Response bias and response monitoring: Evidence from healthy older adults and patients with mild Alzheimer's disease.

Patients with Alzheimer's disease (AD) often exhibit an abnormally liberal response bias in recognition memory tests, responding "old" more frequently than "new." Investigations have shown patients can to shift to a more conservative response bias when given instructions. We examined if patients with mild AD could alter their response patterns when the ratio of old items is manipulated without explicit instruction. Healthy older adults and AD patients studied lists of words and then were tested in three old/new ratio conditions (30%, 50%, or 70% old items). A subset of participants provided estimates of how many old and new items they saw in the memory test. We demonstrated that both groups were able to change their response patterns without the aid of explicit instructions. Importantly, AD patients were more likely to estimate seeing greater numbers of old than new items, whereas the reverse was observed for older adults. Elevated estimates of old items in AD patients suggest their liberal response bias may be attributed to their reliance on familiarity. We conclude that the liberal response bias observed in AD patients is attributable to their believing that more of the test items are old and not due to impaired meta-memorial monitoring abilities.

Preserved conceptual implicit memory for pictures in patients with Alzheimer's disease.

The current study examined different aspects of conceptual implicit memory in patients with mild Alzheimer's disease (AD). Specifically, we were interested in whether priming of distinctive conceptual features versus general semantic information related to pictures and words would differ for the mild AD patients and healthy older adults. In this study, 14 healthy older adults and 15 patients with mild AD studied both pictures and words followed by an implicit test section, where they were asked about distinctive conceptual or general semantic information related to the items they had previously studied (or novel items). Healthy older adults and patients with mild AD showed both conceptual priming and the picture superiority effect, but the AD patients only showed these effects for the questions focused on the distinctive conceptual information. We found that patients with mild AD showed intact conceptual picture priming in a task that required generating a response (answer) from a cue (question) for cues that focused on distinctive conceptual information. This experiment has helped improve our understanding of both the picture superiority effect and conceptual implicit memory in patients with mild AD in that these findings support the notion that conceptual implicit memory might potentially help to drive familiarity-based recognition in the face of impaired recollection in patients with mild AD.

The effect of echo time and post-processing procedure on blood oxygenation level-dependent (BOLD) functional connectivity analysis.

While spontaneous BOLD fMRI signal is a common tool to map functional connectivity, unexplained inter- and intra-subject variability frequently complicates interpretation. Similar to evoked BOLD fMRI responses, spontaneous BOLD signal is expected to vary with echo time (TE) and corresponding intra/extravascular sensitivity. This may contribute to discrepant conclusions even following identical post-processing pipelines. Here we applied commonly-utilized independent component analysis (ICA) as well as seed-based correlation analysis and investigated default mode network (DMN) and visual network (VN) detection from BOLD data acquired at three TEs (3T; TR=2500ms; TE=15ms, 35ms, and 55ms) and from quantitative R2* maps. Explained variance in ICA analysis was significantly higher (P<0.05) when R2*-derived maps were considered relative to single-TE data with no post-processing. While explained variance in the BOLD data increased with motion correction, R2* derived DMN and VN were minimally affected by motion correction. Explained variance increased in all data when physiological noise confounds were removed using CompCor. Notably, the R2*-derived connectivity patterns were least affected by motion and physiological noise confounds in a seed-based correlation analysis. Intermediate (35ms) and long (55ms) TE data provided similar spatial and temporal characteristics only after reducing motion and physiological noise contamination. Results provide an exemplar for how 3T spontaneous BOLD network detection varies with TE and post-processing procedure over the range of commonly acquired TE values.

Memory-related eye movements challenge behavioral measures of pattern completion and pattern separation.

The hippocampus creates distinct episodes from highly similar events through a process called pattern separation and can retrieve memories from partial or degraded cues through a process called pattern completion. These processes have been studied in humans using tasks where participants must distinguish studied items from perceptually similar lure items. False alarms to lures (incorrectly reporting a perceptually similar item as previously studied) are thought to reflect pattern completion, a retrieval-based process. However, false alarms to lures could also result from insufficient encoding of studied items, leading to impoverished memory of item details and a failure to correctly reject lures. The current study investigated the source of lure false alarms by comparing eye movements during the initial presentation of items to eye movements made during the later presentation of item repetitions and similar lures in order to assess mnemonic processing at encoding and retrieval, respectively. Relative to other response types, lure false alarms were associated with fewer fixations to the initially studied items, suggesting that false alarms result from impoverished encoding. Additionally, lure correct rejections and lure false alarms garnered more fixations than hits, denoting additional retrieval-related processing. The results suggest that measures of pattern separation and completion in behavioral paradigms are not process-pure.

