Investigation of the relationship between visual feature binding in short- and long-term memory in healthy aging.

Binding visual features into coherent object representations is essential both in short- and long-term memory. However, the relationship between feature binding processes at different memory delays remains unexplored. Here, we addressed this question by using the Mnemonic Similarity Task and a delayed-estimation working memory task on a large sample of older adults. The results revealed that higher propensity to misbind object features in working memory is associated with lower lure discrimination performance in the mnemonic similarity task, suggesting that shared feature binding processes underlie the formation of coherent short- and long-term visual object memory representations.

Pattern separation beyond the hippocampus: A high-resolution whole-brain investigation of mnemonic discrimination in healthy adults.

Episodic memory depends on the computational process of pattern separation in order to establish distinct memory representations of similar episodes. Studies of pattern separation in humans rely on mnemonic discrimination tasks, which have been shown to tax hippocampal-dependent pattern separation. Although previous neuroimaging research has focused on hippocampal processing, little is known about how other brain regions, known to be involved in recognition memory performance, are involved in mnemonic discrimination tasks. Conversely, neuroimaging studies of pattern separation with whole-brain coverage lack spatial resolution to localize activation to hippocampal subfields. In this study, 48 healthy young adult participants underwent whole-brain high-resolution functional MRI (fMRI) scanning while completing a mnemonic discrimination task. A priori region-of-interest analyses revealed activation patterns consistent with pattern separation in distinct hippocampal subregions, particularly in the subiculum. Connectivity analyses revealed a network of cortical regions consistent with the memory retrieval network where fMRI activation was correlated with hippocampal activation. An exploratory whole-brain analysis revealed widespread activation differentially associated with performance of the mnemonic discrimination task. Taken together, these results suggest that a network of brain regions contribute to mnemonic discrimination performance, with the hippocampus and parahippocampal cortex as a hub in the network displaying clear signals consistent with pattern separation and regions such as the dorsal medial prefrontal cortex particularly important for successful lure discrimination.

A direct comparison between ERP and fMRI measurements of food-related inhibitory control: Implications for BMI status and dietary intake.

Obesity and maintaining a healthy diet have important implications for physical and mental health. One factor that may influence diet and obesity is inhibitory control. We tested how N2 and P3 amplitude, event-related potential (ERP) components that reflect inhibitory control, and functional magnetic resonance imaging (fMRI) activity in brain regions associated with inhibitory control differed toward high- and low-calorie food stimuli across BMI status. We also assessed the relationship between neural indices of food-related inhibitory control and laboratory and daily food intake. Fifty-four individuals (17 normal-weight; 18 overweight; 19 individuals with obesity) completed two food-based go/no-go tasks (one with high- and one with low-calorie foods as no-go stimuli), once during ERP data acquisition and once during fMRI data acquisition. After testing, participants were presented with an ad libitum weighed food buffet. Participants also recorded their food intake using the Automated Self-Administered 24-hour Dietary Recall (ASA24) system across four days. Individuals recruited more inhibitory control when withholding responses towards high-compared to low-calorie foods, although this effect was more consistent for N2 than P3 or fMRI assessments. BMI status did not influence food-related inhibitory control. A larger inhibitory response as measured by N2 amplitude was related to increased ASA24 food intake; P3 amplitude and fMRI region of interest activity did not predict ASA24 intake; neither method predicted food intake from the buffet. ERP and fMRI measurements show similar neural responses to food, although N2 amplitude may be somewhat more sensitive in detecting differences between food types and predicting self-reports of food intake.

The effects of sleep on the neural correlates of pattern separation.

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus, overcomes this interference by establishing nonoverlapping memory representations. Although it is widely accepted that declarative memories are consolidated during sleep, the effects of sleep on pattern separation have yet to be elucidated. We used whole-brain, high-resolution functional neuroimaging to investigate the effects of sleep on a task that places high demands on pattern separation. Sleep had a selective effect on memory specificity and not general recognition memory. Activity in brain regions related to memory retrieval and cognitive control demonstrated an interaction between sleep and delay. Surprisingly, there was no effect of sleep on hippocampal activity using a group-level analysis. To further understand the role of the hippocampus on our task, we performed a representational similarity analysis, which showed that hippocampal activation was biased toward pattern separation relative to cortical activation and that this bias increased following a delay (regardless of sleep). Cortical activation, conversely, was biased toward pattern completion and this bias was preferentially enhanced by sleep.

