Cognitive Performance After Repeated Exposure to Transcranial Direct Current Stimulation (tDCS) During Sleep Deprivation

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h. We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory. The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval). The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity. Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex. Copyright © 2013 Elsevier Inc. All rights reserved.