Mechanisms underlying age- and performance-related differences in working memory.

This study took advantage of the subsecond temporal resolution of ERPs to investigate mechanisms underlying age- and performance-related differences in working memory. Young and old subjects participated in a verbal n-back task with three levels of difficulty. Each group was divided into high and low performers based on accuracy under the 2-back condition. Both old subjects and low-performing young subjects exhibited impairments in preliminary mismatch/match detection operations (indexed by the anterior N2 component). This may have undermined the quality of information available for the subsequent decision-making process (indexed by the P3 component), necessitating the appropriation of more resources. Additional anterior and right hemisphere activity was recruited by old subjects. Neural efficiency and the capacity to allocate more resources to decision-making differed between high and low performers in both age groups. Under low demand conditions, high performers executed the task utilizing fewer resources than low performers (indexed by the P3 amplitude). As task requirements increased, high-performing young and old subjects were able to appropriate additional resources to decision-making, whereas their low-performing counterparts allocated fewer resources. Higher task demands increased utilization of processing capacity for operations other than decision-making (e.g., sustained attention) that depend upon a shared pool of limited resources. As demands increased, all groups allocated additional resources to the process of sustaining attention (indexed by the posterior slow wave). Demands appeared to have exceeded capacity in low performers, leading to a reduction of resources available to the decision-making process, which likely contributed to a decline in performance.

PSEUDOHYPOPHOSPHATEMIA IN A PATIENT WITH MULTIPLE MYELOMA.

OBJECTIVE: To discuss the diagnosis and management of paraprotein interference in the setting of multiple myeloma (MM). METHODS: We discuss the evaluation of hypophosphatemia in a patient with MM and present a review of the relevant literature. RESULTS: Our patient, who had a history of MM, was found to have persistently undetectable serum phosphate which did not respond to aggressive phosphate replacement. His clinical condition was not consistent with severe phosphate depletion and hence paraprotein interference secondary to MM was suspected. Re-analyzation of samples on a different machine showed normal serum inorganic phosphate levels. CONCLUSION: Paraprotein interference from MM causing pseudohypophosphatemia can be overlooked and lead to unnecessary treatment. Recognition of this phenomenon is important to all clinicians, especially in light of potential complications of unnecessary treatment.

Cognitive status impacts age-related changes in attention to novel and target events in normal adults.

In this study, the authors investigated the relationship between the cognitive status of normal adults and age-related changes in attention to novel and target events. Old, middle-age, and young subjects, divided into cognitively high and cognitively average performing groups, viewed repetitive standard stimuli, infrequent target stimuli, and unique novel visual stimuli. Subjects controlled viewing duration by a button press that led to the onset of the next stimulus. They also responded to targets by pressing a foot pedal. The amount of time spent looking at different kinds of stimuli served as a measure of visual attention and exploratory activity. Cognitively high performers spent more time viewing novel stimuli than cognitively average performers. The magnitude of the difference between cognitively high and cognitively average performing groups was largest among old subjects. Cognitively average performers had slower and less accurate responses to targets than cognitively high performers. The results provide strong evidence that the link between engagement by novelty and higher cognitive performance increases with age. Moreover, the results support the notion of there being different patterns of normal cognitive aging and the need to identify the factors that influence them.

ERP correlates of Remember/Know decisions: association with the late posterior negativity.

A number of studies have utilized the Remember/Know paradigm to determine event-related potential (ERP) correlates of recollection and familiarity. However, no prior work has been specifically directed at examining the processing involved in making the Remember/Know distinction. The following study employed a two-step recognition memory test in which participants first decided whether they recognized a word from a prior study list (Old/New decision); if they did, they then determined whether it was recognized on the basis of recollection ('Remember' responses) or familiarity ('Know' responses). By time-locking ERPs to the initial Old/New decision, processing related to making the introspective Remember/Know judgment was isolated. This methodology revealed a posterior negativity that was largest for 'Remember' responses. Previous work has described a late posterior negativity which appears to be related to the search for and recapitulation of study details. Such processing may be critical in making Remember/Know determinations.

Use of a 90-Minute Admission Window and Front-Fill System to Reduce Work Compression on a General Medicine Inpatient Teaching Service.