Motivational Impact of Palatable Food Correlates With Functional Brain Responses to Food Images in Adolescents.

Objective: To examine associations between motivational impact of palatable foods and neural activity in brain regions involved in inhibitory control among adolescents. Methods: Thirty-four adolescents aged 14-20 years underwent functional magnetic resonance imaging while viewing images of high- and low-energy foods. Participants completed the Power of Food Scale (PFS). Whole-brain analyses of variance tested for neural activation differences and correlations between brain activation and PFS scores were tested. Results: We found an interaction between food type (high energy vs. low energy) and PFS scores in the right dorsolateral prefrontal cortex and right inferior parietal lobule. We also found that PFS scores correlated negatively with activation to high-energy foods in prefrontal cortical and parietal regions. Conclusions: These findings suggest that individuals with high motivation for high-energy foods also demonstrate lower neural activation in inhibition-related brain regions when viewing images of high-energy foods, indicating that they may have difficulty inhibiting consumption impulses.

When recognition memory is independent of hippocampal function.

Hippocampal damage has been thought to result in broad memory impairment. Recent studies in humans, however, have raised the possibility that recognition memory for faces might be spared. In five experiments we investigated face recognition in patients with hippocampal lesions (H) or large medial temporal lobe (MTL) lesions, including patients where neurohistological information was available. Recognition of novel faces was unequivocally intact in H patients but only at a short retention interval. Recognition memory for words, buildings, inverted faces, and famous faces was impaired. For MTL patients, recognition memory was impaired for all materials and across all retention intervals. These results indicate that structures other than the hippocampus, perhaps the perirhinal cortex, can support face recognition memory in H patients under some conditions. The fact that the faces were novel when recognition memory was intact does not fully account for our findings. We propose that the role of the hippocampus in recognition memory is related to how recognition decisions are accomplished. In typical recognition tasks, participants proceed by forming an association between a study item and the study list, and the recognition decision is later made based on whether participants believe the item was on the study list. We suggest that face recognition is an exception to this principle and that, at short retention intervals, participants can make their recognition decisions without making explicit reference to the study list. Important features of faces that might make face recognition exceptional are that they are processed holistically and are difficult to verbally label.

Long-term cognitive and neuroanatomical stability in patients with anoxic amnesia: A Case Report.

BACKGROUND: Anoxia can result in selective hippocampal damage with associated impairments in declarative memory. Whilst memory impairments and brain structures are thought to be stable, there are little data regarding the effects of ageing or change over time in patients with amnesia from anoxic brain injury. METHODS: To assess change over time, we compared structural magnetic resonance imaging (MRI) with data obtained over ten years previously in two well-characterized patients with amnesia (JRW and RS) who experienced an anoxic brain injury. Six healthy, age-matched control participants were recruited to compare brain volumes with the patients at Time 2. Wechsler adult intelligence scale-revised and Wechsler memory scale-revised scores were compared to scores on the same tests administered 13 and 19 years prior. RESULTS: Patients with amnesia had significantly smaller hippocampal volumes than controls, but comparable medial temporal lobe and ventricular volumes. Memory, intellectual function and brain volumes were stable over time. CONCLUSION: Patients with an amnesia due to anoxia have memory impairments and smaller hippocampal volumes compared to controls; however, memory, intelligence and structural volumes remain stable over time. At ages 50 and 57, they do not appear to have early age-associated cognitive decline that is sometimes observed in patients with traumatic brain injury.

Topical Review: Unique Contributions of Magnetic Resonance Imaging to Pediatric Psychology Research.