Vessel-encoded arterial spin labeling (VE-ASL) reveals elevated flow territory asymmetry in older adults with substandard verbal memory performance.

PURPOSE: To evaluate how flow territory asymmetry and/or the distribution of blood through collateral pathways may adversely affect the brain's ability to respond to age-related changes in brain function. These patterns have been investigated in cerebrovascular disease; however, here we evaluated how flow-territory asymmetry related to memory generally in older adults. MATERIALS AND METHODS: A multi-faceted MRI protocol, including vessel-encoded arterial spin labeling capable of flow territory mapping, was applied to assess how flow territory asymmetry; memory performance (CERAD-Immediate Recall); cortical cerebral blood flow (CBF), white matter lesion (WML) count, and cortical gray matter volume were related in older healthy control volunteers (HC; n = 15; age = 64.5 ± 7 years) and age-matched mild cognitive impairment volunteers (MCI; n = 7; age = 62.7 ± 3.7 years). RESULTS: An inverse relationship was found between memory performance and flow territory asymmetry in HC volunteers (P = 0.04), which reversed in MCI volunteers (P = 0.04). No relationship was found between memory performance and cortical tissue volume in either group (P > 0.05). Group-level differences for HC volunteers performing above versus below average on CERAD-I were observed for flow territory asymmetry (P < 0.02) and cortical volume (P < 0.05) only. CONCLUSION: Findings suggest that flow territory asymmetry may correlate more sensitively with memory performance than CBF, atrophy and WML count in older adults.

The temporal dynamics of visual object priming.

Priming reflects an important means of learning that is mediated by implicit memory. Importantly, priming occurs for previously viewed objects (item-specific priming) and their category relatives (category-wide priming). Two distinct neural mechanisms are known to mediate priming, including the sharpening of a neural object representation and the retrieval of stimulus-response mappings. Here, we investigated whether the relationship between these neural mechanisms could help explain why item-specific priming generates faster responses than category-wide priming. Participants studied pictures of everyday objects, and then performed a difficult picture identification task while we recorded event-related potentials (ERP). The identification task gradually revealed random line segments of previously viewed items (Studied), category exemplars of previously viewed items (Exemplar), and items that were not previously viewed (Unstudied). Studied items were identified sooner than Unstudied items, showing evidence of item-specific priming, and importantly Exemplar items were also identified sooner than Unstudied items, showing evidence of category-wide priming. Early activity showed sustained neural suppression of parietal activity for both types of priming. However, these neural suppression effects may have stemmed from distinct processes because while category-wide neural suppression was correlated with priming behavior, item-specific neural suppression was not. Late activity, examined with response-locked ERPs, showed additional processes related to item-specific priming including neural suppression in occipital areas and parietal activity that was correlated with behavior. Together, we conclude that item-specific and category-wide priming are mediated by separate, parallel neural mechanisms in the context of the current paradigm. Temporal differences in behavior are determined by the timecourses of these distinct processes.

Pattern separation and pattern completion in Alzheimer's disease: evidence of rapid forgetting in amnestic mild cognitive impairment.

Over the past four decades, the characterization of memory loss associated with Alzheimer's disease (AD) has been extensively debated. Recent iterations have focused on disordered encoding versus rapid forgetting. To address this issue, we used a behavioral pattern separation task to assess the ability of the hippocampus to create and maintain distinct and orthogonalized visual memory representations in patients with amnestic mild cognitive impairment (aMCI) and mild AD. We specifically used a lag-based continuous recognition paradigm to determine whether patients with aMCI and mild AD fail to encode visual memory representations or whether these patients properly encode representations that are rapidly forgotten. Consistent with the rapid forgetting hypothesis of AD, we found that patients with aMCI demonstrated decreasing pattern separation rates as the lag of interfering objects increased. In contrast, patients with AD demonstrated consistently poor pattern separation rates across three increasingly longer lags. We propose a continuum that reflects underlying hippocampal neuropathology whereby patients with aMCI are able to properly encode information into memory but rapidly lose these memory representations, and patients with AD, who have extensive hippocampal and parahippocampal damage, cannot properly encode information in distinct, orthogonal representations. Our results also revealed that whereas patients with aMCI demonstrated similar behavioral pattern completion rates to healthy older adults, patients with AD showed lower pattern completion rates when we corrected for response bias. Finally, these behavioral pattern separation and pattern completion results are discussed in terms of the dual process model of recognition memory.

Inverse correspondence between hippocampal perfusion and verbal memory performance in older adults.

