Elsevier

Neurobiology of Aging

Volume 61, January 2018, Pages 245-254
Neurobiology of Aging

Regular article
Neuronal and behavioral effects of multi-day brain stimulation and memory training

https://doi.org/10.1016/j.neurobiolaging.2017.09.017Get rights and content

Abstract

Strategies for memory enhancement, especially for the older population, are of great scientific and public interest. Here, we aimed at investigating neuronal and behavioral effects of transcranial direct current stimulation (tDCS) paired with memory training. Young and older adults were trained on an object-location-memory task on 3 consecutive days with either anodal or sham tDCS. Recall performance was assessed immediately after training, 1 day and 1 month later, as well as performance on trained function and transfer task. Resting-state functional magnetic resonance imaging was conducted at baseline and at 1-day follow-up to analyze functional coupling in the default mode network. Anodal tDCS led to superior recall performance after training, an associated increase in default mode network strength and enhanced trained function and transfer after 1 month. Our findings suggest that tDCS-accompanied multi-day training improves performance on trained material, is associated with beneficial memory network alterations, and transfers to other memory tasks. Our study provides insight into tDCS-induced behavioral and neuronal alterations and will help to develop interventions against age-related cognitive decline.

Introduction

Research on the combination of cognitive training protocols with noninvasive transcranial brain stimulation (NIBS) techniques has gained attention as a means for cognitive enhancement in both young and older adults (Elmasry et al., 2015, Passow et al., 2017, Perceval et al., 2016). Given decline of cognitive function even in healthy aging, combined NIBS-training protocols are of particular relevance for older adults (Mameli et al., 2014, Perceval et al., 2016). Especially, the modulation of brain plasticity with transcranial direct current stimulation (tDCS) concurrent to intense task practice over multiple days holds promise to induce sustained improvements of trained and untrained functions (Au et al., 2017, Berryhill, 2017, Kuo and Nitsche, 2012, Mameli et al., 2014). The benefits of cognitive training regimes alone, as well as the additive effects of tDCS on trained and untrained functions, have been challenged recently (Horvath et al., 2015, Melby-Lervag et al., 2016, Nilsson et al., 2017). Those benefits have come into question particularly in older populations, due to reduced neuroplasticity, deficient neurotransmitter systems, and in general, higher interindividual variability in the course of aging (Dahlin et al., 2008, Passow et al., 2017, von Bastian and Oberauer, 2014).

In young adults, the additive application of tDCS concurrent to cognitive training over multiple days has been suggested to produce faster performance gains and more generalized cognitive improvements (Elmasry et al., 2015, Ruf et al., 2017). However, the robustness of these effects has been questioned (Horvath et al., 2015, Mancuso et al., 2016). Beneficial effects on the trained task have been observed in young adults for working memory (Au et al., 2016, Martin et al., 2013, Richmond et al., 2014, Ruf et al., 2017) and for associative learning (Meinzer et al., 2014). Anodal tDCS over dorsolateral prefrontal cortices during a 3-day 3-back training enhanced learning and resulted in maintenance and transfer of training gains after 9 months (Ruf et al., 2017). Anodal tDCS over the left posterior temporoparietal junction during a 5-day learning of new object-name associations led to faster and more pronounced learning success compared to the sham stimulation group, resulting in persistent gains after 1 week (Meinzer et al., 2014).

In older adults, tDCS may constitute a promising approach to restore functions and counteract age-related cognitive decline (Mameli et al., 2014, Perceval et al., 2016). Effects of tDCS-accompanied multi-day training have been investigated only for working memory processes (Jones et al., 2015, Nilsson et al., 2017, Park et al., 2014, Stephens and Berryhill, 2016). The combination of working memory practice with concurrent anodal tDCS over the right prefrontal cortex led to maintained gains on trained and untrained visuospatial working memory functions (Jones et al., 2015) and, beyond that, exerted beneficial effects on ecologically valid far transfer tasks (Stephens and Berryhill, 2016). However, evidence that tDCS-accompanied training causes longer-lasting and more transferable cognitive enhancement than training alone is scarce and still debated. This may be due to heterogeneous methodological approaches and the presence of null findings as well (Elmasry et al., 2015, Talsma et al., 2016). In a recent study with a large group of older adults, anodal prefrontal tDCS over 20 sessions during a complex working memory training failed to modulate either training gains or immediate transfer (Nilsson et al., 2017).