OBJECTIVE: This review aims to provide a brief introduction of the utility of magnetic resonance imaging (MRI) methods in pediatric psychology research, describe several exemplar studies that highlight the unique benefits of MRI techniques for pediatric psychology research, and detail methods for addressing several challenges inherent to pediatric MRI research. METHODS: Literature review. RESULTS: Numerous useful applications of MRI research in pediatric psychology have been illustrated in published research. MRI methods yield information that cannot be obtained using neuropsychological or behavioral measures. CONCLUSIONS: Using MRI in pediatric psychology research may facilitate examination of neural structures and processes that underlie health behaviors. Challenges inherent to conducting MRI research with pediatric research participants (e.g., head movement) may be addressed using evidence-based strategies. We encourage pediatric psychology researchers to consider adopting MRI techniques to answer research questions relevant to pediatric health and illness.

Structural and functional correlates of behavioral pattern separation in the hippocampus and medial temporal lobe.

Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In this study, we used magnetic resonance imaging (MRI) to measure the volumes of MTL regions of interest, including hippocampal subfields (dentate gyrus, CA3, CA1, and subiculum) in healthy older and younger adults. Additionally, we used diffusion tensor imaging to measure white matter integrity for both groups. Finally, we used functional MRI to acquire resting functional connectivity measures for both groups. We show that, along with age, the volume of left CA3/dentate gyrus predicts memory performance. Differences in fractional anisotropy and the strength of resting functional connections between the hippocampus and other cortical structures implicated in memory processing were not significant predictors of performance. As previous studies have only hinted, it seems that the size of left CA3/dentate gyrus contributes more to successful discrimination between similar mnemonic representations than other hippocampal sub-fields, MTL structures, and other neuroimaging correlates. Accordingly, the implications of aging and atrophy on lure discrimination capacities are discussed.

Right frontal pole cortical thickness and social competence in children with chronic traumatic brain injury: cognitive proficiency as a mediator.

OBJECTIVE: To examine the association between right frontal pole cortical thickness, social competence, and cognitive proficiency in children participants with a history of chronic traumatic brain injury (TBI). PARTICIPANTS: Twenty-three children (65% male; M age = 12.8 years, SD = 2.3 years) at least 1 year post-injury (M = 3.3 years, SD = 1.7 years) were evaluated with the Cognitive Proficiency Index (CPI) from the Wechsler Intelligence Scale for Children, 4th Edition, and their caregiver completed the Child Behavior Checklist. Social competence was evaluated with the Social Competence and Social Problems subscales from the Child Behavior Checklist. Right frontal pole cortical thickness was calculated via FreeSurfer from high-resolution 3-dimensional T1 magnetic resonance imaging scans. RESULTS: Direct effect of right frontal pole cortical thickness on social competence was significant (ß = 14.09, SE = 4.6, P < .01). Right frontal pole cortical thickness significantly predicted CPI (ß = 18.44, SE = 4.9, P < .05), and CPI significantly predicted social competence (ß = 0.503, SE = 0.17, P < .01). Findings were consistent with the hypothesized mediation model. CONCLUSIONS: The association between right frontal lobe cortical integrity and social competence in pediatric participants with chronic TBI may be mediated through cognitive proficiency.

Visual object pattern separation varies in older adults.

Young and nondemented older adults completed a visual object continuous recognition memory task in which some stimuli (lures) were similar but not identical to previously presented objects. The lures were hypothesized to result in increased interference and increased pattern separation demand. To examine variability in object pattern separation deficits, older adults were divided into impaired and unimpaired groups based on performance on a standardized serial list-learning task. Impaired older adults showed intact recognition memory, but were impaired relative to young and unimpaired older adults when identifying similar lure stimuli, demonstrating that object pattern separation varies in older adults.

Memory retrieval effects as a function of differences in phenomenal experience.

Conscious experience and perception are restricted to a single perspective. Although evidence to suggest differences in phenomenal experience can produce observable differences in behavior, it is not well understood how these differences might influence memory. We used fMRI to scan n = 49 participants while they encoded and performed a recognition memory test for faces and words. We calculated a cognitive bias score reflecting individual participants' propensity toward either Visual Imagery or Internal Verbalization based on their responses to the Internal Representations Questionnaire (IRQ). Neither visual imagery nor internal verbalization scores were significantly correlated with memory performance. In the fMRI data, there were typical patterns of activation differences between words and faces during both encoding and retrieval. There was no effect of internal representation bias on fMRI activation during encoding. At retrieval, however, a bias toward visualization was positively correlated with memory-related activation for both words and faces in inferior occipital gyri. Further, there was a crossover interaction in a network of brain regions such that visualization bias was associated with greater activation for words and verbalization bias was associated with greater activation for faces, consistent with increased effort for non-preferred stimulus retrieval. These findings suggest that individual differences in cognitive representations affect neural activation across different types of stimuli, potentially affecting memory retrieval performance.