BACKGROUND: Duty hour limits have shortened intern shifts without concurrent reductions in workload, creating work compression. Multiple admissions during shortened shifts can result in poor training experience and patient care. OBJECTIVE: To relieve work compression, improve resident satisfaction, and improve duty hour compliance in an academic internal medicine program. METHODS: In 2014, interns on general ward services were allotted 90 minutes per admission from 3 pm to 7 pm, when the rate of admissions was high. Additional admissions arriving during the protected period were directed to hospitalists. Resident teams received 2 patients admitted by the night float team to start the call day (front-fill). RESULTS: Of the 51 residents surveyed before and after the implementation of the intervention, 39 (77%) completed both surveys. Respondents reporting an unmanageable workload fell from 14 to 1 (P < .001), and the number of residents reporting that they felt unable to admit patients in a timely manner decreased from 14 to 2 (P < .001). Reports of adequate time with patients increased from 16 to 36 (P < .001), and residents indicating that they had time to learn from patients increased from 19 to 35 (P < .001). Reports of leaving on time after call days rose from 12 to 33 (P < .01), and overall satisfaction increased from 26 to 35 (P = .002). Results were similar when residents were resurveyed 6 months after the intervention. CONCLUSIONS: Call day modifications improved resident perceptions of their workload and time for resident learning and patient care.

Episodic memory in Alzheimer's disease: separating response bias from discrimination.

Most studies examining episodic memory in Alzheimer's disease (AD) have focused on patients' impaired ability to remember information, leading to poor discrimination between studied and unstudied items at test. Poor discrimination, however, can also be attributable to an abnormally high rate of false alarms. One cause of a high false alarm rate is an abnormally liberal response bias; that is, responding "old" too liberally to the test items. In the present study, discrimination and response bias were evaluated when participants were given a series of progressively longer study-test lists of unrelated words. As expected, patients with AD showed overall worse discrimination and a more liberal response bias compared with older adult controls. Critically, patients with AD also showed a more liberal response bias than older adults when discrimination was matched between the groups after performance was equated by giving the older adult controls a more difficult test than the patients with AD. This result confirms that the patients' abnormally liberal response bias is not simply attributable to their poor discrimination. Correlation analyses suggest that the patients' liberal response bias is related to the degree of their episodic memory deficit, which may in turn be related to the severity of their disease. Thus, our research suggests that as AD progresses two distinct abnormalities of episodic memory develop: worse discrimination and a more liberal response bias. Possible explanations of this liberal response bias in patients with AD are discussed.

ERP correlates of item recognition memory: effects of age and performance.

Decline in episodic memory is a common feature of healthy aging. Event-related potential (ERP) studies in young adults have consistently reported several modulations thought to index memory retrieval processes, but relatively limited work has explored the impact of aging on them. Further, work with functional imaging has demonstrated differential neural recruitment in elderly subjects depending on their level of cognitive performance which may reflect compensatory or, alternatively, inefficient processing. In the present study we examined the effect of aging and level of performance on both early (FN400, LPC) and later [late frontal effect (LFE)] ERP indices of recognition memory. We found that the FN400 and LPC were absent or attenuated in the older group relative to young adults, but that the LFE was actually increased, analogous to findings in the functional imaging literature. Additionally, the latter effect was most prominent in the poorer performing older participants. These findings suggest that weak memory retrieval supported by earlier ERP modulations, may lead to an enhanced LFE in the service of additional retrieval attempts.

Age-related changes in early novelty processing as measured by ERPs.

This study investigated age-related changes in the early processing of novel visual stimuli using ERPs. Well-matched old (n=30), middle-aged (n=30), and young (n=32) subjects were presented standard, target/rare, and perceptually novel visual stimuli under Attend and Ignore conditions. Our results suggest that the anterior P2 component indexes the motivational salience of a stimulus as determined by either task relevance or novelty. Its enhancement by focused attention does not decrease with age. Its responsiveness to novel stimuli is particularly striking in older adults. The age-related increase in the anterior P2 to novel visual stimuli does not appear to be due to impaired inhibitory control associated with aging. Rather, the enhanced anterior P2 to novel stimuli in older adults may be linked to age-related changes in the process of matching unusual visual stimuli to stored representations, which is indexed by the temporally overlapping anterior N2 component whose amplitude substantially decreases with age.

Preserved metamemorial ability in patients with mild Alzheimer's disease: shifting response bias.

Patients with mild Alzheimer's disease (AD) display a greater tendency to endorse unstudied items as "old" on memory tests than healthy older adults. This liberal response bias may result in mistaken beliefs about the completion of common tasks. This research attempted to determine whether it was possible to shift the response bias of mild AD patients to be more conservative on a recognition memory test through behavioral intervention. Patients with mild AD and matched controls were evaluated with two almost identical paradigms, separated by about one week. For each session, 30 words were studied and 60 words (half studied, half novel) were shown at test. During one session participants were told that 30% of words were old, and at the other session that 70% were old. We found that both groups were able to shift their response bias between the two conditions. That patients with mild AD were able to successfully shift their response bias demonstrates that--despite their overall liberal response bias and poor memory relative to controls--one component of metamemorial ability is preserved in patients with mild AD.

To ignore or explore: top-down modulation of novelty processing.