Understanding physiological changes that precede irreversible tissue damage in age-related pathology is central to optimizing treatments that may prevent, or delay, cognitive decline. Cerebral perfusion is a tightly regulated physiological property, coupled to tissue metabolism and function, and abnormal (both elevated and reduced) hippocampal perfusion has been reported in a range of cognitive disorders. However, the size and location of the hippocampus complicates perfusion quantification, as many perfusion techniques acquire data with spatial resolution on the order of or beyond the size of the hippocampus, and are thus suboptimal in this region (especially in the presence of hippocampal atrophy and reduced flow scenarios). Here, the relationship between hippocampal perfusion and atrophy as a function of memory performance was examined in cognitively normal healthy older adults (n = 20; age=67 ± 7 yr) with varying genetic risk for dementia using a custom arterial spin labeling acquisition and analysis procedure. When controlling for hippocampal volume, it was found that hippocampal perfusion correlated inversely (P = 0.04) with memory performance despite absent hippocampal tissue atrophy or white matter disease. The hippocampal flow asymmetry (left hippocampus perfusion-right hippocampus perfusion) was significantly (P = 0.04) increased in APOE-ϵ4 carriers relative to noncarriers. These findings demonstrate that perfusion correlates more strongly than tissue volume with memory performance in cognitively normal older adults, and furthermore that an inverse trend between these two parameters suggests that elevation of neuronal activity, possibly mediated by neuroinflammation and/or excitation/inhibition imbalance, may be closely associated with minor changes in memory performance.

A case of hyperthymesia: rethinking the role of the amygdala in autobiographical memory.

Much controversy has been focused on the extent to which the amygdala belongs to the autobiographical memory (AM) core network. Early evidence suggested the amygdala played a vital role in emotional processing, likely helping to encode emotionally charged stimuli. However, recent work has highlighted the amygdala's role in social and self-referential processing, leading to speculation that the amygdala likely supports the encoding and retrieval of AM. Here, cognitive as well as structural and functional magnetic resonance imaging data was collected from an extremely rare individual with near-perfect AM, or hyperthymesia. Right amygdala hypertrophy (approximately 20%) and enhanced amygdala-to-hippocampus connectivity (>10 SDs) was observed in this volunteer relative to controls. Based on these findings and previous literature, we speculate that the amygdala likely charges AMs with emotional, social, and self-relevance. In heightened memory, this system may be hyperactive, allowing for many types of autobiographical information, including emotionally benign, to be more efficiently processed as self-relevant for encoding and storage.

Using mental imagery to improve memory in patients with Alzheimer disease: trouble generating or remembering the mind's eye?

This study was conducted to understand whether patients with mild Alzheimer disease (AD) could use general or self-referential mental imagery to improve their recognition of visually presented words. Experiment 1 showed that, unlike healthy controls, patients generally did not benefit from either type of imagery. To help determine whether the patients' inability to benefit from mental imagery at encoding was due to poor memory or due to an impairment in mental imagery, participants performed 4 imagery tasks with varying imagery and cognitive demands. Experiment 2 showed that patients successfully performed basic visual imagery, but degraded semantic memory, coupled with visuospatial and executive functioning deficits, impaired their ability to perform more complex types of imagery. Given that patients with AD can perform basic mental imagery, our results suggest that episodic memory deficits likely prevent AD patients from storing or retrieving general mental images generated during encoding. Overall, the results of both experiments suggest that neurocognitive deficits do not allow patients with AD to perform complex mental imagery, which may be most beneficial to improving memory. However, our data also suggest that intact basic mental imagery and rehearsal could possibly be helpful if used in a rehabilitation multisession intervention approach.

Using pictures and words to understand recognition memory deterioration in amnestic mild cognitive impairment and Alzheimer's disease: a review.

Difficulty recognizing previously encountered stimuli is one of the earliest signs of incipient Alzheimer's disease (AD). Work over the last 10 years has focused on how patients with AD and those in the prodromal stage of amnestic mild cognitive impairment make recognition decisions for visual and verbal stimuli. Interestingly, both groups of patients demonstrate markedly better memory for pictures over words, to a degree that is significantly greater in magnitude than their healthy older counterparts. Understanding this phenomenon not only helps to conceptualize how memory breaks down in AD, but also potentially provides the basis for future interventions. This review critically examines recent recognition memory work using pictures and words in the context of the dual-process theory of recognition and current hypotheses of cognitive breakdown in the course of very early AD.

The picture superiority effect in patients with Alzheimer's disease and mild cognitive impairment.

