Event-Related Potentials as Markers of Efficacy for Combined Working Memory Training and Transcranial Direct Current Stimulation Regimens: A Proof-of-Concept Study.

Our brains are often under pressure to process a continuous flow of information in a short time, therefore facing a constantly increasing demand for cognitive resources. Recent studies have highlighted that a lasting improvement of cognitive functions may be achieved by exploiting plasticity, i.e., the brain's ability to adapt to the ever-changing cognitive demands imposed by the environment. Transcranial direct current stimulation (tDCS), when combined with cognitive training, can promote plasticity, amplify training gains and their maintenance over time. The availability of low-cost wearable devices has made these approaches more feasible, albeit the effectiveness of combined training regimens is still unclear. To quantify the effectiveness of such protocols, many researchers have focused on behavioral measures such as accuracy or reaction time. These variables only return a global, non-specific picture of the underlying cognitive process. Electrophysiology instead has the finer grained resolution required to shed new light on the time course of the events underpinning processes critical to cognitive control, and if and how these processes are modulated by concurrent tDCS. To the best of our knowledge, research in this direction is still very limited. We investigate the electrophysiological correlates of combined 3-day working memory training and non-invasive brain stimulation in young adults. We focus on event-related potentials (ERPs), instead of other features such as oscillations or connectivity, because components can be measured on as little as one electrode. ERP components are, therefore, well suited for use with home devices, usually equipped with a limited number of recording channels. We consider short-, mid-, and long-latency components typically elicited by working memory tasks and assess if and how the amplitude of these components are modulated by the combined training regimen. We found no significant effects of tDCS either behaviorally or in brain activity, as measured by ERPs. We concluded that either tDCS was ineffective (because of the specific protocol or the sample under consideration, i.e., young adults) or brain-related changes, if present, were too subtle. Therefore, we suggest that other measures of brain activity may be more appropriate/sensitive to training- and/or tDCS-induced modulations, such as network connectivity, especially in young adults.

Older adults with lower working memory capacity benefit from transcranial direct current stimulation when combined with working memory training: A preliminary study.

Aging is a very diverse process: successful agers retain most cognitive functioning, while others experience mild to severe cognitive decline. This decline may eventually negatively impact one's everyday activities. Therefore, scientists must develop approaches to counteract or, at least, slow down the negative change in cognitive performance of aging individuals. Combining cognitive training and transcranial direct current stimulation (tDCS) is a promising approach that capitalizes on the plasticity of brain networks. However, the efficacy of combined methods depends on individual characteristics, such as the cognitive and emotional state of the individual entering the training program. In this report, we explored the effectiveness of working memory training, combined with tDCS to the right dorsolateral prefrontal cortex (DLPFC), to manipulate working memory performance in older individuals. We hypothesized that individuals with lower working memory capacity would benefit the most from the combined regimen. Thirty older adults took part in a 5-day combined regimen. Before and after the training, we evaluated participants' working memory performance with five working memory tasks. We found that individual characteristics influenced the outcome of combined cognitive training and tDCS regimens, with the intervention selectively benefiting old-old adults with lower working memory capacity. Future work should consider developing individualized treatments by considering individual differences in cognitive profiles.

Impact of tDCS on working memory training is enhanced by strategy instructions in individuals with low working memory capacity.

Interventions to improve working memory, e.g. by combining task rehearsal and non-invasive brain stimulation, are gaining popularity. Many factors, however, affect the outcome of these interventions. We hypothesize that working memory capacity at baseline predicts how an individual performs on a working memory task, by setting limits on the benefit derived from tDCS when combined with strategy instructions; specifically, we hypothesize that individuals with low capacity will benefit the most. Eighty-four participants underwent two sessions of an adaptive working memory task (n-back) on two consecutive days. Participants were split into four independent groups (SHAM vs ACTIVE stimulation and STRATEGY vs no STRATEGY instructions). For the purpose of analysis, individuals were divided based on their baseline working memory capacity. Results support our prediction that the combination of tDCS and strategy instructions is particularly beneficial in low capacity individuals. Our findings contribute to a better understanding of factors affecting the outcome of tDCS when used in conjunction with cognitive training to improve working memory. Moreover, our results have implications for training regimens, e.g., by designing interventions predicated on baseline cognitive abilities, or focusing on strategy development for specific attentional skills.

