No Effect of Anodal tDCS on Verbal Episodic Memory Performance and Neurotransmitter Levels in Young and Elderly Participants

Abstract

Healthy ageing is accompanied by cognitive decline that affects episodic memory processes in particular. Studies showed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may counteract this cognitive deterioration by increasing excitability and inducing neuroplasticity in the targeted cortical region. While stimulation gains are more consistent in initial low performers, relying solely on behavioural measures to predict treatment benefits does not suffice for a reliable implementation of this method as a therapeutic option. Hence, an exploration of the underlying neurophysiological mechanisms regarding the differential stimulation effect is warranted. Glutamatergic metabolites (Glx) and γ-aminobutyric acid (GABA) are involved in learning and memory processes and can be influenced with tDCS; wherefore, they present themselves as potential biomarkers for tDCS-induced behavioural gains, which are affiliated with neuroplasticity processes. In the present randomized, double-blind, sham-controlled, crossover study, 33 healthy young and 22 elderly participants received anodal tDCS to their left DLPFC during the encoding phase of a verbal episodic memory task. Using MEGA-PRESS edited magnetic resonance spectroscopy (MRS), Glx and GABA levels were measured in the left DLPFC before and after the stimulation period. Further, we tested whether baseline performance and neurotransmitter levels predicted subsequent gains. No beneficial group effects of tDCS emerged in either verbal retrieval performances or neurotransmitter concentrations. Moreover, baseline performance levels did not predict stimulation-induced cognitive gains, nor did Glx or GABA levels. Nevertheless, exploratory analyses suggested a predictive value of the Glx : GABA ratio, with lower ratios at baseline indicating greater tDCS-related gains in delayed recall performance. This highlights the importance of further studies investigating neurophysiological mechanisms underlying previously observed stimulation-induced cognitive benefits and their respective interindividual heterogeneity.

Opposite pattern of transcranial direct current stimulation effects in middle-aged and older adults: Behavioral and neurophysiological evidence

“…Some tDCS studies have reported memory improvement in healthy older adults when stimulating the prefrontal cortex ( Manenti et al, 2013 , 2017 ; Sandrini et al, 2014 , 2016 , 2019 ; Medvedeva et al, 2019 ; Huo et al, 2020 ) or the left temporoparietal cortex ( Antonenko et al, 2019 ). On the other hand, other studies applying tDCS over the prefrontal cortex reported no effects or even a worsening in aging ( Leach et al, 2016 , 2019 ; Peter et al, 2019 ; Habich et al, 2020a , b ). Therefore, it is clear that brain responsiveness to tDCS shows high inter-individual variability.…”

“…Furthermore, it has been proposed that the leeway for tDCS modulation depends on the dissociation of the neural system from a previous optimal state. Therefore, whereas middle-aged adults might function close to their homoeostatic optimum (with a relatively small margin for tDCS improvement), older adults might shift away from it, possibly making their brain more amenable to tDCS-induced gains ( Habich et al, 2020a , b ).…”

Anodal Transcranial Direct Current Stimulation Over Prefrontal Cortex Slows Sequence Learning in Older Adults

“…However, the older adult participants who received stimulation during practice no longer had a motor performance deficit. While the findings from these studies suggest that tDCS may improve motor learning for older adults, other studies show either no benefit or even poorer performance when tDCS is paired with task practice (Mooney et al, 2019;Muffel et al, 2019;Habich et al, 2020;Chow et al, 2021). For example, one study found no benefit of a single session of anodal M1 tDCS as older and young adult participants learned a sequential isometric force task using their non-dominant hand during practice (Mooney et al, 2019).…”

Effects of Transcranial Direct Current Stimulation (tDCS) on Cognitive Performance and Cerebral Oxygen Hemodynamics: A Systematic Review

“…Yet others have proposed that factors such as baseline performance or education level, as opposed to age, may modulate tDCS efficacy in older adults (Berryhill and Jones, 2012 ; Learmonth et al, 2015 ). Clearly, this is an area that warrants further study, and may even require tDCS protocols that are adapted to address the structural and neuroanatomical changes associated with aging brains (Habich et al, 2020 ).…”