Person:

Rentz, Dorene

Recent investigations that suggest selective attention (SA) is dependent on top-down control mechanisms lead to the expectation that individuals with high executive capacity (EC) would exhibit more robust neural indices of SA. This prediction was tested by using event-related potentials (ERPs) to examine differences in markers of information processing across 25 subjects divided into two groups based on high vs. average EC, as defined by neuropsychological test scores. Subjects performed an experimental task requiring SA to a specified color. In contrast to expectation, individuals with high and average EC did not differ in the size of ERP indices of SA: the anterior Selection Positivity (SP) and posterior Selection Negativity (SN). However, there were substantial differences between groups in markers of subsequent processing, including the anterior N2 (a measure of attentional control) and the P3a (an index of the orienting of attention). EC predicted speed of processing at both early and late attentional stages. Individuals with lower EC exhibited prolonged SN, P3a, and P3b latencies. However, the delays in carrying out SA operations did not account for subsequent delays in decision making, or explain excessive orienting and reduced attentional control mechanisms in response to stimuli that should have been ignored. SN latency, P3 latency, and the size of the anterior N2 made independent contributions to the variance of EC. In summary, our findings suggest that current views regarding the relationship between top-down control mechanisms and SA may need refinement.

Recently published guidelines suggest that the most opportune time to treat individuals with Alzheimer’s disease is during the preclinical phase of the disease. This is a phase when individuals are defined as clinically normal but exhibit evidence of amyloidosis, neurodegeneration and subtle cognitive/behavioral decline. While our standard cognitive tests are useful for detecting cognitive decline at the stage of mild cognitive impairment, they were not designed for detecting the subtle cognitive variations associated with this biomarker stage of preclinical Alzheimer’s disease. However, neuropsychologists are attempting to meet this challenge by designing newer cognitive measures and questionnaires derived from translational efforts in neuroimaging, cognitive neuroscience and clinical/experimental neuropsychology. This review is a selective summary of several novel, potentially promising, approaches that are being explored for detecting early cognitive evidence of preclinical Alzheimer’s disease in presymptomatic individuals.

One mechanism that may allow older adults to continue to successfully perform certain cognitive tasks is to allocate more resources than their younger counterparts. Most prior studies have not included individuals beyond their 70s. Here, we investigated whether compensatory increases in neural activity previously observed in cognitively high-performing young-old adults would continue into old-old age. Event-related potentials were recorded from 72 cognitively high performing subjects, aged 18 to 96 years old, while they participated in a subject-controlled novelty oddball paradigm in which they determined viewing duration of standard, target, and novel visual stimuli. Compared to young and middle-aged subjects, both young-old and old-old subjects exhibited an impairment of preliminary mismatch/match detection operations, indexed by an attenuated anterior N2 component. This may have placed a greater burden on the subsequent controlled decision-making process, indexed by the P3, necessitating the allocation of more resources. The relationship between age and resource allocation, as measured by P3 amplitude, from midlife to very old age (45-96 years old) followed an inverted u-shaped curve (quadratic function). It peaked between the late 60s and early 70s. Thereafter, there was an inverse relationship between age and resource appropriation. This relationship remained significant after controlling for differences in task performance and MMSE. Examining the size of the P3 component across different age groups suggests that although cognitively high performing adults in their early 80s exhibit a reduction in P3 amplitude, they have a relatively well-preserved capacity to appropriate resources. However, by the late 80s, there is a robust decline (relative to young-old adults) in the size of the P3. Our results indicate that when carrying out controlled processing linked to directing attention to salient events, cognitively high performers reach the boundary of their capacity, albeit relatively late in life. This limits their ability to appropriate additional resources as compensatory activity for age-related impairments in earlier visual processing, and suggests that such a mechanism does not tend to "survive" old-old age.

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.

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.

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.

Cognitive reserve among highly intelligent older individuals makes detection of early Alzheimer's disease (AD) difficult. We tested the hypothesis that mild memory impairment determined by IQ-adjusted norms is associated with single photon emission computed tomography (SPECT) perfusion abnormality at baseline and predictive of future decline. Twenty-three subjects with a Clinical Dementia Rating (CDR) score of 0, were reclassified after scores were adjusted for IQ into two groups, 10 as having mild memory impairments for ability (IQ-MI) and 13 as memory-normal (IQ-MN). Subjects underwent cognitive and functional assessments at baseline and annual follow-up for 3 years. Perfusion SPECT was acquired at baseline. At follow-up, the IQ-MI subjects demonstrated decline in memory, visuospatial processing, and phonemic fluency, and 6 of 10 had progressed to a CDR of 0.5, while the IQ-MN subjects did not show decline. The IQ-MI group had significantly lower perfusion than the IQ-MN group in parietal/precuneus, temporal, and opercular frontal regions. In contrast, higher perfusion was observed in IQ-MI compared with IQ-MN in the left medial frontal and rostral anterior cingulate regions. IQ-adjusted memory impairment in individuals with high cognitive reserve is associated with baseline SPECT abnormality in a pattern consistent with prodromal AD and predicts subsequent cognitive and functional decline.

The animal literature suggests that exposure to more complex, novel environments promotes neurogenesis and cognitive performance in older animals. Studies in humans indicate that participation in intellectually stimulating activities may serve as a buffer against mental decline and help to sustain cognitive abilities. Here, we show that across old adults, increased responsiveness to novel events (as measured by viewing duration and the size of the P3 event-related potential) is strongly linked to better performance on neuropsychological tests, especially those involving attention/executive functions. Cognitively high performing old adults generate a larger P3 response to visual stimuli than cognitively average performing adults. These results suggest that cognitively high performing adults successfully manage the task by appropriating more resources and that the increased size of their P3 component represents a beneficial compensatory mechanism rather than less efficient processing.

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 one's internal model of the environment to take into account a novel event.

Background: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment.

Objective: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events.

Methods: While event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic.

Results: P3 amplitude to novel stimuli was significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R2 = 0.52) and inversely correlated with apathy severity.

Conclusions: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.