The effects of tDCS on brain connectivity have been studied in single-session investigations, but the neuronal correlates of tDCS-accompanied multi-day cognitive training in neural networks that subserve the complex memory processes are largely unknown (Elmasry et al., 2015, Wang and Voss, 2015). Changes in local spontaneous brain activity and functional network connectivity have been suggested as potential underlying mechanisms of tDCS-induced performance enhancement (Elmasry et al., 2015, Hunter et al., 2013, Meinzer et al., 2012). Recent research, focusing on interindividual variability of tDCS effects, has recognized age as one of the factors affecting responsiveness to tDCS (Antonenko et al., 2017, Meinzer et al., 2013, Summers et al., 2016). Studies using resting-state functional magnetic resonance imaging (rs-fMRI) for the assessment of functional network connectivity during the absence of a task revealed that the default mode network (DMN) represents the most prominent large-scale brain network–mediating episodic memory processes (for recent reviews, see Jeong et al., 2015, Kim, 2016). Declines in DMN connectivity are evident in healthy and pathological aging (Jones et al., 2011), predict age-related decrease in episodic memory performance (Fjell et al., 2015, Wang et al., 2010, Ward et al., 2015), and may thus represent a sensitive biomarker for memory deficits (Salami et al., 2014). In fact, recent studies have observed increased DMN functional connectivity following anodal tDCS over the dorsolateral prefrontal cortex (Keeser et al., 2011) and as a result of training-induced cognitive improvement (Cao et al., 2016, Chapman et al., 2015).

This is the first study examining the effects of a combined tDCS-plus-training approach with the focus on episodic memory functions on the behavioral level, and in parallel, its impact on DMN functional connectivity. We administered a visuospatial memory training over multiple days with concurrent anodal tDCS in young and older adults. Our aim was to investigate the impact of tDCS and training, versus training alone (sham control), on functional network coupling of the DMN and associated recall performance, as well as transfer on trained and untrained functions. We hypothesized that tDCS-accompanied episodic memory training would improve performance on trained and untrained tasks compared to sham stimulation in both young and older adults. Furthermore, as higher connectivity strength in the DMN most likely reflects augmented network efficiency, we expected to observe an associated increase in network strength after anodal tDCS. As brain-behavior associations have shown to be age dependent, with stronger relationships in later life for most cognitive domains (Antonenko and Floel, 2014, Grady et al., 2003, Madden et al., 2004, Nyberg et al., 2012), we expected this association to be more pronounced in older adults.

Section snippets

Participants

Forty healthy adults participated in the study. The study sample comprised 20 younger (12 women; mean age [standard deviation {SD}]/range: 25 years [4]/19–34) and 20 older adults (14 women; mean age [SD]/range: 70 years [6]/60–78). All were native German speakers and had no history of neurological or psychiatric disorders. To assure cognitive functioning within age-related norms, healthy older participants underwent neuropsychological screening before study inclusion (Consortium to Establish a

Transcranial DCS–accompanied OLM training improved recall performance

Performance on each learning block and recall of each day of the visuospatial memory training as well as recall of the trained material 1 day and 1 month after training is shown in Fig. 2.

Discussion

Here, we examined the neuronal and behavioral effects of a tDCS-accompanied episodic memory training in young and healthy older adults. Participants received either anodal or sham tDCS during the first 20 minutes of training on each of the 3 training days. We found that anodal tDCS led to a significantly larger recall performance (as assessed by recall 1 day after training) compared with sham stimulation. Furthermore, functional network coupling of the DMN increased after training in

Conclusions

In translational neuroscience, an increased understanding of the neuronal and transfer effects of memory-enhancing interventions is pivotal. Importantly, investigation of mechanisms and long-term behavioral effects of training is necessary to develop ecologically valid interventions against age-related cognitive decline. Here, we provide first evidence for the efficacy of a combined approach that may exert beneficial effects on immediate episodic memory performance, associated neuronal network

Disclosure statement

The authors have no actual or potential conflicts of interest.

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, FL 379-10) and the Bundesministerium für Bildung und Forschung (BMBF, 01GQ1424A). The authors thank Magda E. Cesarz, Thorge Profitlich, and Almut Dünnebeil for helping in data acquisition, Franziska Krobisch for statistical assistance, and Gloria Benson for proofreading and language editing.

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