BRAINSTORMING: A study protocol for a randomised double-blind clinical trial to assess the impact of concurrent brain stimulation (tDCS) and working memory training on cognitive performance in Acquired Brain Injury (ABI).

BACKGROUND: Acquired Brain Injury (ABI) admissions have an incidence of 385 per 100,000 of the population in the UK, and as brain injury often involves the frontal networks, cognitive domains affected are likely to be executive control, working memory, and problem-solving deficits, resulting in difficulty with everyday activities. The above observations make working memory, and related constructs such as attention and executive functioning attractive targets for neurorehabilitation. We propose a combined home-based rehabilitation protocol involving the concurrent administration of a working memory training program (adaptive N-back task) with non-invasive transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex to promote long-lasting modification of brain areas underlying working memory function. METHOD: Patients with a working memory deficit will be recruited and assigned to two age-matched groups receiving working memory training for 2 weeks: an active group, receiving tDCS (2 mA for 20 min), and a control group, receiving sham stimulation. After the end of the first 2 weeks, both groups will continue the working memory training for three more weeks. Outcome measures will be recorded at timepoints throughout the intervention, including baseline, after the 2 weeks of stimulation, at the end of the working memory training regimen and 1 month after the completion of the training. DISCUSSION: The aim of the study is to assess if non-invasive tDCS stimulation has an impact on performance and benefits of a working memory training regimen. Specifically, we will examine the impact of brain stimulation on training gains, if changes in gains would last, and whether changes in training performance transfer to other cognitive domains. Furthermore, we will explore whether training improvements impact on everyday life activities and how the home-based training regimen is received by participants, with the view to develop an effective home healthcare tool that could enhance working memory and daily functioning. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov: NCT04010149 on July 8, 2019.

Event-related potential and EEG oscillatory predictors of verbal memory in mild cognitive impairment.

Reliable biomarkers of memory decline are critical for the early detection of Alzheimer's disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer's disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer's disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |r s| < 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1-4 Hz) is strongly correlated (r = 0.94, P < 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R 2 ' s in 0.45-0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer's disease.

EEG oscillations during word processing predict MCI conversion to Alzheimer's disease.

Only a subset of mild cognitive impairment (MCI) patients progress to develop a form of dementia. A prominent feature of Alzheimer's disease (AD) is a progressive decline in language. We investigated if subtle anomalies in EEG activity of MCI patients during a word comprehension task could provide insight into the likelihood of conversion to AD. We studied 25 amnestic MCI patients, a subset of whom developed AD within 3-years, and 11 elderly controls. In the task, auditory category descriptions (e.g., 'a type of wood') were followed by a single visual target word either semantically congruent (i.e., oak) or incongruent with the preceding category. We found that the MCI convertors group (i.e. patients that would go on to convert to AD in 3-years) had a diminished early posterior-parietal theta (3-5 Hz) activity induced by first presentation of the target word (i.e., access to lexico-syntactic properties of the word), compared to MCI non-convertors and controls. Moreover, MCI convertors exhibited oscillatory signatures for processing the semantically congruent words that were different from non-convertors and controls. MCI convertors thus showed basic anomalies for lexical and meaning processing. In addition, both MCI groups showed anomalous oscillatory signatures for the verbal learning/memory of repeated words: later alpha suppression (9-11 Hz), which followed first presentation of the target word, was attenuated for the second and third repetition in controls, but not in either MCI group. Our findings suggest that a subtle breakdown in the brain network subserving language comprehension can be foretelling of conversion to AD.