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.
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.
Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique which delivers a constant electric current over the scalp to modulate cortical excitability [1,2,3]. Different montages of tDCS may induce diverse effects on brain networks, which are directly dependent on the electrodes positioning and polarity. While anodal tDCS is believed to enhance cortical excitability, cathodal tDCS diminishes the excitation of stimulated areas, and these electrodes montages define the polarity-specific effects of the stimulation [4,5,6]. Due to the effects of tDCS on modulating cortical excitability, especially when applied to the primary motor cortex , this method of brain stimulation has been intensively investigated for motor function improvement both in healthy subjects [7, 8] and in various neurological pathologies [9, 10]. Neurological conditions that may obtain benefits from the use of tDCS include Stroke [11,12,13,14], Parkinson’s disease , Multiple Sclerosis [16, 17], among others.
The mechanisms of action underlying the modulation of neuronal activity induced by tDCS are still not completely understood. However, studies have demonstrated that the electric current generated by tDCS interferes in the resting membrane potential of neuronal cells, which modulates spontaneous brain circuits activity [1,2,3]. Some studies have suggested that tDCS could have an effect on neuronal synapsis’ strength, altering the activity of NMDA and GABA receptors, thus triggering plasticity process, such as long-term potentiation (LTP) and long-term depression (LTD) [18, 19]. The long-term effects of tDCS are also thought to be associated to changes in protein synthesis and gene expression [20, 21]. Additionally, neuroimaging study showed blood flow changes following stimulation, which may be related to a direct effect of tDCS over blood flow, with an increase in oxygen supply on cortical areas and subsequent enhancement of neuronal excitability . Given these mechanisms, tDCS seems to be a potential valuable tool to stimulate brain activity and plasticity following a brain damage.
The advantages of using tDCS include its low cost, ease of application, and safety. To date, there is no evidence of severe adverse events following tDCS in healthy individuals, as well as in patients with neurological conditions, such as stroke [23, 24]. Among the potential side effects presented after this type of stimulation, the most common ones consist of burn sensation, itching, transient skin irritation, tingling under the electrode, headache, and low intensity discomfort . As serious and irreversible side effects have not been reported, tDCS is considered a relatively safe and tolerable strategy of non-invasive brain stimulation.
The modifications of physiological and clinical responses induced by tDCS are extremely variable, as this type of stimulation can induce both adaptive or maladaptive plastic changes, and a wide spectrum of tDCS parameters influence the effects of this technique. Electrodes combination, montage and shape can easily interfere in the enhancement or inhibition of cortical excitability [6, 26]. Other parameters that may influence these outcomes include current intensity, current flow direction, skin preparation, and stimulation intervals [3, 27, 28] . In addition, in clinical populations, the heterogeneity of the brain lesions can also influence the inconsistency in tDCS effects . Despite the goal of tDCS of modulating cortical areas by using different parameters, some studies have showed that, by altering cortical excitability, the electrical field could reach subcortical structures, such as basal ganglia, due to brain connections between cortical and subcortical areas [30,31,32,33]. This potential effect on deeper brain structure has supported the broad investigation of tDCS in various disorders, even if the cortical region under stimulating electrode is not directly linked to the neurological condition being investigated. Indeed, the current variable and moderate effect sizes from clinical tDCS studies in stroke encourage researchers to test alternative targets to promote motor recovery in this condition.
In this review, we discuss evidence on the application of four different tDCS montages to promote and enhance motor rehabilitation:  anodal tDCS ipsilateral and cathodal tDCS bilateral,  combination of central and peripheral stimulation,  prefrontal montage and  cerebellar stimulation.[…]