Age-related Working Memory Decline Research Articles

Can Brief Listening to Mozart's Music Improve Visual Working Memory? An Update on the Role of Cognitive and Emotional Factors.

The aim of this research was to enhance understanding of the relationship between brief music listening and working memory (WM) functions. The study extends a previous large-scale experiment in which the effects of brief exposure to music on verbal WM were explored. In the present second phase of the experiment, these effects were assessed for the visuospatial subcomponent of WM. For that aim, visuospatial WM was measured using the Corsi blocks task-backwards and Visual Patterns Test in a large sample of 311 young and older adults after being exposed to musical excerpts coming from different music composers (Mozart, Vivaldi, Glass). To account for possible effects of arousal, a silence condition was used. Individual preference for music excerpts and emotional reactions to each condition were also subjectively rated using the Positive and Negative Affect Schedule (PANAS) to account for the role of emotional reactions in shaping subsequent cognitive performance. Results showed that music affected the visuospatial sketchpad of WM. In line with the previously described Mozart effect, only Mozart's music had a significant positive impact on visuospatial WM in the two age groups, regardless of preferences, and on overall age-related WM decline in older adults. The Mozart effect was more prominent for the VPT than the Corsi task and was also expressed for the prevailing positive effect. These observations are in contrast to the selective influence of Vivaldi's music on verbal WM that was detected in our first study. Together, the results demonstrate a differential music influence on the phonological loop and on the visuospatial sketchpad. They thus contribute to the debate of whether music has the potential to affect distinct processes within working memory in an excerpt- or composer-specific manner. Also, they suggest that emotional activation and central executive attention are essentially involved in modulating the influence of music on subsequent cognition. These findings can assist in the selection of music excerpts used in cognitive rehabilitation programs that focus on visuospatial skills.

Decomposing neurophysiological underpinnings of age-related decline in visual working memory

Exploring the neural basis of age-related decline in working memory is vital in our aging society. Previous electroencephalographic studies suggested that the contralateral delay activity (CDA) may be insensitive to age-related decline in lateralized visual working memory (VWM) performance. Instead, recent evidence indicated that task-induced alpha power lateralization decreases in older age. However, the relationship between alpha power lateralization and age-related decline of VWM performance remains unknown, and recent studies have questioned the validity of these findings due to confounding factors of the aperiodic signal. Using a sample of 134 participants, we replicated the age-related decrease of alpha power lateralization after adjusting for the aperiodic signal. Critically, the link between task performance and alpha power lateralization was found only when correcting for aperiodic signal biases. Functionally, these findings suggest that age-related declines in VWM performance may be related to the decreased ability to prioritize relevant over irrelevant information. Conversely, CDA amplitudes were stable across age groups, suggesting a distinct neural mechanism possibly related to preserved VWM encoding or early maintenance.

Age-Related Changes in Functional Connectivity during the Sensorimotor Integration Detected by Artificial Neural Network.

Large-scale functional connectivity is an important indicator of the brain’s normal functioning. The abnormalities in the connectivity pattern can be used as a diagnostic tool to detect various neurological disorders. The present paper describes the functional connectivity assessment based on artificial intelligence to reveal age-related changes in neural response in a simple motor execution task. Twenty subjects of two age groups performed repetitive motor tasks on command, while the whole-scalp EEG was recorded. We applied the model based on the feed-forward multilayer perceptron to detect functional relationships between five groups of sensors located over the frontal, parietal, left, right, and middle motor cortex. Functional dependence was evaluated with the predicted and original time series coefficient of determination. Then, we applied statistical analysis to highlight the significant features of the functional connectivity network assessed by our model. Our findings revealed the connectivity pattern is consistent with modern ideas of the healthy aging effect on neural activation. Elderly adults demonstrate a pronounced activation of the whole-brain theta-band network and decreased activation of frontal–parietal and motor areas of the mu-band. Between-subject analysis revealed a strengthening of inter-areal task-relevant links in elderly adults. These findings can be interpreted as an increased cognitive demand in elderly adults to perform simple motor tasks with the dominant hand, induced by age-related working memory decline.

Working Memory Training Effects on White Matter Integrity in Young and Older Adults.