A parametric investigation of pattern separation processes in the medial temporal lobe.

The hippocampus is thought to be involved in memory formation and consolidation, with computational models proposing the process of pattern separation as a means for encoding overlapping memories. Previous research has used semantically related targets and lures to investigate hippocampal responses to mnemonic interference. Here, we attempted to define the response function of the human hippocampus and its inputs during pattern separation by parametrically varying target-lure similarity in a continuous recognition task. We also investigated the effect of task demands (intentional vs incidental encoding) on pattern separation processes. We collected functional magnetic resonance imaging data while participants were shown a series of objects. In the intentional paradigm, participants identified objects as "new" (novel stimuli), "old" (exact repetitions), or "rotated" (previously seen objects that were subsequently rotated by varied degrees). In the incidental paradigm, participants were shown the same stimuli but identified objects as "toy" or "not toy." Activation in the hippocampus was best fit with a power function, consistent with predictions made by computational models of pattern separation processes in the hippocampus. The degree of pattern separation was driven by the information most relevant to the task: pattern separation was seen in the left hippocampus when semantic information was more important to the task and seen in the right hippocampus when spatial information was more important. We also present data illustrating that top-down processes modulate activity in the ventral visual processing stream.

A demonstration that the hippocampus supports both recollection and familiarity.

Recognition memory is thought to depend on two distinct processes: recollection and familiarity. There is debate as to whether damage to the hippocampus selectively impairs recollection or whether it impairs both recollection and familiarity. If hippocampal damage selectively impairs recollection but leaves familiarity intact, then patients with circumscribed hippocampal lesions should exhibit the full normal range of low-confidence and high-confidence familiarity-based recognition. High-confidence, familiarity-based decisions are ordinarily accompanied by successful recollection (when memory is intact). However, patients with hippocampal lesions, if recollection is impaired, should frequently experience high-confidence, familiarity-based recognition in the absence of recollection, and this circumstance (termed the "butcher-on-the-bus" phenomenon) should occur more often in patients than in healthy controls. We tested five patients with circumscribed hippocampal damage, asking them to recognize recently studied words as well as to remember the context in which the items were studied. Relative to controls, the patients exhibited no increased tendency to experience the butcher-on-the-bus phenomenon. The simplest explanation of the results is that hippocampal damage impairs familiarity as well as recollection. The same conclusion was suggested when two competing models of recognition memory were used to analyze the data.

Medial temporal lobe activity can distinguish between old and new stimuli independently of overt behavioral choice.

We collected fMRI data and confidence ratings as participants performed a recognition memory task that intermixed recently studied words and new (non-studied) words. We first replicated a typical finding from such studies; namely, increasing activity in medial temporal lobe structures with increasing confidence in the old/new decision. Because there are greater proportions of old items at higher confidence levels, such activity could be related to the confidence ratings or to whether items are old or new. When activity associated with old and new items was analyzed separately, we found that activity in the hippocampus bilaterally, as well as in anterior parahippocampal gyrus, was associated with the actual old/new status of the items rather than to which items participants believed to be old. Accordingly, activity in the medial temporal lobe can be modulated by the old/new status of stimuli and does not always track the behavioral response.

These things take time: what is the role of the hippocampus in recognition memory over extended delays?

In a clever experimental design, Tallman, Clark, and Smith (this issue) tested the changes in fMRI activation and functional connectivity in the hippocampus and cortex as a function of memory age. They found that activation changed according to a power function (both increasing and decreasing) in several cortical regions but not within the hippocampus or medial temporal lobe (MTL). Further, functional connectivity increased with memory age between cortical regions but decreased for the hippocampus. Taken together, these results offer strong support for the standard consolidation model. However, they leave open the question of what role the hippocampus plays in recognition memory performance.