The fact that pictures are better remembered than words has been reported in the literature for over 30 years. While this picture superiority effect has been consistently found in healthy young and older adults, no study has directly evaluated the presence of the effect in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Clinical observations have indicated that pictures enhance memory in these patients, suggesting that the picture superiority effect may be intact. However, several studies have reported visual processing impairments in AD and MCI patients which might diminish the picture superiority effect. Using a recognition memory paradigm, we tested memory for pictures versus words in these patients. The results showed that the picture superiority effect is intact, and that these patients showed a similar benefit to healthy controls from studying pictures compared to words. The findings are discussed in terms of visual processing and possible clinical importance.

An evaluation of recollection and familiarity in Alzheimer's disease and mild cognitive impairment using receiver operating characteristics.

There is a need to investigate exactly how memory breaks down in the course of Alzheimer's disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions.

Response bias for picture recognition in patients with Alzheimer disease.

OBJECTIVE: To investigate whether changing recognition stimuli from words to pictures would alter response bias in patients with Alzheimer disease (AD). BACKGROUND: Response bias is an important aspect of memory performance in patients with AD, as they show an abnormally liberal response bias compared with healthy older adults. We have previously found that despite changes in discrimination produced by varying the study and test list length, response bias remained remarkably stable in both patients with AD and older adult controls. METHODS: Patients with mild AD and healthy older adults underwent two separate study-test sessions of pictures and words. For both pictures and words, increasing study-test list lengths were used to determine whether bias changed as a factor of discrimination or task difficulty. RESULTS: Consistent with apriori hypotheses, healthy older adults showed increased discrimination and shifted to a more liberal response bias for pictures compared with words. In contrast, despite their higher level of discrimination for pictures, patients with AD showed a similar response bias for both pictures and words. Bias was consistent across varying study-test lengths for both groups. CONCLUSIONS: These results suggest that response bias is a relatively invariant factor of an individual with AD that remains liberal regardless of discrimination or stimulus type.

Exposing an "Intangible" Cognitive Skill Among Collegiate Football Players: III. Enhanced Reaction Control to Motion.

Football is played in a dynamic, often unpredictable, visual environment in which players are challenged to process and respond with speed and flexibility to critical incoming stimulus events. To meet this challenge, we hypothesize that football players possess, in conjunction with their extraordinary physical skills, exceptionally proficient executive cognitive control systems that optimize response execution. It is particularly important for these systems to be proficient at coordinating directional reaction and counter-reaction decisions to the very rapid lateral movements routinely made by their opponents during a game. Despite the importance of this executive skill to successful on-field performance, it has not been studied in football players. To fill this void, we compared the performances of Division I college football players (n = 525) and their non-athlete age counterparts (n = 40) in a motion-based stimulus-response compatibility task that assessed their proficiency at executing either compatible (in the same direction) or incompatible (in the opposite direction) lateralized reactions to a target's lateral motion. We added an element of decision uncertainty and complexity by giving them either sufficient or insufficient time to preload the response decision rule (i.e., compatible vs. incompatible) prior to the target setting in motion. Overall, football players were significantly faster than non-athlete controls in their choice reactions to a target's lateral motion. The reactions of all participants slowed when issuing incompatible counter-reactions to a target's lateral motion. For football players, this cost was reduced substantially compared to controls when given insufficient time to preload the decision rule, indicating that they exerted more efficient executive control over their reactions and counter-reactions when faced with decision uncertainty at the onset of stimulus motion. We consider putative sources of their advantage in reacting to a target's lateral motion and discuss how these findings advance the hypothesis that football players utilize highly-proficient executive control systems to overcome processing conflicts during motor performance.

Parietal contributions to recollection: electrophysiological evidence from aging and patients with parietal lesions.

There has been much recent investigation into the role of parietal cortex in memory retrieval. Proposed hypotheses include attention to internal memorial representations, an episodic working memory-type buffer, and an accumulator of retrieved memorial information. The current investigation used event-related potentials (ERPs) to test the episodic buffer hypothesis, and to assess the memorial contribution of parietal cortex in younger and older adults, and in patients with circumscribed lateral parietal lesions. In a standard recognition memory paradigm, subjects studied color pictures of common objects. One-third of the test items were presented in the same viewpoint as the study phase, one-third were presented in a 90 degrees rotated viewpoint, and one-third were presented in a noncanonical viewpoint. Conflicting with the episodic buffer hypothesis, results revealed that the duration of the parietal old/new effect was longest for the canonical condition and shortest for the noncanonical condition. Results also revealed that older adults demonstrated a diminished parietal old/new effect relative to younger adults. Consistent with previous data reported by Simons et al., patients with lateral parietal lesions showed no behavioral impairment compared to controls. Behavioral and ERP data from parietal lesion patients are presented and discussed. From these results, the authors speculate that the parietal old/new effect may be the neural correlate of an individual's subjective recollective experience.

