Transcranial direct current stimulation: the effect on functional outcomes in the pain and motor domains

Abstract

The physiological effects of transcranial direct current stimulation (tDCS) in the living human brain were verified experimentally in the early 2000's. A series of studies from Göttingen, Germany, shows that consistently, anodal stimulation lead to increased cortical excitability, while cathodal stimulation leads to increased cortical inhibition. Since then, the effect of tDCS has been further explored, both in terms of basic physiology, and on functional outcomes. The method, when applied according to existing protocols, is associated with no serious safety concerns. Early clinical studies has shown that tDCS stimulation can lead to symptom relief, or improved rehabilitation, in a number of conditions assumed to be associated with devious brain function. The results from early phase clinical studies on chronic pain has yielded encouraging results, but in order to conclude on the clinical efficacy of tDCS in its current application, there is a need for larger, rigorously designed studies. In healthy volunteers, the effects of tDCS has been tested on various outcomes. In experimentally induced pain, the effects appear to be less consistent then in clinical pain. In the motor domain, some studies indicate that in healthy volunteers, motor performance and motor learning can be facilitated by tDCS. However, the effects appear to be sensitive to how the stimulation is conducted, and how and when the outcomes are measured. <p> This thesis describes two experiments and one clinical trial that investigated the effect of anodal tDCS over the primary motor cortex (M1) on functionally relevant outcomes, namely experimentally induced and clinical pain, and motor learning and performance on two neuropsychological tests that are commonly employed in clinical practice. The aim of Report I was to test the effect of a single session of anodal tDCS with a duration of 7 minutes and a current intensity of 2 milliampere (mA) on experimentally induced heat pain in healthy volunteers. In order to estimate the placebo effect, a no treatment condition was included in addition to active and sham tDCS. Thus, 75 healthy volunteers were randomized into 3 groups. At pretest, during stimulation and at posttest, pain stimuli were presented as thermode heat at temperatures of 43ºC, 45ºC and 47ºC. Additionally at each time point, heat pain thresholds were measured. Pain intensity was measured with a computerized visual analog scale (COVAS). Subjective stress was measured with adjective pairs from the Stress/Arousal Adjective Check List (SACL) and rated with a 0-10 numeric rating scale (NRS), and blood pressure, an indicator of objective stress, were measured with an automatic blood pressure monitor. The results indicated that, at the highest temperature, the active tDCS group reported greater pain reduction from pretest to posttest. However, the repeated measures data indicated that the response of the sham tDCS group consistently had a response pattern that were more similar to the active tDCS group than the no treatment group, indicating that the tDCS procedure might induce placebo responses that influenced the pain ratings. <p>The aim of the experiment in Report II was to test the effect of 20 minutes 2 mA anodal tDCS over the M1 on performance and practice effect on two commonly used neuropsychological tests measuring fine motor (Grooved Pegboard Test, GPT) and psychomotor (Trail Making test B, TMT-B) speed. In order do so, a similar study design as in Report II was employed, but with longer stimulation duration. A total of 60 healthy volunteers were randomized into 3 groups, and the neuropsychological tests were administered before, during and after stimulation. Control variables were registered to investigate the effect of overt anatomical and behavioral characteristics on the outcomes. The results indicated no effect of active tDCS on motor learning and performance. In fact all groups performed similarly at each time point. Interestingly, and uniquely for the active tDCS group, higher caffeine intake and lower inter electrode impedance predicted improved motor learning. <p>The aim of the randomized controlled trial in Report III was to investigate the effect of anodal tDCS on pain in fibromyalgia (FIM). A total of 48 patients, receiving active or sham tDCS, completed the study. Stimulation was administered in a similar fashion as in Report II, but over 5 consecutive days. Thus the study design was a between group design with 7 repeated measures (pretest, treatment x 5, posttest). Pain intensity, pain unpleasantness, stress, and tension (the latter 2 derived from the SACL used in Report I) were measured with short message service (SMS) text messages 3 times daily for 30 days before stimulation (mean of 30 days: pretest), during the treatment days, and for 30 days after stimulation (mean of 30 days: posttest). In addition, daily function and psychiatric symptoms were measured before and after the stimulation. The results indicated that active tDCS statistically reduced pain in the patients compared to sham tDCS. However, the effect sizes were small, and the results might indicate that the achieved pain reduction was of limited clinical importance. The overall conclusions from the experiments involving healthy volunteers (Report I and II) is that anodal tDCS over the M1 is ineffective in reducing acute pain and improving motor learning and performance. In FIM patients (Report III) 5 consecutive sessions of tDCS is capable of inducing statistically significant pain relief, and improved stimulation protocols should be investigated in order to make the treatment clinically effective.