Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults

Abstract

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation.

Figures

Figure 1

Study flow (a) and course of an experimental visit (b). (a) During a screening visit (V0), inclusion and exclusion criteria were evaluated for each participant on the basis of anamnesis, medical and neuropsychological examination, electrocardiogram, magnetic resonance imaging (MRI) scan, and blood tests. From 48 screened subjects, 40 subjects were included and randomized into four treatment groups (with 5 young and 5 older subjects each) with four different sequences of intervention conditions (A, B, C, and D). Maximal 2 weeks after V0, the four experimental visits (V1, V2, V3, and V4) were scheduled. (b) Each experimental visit comprised a learning session during which participants performed the objects-location learning (LOCATO) task with brain stimulation (anodal transcranial direct current stimulation (atDCS) vs sham) and drug intake (selective serotonin reuptake inhibitor (SSRI) vs placebo) 2 h before. The learning session consisted of three learning blocks and was followed by immediate and delayed cued recall tasks (recall 1, 2, 3, and 4). Between the experimental visits (V1, V2, V3, and V4) was a wash-out phase of at least 2 weeks (maximum 4 weeks).

Figure 2

Immediate recall scores (primary outcome) for the four intervention conditions. Displayed is the mean score (in % correct responses, 95% CI) for each condition in young (n=20) and older participants (n=20) based on the calculated mixed linear model (ie, values adjusted for individual learning performance measured by learning success at the end of the last learning block) and test–retest effect over the four experimental visits comprising 157 data points in total.