ObjectivesWorking memory is essential for daily life skills like reading comprehension, reasoning, and problem-solving. Healthy aging of the brain goes along with working memory decline that can affect older people’s independence in everyday life. Interventions in the form of cognitive training are a promising tool for delaying age-related working memory decline, yet the underlying structural plasticity of white matter is hardly studied.MethodsWe conducted a longitudinal diffusion tensor imaging study to investigate the effects of an intensive four-week adaptive working memory training on white matter integrity quantified by global and tract-wise mean diffusivity. We compared diffusivity measures of fiber tracts that are associated with working memory of 32 young and 20 older participants that were randomly assigned to a working memory training group or an active control group.ResultsThe behavioral analysis showed an increase in working memory performance after the four-week adaptive working memory training. The neuroanatomical analysis revealed a decrease in mean diffusivity in the working memory training group after the training intervention in the right inferior longitudinal fasciculus for the older adults. There was also a decrease in mean diffusivity in the working memory training group in the right superior longitudinal fasciculus for the older and young participants after the intervention.ConclusionThis study shows that older people can benefit from working memory training by improving their working memory performance that is also reflected in terms of improved white matter integrity in the superior longitudinal fasciculus and the inferior longitudinal fasciculus, where the first is an essential component of the frontoparietal network known to be essential in working memory.

Effects of Computerized Updating and Inhibition Training in Older Adults: The ACTOP Three-Arm Randomized Double-Blind Controlled Trial.

Background: Working memory (WM) capacity declines with advancing age, which impacts the ability to carry out complex cognitive activities in everyday life. Updating and inhibition processes have been identified as some of the most critical attentional control processes of WM and are linked to age-related WM decline. The general aim of the Attentional Control Training in Older People (ACTOP) study was to perform a side-by-side comparison of updating and inhibition training to examine their respective efficacy and transfer in cognitively healthy older adults.Method: The study was a three-arm, double-blind, randomized controlled trial registered with the US National Institutes of Health clinical trials registry. Ninety older adults were randomly assigned to 12 half-hour sessions of updating (N-back type exercises), inhibition (Stroop-like exercises) computerized training or active control (general knowledge quiz game). A group of thirty younger adults completed all proximal and WM transfer tasks without training to assess age-related deficits prior to training and whether training reduces these deficits.Results: Piecewise mixed models show quick improvement of performance during training for both updating and inhibition training. During updating training, the progression was more pronounced for the most difficult (3-back) than for the least (1-back) difficult level until the ninth session. Updating and inhibition training groups improved performance on all proximal and WM transfer measures but these improvements did not differ from the active control group. Younger adults outperformed older ones on all transfer tasks prior to training. However, this was no longer the case following training for two transfer tasks regardless of the training group.Conclusion: The overall results from this study suggest that attentional control training is effective in improving updating and inhibition performance on training tasks. The optimal dose to achieve efficacy is ~9 half-hour sessions and the dose effect was related to difficulty level for updating training. Despite an overall improvement of older adults on all transfer tasks, neither updating nor inhibition training provided additional improvements in comparison with the active control condition. This suggests that the efficacy of process-based training does not directly affect transfer tasks.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03532113

Maintenance vs. Manipulation in Auditory Verbal Working Memory in the Elderly: New Insights Based on Temporal Dynamics of Information Processing in the Millisecond Time Range.

Working memory (WM) is a limited-capacity cognitive system that allows the storage and use of a limited amount of information for a short period of time. Two WM processes can be distinguished: maintenance (i.e., storing, monitoring, and matching information) and manipulation (i.e., reordering and updating information). A number of studies have reported an age-related decline in WM, but the mechanisms underlying this deterioration need to be investigated. Previous research, including studies conducted in our laboratory, revealed that age-related cognitive deficits are related to decreased millisecond timing, i.e., the ability to perceive and organize incoming events in time. The aim of the current study was: (1) to identify in the elderly the brain network involved in the maintenance and manipulation WM processes; and (2) to use an fMRI task to investigate the relation between the brain activity associated with these two processes and the efficiency of temporal information processing (TIP) on a millisecond level reflected by psychophysical indices. Subjects were 41 normal healthy elderly people aged from 62 to 78 years. They performed: (1) an auditory verbal n-back task for assessing WM efficiency in an MRI scanner; and (2) a psychophysical auditory temporal-order judgment (TOJ) task for assessing temporal resolution in the millisecond domain outside the scanner. The n-back task comprised three conditions (0-, 1-, and 2-back), which allowed maintenance (1- vs. 0-back comparisons) and manipulation (2- vs. 1-back comparisons) processes to be distinguished. Results revealed the involvement of a similar brain network in the elderly to that found in previous studies. However, during maintenance processes, we found relatively limited and focused activations, which were significantly extended during manipulation. A novel result of our study, never reported before, is an indication of significant moderate correlations between the efficiency of WM and TIP. These correlations were found only for manipulation but not for maintenance. Our results confirmed the hypothesis that manipulation in the elderly is a dynamic process requiring skilled millisecond timing with high temporal resolution. We conclude that millisecond timing contributes to WM manipulation in the elderly, but not to maintenance.

