Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.

Early detection may be the key to developing therapies that will combat Alzheimer's disease (AD). It has been consistently demonstrated that one of the main pathologies of AD, tau, is present in the brain decades before a clinical diagnosis. Tau pathology follows a stereotypical route through the medial temporal lobe beginning in the entorhinal and perirhinal cortices. If early pathology leads to very subtle changes in behavior, it may be possible to detect these changes in subjects years before a clinical diagnosis can currently be made. We aimed to discover if cognitively normal middle-aged adults (40-60 years old) at increased risk for AD due to family history would have impaired performance on a cognitive task known to challenge the perirhinal cortex. Using an oddity detection task, we found that subjects with a family history of AD had lowered accuracy without demonstrating differences in rate of acquisition. There were no differences between subjects' medial temporal lobe volume or cortical thickness, indicating that the changes in behavior were not due to significant atrophy. These results demonstrate that subtle changes in perceptual processing are detectable years before a typical diagnosis even when there are no differences detectable in structural imaging data. Anatomically-targeted cognitive testing may be useful in identifying subjects in the earliest stages of AD.

Eye movements in Alzheimer's disease.

A growing body of literature has investigated changes in eye movements as a result of Alzheimer's disease (AD). When compared to healthy, age-matched controls, patients display a number of remarkable alterations to oculomotor function and viewing behavior. In this article, we review AD-related changes to fundamental eye movements, such as saccades and smooth pursuit motion, in addition to changes to eye movement patterns during more complex tasks like visual search and scene exploration. We discuss the cognitive mechanisms that underlie these changes and consider the clinical significance of eye movement behavior, with a focus on eye movements in mild cognitive impairment. We conclude with directions for future research.

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.

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.

Understanding age-related reductions in visual working memory capacity: examining the stages of change detection.

Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old-new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old-new effects in frontal and occipital areas and a late central-parietal old-new effect, whereas older adults showed a late right-lateralized parietal old-new effect. The younger adults' early old-new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults' behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults.

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.

Electrophysiological distinctions between recognition memory with and without awareness.

The influence of implicit memory representations on explicit recognition may help to explain cases of accurate recognition decisions made with high uncertainty. During a recognition task, implicit memory may enhance the fluency of a test item, biasing decision processes to endorse it as "old". This model may help explain recognition-without-identification, a remarkable phenomenon in which participants make highly accurate recognition decisions despite the inability to identify the test item. The current study investigated whether recognition-without-identification for pictures elicits a similar pattern of neural activity as other types of accurate recognition decisions made with uncertainty. Further, this study also examined whether recognition-without-identification for pictures could be attained by the use of perceptual and conceptual information from memory. To accomplish this, participants studied pictures and then performed a recognition task under difficult viewing conditions while event-related potentials (ERPs) were recorded. Behavioral results showed that recognition was highly accurate even when test items could not be identified, demonstrating recognition-without-identification. The behavioral performance also indicated that recognition-without-identification was mediated by both perceptual and conceptual information, independently of one another. The ERP results showed dramatically different memory related activity during the early 300 to 500ms epoch for identified items that were studied compared to unidentified items that were studied. Similar to previous work highlighting accurate recognition without retrieval awareness, test items that were not identified, but correctly endorsed as "old," elicited a negative posterior old/new effect (i.e., N300). In contrast, test items that were identified and correctly endorsed as "old," elicited the classic positive frontal old/new effect (i.e., FN400). Importantly, both of these effects were elicited under conditions when participants used perceptual information to make recognition decisions. Conceptual information elicited very different ERPs than perceptual information, showing that the informational wealth of pictures can evoke multiple routes to recognition even without awareness of memory retrieval. These results are discussed within the context of current theories regarding the N300 and the FN400.

Updating objects in visual short-term memory is feature selective.

The purpose of this study was to examine whether the process of updating information in visual short-term memory (VSTM) is object based. We investigated whether modifying the memory of one feature of an object would automatically promote refreshing the memory of all of its other features. The results showed that the facilitative effect of updating was specific to the updated feature of an object and did not spread to its nonupdated features. This feature-selective effect suggests that updating VSTM is not object based (Experiment 1), even though storage was object based (Experiment 2). Control experiments ruled out strategy-based (Experiment 3) and stimulus-related (Experiments 4-6) accounts. Feature-selective updating may indicate that the mechanism used to modify the contents of memory may have a different basis than that used to encode or store information in memory.

Evidence for intact selective attention in Alzheimer's disease patients using a location priming task.

Researchers examining selective attentional mechanisms in patients with Alzheimer's disease (AD) often report impairment in patients' ability to inhibit irrelevant or distracting information. However, in many studies reporting such failures, researchers used tasks that require semantic processing, which a large body of literature documents to be disrupted in AD. The authors of this study used a spatial location-priming task that minimized semantic processing to examine the phenomena of negative priming and facilitative priming in 13 AD patients and 13 healthy older adults. AD patients demonstrated facilitative and negative priming proportionately equivalent to that of older adults. These findings suggest that both the facilitative and inhibitory mechanisms involved in selective attention are preserved in patients with AD and can be revealed in tasks that minimize semantic processing.