Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain-behavior connections have rapidly increased in the last ten years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understanding the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement (e.g., neural target(s) and montages employed) may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system.
Stroke is a neurological deficit induced by the interruption of the blood flow to the brain due to either a vessel occlusion or less frequently an intracerebral hemorrhage (1). Both may induce direct damage of brain tissue at the site of the lesion, along with potential for additional damage in the surrounding tissue, and long-range dysfunction through the interruption of structural and functional pathways in the brain. This also leads to a deregulation of cortical excitability (2–4) and abnormal interhemispheric interactions. Stroke may thus induce many neurological deficits and could result in death. According to the World Stroke Organization, one out of six people will suffer from a stroke, making stroke a leading cause of adult long-term disability worldwide (5–7). Importantly, one of the main challenges after stroke is the loss of one’s functional motor abilities. Research suggests that only 12% of stroke survivors achieve complete motor recovery by 6 months after the stroke (8). In addition, older individuals are more vulnerable to stroke and thus the incidence of stroke is expected to continue rising over the next few decades (9, 10). Accordingly, there is a need to find new potential therapeutic tools to enhance post-stroke motor recovery. Rebalancing interhemispheric interactions and/or restoring excitability in the ipsilesional hemisphere is thought to be beneficial for post-stroke motor recovery (11–17). Thus, techniques aimed at restoring functional brain activity are a promising way to enhance neural recovery after injury. Most of the literature on stroke recovery focuses on the recovery of upper limb motor function. Since the neural mechanisms involved in motor recovery of upper versus lower limbs may differ, in this review, we focus only on upper limb motor recovery after stroke.
Non-invasive brain stimulation (NIBS) techniques show strong therapeutic potential for post-stroke motor rehabilitation due to their ability to modulate cortical excitability (18–21). In particular, transcranial direct current stimulation (tDCS) has emerged as a viable neurorehabilitation tool due to its limited side-effects (22, 23) and safety [e.g., no known risk of neural damage or induction of seizures, as can be found in other NIBS methods like repetitive transcranial magnetic stimulation (rTMS) (24, 25)]. In addition, tDCS stimulators are commercially available and relatively affordable, on the order of several hundred dollars, and application of tDCS is considered relatively simple. By delivering a low-intensity direct current (between 0.5 and 2 mA) to the scalp via two saline-soaked electrodes—an anode and a cathode—tDCS can modulate the transmembrane potential of neurons, modifying cortical excitability and inducing changes in neural plasticity (see Figure 1) (26–30). In addition, recent work has attempted to enhance the spatial resolution of tDCS stimulation, using a new technique called high-definition tDCS (HD-tDCS) (31–34). With this technique, brain regions are more focally targeted using arrays of smaller electrodes arranged on the scalp (Figure 2), using multiple anodes and cathodes (see section on Focal versus Broad Stimulation for a more detailed description). Recently, there has also been increased interest in combining tDCS with imaging methods, such as fMRI or EEG, in order to better understand the local and global effects of tDCS on neural plasticity throughout the brain (35). These methods have all contributed to the growth and interest of tDCS as a viable neuromodulatory method for stroke.