Two modes of tDCS have been used in human stroke rehabilitation studies: anodal tDCS applied to the lesional motor areas or cathodal tDCS to the contralesional motor cortex (). The underlying theory to support both of these approaches is based on the hypothesis that a focal lesion disrupts the balanced interhemispheric inhibition and tDCS facilitates a shift of the imbalance towards a more balanced state. Some support for this disturbance in interhemispheric inhibition comes from electrophysiological and imaging studies, which were referenced previously. Proof-of-principle studies have been performed for both of these approaches with TMS [66
] as well as tDCS [69
]. These studies mostly applied a single session of either TMS or tDCS and evaluated the effects comparing performance in pre- and post-intervention batteries of motoric tests. Some studies that have used tDCS to facilitate the recovery process are summarized in .
Brain model of abnormal interhemispheric inhibition and the therapeutic options to ameliorate this imbalance
Synopsis of stroke recovery studies that used transcranial direct current stimulation
Effects of multiple sessions have been undertaken more recently or are ongoing [70
]. Studies in chronic stroke patients using behavioral parameters and TMS as a diagnostic tool have shown that anodal tDCS of motor regions of the affected hemisphere is associated with improvements in functional tasks and motor parameters, which correlated with the increase in excitability of the lesional hemisphere as indicated by the rise in slope of the recruitment curve and a reduction in the short interval intracortical inhibition (SICI) as evidenced by TMS [73
]. Similar findings have been made recently with regard to cathodal inhibition of the contralesional, unaffected hemisphere [71
]. Preliminary analyses of an ongoing trial in our own institution revealed that 5 days of tDCS combined with occupational therapy in a crossover, sham-controlled study lead to a significant improvement in motor outcomes that lasted for at least 1 week [71
]. The improvement in motor outcomes correlated with a decrease in the contralesional excitability as determined by the slope of the input–output curve of the contralesional hemisphere. Furthermore, in some subjects, following cathodal tDCS of the contralesional (unaffected) hemisphere there was a decrease in the ipsilateral activation when the recovered hand was moving as determined by fMRI (). In contrast to these results, a pilot study by Hesse et al.
, in which patients underwent multiple sessions of anodal tDCS (stimulation applied to the lesional motor regions) combined with robot-assisted arm training protocol in subacute stroke patients, failed to find overall significant improvement even though three out of ten subjects showed significant motor improvements [70
]. The currents used by Hesse et al.
] were of higher magnitude (1.5 mA) than in some other studies, but the duration of stimulation was only 7 min, which differed from parameters in our own study (1 mA for 30 min) or earlier studies by Hummel et al.
(1 mA for 20 min). Considering that the patients enrolled in the study by Hesse et al.
had severe disabilities with FM scores of less than 18 and might not have an intact pyramidal tract [70
], it might be important to consider the integrity of the pyramidal tract in future studies, as a possible determinant of a therapeutic response to any kind of experimental intervention ().
Diffusion tensor imaging in stroke recovery
Since there has been some support for both cathodal stimulation to the nonlesional hemisphere and anodal stimulation to the lesional hemisphere, it remains unclear whether the stimulation of the affected or the nonaffected hemisphere has advantages or disadvantages, since no direct, head-to-head comparisons have been performed. tDCS applied to the nonaffected hemisphere may have some advantages over tDCS applied to the affected hemisphere, since the current density distribution is not disturbed by an underlying stroke with nonhomogenous tissue and there might be a lesser risk of triggering a ‘scar epilepsy’. Obviously, there are several other factors that could explain variability in tDCS out-comes, such as the hemisphere affected (right vs left, dominant vs nondominant), lesion site (e.g., cortical/subcortical vs deep white matter lesions), lesion size, the relation between lesion location and intact pyramidal tract, severity of the initial impairment, age or gender, among others. shows two patients with incomplete recovery. Both patients underwent cathodal tDCS to their nonaffected hemisphere in combination with simultaneous occupational therapy. One of the patients had a prominent improvement while the other had only minimal improvement. While the patient with prominent improvement maintained an intact pyramidal tract (although a reduced number of fibers) in the lesional hemisphere, the patient showing only minor improvements had a disrupted pyramidal tract (). This highlights the importance of pyramidal tract integrity and appropriate selection of candidates for testing noninvasive experimental interventions.