Direct-Current Stimulation Does Little to Improve the Outcome of Working Memory Training in Older Adults

Nilsson, Johanna; Lebedev, Alexander V.; Rydström, Anders; Lövdén, Martin

doi:10.1177/0956797617698139

Cited by 96 publications

(104 citation statements)

References 45 publications

(74 reference statements)

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“…As expected, demographic data and baseline cognitive scores were similar in the two groups. Both groups completed equivalent number of training sessions (Placebo: 18.43 (16)(17)(18)(19)(20)(21), L-dopa: 18.19 (14)(15)(16)(17)(18)(19)(20)(21), two-sample Wilcoxon test, W = 500.5, p=0.77).…”

Section: Resultsmentioning

confidence: 99%

“…Dose selection was motivated by the results from two longitudinal studies completed in the healthy younger population that demonstrated positive effects of the drug on learning and good tolerability (7,16). The cognitive training was designed according to the current recommendations in that it was adaptive in nature, targeted more than one construct (updating and switching), and promoted process-based as opposed to strategy-based improvements by including several training tasks and varying stimuli sets (19). The protocol incorporated three exercises: one focused on the ability to flexibly switch between different tasks (task-switching) and two others on the ability to continuously maintain and update mental representations (running span and n-back).…”

Section: Methodsmentioning

confidence: 99%

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Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial

Lebedev

Nilsson

Lindström

et al. 2018

Preprint

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Cognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effects are small. Basic research has implicated dopaminergic signaling in plasticity. We investigated whether transient enhancement of dopaminergic neurotransmission via administration of L-dopa improves effects of cognitive training on performance.Sixty-three participants for this randomised, parallel-group, double-blind, placebo-controlled trial were recruited via newspaper advertisements. Inclusion criteria were: age of 65-75 years, Mini-Mental State Examination score >25, absence of serious medical conditions. Eligible subjects were randomly allocated to either receive 100/25mg L-dopa/benserazide (n=32) or placebo (n=31) prior to each of twenty cognitive training sessions administered during a fourweek period. Participants and staff were blinded to group assignment. Primary outcomes were latent variables of spatial and verbal fluid intelligence.Compared to the placebo group, subjects receiving L-dopa improved less in spatial intelligence (-0.267 SDs; 95%CI [-0.498, -0.036]; p=0.024). Change in verbal intelligence did not significantly differ between the groups (-0.081 SDs, 95%CI [-0.242, 0.080]; p=0.323). Subjects receiving L-dopa also progressed slower through the training and the groups displayed differential volumetric changes in the substantia nigra. Adverse events occurred for 10 (31%) and 7 (23%) participants in the active and control groups, correspondingly.The results speak against early pharmacological interventions in older healthy adults to improve cognitive functions by targeting the dopaminergic system and provide no support for learningenhancing properties of L-dopa supplements. The findings warrant closer investigation about the cognitive effects of early dopamine-replacement therapy in neurological disorders.This trial was preregistered at the European Clinical Trial Registry, EudraCT#2016-000891-54.Significance. The results put constraints on the hypothesis of a key role of the deteriorated dopaminergic system in age-related decline of learning abilities, and speak against early pharmacological interventions in older healthy adults to improve cognitive functions by targeting the dopaminergic system. Our findings also raise concerns about usefulness of novel L-dopacontaining supplements that claim to have neuroprotective and learning-enhancing properties, and present an urgent need to carefully investigate the cognitive outcomes of early prodopaminergic interventions in clinical populations often receiving substantially larger doses of L-dopa.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial

Lebedev

Nilsson

Lindström

et al. 2018

Preprint

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“…The main study targeted 123 participants and imaging data were acquired for a random subsample of 78 subjects, 25 of whom were excluded from the analyses in keeping with the image quality criteria (see above). See (43) for details. As a part of the study, half of the subjects received transcranial direct current stimulation (tDCS), whereas the other half received sham stimulation.…”