Is the parietal lobe necessary for recollection in humans?

An intriguing puzzle in cognitive neuroscience over recent years has been the common observation of parietal lobe activation in functional neuroimaging studies during the performance of human memory tasks. These findings have surprised scientists and clinicians because they challenge decades of established thinking that the parietal lobe does not support memory function. However, direct empirical investigation of whether circumscribed parietal lobe lesions might indeed be associated with human memory impairment has been lacking. Here we confirm using functional magnetic resonance imaging that significant parietal lobe activation is observed in healthy volunteers during a task assessing recollection of the context in which events previously occurred. However, patients with parietal lobe lesions that overlap closely with the regions activated in the healthy volunteers nevertheless exhibit normal performance on the same recollection task. Thus, although the processes subserved by the human parietal lobe appear to be recruited to support memory function, they are not a necessary requirement for accurate remembering to occur.

Aging memory for pictures: using high-density event-related potentials to understand the effect of aging on the picture superiority effect.

High-density event-related potentials (ERPs) were used to understand the effect of aging on the neural correlates of the picture superiority effect. Pictures and words were systematically varied at study and test while ERPs were recorded at retrieval. Here, the results of the word-word and picture-picture study-test conditions are presented. Behavioral results showed that older adults demonstrated the picture superiority effect to a greater extent than younger adults. The ERP data helped to explain these findings. The early frontal effect, parietal effect, and late frontal effect were all indistinguishable between older and younger adults for pictures. In contrast, for words, the early frontal and parietal effects were significantly diminished for the older adults compared to the younger adults. These two old/new effects have been linked to familiarity and recollection, respectively, and the authors speculate that these processes are impaired for word-based memory in the course of healthy aging. The findings of this study suggest that pictures allow older adults to compensate for their impaired memorial processes, and may allow these memorial components to function more effectively in older adults.

Exposing an "Intangible" Cognitive Skill among Collegiate Football Players: Enhanced Interference Control.

American football is played in a chaotic visual environment filled with relevant and distracting information. We investigated the hypothesis that collegiate football players show exceptional skill at shielding their response execution from the interfering effects of distraction (interference control). The performances of 280 football players from National Collegiate Athletic Association Division I football programs were compared to age-matched controls in a variant of the Eriksen flanker task (Eriksen and Eriksen, 1974). This task quantifies the magnitude of interference produced by visual distraction on split-second response execution. Overall, football athletes and age controls showed similar mean reaction times (RTs) and accuracy rates. However, football athletes were more proficient at shielding their response execution speed from the interfering effects of distraction (i.e., smaller flanker effect costs on RT). Offensive and defensive players showed smaller interference costs compared to controls, but defensive players showed the smallest costs. All defensive positions and one offensive position showed statistically smaller interference effects when compared directly to age controls. These data reveal a clear cognitive advantage among football athletes at executing motor responses in the face of distraction, the existence and magnitude of which vary by position. Individual differences in cognitive control may have important implications for both player selection and development to improve interference control capabilities during play.

Diagnostic retrieval monitoring in patients with frontal lobe lesions: further exploration of the distinctiveness heuristic.

The distinctiveness heuristic is a diagnostic monitoring strategy whereby a subject expects a vivid recollection if a test item has been seen during the study session; the absence of a vivid recollection suggests the test item is novel. Consistent with the hypothesis that memory monitoring is dependent upon the frontal lobes, previous work using a repetition-lag paradigm found that patients with frontal lobe lesions were unable to use the distinctiveness heuristic. Evidence from recent neuroimaging studies, however, has suggested that use of the distinctiveness heuristic decreases the need for frontal processing. The present study used the criterial recollection task to revisit the question of whether patients with frontal lobe lesions are able to use a distinctiveness heuristic. Subjects studied black words paired with the same word in red font, a corresponding picture of the word, or both. They then took three memory tests designed to elicit false recognition of presented items. Both frontal lesion patients and matched control subjects showed intact ability to use the distinctiveness heuristic to reduce false recognition when tested on whether items were previously presented as pictures compared to red words. This use of the distinctiveness heuristic is evidence that patients with frontal lesions can use certain diagnostic monitoring strategies during recognition memory tasks when given guidance in coordinating their decision-making processes. This result suggests that the frontal lobes are necessary for self-initiation of this strategy during recognition memory tasks.