Abstract Attending to novelty is a critical element of human behavior and learning. Novel events can serve as task-irrelevant distracters or as potential sources of engagement by interesting or important aspects of one's environment. An optimally functioning brain should have the capacity to respond differentially to novel events depending on the circumstances in which they occur. In the present study, a subject-controlled variant of the visual novelty oddball paradigm was employed under two different conditions in which novel stimuli were characterized either as distracters from a main task or as potentially meaningful "invitations" to explore the environment. Differences in context, derived from varying the emphasis of task instructions, strongly modulated both the behavioral and electrophysiological response to novelty. This modulation was not observed for processing earlier than the P3 component. Subjects who encountered novel events that served as distracters limited the amount of attention and processing resources they appropriated. Remarkably, under this condition, there were no differences in overall P3 amplitude, late positive slow-wave activity, or viewing duration between rare novel and frequent standard events. In contrast, subjects who encountered novel events as potential opportunities to explore augmented the attention and processing resources directed toward these events (as reflected by a larger P3 amplitude, late positive slow-wave activity, and longer viewing durations). Our results suggest that the processing of novelty within the visual modality involves several stages, including: (1) the relatively automatic detection of unfamiliar, novel stimuli (indexed by the N2); (2) the voluntary allocation of resources determined by the broader context in which a novel event occurs (indexed by the P3); and (3) the sustained processing of novelty (indexed by late positive slow-wave activity). This study provides evidence of the brain's ability to generate differential responses to novel events according to the circumstances under which they are encountered. It also points to a greater degree of top-down modulation of the processing of novelty than has been previously emphasized. We suggest that less commonly studied variables, such as subject control, may provide additional insight into the different ways in which novelty is processed.

Compensatory neural activity distinguishes different patterns of normal cognitive aging.

Most cognitive neuroscientific research exploring the nature of age-associated compensatory mechanisms has compared old adults (high vs. average performers) to young adults (not split by performance), leaving ambiguous whether findings are truly age-related or reflect differences between high and average performers throughout the life span. Here, we examined differences in neural activity (as measured by ERPs) that were generated by high vs. average performing old, middle-age, and young adults while processing novel and target events to investigate the following three questions: (1) Are differences between cognitively high and average performing subjects in the allocation of processing resources (as indexed by P3 amplitude) specific to old subjects, or found throughout the adult life span? (2) Are differences between cognitively high and average performing subjects in speed of processing (as indexed by target P3 latency) of similar magnitude throughout the adult life span? (3) Where along the information processing stream does the compensatory neural activity attributed to cognitively high performing old subjects begin to take place? Our results suggest that high performing old adults successfully manage the task by a compensatory neural mechanism associated with the modulation of controlled processing and the allocation of more resources, whereas high performing younger subjects execute the task more efficiently with fewer resources. Differences between cognitively high and average performers in processing speed increase with age. Middle-age seems to be a critical stage in which substantial differences in neural activity between high and average performers emerge. These findings provide strong evidence for different patterns of age-related changes in the processing of salient environmental stimuli, with cognitive status serving as a key mediating variable.

Memory for choices in Alzheimer's disease.

Despite their cognitive impairment, patients with mild Alzheimer's disease (AD) often make important life choices. When making choices, people frequently attempt to directly compare the features of different options, rather than evaluating each option separately. Not every feature has an analogous (or alignable) feature in the other option, however. In 2005, Mather's group found that both younger and older adults filled in such gaps when remembering, creating features in the other option to contrast with existing features. In the present study, such effects of alignability on recognition memory were not found in patients with mild AD. This finding suggests that patients with mild AD are less likely to engage in feature-by-feature comparison processes across choice options, a change that may lead them to make qualitatively different choices than healthy older adults.

False recognition of emotional word lists in aging and Alzheimer disease.

OBJECTIVE: To examine 3 different aspects of the emotional memory effect in aging and Alzheimer disease (AD): item-specific recollection, gist memory, and recognition response bias. METHOD: Younger adults, older adults, and patients with AD performed a false recognition memory test in which participants were tested on "lure" items that were not seen at study, but were semantically related to the study items. Participants were tested on 5 emotional and 5 non-emotional lists. RESULTS: In addition to finding an increase in true recognition for emotional versus non-emotional items in healthy younger and older adults but not in patients with AD, and confirming that emotional items led younger adults to shift their response bias to a more liberal one, 3 novel findings were observed. First, the emotional effect on response bias was also observed in healthy older adults. Second, the opposite emotional effect on response bias was observed in patients with AD. Third, emotional items did not lead to an improvement in item-specific recollection or gist memory. CONCLUSIONS: Although healthy older adults show the normal amygdala-modulated criterion shift for emotional items-influencing their subjective feeling that information has been previously encountered, the amygdala pathology present in early AD may disrupt this influence.