HD-tDCS on neurological disease, pain relief, and motor learning/rehabilitation
The so-called “conventional” tDCS, which uses large electrode pads involved in sponges embedded with saline solution, apply a diffuse electrical current to the brain which stimulates not only the target area but also unwanted regions in a non-predictable fashion. This presents a significant limitation given the low precision of stimulation (focality), which makes it difficult to discern which area contributed to the outcomes. In this regard, HD-tDCS uses a series of small electrodes over the target which circumscribes the stimulation to the diameter of the electrodes and presents improved focality as compared to the conventional tDCS (for a specific view of the HD-tDCS technique see [
300]. Datta et al. [
37] showed that a ring electrodes HD-tDCS montage (4 × 1) provided gyri precise stimulation while tDCS using electrodes pads (7 × 5 cm) resulted in a diffuse electric field (Fig.
2). Interestingly, the peak electric field was found to be not underneath the active electrode in the conventional tDCS, as it is usually presumed, while the HD-tDCS resulted in peak electric field at the sulci and gyri underneath the active electrode [
37]. Experimental evidence has suggested that HD-tDCS may induce superior results compared to conventional tDCS [
34]. For instance, Kuo et al. [
34] compared the effects of conventional tDCS (electrode area 35 cm
2) to HD-tDCS (4 × 1 ring configuration) using 2 mA for 10 min on corticospinal excitability, using MEP, in healthy participants. They showed that HD-tDCS induced greater modulation in MEP and this effect lasted longer than conventional tDCS (i.e., more than two and less than 6 hours) [
34]. Interestingly, HD-tDCS presented a delayed peak effect magnitude, which occurred 30 min after tDCS [
34]. These present important implications for the use of tDCS during training/therapy, given that the effect of conventional tDCS seems to decrease linearly over time. Thus, HD-tDCS represents a recent advance in NIBS considering that it overcomes the limitation of conventional tDCS. So far, however, few studies have compared whether this increased focality promoted by HD-tDCS could result in more significant improvements in the outcomes. This could be mainly because this technology is relatively new. tDCS has shown promising results for various neurological diseases [
301‐
303]. For instance, Aleman et al. [
302] conducted a meta-analysis of controlled trials and showed that NIBS of the frontal cortex improved negative symptoms of patients with schizophrenia, but the evidence for transcranial magnetic stimulation was stronger than for tDCS. Also, the existent literature supports the positive effects of a-tDCS on improving cognitive capacity in both healthy individuals and neuropsychiatric patients [
301,
304]. Hogeveen et al. [
305] compared the effect of HD-tDCS to three montages of conventional tDCS on response inhibition in healthy adults and found similar improvements for both forms of tDCS. On the other hand, Gozenman and Berryhill [
306] showed that individuals with lower baseline working memory capacity benefited more from HD-tDCS than from conventional tDCS. In addition, an impressive result was presented by Trofimov et al. [
307] who demonstrated that HD-tDCS (1 mA for 20 min) 21 days after a TBI reduced the number of areas with hypoperfusion and ischemia, increased cerebral blood flow, cerebral blood volume, and shortened mean transit time in 19 patients with TBI.
For some diseases/symptoms, however, there is still little evidence and the effectiveness of tDCS is uncertain. For instance, Elsner et al. [
299] conducted a meta-analysis and concluded that there is insufficient evidence to determine the effect of tDCS on PD patients. A study by Dagan et al. [
138] compared the effect of a single session of tDCS over M1 (single-target) and simultaneous stimulation of M1 and DLPFC (multi-target) using HD-tDCS on motor and cognitive function in PD patients. They found improvements in motor (i.e., reduced severity of freezing of gate, timed up and go performance, gait speed) and cognitive (i.e. Stroop interference test) performance only after multi-target stimulation [
138]. This suggests that HD-tDCS targeting both motor and cognitive regions may be more effective than single M1 stimulation for PD. Studies using HD-tDCS for PD are scarce so that it remains relatively unexplored whether this technique could produce better results compared to conventional tDCS. Similar to PD, the extant literature does not support the efficacy of tDCS for treating auditory hallucinations, a common symptom of schizophrenia [
308]. However, two recent studies used HD-tDCS for auditory hallucinations with promising results [
309,
310]. Sreeraj et al. [
309] applied HD-tDCS using the 4 × 1 ring montage with a cathode as the central electrode over CP5 (i.e. left temporoparietal junction) with 2 mA for 20 min, two sessions per day for five days on 19 schizophrenia patients and found a significant reduction in persisting auditory hallucinations. Similarly, a case series study in patients with dementia presenting severe auditory hallucinations suggested that HD-tDCS appears to be an effective treatment option [
310].
