Kirk R. Daffner

When False Recognition Is Unopposed by True Recognition: Gist-Based Memory Distortion in Alzheimer's Disease

The authors examined false recognition of semantic associates in patients with probable Alzheimers disease (AD), older adults, and young adults using a paradigm that provided rates of false recognition after single and multiple exposures to word lists. Using corrected false recognition scores to control for unrelated false alarms, the authors found that (a) the level of false recognition after a single list exposure was lower in AD patients than in controls; (b) across 5 trials, false recognition increased in AD patients, decreased in young adults, and showed a fluctuating pattern in older adults; and (c) all groups showed an increase in true recognition over the 5 trials. Analyses suggested that AD patients built up semantic gist across trials, whereas both control groups were able to use increased item-specific recollection and more conservative response criteria to suppress gist-based false alarms.

Associative Recognition in Alzheimer's Disease: Evidence for Impaired Recall-to-Reject.

Patients with mild Alzheimers disease (AD) were compared with age-matched control subjects on an associative recognition task. Subjects studied pairs of unrelated words and were later asked to distinguish between these same studied pairs (intact) and new pairs that contained either rearranged studied words (rearranged) or non-studied words (non-studied). Studied pairs were presented either once or 3 times. Repetition increased hits to intact pairs in both groups, but repetition increased false alarms to rearranged pairs only in patients. This latter pattern indicates that repetition increased familiarity of the rearranged pairs, but only the control subjects were able to counter this familiarity by recalling the originally studied pairs (a recall-to-reject process). AD impaired this recall-to-reject process, leading to more familiarity based false alarms. These data support the idea that recollection-based monitoring processes are impaired in mild AD.

Frontal and Parietal Components of a Cerebral Network Mediating Voluntary Attention to Novel Events

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating ones internal model of the environment to take into account a novel event.

Regulation of attention to novel stimuli by frontal lobes: an event-related potential study.

THIS study examined the relationship between orienting responses to novel events and subsequent exploratory behavior. The N2-P3 electrophysiologic component of the orienting response was found to be larger for novel than repetitive background stimuli. Across subjects, the amplitude of this N2-P3 response in frontal regions strongly predicted the proportional increase in the duration of viewing directed toward novel compared to background stimuli. Within subjects, larger N2-P3 amplitudes in response to novel stimuli were associated with longer viewing durations on those stimuli. These results suggest that the N2-P3 component of the orienting response reflects the activity of a neural system involving frontal networks that dynamically regulates the subsequent allocation of attentional resources to novel stimuli.

Diminished curiosity in patients with probable Alzheimer's disease as measured by exploratory eye movements

Clinical accounts of Alzheimers disease (AD) suggest that some patients exhibit markedly diminished curiosity and initiative early in the course of their illness. Such behavioral changes are extremely difficult to measure experimentally. We studied one aspect of curiosity by measuring exploratory eye movements in response to provocative visual stimuli in 12 patients with probable AD and 10 matched controls. Subjects viewed slides, each of which contained an incongruous or irregular figure paired with a congruous or regular one. Unlike controls, who spent significantly more time viewing the incongruous stimuli, AD patients distributed their viewing time equally and spent significantly less time than controls looking at the novel stimuli. Additionally, when presented with picture slides containing an unexpected element, AD patients exhibited diminished visual exploration overall and decreased attention to the incongruous part. Further analyses suggest that the results cannot be adequately explained by a general decline in cognition or by problems with ocular motility or directing visual attention. We conclude that AD patients exhibit diminished curiosity which can be measured by the study of exploratory eye movements.

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.

Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals

Identifying high-functioning older individuals in preclinical phases of Alzheimers disease (AD) may require more sensitive methods than the standard approach. The authors explored the utility of adjusting for premorbid intelligence to predict progressive cognitive decline or Mild Cognitive Impairment (MCI) in 42 highly intelligent older individuals. When scores were adjusted for baseline IQ, 9 participants had executive impairments, 11 had memory impairments, and 22 scored in the normal range. None were impaired according to standard age norms. Three and a half years later, 9 participants with IQ-adjusted memory impairment declined in naming, visuospatial functioning, and memory; 6 convened to MCI. Three participants with normal memory declined. Implications for using IQ-adjusted norms to predict preclinical AD are discussed.

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.

The Influence of Stimulus Deviance on Electrophysiologic and Behavioral Responses to Novel Events

This study investigated the role of stimulus deviance in determining electrophysiologic and behavioral responses to novelty. Stimulus deviance was defined in terms of differences either from the immediately preceding context or from long-term experience. Subjects participated in a visual event-related potential (ERP) experiment, in which they controlled the duration of stimulus viewing with a button press, which served as a measure of exploratory behavior. Each of the three experimental conditions included a frequent repetitive background stimulus and infrequent stimuli that deviated from the background stimulus. In one condition, both background and deviant stimuli were simple, easily recognizable geometric figures. In another condition, both background and deviant stimuli were unusual/unfamiliar figures, and in a third condition, the background stimulus was a highly unusual figure, and the deviant stimuli were simple, geometric shapes. Deviant stimuli elicited larger N2-P3 amplitudes and longer viewing durations than the repetitive background stimulus, even when the deviant stimuli were simple, familiar shapes and the background stimulus was a highly unusual figure. Compared to simple, familiar deviant stimuli, unusual deviant stimuli elicited larger N2-P3 amplitudes and longer viewing times. Within subjects, the deviant stimuli that evoked the largest N2-P3 responses also elicited the longest viewing durations. We conclude that deviance from both immediate context and long-term prior experience contribute to the response to novelty, with the combination generating the largest N2-P3 amplitude and the most sustained attention. The amplitude of the N2-P3 may reflect how much uncertainty is evoked by a novel visual stimulus and signal the need for further exploration and cognitive processing.

Memory and Emotions for the September 11, 2001, Terrorist Attacks in Patients With Alzheimer's Disease, Patients With Mild Cognitive Impairment, and Healthy Older Adults

National traumatic events can produce extremely vivid memories. Using a questionnaire administered during telephone interviews, the authors investigated emotional responses to, and memory for. the September 11, 2001, terrorist attacks in patients with Alzheimers disease (AD), patients with mild cognitive impairment (MCI), and healthy older adults in the initial weeks following the event and again 3-4 months later. There were several notable findings. First, patients with AD showed less memory than patients with MCI and older adults. Second, patients with AD, but not patients with MCI or older adults, appeared to retain more memory for personal versus factual information. Third, patients with AD and older adults did not differ in the intensity of their reported emotional responses to the attacks, whereas patients with MCI reported relatively less intense emotional responses. Last, distortions of memory for personal information were frequent for all participants but were more common in patients with AD.