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Neural correlates of working memory training: Evidence for plasticity in older adults.

ABSTRACT: Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.

SUBMITTER: Iordan AD

PROVIDER: S-EPMC7755422 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Neural correlates of working memory training: Evidence for plasticity in older adults.

Iordan Alexandru D AD Cooke Katherine A KA Moored Kyle D KD Katz Benjamin B Buschkuehl Martin M Jaeggi Susanne M SM Polk Thad A TA Peltier Scott J SJ Jonides John J Reuter-Lorenz Patricia A PA

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Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults ...[more]

PMID: 32376302

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Project description:N-back working memory (WM) tasks necessitate the maintenance and updating of dynamic rehearsal sets during performance. The delayed matching-to-sample (dMTS) task is another WM task, which in turn involves the encoding, maintenance, and retrieval of stimulus representations in sequential order. Because both n-back and dMTS engage WM function, we hypothesized that compared to a control task not taxing WM, training on the n-back task would be associated with better performance on dMTS by virtue of training a shared mental capacity. We tested this hypothesis by randomly assigning subjects (N = 43) to train on either the n-back (including 2-back and 3-back levels) or an active control task. Following training, dMTS was administered in the fMRI scanner. The n-back group performed marginally better than the active control group on dMTS. In addition, although the n-back group improved more on the less difficult 2-back level than the more difficult 3-back level across training sessions, it was improvement on the 3-back level that accounted for 21% of the variance in dMTS performance. For the control group, improvement in training across sessions was unrelated to dMTS performance. At the neural level, greater activation in the left inferior frontal gyrus, right posterior parietal cortex, and the cerebellum distinguished the n-back group from the control group in the maintenance phase of dMTS. Degree of improvement on the 3-back level across training sessions was correlated with activation in right lateral prefrontal and motor cortices in the maintenance phase of dMTS. Our results suggest that although n-back training is more likely to improve performance in easier blocks, it is improvement in more difficult blocks that is predictive of performance on a target task drawing on WM. In addition, the extent to which training on a task can transfer to another task is likely due to the engagement of shared cognitive capacities and underlying neural substrates-in this case WM.

Project description:Potent combined antiretroviral therapy decreased the incidence and severity of HIV-associated neurocognitive disorders (HAND); however, no specific effective pharmacotherapy exists for HAND. Patients with HIV commonly have deficits in working memory and attention, which may negatively impact many other cognitive domains, leading to HAND. Since HAND may lead to loss of independence in activities of daily living and negative emotional well-being, and incur a high economic burden, effective treatments for HAND are urgently needed. This study aims to determine whether adaptive working memory training might improve cognitive functions and neural network efficiency and possibly decrease neuroinflammation. This study also aims to assess whether subjects with the LMX1A-rs4657412 TT(AA) genotype show greater training effects from working memory training than TC(AG) or CC(GG)-carriers.60 HIV-infected and 60 seronegative control participants will be randomized to a double-blind active-controlled study, using adaptive versus non-adaptive Cogmed Working Memory Training® (CWMT), 20-25 sessions over 5-8 weeks. Each subject will be assessed with near- and far-transfer cognitive tasks, self-reported mood and executive function questionnaires, and blood-oxygenation level-dependent functional MRI during working memory (n-back) and visual attention (ball tracking) tasks, at baseline, 1-month, and 6-months after CWMT. Furthermore, genotyping for LMX1A-rs4657412 will be performed to identify whether subjects with the TT(AA)-genotype show greater gain or neural efficiency after CWMT than those with other genotypes. Lastly, cerebrospinal fluid will be obtained before and after CWMT to explore changes in levels of inflammatory proteins (cytokines and chemokines) and monoamines.Improving working memory in HIV patients, using CWMT, might slow the progression or delay the onset of HAND. Observation of decreased brain activation or normalized neural networks, using fMRI, after CWMT would lead to a better understanding of how neural networks are modulated by CWMT. Moreover, validating the greater training gain in subjects with the LMX1A-TT(AA) genotype could lead to a personalized approach for future working memory training studies. Demonstrating and understanding the neural correlates of the efficacy of CWMT in HIV patients could lead to a safe adjunctive therapy for HAND, and possibly other brain disorders.ClinicalTrial.gov, NCT02602418.

Dataset Information

Neural correlates of working memory training: Evidence for plasticity in older adults.

Publications

Neural correlates of working memory training: Evidence for plasticity in older adults.

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