Meta-analytical evidence has shown that a-tDCS over the S1 and M1 increase the sensory and pain threshold in healthy individuals [
311]. Similarly, a-tDCS over M1 and DLPFC decreased pain levels in patients suffering from CP [
247,
311,
312], which represent an improvement clinically significant, as well as in quality of life [
247]. But only two studies with HD-tDCS were included [
313]. Interestingly, it has also been shown in another meta-analysis that c-tDCS over S1 and M1 increased sensory and pain thresholds in healthy individuals and pain levels in patients [
314]. Similar results were found by Villamar et al. [
313] that showed both anodal and cathodal HD-tDCS reduced pain perception in patients with fibromyalgia. As previously presented, HD-tDCS presents improved focality in comparison to conventional tDCS. DaSilva et al. [
315] tested a variety of tDCS montages targeting brain regions related to the pain processing used in studies involving migraine and pain control and compared conventional to HD-tDCS with high-resolution computational forward modeling. They showed that conventional tDCS montages presented large current flow and peaks of current flow often not at the target of stimulation, occurring in deeper brain regions, which in some cases were not even related to the outcome (e.g. visual cortex) [
315]. On the other hand, HD-tDCS montages enhanced focality with peak current flow in subcortical areas at negligible levels [
315]. Studies comparing conventional to HD-tDCS for pain have shown similar outcomes, however, for patients with tinnitus [
316]. Remarkably, Castillo-Saavedra et al. [
310] performed a phase II open-label trial aiming to define a treatment protocol for clinical treatment of pain in fibromyalgia using HD-tDCS. They found that both responders and non-responders similarly improved quality of life and decreased pain with a clinically significant pain reduction of 50% in half of the sample [
317]. Finally, the authors estimated 15 sessions of HD-tDCS to reach clinically meaningful outcomes [
317].
Regarding motor performance, a recent meta-analysis confirmed that a-tDCS increases corticospinal excitability of the M1 (i.e. MEP size), intracortical facilitation and decrease short-interval intracortical inhibition in healthy individuals [
318,
319], which could implicate increased motor performance, but only one study using HD-tDCS was included [
34]. Different studies have used tDCS for motor performance enhancement, with some showing positive results while others null results (see the meta-analysis by Machado et al. [
320] for a detailed discussion on the effect of tDCS on exercise performance). Radel et al. [
321] and Flood et al. [
322] were the only two studies to test the effects of HD-tDCS (4X1 ring montage) on the time to task failure on a submaximal contraction of the elbow flexors and knee extensors, respectively, in healthy adults and showed no improvement. These results were confirmed in a recent meta-analysis that showed no significant improvement in isometric strength performance [
323]. On the other hand, HD-tDCS (1 mA for 15 min) over bilateral M1 during motor training (3 days) improved unimanual and bimanual dexterity in healthy individuals, suggesting a positive effect on motor learning [
324,
325]. However, these studies did not include groups receiving conventional tDCS to compare efficiency between both techniques. Similar results of motor learning were also shown with conventional tDCS (2 mA for 20 min) over the M1 applied during motor training (5 days) in healthy individuals [
326]. In fact, meta-analytical evidence has confirmed that both single and multiple session of tDCS applied over the M1 improves motor learning in healthy individuals and post-stroke patients [
133,
327]. So far, Cole et al. [
328] performedthe only study comparing the effects of conventional and HD-tDCS (4X1) over the M1 on motor learning in a group of children. Participants underwent training over five consecutive days and were assessed at baseline, post-training and 6 weeks after training (i.e., retention). Both conventional and HD-tDCS similarly improved motor learning not only after training but also after 6 weeks as compared to the sham group [
328].
In sum, HD-tDCS holds the promise to be more effective than conventional tDCS, though since it is a relatively new technique, there is a small number of studies using HD-tDCS, and especially, comparing both forms of stimulation. Soon, systematic reviews and meta-analytical studies may be able to compare outcomes between techniques to elucidate efficiency. So far, the results found for HD-tDCS are at least comparable to conventional tDCS.