Philip C. Ko

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 Alzheimers 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.

Improvement of a face perception deficit via subsensory galvanic vestibular stimulation

The remediative effect of galvanic vestibular stimulation (GVS) was investigated in a patient who, following right hemisphere damage, is profoundly unable to recognize faces. We administered a two-alternative forced choice match-to-sample task in which the patient had to choose which of two faces matched a sample face presented directly above, while bipolar, transcutaneous current was applied to the left and right vestibular nerves at a level below the patients sensory threshold. Performance improved beyond the chance-level observed prestimulation, and relied on reversing the electrode polarity across two separate blocks of trials, such that each mastoid received positive current for one block and then negative charge for the next. Although our study involved only a single case, the data provide preliminary evidence that a deficit in perceptual face matching can be reduced by GVS. This raises the intriguing possibility that other unilateral visual disorders may also respond in such a manner.

Unilateral damage to the right cerebral hemisphere disrupts the apprehension of whole faces and their component parts.

Although most cases of acquired prosopagnosia are accompanied by bilateral brain lesions, a number also arise following right unilateral lesions. The prevailing consensus is that right hemisphere damage disrupts the configural apprehension of faces, which in turn forces a reliance on part-based processing. Here we describe a patient who following right hemisphere damage is not only unable to apprehend the configural aspects of faces, but is also unable to apprehend their component parts when these are presented within a whole, upright face. Intriguingly, the patient is able to apprehend face parts when these are presented in isolation, within inverted faces, or in unfamiliar, scrambled arrangements. Furthermore, the patient can make use of configural information to detect local changes in non-face stimuli. The findings uncover a hitherto unreported form of impairment following right unilateral damage, and raise questions about the role of the left hemisphere in processing local information.

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.

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.

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.

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.

Is it better to burn out or fade away? The effect of sudden offsets on target recovery

(5) Participants selected dots with the mouse. Accuracy = # targets selected / # targets. Experiment 2: Is it better to burn out or just disappear? HYPOTHESIS 1: If transients facilitate memory for object position, performance should be higher when objects BURN out compared to when there is NO BURN at offset. Experiment 3: Does the burn trigger memory for position? HYPOTHESIS: If the BURN triggers memory for object position, performance should be affected by the spatial congruency of the burn onset and the post-blank position.