Cindy Lustig

Disruption of Large-Scale Brain Systems in Advanced Aging

Cognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimers disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition.

Functional deactivations: Change with age and dementia of the Alzheimer type

Young adults typically deactivate specific brain regions during active task performance. Deactivated regions overlap with those that show reduced resting metabolic activity in aging and dementia, raising the possibility of a relation. Here, the magnitude and dynamic temporal properties of these typically deactivated regions were explored in aging by using functional MRI in 82 participants. Young adults (n = 32), older adults without dementia (n = 27), and older adults with early-stage dementia of the Alzheimer type (DAT) (n = 23) were imaged while alternating between blocks of an active semantic classification task and a passive fixation baseline. Deactivation in lateral parietal regions was equivalent across groups; in medial frontal regions, it was reduced by aging but was not reduced further by DAT. Of greatest interest, a medial parietal/ posterior cingulate region showed differences between young adults and older adults without dementia and an even more marked difference with DAT. The temporal profile of the medial parietal/posterior cingulate response suggested that it was initially activated by all three groups, but the response in young adults quickly reversed sign, whereas DAT individuals maintained activation throughout the task block. Exploratory whole-brain analyses confirmed the importance of medial parietal/posterior cingulate cortex differences in aging and DAT. These results introduce important opportunities to explore the functional properties of regions showing deactivations, how their dynamic functional properties relate to their baseline metabolic rates, and how they change with age and dementia.

Aging, Training, and the Brain: A Review and Future Directions

As the population ages, the need for effective methods to maintain or even improve older adults’ cognitive performance becomes increasingly pressing. Here we provide a brief review of the major intervention approaches that have been the focus of past research with healthy older adults (strategy training, multi-modal interventions, cardiovascular exercise, and process-based training), and new approaches that incorporate neuroimaging. As outcome measures, neuroimaging data on intervention-related changes in volume, structural integrity; and functional activation can provide important insights into the nature and duration of an intervention’s effects. Perhaps even more intriguingly, several recent studies have used neuroimaging data as a guide to identify core cognitive processes that can be trained in one task with effective transfer to other tasks that share the same underlying processes. Although many open questions remain, this research has greatly increased our understanding of how to promote successful aging of cognition and the brain.

Brain aging: reorganizing discoveries about the aging mind

New discoveries challenge the long-held view that aging is characterized by progressive loss and decline. Evidence for functional reorganization, compensation and effective interventions holds promise for a more optimistic view of neurocognitive status in later life. Complexities associated with assigning function to age-specific activation patterns must be considered relative to performance and in light of pathological aging. New biological and genetic markers, coupled with advances in imaging technologies, are enabling more precise characterization of healthy aging. This interdisciplinary, cognitive neuroscience approach reveals dynamic and optimizing processes in aging that might be harnessed to foster the successful aging of the mind.

Working memory span and the role of proactive interference.

The authors investigated the possibility that working memory span tasks are influenced by interference and that interference contributes to the correlation between span and other measures. Younger and older adults received the span task either in the standard format or one designed to reduce the impact of interference with no impact on capacity demands. Participants then read and recalled a short prose passage. Reducing the amount of interference in the span task raised span scores, replicating previous results (C. P. May, L. Hasher, & M. J. Kane, 1999). The same interference-reducing manipulations that raised span substantially altered the relation between span and prose recall. These results suggest that span is influenced by interference, that age differences in span may be due to differences in the ability to overcome interference rather than to differences in capacity, and that interference plays an important role in the relation between span and other tasks.

Preserved Neural Correlates of Priming in Old Age and Dementia

Implicit memory, including priming, can be preserved in aging and dementia despite impairment of explicit memory. To explore the neural correlates of preserved memory ability, whole-brain functional MRI (fMRI) was used during a repetition priming paradigm to study 34 young adults, 33 older adults without dementia, and 24 older adults in the early stages of dementia of the Alzheimer type (DAT). Both older adult groups showed repetition-based response time benefits (priming) and changes in activation along inferior frontal gyrus similar to those shown by young adults. Across all three groups, repetition-related response time reductions correlated with prefrontal activity reductions, demonstrating a direct relation between priming and fMRI-measured activity change. These results suggest that despite difficulties with deliberate memory, both older adults without dementia and those with early-stage DAT can modify behavior mediated by prefrontal contributions, making these preserved abilities an attractive target for cognitive training and rehabilitation.

Paying Attention to Time as one Gets Older

Age-related changes in attention and interval timing as a function of time of day were examined using a temporal bisection task with single and compound auditory and visual stimuli. Half of the participants in each age group were tested in the morning, and half were tested in the afternoon. Duration judgments were found to be shorter for visual signals than for auditory signals. This discrepancy was greater in the morning than in the afternoon and larger for the older than for the younger adults. Young adults showed equal sensitivity to signal duration for single and compound trials and higher sensitivity in the afternoon than in the morning for both signal modalities. In contrast, older adults showed impaired sensitivity on compound trials and the greatest sensitivity overall to single visual trials in the morning. These results suggest that age-related reductions in attentional resources may cause older adults to focus on signals that require controlled attention during specific phases of the circadian cycle.

Not “just” a coincidence: Frontal‐striatal interactions in working memory and interval timing

The frontal cortex and basal ganglia play central roles in working memory and in the ability to time brief intervals. We outline recent theoretical and empirical work to suggest that working memory and interval timing rely not only on the same anatomic structures, but also on the same neural representation of a specific stimulus. Specifically, cortical neurons may fire in an oscillatory fashion to form representations of stimuli, and the striatum (a basal ganglia structure) may detect those patterns of cortical firing that occur co‐incident to important events. Information about stimulus identity can be extracted from which cortical neurons are involved in the representation, and information about duration can be extracted from their relative phase. The principles derived from these biologically based models also fit well with a family of behaviourally based models that emphasise the importance of time in many working memory phenomena.

Long-Term Memory for the Terrorist Attack of September 11: Flashbulb Memories, Event Memories, and the Factors that Influence Their Retention.

More than 3,000 individuals from 7 U.S. cities reported on their memories of learning of the terrorist attacks of September 11, as well as details about the attack, 1 week, 11 months, and/or 35 months after the assault. Some studies of flashbulb memories examining long-term retention show slowing in the rate of forgetting after a year, whereas others demonstrate accelerated forgetting. This article indicates that (a) the rate of forgetting for flashbulb memories and event memory (memory for details about the event itself) slows after a year, (b) the strong emotional reactions elicited by flashbulb events are remembered poorly, worse than nonemotional features such as where and from whom one learned of the attack, and (c) the content of flashbulb and event memories stabilizes after a year. The results are discussed in terms of community memory practices.

Enhanced Control of Attention by Stimulating Mesolimbic–Corticopetal Cholinergic Circuitry

Sustaining and recovering attentional performance requires interactions between the brains motivation and attention systems. The first experiment demonstrated that in rats performing a sustained attention task (SAT), presentation of a distractor (dSAT) augmented performance-associated increases in cholinergic neurotransmission in prefrontal cortex. Because stimulation of NMDA receptors in the shell of the nucleus accumbens activates PFC cholinergic neurotransmission, a second experiment demonstrated that bilateral infusions of NMDA into the NAc shell, but not core, improved dSAT performance to levels observed in the absence of a distractor. A third experiment demonstrated that removal of prefrontal or posterior parietal cholinergic inputs, by intracortical infusions of the cholinotoxin 192 IgG-saporin, attenuated the beneficial effects of NMDA on dSAT performance. Mesolimbic activation of cholinergic projections to the cortex benefits the cognitive control of attentional performance by enhancing the detection of cues and the filtering of distractors.