Social housing protects against age-related working memory decline independently of physical enrichment in rats

Longitudinal human studies suggest that as we age, sociality provides protective benefits against cognitive decline. However, little is known about the underlying neural mechanisms. Rodent studies, which are ideal for studying cognition, fail to examine the independent effects of social housing while controlling for physical enrichment in all groups. In this study, rats were socially housed or nonsocially housed throughout their lifespan and tested in the radial arm maze to measure working memory (WM) and reference memory longitudinally at 3 ages. In old age, exclusively, socially housed rats made significantly less WM errors than nonsocially housed rats, while reference memory errors did not differ between groups at any age. Anxiety, as assessed behaviorally and physiologically, could not account for the observed differences in WM. These data provide the first evidence that social enrichment alone can prevent age-related WM deficits in spite of the effects of practice seen in longitudinal designs. Importantly, our model will facilitate future investigations into the mechanisms underlying the neuroprotective benefits of sociability in old age.

ENHANCED PARIETAL-CINGULATE CONNECTIVITY FOLLOWING ALTERED CORTICAL ACTIVATION IMPROVES WORKING MEMORY PERFORMANCE IN OLD AGE

Substantial working memory (WM) decline in aging has been thought as one of the factors triggering the cognitive aging procedure, it is even more important when you consider the remarkable WM impairment in diseases like Alzheimer's disease (AD). In past few years, growing fMRI evidences have attributed the WM decline to cortical activation changes, especially in frontal and parietal regions. However, as the fact of cortical coordination in supporting cognitive process, task-based functional connectivity is thought to make direct and considerable contribution to WM alteration. Hence, we explore both the cortical activity and the background connectivity during WM tasks to explore their role in age-related WM decline. 166 participants who aged 55 to 86 years old, scored 24 or higher on MMSE and had at least 6 years of education were included. Neuropsychological profiles and nback task fMRI data were acquired from each participant. Task-related activation was examined on contrast images created by subtracting the 0-back images from the 2-back images, and the ROI-based background functional connectivity was calculated on the residual image obtained by regressing task-related signal and nuisance variables. General linear models were performed to explore the age effect on activation and connectivity, and their relationship with WM decline. Significant age-related decline was found in accuracy rate of nback tasks (0-, 1-, and 2-back), while reaction time was only remarkably increased in 0- and 1-back (p < 0.05). During the task, activation of right inferior parietal gyrus (IPG) and deactivation of left anterior cingulum gyrus (ACG) were attenuated with age (alphasim corrected p < 0.05), both mediating age impact on task performance. Further analyses on ROI-based functional connectivity revealed that connectivity between IPG and left middle cingulum gyrus (MCG), between ACG and left IPG and right angular gyrus (AG) were all enhanced during aging (alphasim corrected p < 0.05). More importantly, IPG-MCG and ACG-IPG connectivity could positively predicted individual's task performance, independent of task-related activation/deactivation alteration (p<0.05).

Age-Related Changes in 1/f Neural Electrophysiological Noise.

Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in neural communication.

Trying to Put the Puzzle Together: Age and Performance Level Modulate the Neural Response to Increasing Task Load within Left Rostral Prefrontal Cortex.

Age-related working memory decline is associated with functional cerebral changes within prefrontal cortex (PFC). Kind and meaning of these changes are heavily discussed since they depend on performance level and task load. Hence, we investigated the effects of age, performance level, and load on spatial working memory retrieval-related brain activation in different subregions of the PFC. 19 younger (Y) and 21 older (O) adults who were further subdivided into high performers (HP) and low performers (LP) performed a modified version of the Corsi Block-Tapping test during fMRI. Brain data was analyzed by a 4 (groups: YHP, OHP, YLP, and OLP) × 3 (load levels: loads 4, 5, and 6) ANOVA. Results revealed significant group × load interaction effects within rostral dorsolateral and ventrolateral PFC. YHP showed a flexible neural upregulation with increasing load, whereas YLP reached a resource ceiling at a moderate load level. OHP showed a similar (though less intense) pattern as YHP and may have compensated age-effects at high task load. OLP showed neural inefficiency at low and no upregulation at higher load. Our findings highlight the relevance of age and performance level for load-dependent activation within rostral PFC. Results are discussed in the context of the compensation-related utilization of neural circuits hypothesis (CRUNCH) and functional PFC organization.

