Predicting the effect of transcranial direct current stimulation on brain excitability

Transcranial direct current stimulation (TDCS) has been shown to increase the
excitability of the brain, enhance the effect of motor training, and improve
recovery after stroke. However, the results of TDCS are variable. Therefore, a
recently updated Cochrane review advised that *future studies should
particularly engage those who may benefit most from TDCS*. In healthy subjects,
two subject specific factors that could influence the effect of tDCS on brain
excitability have been described: BDNF genotype and APLM latency (a measure
for brain connectivity). In these, studies brain excitability is measured by
applying Transcranial Magnetic Stimulation (TMS) over the motor cortex and
measuring the amplitudes of the subsequent motor evoked potential (MEP) in the
Electromyography (EMG) signal of the target muscle. However, the large
limitation in these previous studies is the complete absence of a placebo TDCS
condition. This means that the subject specific factors (BDNF genotype and APLM
latency) could have interacted with other sources of increased variability over
time, such as such as an accumulation effect of single-pulse TMS or increasing
fatigue. Therefore, the primary goal of this study is to verify the main effect
of TDCS on brain excitability and the interaction effects of BDNF genotype and
APLM latency on this main effect, in a randomized placebo-controlled trial. A
secondary goal of this study is to assess if BDNF genotype and APLM provide
additional predictive value for the effect of TDCS in a second set of
measurements (placebo and anodal). The results of this study will aid in the
overarching goal within rehabilitation medicine for a more personalized
application of neuromodulation treatment.

Primary Objective: To verify the main effect of TDCS on brain excitability and
the interaction effects of BDNF genotype and APLM latency on this main effect.
Secondary Objectives: Compare different prediction models for the main effect
of TDCS in a second measurement pair (anodal - placebo). Compare effect size of
the main effect of anodal TDCS when two different outcome measures for brain
excitability are used: MEP amplitude and input-output curve (IO curve).

randomized double-blind placebo controlled intervention study

TDCS will be applied over the primary motor cortex with 2mA during 90 seconds
(placebo), or with 2mA for 20 minutes (anodal).

Participants will visit the Erasmus MC on 4 days for a total of 6,5 hours. In
this study the state of the art safety measures are applied as described in
recent brain stimulation reviews. Therefore, there is no elevated risk of
seizures or other serious events. The risks associated with this study are
small. TDCS stimulation can induce an itching sensation of the skin.
Discharging of the TMS coil at higher intensity levels can produce loud sounds.
Furthermore, discharging the coil could cause temporary discomfort in the
muscles on the head.