Genetic polymorphisms do not predict inter-individual variability to cathodal transcranial direct current stimulation of the primary motor cortex

High variability between individuals (i.e. inter-individual variability) in response to transcranial direct current stimulation (tDCS) has become a commonly reported issue in the tDCS literature in recent years. Inherent genetic differences between individuals has been proposed as a contributing factor to observed response variability. This study investigated whether tDCS inter-individual variability was genetically mediated. A large sample-size of sixty-one healthy males received cathodal-tDCS (c-tDCS) and sham-tDCS, of the primary motor cortex at 1mA and 10-minutes via 6x4cm active and 7x5cm return electrodes. Corticospinal excitability (CSE) was assessed via twenty-five single-pulse transcranial magnetic stimulation motor evoked potentials (MEP). Intracortical inhibition (ICI) was assessed via twenty-five 3ms inter-stimulus interval (ISI) paired-pulse MEPs, known as short-interval intracortical inhibition (SICI). Intracortical facilitation (ICF) was assessed via twenty-five 10ms ISI paired-pulse MEPs. Gene variants encoding for excitatory and inhibitory neuroreceptors were determined via saliva samples. Pre-determined thresholds and statistical cluster analyses were used to subgroup individuals. Two distinct subgroups were identified, responders reducing CSE following c-tDCS and non-responders showing no reduction or even increase in CSE. Differences in CSE between responders and non-responders following c-tDCS were not explained by changes in SICI or ICF. No significant relationships were reported between gene variants and inter-individual variability to c-tDCS suggesting the chosen gene variants did not influence the activity of the neuroreceptors involved in eliciting changes in CSE in responders following c-tDCS. In this largest c-tDCS study of its kind, novel insights were reported into the contribution genetic factors may play in observed inter-individual variability to c-tDCS.