Visually encoded working memory is closely associated with mobility in older adults

Previous research suggests that older adults' motor performance is associated with cognitive function. Although this has been reported especially for executive function, it is not yet clear for various types of working memory (WM). In fact, age-related decline in WM is more severe for faces than other types of visual objects. The present study focused on the relationship between diverse WM and two types of motor performance (mobility and manual dexterity), which are implicated in pathological decline. To measure diverse WM, we adopted N-back tasks using three distinct types of stimuli (numbers, locations, and faces). Mobility was measured with the timed up and go test and manual dexterity was measured with the Pegboard Test. Participants were community-dwelling older adults (age: mean 78.6 years). Comparisons of younger and older adults' N-back performances indicated that WM for faces is more sensitive to aging compared with WM for the other stimuli. Correlation analyses within the older group indicated that WM tasks mainly correlated with mobility, but less so with manual dexterity. Among the three types of WM, spatial WM and face WM had significant partial correlation coefficients with mobility after age and general cognitive decline were controlled. These results indicate that visually encoded WM is associated only with mobility, although general cognitive function is related to both motor abilities. The selective association between the visually encoded WM and mobility is discussed in terms of the interactive processes between executive processing and perceptual encoding, where dynamic visual processing for locomotion plays a role.

Age-related differences in working memory: ERPs reveal age-related delays in selection- and inhibition-related processes

ABSTRACTFaulty inhibition is implicated in age-related working memory decline. ERP signs of selection and inhibition of items in working memory (WM) are, respectively, a cue-locked parietal positivity (∼350 ms) and a probe-locked frontal negativity (∼520 ms). To determine when in the older age range differences in selective and inhibitory processes might occur, ERPs were recorded in a WM task from 20 young (20–28), 20 young–old (60–70), and 20 old–old (71–82) adults. A 4-digit display was followed by a cue indicating which 2 of 4 digits were relevant. Proactive interference (PI), the reaction time difference between a matching and non-matching to-be-ignored digit was larger, relative to the young, in both older groups. Compared to the young, both the cue- and probe-locked activities were prolonged in the older groups. Although there were no topographic differences among the age groups, the prolonged PI and associated ERPs suggest a relative age-related deficit in inhibition.

Neuronal basis of age-related working memory decline

Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.

On the Relative Role of Inhibition in Age-Related Working Memory Decline

ABSTRACT In this cross-sectional study, the mediating role of inhibition relative to speed in age-related working memory decline on different tasks was investigated. It was hypothesized that the role of inhibition is marginal or absent in a relatively “passive” or simple working memory task, but present in a relatively “active” or complex task in which the processing, rather than the storage capacity of working memory, is addressed. This hypothesis was tested with a structural equation model that was fitted on a subsample (N = 213) of the Maastricht Aging Study (MAAS). The first trial of the Verbal Learning Test (VLT) served as the passive test and the Self-Paced Auditory Serial Addition Task (SPASAT) as the active test. Results showed that the role of inhibition was absent in predicting VLT performance, whereas it was comparable to the role of speed in predicting SPASAT performance. These findings suggest a relative, task-dependent role of inhibition in explaining age-related memory decline.

Age-related working memory impairment is correlated with increases in the L-type calcium channel protein α 1D (Ca v1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment

The hippocampus is critical for spatial memory formation in rodents. Calcium currents through L-type voltage-sensitive calcium channels (L-VSCCs) are increased in CA1 neurons of the hippocampus of aged rats. We have recently shown that expression of the calcium conducting L-VSCC subunit α 1D (Ca v1.3) is selectively increased in area CA1 of aged rats. We and others have speculated that excessive Ca 2+ influx through L-VSCC may be detrimental to memory formation. Therefore, we investigated the relationship between age-related working memory decline and α 1D protein expression in the hippocampus. In addition, we studied the effects of chronic treatment with the L-VSCC antagonist nimodipine (NIM) on age-related working memory deficits and α 1D expression in the hippocampus. Here we report that age-related increases in α 1D expression in area CA1 correlate with working memory impairment in Fischer 344 rats. Furthermore, we demonstrate that chronic NIM treatment ameliorates age-related working memory deficits and reduces expression of α 1D protein in the hippocampus. The present results suggest that L-VSCCs participate in processes underlying memory formation and that increases in L-VSCC protein and currents observed with aging may play a role in age-related memory decline. Furthermore, the amelioration in age-related memory decline produced by NIM treatment may be mediated, at least in part, by reductions in the abnormally high levels of α 1D protein in the aged hippocampus. These findings may have implications for patients with Alzheimer’s disease, who show increased L-VSCC protein expression in the hippocampus, and for patients receiving chronic treatment with L-VSCC antagonists.