The contributions of eye gaze fixations and target-lure similarity to behavioral and fMRI indices of pattern separation and pattern completion.

Pattern separation and pattern completion are generally studied in humans using mnemonic discrimination tasks such as the Mnemonic Similarity Task (MST) where participants identify similar lures and repeated items from a series of images. Failures to correctly discriminate lures are thought to reflect a failure of pattern separation and a propensity toward pattern completion. Recent research has challenged this perspective, suggesting that poor encoding rather than pattern completion accounts for the occurrence of false alarm responses to similar lures. In two experiments, participants completed a continuous recognition task version of the MST while eye movement (Experiments 1 and 2) and fMRI data (Experiment 2) were collected. In Experiment 1, we replicated the result that fixation counts at study predicted accuracy on lure trials (consistent with poor encoding predicting mnemonic discrimination performance), but this effect was not observed in our fMRI task. In both experiments, we found that target-lure similarity was a strong predictor of accuracy on lure trials. Further, we found that fMRI activation changes in the hippocampus were significantly correlated with the number of fixations at study for correct but not incorrect mnemonic discrimination judgments when controlling for target-lure similarity. Our findings indicate that while eye movements during encoding predict subsequent hippocampal activation changes for correct mnemonic discriminations, the predictive power of eye movements for activation changes for incorrect mnemonic discrimination trials was modest at best.

Neural basis of the cognitive map: path integration does not require hippocampus or entorhinal cortex.

The hippocampus and entorhinal cortex have been linked to both memory functions and to spatial cognition, but it has been unclear how these ideas relate to each other. An important part of spatial cognition is the ability to keep track of a reference location using self-motion cues (sometimes referred to as path integration), and it has been suggested that the hippocampus or entorhinal cortex is essential for this ability. Patients with hippocampal lesions or larger lesions that also included entorhinal cortex were led on paths while blindfolded (up to 15 m in length) and were asked to actively maintain the path in mind. Patients pointed to and estimated their distance from the start location as accurately as controls. A rotation condition confirmed that performance was based on self-motion cues. When demands on long-term memory were increased, patients were impaired. Thus, in humans, the hippocampus and entorhinal cortex are not essential for path integration.

Detailed recollection of remote autobiographical memory after damage to the medial temporal lobe.

Previous findings of intact remote autobiographical memory in patients with medial temporal lobe damage have been questioned on the grounds that the narrative recollections were impoverished and fact-like and that the methods were not sufficiently sensitive to detect an impairment. We adopted a newer method, the Autobiographical Interview [Levine B, Svoboda E, Hay JF, Winocur G, Moscovitch M (2002) Psychol Aging 17:677-689], which uses extensive probing to elicit an average of 50 or more details per memory (in contrast to the approximately 20 details per memory elicited with previous methods). We found that autobiographical recollection was impaired in patients with medial temporal lobe damage when memories were drawn from the recent past but fully intact when memories were drawn from the remote past. Impaired remote autobiographical memory, which has sometimes been reported with this and other tests, is likely caused by significant damage outside the medial temporal lobe.

Recognition without awareness: an elusive phenomenon.

Two recent studies described conditions under which recognition memory performance appeared to be driven by nondeclarative memory. Specifically, participants successfully discriminated old images from highly similar new images even when no conscious memory for the images could be retrieved. Paradoxically, recognition performance was better when images were studied with divided attention than when images were studied with full attention. Furthermore, recognition performance was better when decisions were rated as guesses than when decisions were associated with low or high confidence. In three experiments, we adopted the paradigm used in the earlier studies in an attempt to repeat this intriguing work. Our attempts were unsuccessful. In all experiments, recognition was better when images were studied with full attention than when images were studied with divided attention. Recognition was also better when participants indicated high or low confidence in their decision than when they indicated that their decision was a guess. Thus, our results conformed to what typically has been reported in studies of recognition memory, and we were unable to demonstrate recognition without awareness. We encourage others to explore this paradigm, and to try to identify conditions under which the phenomenon might be demonstrated.