Section: Methodsmentioning

confidence: 99%

“…The cognitive training took place the week after an extensive 5-day assessment of cognitive functions. See (43) for details and a comparative description of the two batteries.…”

Section: Methodsmentioning

confidence: 99%

“…The battery was identical on both occasions and included a number of diverse cognitive tests measuring switching (task- and rule-switching), updating (n-back, running span), attention (temporal expectancy, perceptual matching), episodic memory (verbal and spatial recall), and spatial (WASI, Raven’s, BETA matrices) and verbal (Syllogisms, BIS Analogies, ETS Kit inference) reasoning. See (43) for detailed description of the cognitive assessment.…”

Section: Methodsmentioning

confidence: 99%

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Working memory and reasoning benefit from different modes of large-scale brain dynamics in healthy older adults

Lebedev

Nilsson

Lövdén

2017

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Researchers have proposed that solving complex reasoning problems, a key indicator of fluid intelligence, involves the same cognitive processes as solving working memory tasks. This proposal is supported by an overlap of the functional brain activations associated with the two types of tasks and by high correlations between inter-individual differences in performance. We replicated these findings in fifty-three older subjects but also showed that solving reasoning and working memory problems benefits from different configurations of the functional connectome and that this dissimilarity increases with higher difficulty load. Specifically, superior performance in a typical working memory paradigm (n-back) was associated with up-regulation of modularity (increased between-network segregation), whereas performance in the reasoning task was associated with effective down-regulation of modularity. We also showed that working memory training promotes task-invariant increases in modularity. Since superior reasoning performance is associated with down-regulation of modular dynamics, training may thus have fostered an inefficient way of solving the reasoning tasks. This could help explain why working memory training does little to promote complex reasoning performance. The study concludes that complex reasoning abilities cannot be reduced to working memory and suggests the need to reconsider the feasibility of using working memory training interventions to attempt to achieve effects that transfer to broader cognition.

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Neural basis of induced phantom limb pain relief

Kikkert

Mezue

O’Shea

et al. 2019

Annals of Neurology

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Objective Phantom limb pain (PLP) is notoriously difficult to treat, partly due to an incomplete understanding of PLP‐related disease mechanisms. Noninvasive brain stimulation (NIBS) is used to modulate plasticity in various neuropathological diseases, including chronic pain. Although NIBS can alleviate neuropathic pain (including PLP), both disease and treatment mechanisms remain tenuous. Insight into the mechanisms underlying both PLP and NIBS‐induced PLP relief is needed for future implementation of such treatment and generalization to related conditions. Methods We used a within‐participants, double‐blind, and sham‐controlled design to alleviate PLP via task‐concurrent NIBS over the primary sensorimotor missing hand cortex (S1/M1). To specifically influence missing hand signal processing, amputees performed phantom hand movements during anodal transcranial direct current stimulation. Brain activity was monitored using neuroimaging during and after NIBS. PLP ratings were obtained throughout the week after stimulation. Results A single session of intervention NIBS significantly relieved PLP, with effects lasting at least 1 week. PLP relief associated with reduced activity in the S1/M1 missing hand cortex after stimulation. Critically, PLP relief and reduced S1/M1 activity correlated with preceding activity changes during stimulation in the mid‐ and posterior insula and secondary somatosensory cortex (S2). Interpretation The observed correlation between PLP relief and decreased S1/M1 activity confirms our previous findings linking PLP with increased S1/M1 activity. Our results further highlight the driving role of the mid‐ and posterior insula, as well as S2, in modulating PLP. Lastly, our novel PLP intervention using task‐concurrent NIBS opens new avenues for developing treatment for PLP and related pain conditions. ANN NEUROL 2019;85:59–73.

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Direct-Current Stimulation Does Little to Improve the Outcome of Working Memory Training in Older Adults

Cited by 96 publications

References 45 publications

Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial

Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial

Working memory and reasoning benefit from different modes of large-scale brain dynamics in healthy older adults

Neural basis of induced phantom limb pain relief

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