgments indicated that these strong and hard-to-scale memories were often based on familiarity (not just recollection). Providing error feedback on a plurals discrimination task finally produced a high-confidence criterion shift. The authors suggest that the ability to scale strong (and almost perfectly accurate) memories may be limited because of the absence of differential error feedback for very strong memories in the past (the kind of differential error feedback that may account for the memory-scaling expertise that participants otherwise exhibit).
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