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 doubleblind, 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+SSRI4atDCS+placebo and atDCS+SSRI4sham+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.

Impact of Transcranial Direct Current Stimulation (tDCS) on Neuronal Functions

“…Incremental increases in extracellular serotonin levels, using selective serotonin reuptake inhibitor (SSRI), boost anodal facilitation of MEP and caused ctDCS to have an excitatory effect (Nitsche et al, 2009). Moreover, atDCS of the temporal cortex improved memory formation when serotonergic neurotransmission was enhanced simultaneously (Prehn et al, 2016). Thus, tDCS magnifies the activity of serotonergic system.…”

No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults

“…Moreover, the use of a higher dose might be problematic, because of safety and tolerability reasons in the meaning of increasing the risk of side effects which could in turn negatively affect subject blinding. Given that we have previously found positive effects with the application of 1 mA on OLM (Floel et al, 2012 ; Antonenko et al, 2017 ; Prehn et al, 2017 ), alternative factors, e.g., timing in relation to task, interindividual differences, or a combination, might contribute to null finding.…”

“…Electrodes were attached to the scalp using rubber bands. Given that right temporoparietal region is implicated in the acquisition of OLM (Postma et al, 2008 ) and anodal tDCS over this area has been shown to improve performance on a similar version of the task employed in our study (Floel et al, 2012 ; Prehn et al, 2017 ) this site was selected for anodal simulation. Note, that the larger size of the cathode renders the stimulation density functionally ineffective.…”

Impact of 3-Day Combined Anodal Transcranial Direct Current Stimulation-Visuospatial Training on Object-Location Memory in Healthy Older Adults and Patients with Mild Cognitive Impairment

“…The active electrode (anode, 5x7 cm 2 ) was positioned over the right temporoparietal cortex, centered on T6 (according to international EEG 10-20 System) known to be implicated in acquisition of OLM [75]. Moreover, atDCS over this area has been shown to improve performance on a similar version of the task employed in our study [25,76]. The return electrode (cathode, 10×10 cm 2 ) was placed contralateral over the left supraorbital area (see also Fig.…”