Behavioral effects of transcranial pulsed current stimulation (tPCS): Speed-accuracy tradeoff in attention switching task.

Transcranial pulsed current stimulation (tPCS) has been shown to increase inter-hemispheric coherence of brain oscillatory activity, mainly in fronto-temporal regions, leading to enhancement of functional connectivity across neural networks. The question is whether tPCS can modulate behavior significantly. Our aim was to identify the effects of tPCS on paired associative learning task (PALT) and attention switching task (AST), and to further categorize physiological autonomic responses by heart rate variability and electrodermal activity measurements before and after task performance. Thirty healthy volunteers were randomized to receive a single session of sham or active 2mA tPCS stimulation with a random frequency between 1 and 5Hz. We show that active tPCS significantly improved response time in the AST compared to sham stimulation, so that subjects who received active tPCS significantly exhibit decreased switching cost between repeat and switch trials. No differences were found in response accuracy on AST and PALT. No significant changes were observed in physiological parameters. Based on our results, we suggest that tPCS has a more pronounced effect on tasks that require the increase of functional connectivity across pre-existent neural circuitry, rather than on tasks that require the development of new learning circuits or the creation of new connections.

Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization.

Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. ONLINE REGISTRATION: Registered in Clinicaltrials.gov under registry number NCT01842009. PERSPECTIVE: In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined.

Optimal random frequency range in transcranial pulsed current stimulation indexed by quantitative electroencephalography.

Given the recent results provided by previous investigations on transcranial pulsed current stimulation (tPCS) demonstrating its modulatory effects on cortical connectivity; we aimed to explore the application of different random pulsed frequencies. The utility of tPCS as a neuromodulatory technique for cognition performance will come as additional frequency ranges are tested with the purpose to find optimal operational parameters for tPCS. This study was designed to analyze the effects of tPCS using the following random frequencies; 1-5, 6-10, and 11-15 Hz compared with sham on quantitative electroencephalographic changes in the spectral power and interhemispheric coherence of each electroencephalographic frequency band. This was a parallel, randomized, double-blinded, sham-controlled trial. Forty healthy individuals older than 18 years were eligible to participate. The main outcomes were differences in the spectral power analysis and interhemispheric coherence as measured by quantitative electroencephalography. Participants were randomly allocated to four groups of random frequency stimulation and received a single session of stimulation for 20 min with a current intensity of 2 mA delivered by bilateral periauricular electrode clips. We found that a random pulsed frequency between 6-10 Hz significantly increased the power and coherence in frontal and central areas for the alpha band compared with sham stimulation, while 11-15 Hz tPCS decreased the power for the alpha and theta bandwidth. Our findings corroborate the hypothesis that a random frequency ranging into the boundaries of 6-10 Hz induces changes in the naturally occurring alpha oscillatory activity, providing additional data for further studies with tPCS.

Cognitive effects and autonomic responses to transcranial pulsed current stimulation.

Transcranial pulsed current stimulation (tPCS) is emerging as an option in the field of neuromodulation; however, little is known about its effects on cognition and behavior and its neurophysiological correlates as indexed by autonomic responses. Our aim was to identify the effects of tPCS on arithmetic processing and risk-taking behavior, and to further categorize physiological autonomic responses by heart rate variability (HRV) and electrodermal activity measurements before, during, and after exposure to task performance and stimulation. Thirty healthy volunteers were randomized to receive a single session of sham or active stimulation with a current intensity of 2 mA and a random frequency between 1 and 5 Hz. Our results showed that tPCS has a modest and specific effect on cognitive performance as indexed by the cognitive tasks chosen in this study. There was a modest effect of active tPCS only on performance facilitation on a complex-level mathematical task as compared to sham stimulation. On autonomic responses, we observed that HRV total power increased while LF/HF ratio decreased in the tPCS active group compared to sham. There were no group differences for adverse effects. Based on our results, we conclude that tPCS, in healthy subjects, has a modest and specific cognitive effect as shown by the facilitation of arithmetical processing on complex mathematical task. These effects are accompanied by modulation of the central autonomic network providing sympathetic-vagal balance during stressful conditions. Although behavioral results were modest, they contribute to the understanding of tPCS effects and cognitive enhancement.

Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia.

QEEG indexed frontal connectivity effects of transcranial pulsed current stimulation (tPCS): A sham-controlled mechanistic trial.

Transcranial pulsed current stimulation (tPCS) is a non-invasive brain stimulation technique that employs weak, pulsed current at different frequency ranges, inducing electrical currents that reach cortical and subcortical structures. Very little is known about its effects on brain oscillations and functional connectivity and whether these effects are dependent on the frequency of stimulation. Our aim was to evaluate the effects of tPCS with different frequency ranges in cortical oscillations indexed by high-resolution qEEG changes for power and interhemispheric coherence. Thirty-eight healthy subjects were enrolled and received a single 20-min session of either sham or active stimulation with 1 Hz, 100 Hz or random frequency (1-5 Hz). We conducted an exploratory analysis to detect changes in mean power for theta, alpha and beta, and interhemispheric coherence for alpha and theta and four different sub-bands cognitive and non-specific adverse effects were recorded. We found that active stimulation with a random frequency ranging between 1 and 5 Hz is able to significantly increase functional connectivity for the theta and low-alpha band as compared to sham and active stimulation with either 1 or 100 Hz. Based on these findings, we discuss the possible effects of tPCS on resting functional connectivity for low-frequency bands in fronto-temporal areas. Future studies should be conducted to investigate the potential benefit of these induced changes in pathologic states.