Background Transcranial direct current stimulation (tDCS) has been investigated over the years due to its short and also long-term effects on cortical excitability and neuroplasticity. Although its mechanisms to improve motor function are not fully understood, this technique has been suggested as an alternative therapeutic method for motor rehabilitation, especially those with motor function deficits. When applied to the primary motor cortex, tDCS has shown to improve motor function in healthy individuals, as well as in patients with neurological disorders. Based on its potential effects on motor recovery, identifying optimal targets for tDCS stimulation is essential to improve knowledge regarding neuromodulation as well as to advance the use of tDCS in clinical motor rehabilitation. Methods and results Therefore, this review discusses the existing evidence on the application of four different tDCS montages to promote and enhance motor rehabilitation: (1) anodal ipsilesional and cathodal contralesional primary motor cortex tDCS, (2) combination of central tDCS and peripheral electrical stimulation, (3) prefrontal tDCS montage and (4) cerebellar tDCS stimulation. Although there is a significant amount of data testing primary motor cortex tDCS for motor recovery, other targets and strategies have not been sufficiently tested. This review then presents the potential mechanisms and available evidence of these other tDCS strategies to promote motor recovery. Conclusions In spite of the large amount of data showing that tDCS is a promising adjuvant tool for motor rehabilitation, the diversity of parameters, associated with different characteristics of the clinical populations, has generated studies with heterogeneous methodologies and controversial results. The ideal montage for motor rehabilitation should be based on a patient-tailored approach that takes into account aspects related to the safety of the technique and the quality of the available evidence.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on costeffectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period.Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.