Sham transcranial electrical stimulation and its effects on corticospinal excitability: a systematic review and meta-analysis

Sham stimulation is used in randomized controlled trials (RCTs) to assess the efficacy of active stimulation and placebo effects. It should mimic the characteristics of active stimulation to achieve blinding integrity. The present study was a systematic review and meta-analysis of the published literature to identify the effects of sham transcranial electrical stimulation (tES) - including anodal and cathodal transcranial direct current stimulation (a-tDCS, c-tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) - on corticospinal excitability (CSE), compared to baseline in healthy individuals. Electronic databases - PubMed, CINAHL, Scopus, Science Direct and MEDLINE (Ovid) - were searched for RCTs of tES from 1990 to March 2017. Thirty RCTs were identified. Using a random-effects model, meta-analysis of a-tDCS, c-tDCS, tACS, tRNS and tPCS studies showed statistically non-significant pre-post effects of sham interventions on CSE. This review found evidence for statically non-significant effects of sham tES on CSE

Sham transcranial electrical stimulation and its effects on corticospinal excitability: a systematic review and meta-analysis

Sham stimulation is used in randomized controlled trials (RCTs) to assess the efficacy of active stimulation and placebo effects. It should mimic the characteristics of active stimulation to achieve blinding integrity. The present study was a systematic review and meta-analysis of the published literature to identify the effects of sham transcranial electrical stimulation (tES) - including anodal and cathodal transcranial direct current stimulation (a-tDCS, c-tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) - on corticospinal excitability (CSE), compared to baseline in healthy individuals. Electronic databases - PubMed, CINAHL, Scopus, Science Direct and MEDLINE (Ovid) - were searched for RCTs of tES from 1990 to March 2017. Thirty RCTs were identified. Using a random-effects model, meta-analysis of a-tDCS, c-tDCS, tACS, tRNS and tPCS studies showed statistically non-significant pre-post effects of sham interventions on CSE. This review found evidence for statically non-significant effects of sham tES on CSE

The effects of monophasic anodal transcranial pulsed current stimulation on corticospinal excitability and motor performance in healthy young adults : a randomized double-blinded sham-controlled study

Introduction: Transcranial pulsed current stimulation (tPCS) could be used to deliver electrical pulses at different frequencies to entrain the cortical neurons of the brain. Frequency dependence of these pulses in the induction of changes in corticospinal excitability (CSE) has not been reported. Objective: We aimed to assess the effect of anodal tPCS (a-tPCS) at theta (4 Hz), and gamma (75 Hz) frequencies on CSE as assessed by the peak-to-peak amplitude of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) and motor performance. Method: In a randomized, double-blinded, sham-controlled, crossover design study, 17 healthy participants attended 3 experimental sessions and received either a-tPCS at 4 and 75 Hz, or sham a-tPCS with 1.5 mA for 15 min. The amplitude of TMS-induced resting MEPs and time for completion of the grooved pegboard test were recorded at baseline, immediately after, and 30 min after a-tPCS. Results: Both a-tPCS at 75 and 4 Hz showed significantly increased CSE compared with sham. The a-tPCS at 75 Hz induced significantly higher CSE changes compared with 4 Hz. There was a significant increase in intracortical facilitation and a significant reduction in short-interval intracortical inhibition with both 4 and 75 Hz stimulations. However, the inhibition and facilitation did not correlate with CSE. Motor performance was unaffected by the interventions. Conclusion: The high CSE changes in M1 in a-tPCS at 75 Hz provide an initial understanding of the frequency-specific effect of a-tPCS. More research is needed to establish this concept and to assess its behavioral relevance. Transcranial pulsed current stimulation (tPCS) is a novel brain stimulation technique that can modulate neural oscillation via the pulsatile current induced by the stimulation. Using anodal tPCS, we demonstrate the neuromodulatory effect induced by the stimulation at theta and gamma frequencies. Our findings recommend anodal tPCS as a potential therapeutic tool for treating many neurological conditions with altered theta and gamma neural oscillatory activity. © Copyright 2022, Mary Ann Liebert, Inc., publishers

Comparison of Rossini–Rothwell and adaptive threshold‐hunting methods on the stability of TMS induced motor evoked potentials amplitudes

Several methods can be used to determine the resting motor threshold (RMT) and by that recording transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs). However, no research has compared the test retest reliability of these methods. Thus, the aim of this study was to determine intra‐ and inter‐session reliability of Rossini–Rothwell (R–R) and parameter estimation by sequential testing (PEST) methods on TMS‐induced MEPs and comparison of these two methods on RMT. Twelve healthy individuals participated in this study three times (T1, T2 and T3) over two days. TMS was applied using both R–R and PEST to estimate RMT and average of 25 MEPs were acquired at each of the three time points. The intra‐class correlation coefficient indicated high intra‐session reliability in the MEP amplitudes for both methods (0.79 and 0.88, R–R and PEST respectively). The RMT and MEP amplitudes had higher inter‐session reliability in both methods (0.99 and 0.998, R–R and PEST respectively 0.84 and 0.76, R–R and PEST respectively). There was no significant difference between methods for RMT at both T1 (maximum stimulator output of R–R vs. PEST, 33.7% ± 7.7% vs. 33.8% ± 7.6%, p = 0.75) and T3 (maximum stimulator output of R–R vs. PEST, 33.5% ± 7.3% vs. 33.7% ± 7.3%, p = 0.19). There was a significant positive correlation between the methods' estimates of RMT, with PEST requiring significantly fewer stimuli. This study shows that the R–R and PEST methods have high intra‐and inter‐session reliability and the same precision, with PEST having the advantage over R–R in speed of estimation of RMT. R–R and PEST methods are highly reliable for finding RMT, and that there is no difference between TMS‐induced MEPs derived with the methods when measured on two occasions on the same day or between days

Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta‐analysis

Numerous studies have explored the effects of transcranial electrical stimulation (tES) – including anodal transcranial direct current stimulation (a‐tDCS), cathodal transcranial direct current stimulation (c‐tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) – on corticospinal excitability (CSE) in healthy populations. However, the efficacy of these techniques and their optimal parameters for producing robust results has not been studied. Thus, the aim of this systematic review was to consolidate current knowledge about the effects of various parameters of a‐tDCS, c‐tDCS, tACS, tRNS and tPCS on the CSE of the primary motor cortex (M1) in healthy people. Leading electronic databases were searched for relevant studies published between January 1990 and February 2017 126 articles were identified, and their results were extracted and analysed using RevMan software. The meta‐analysis showed that a‐tDCS application on the dominant side significantly increases CSE (P < 0.01) and that the efficacy of a‐tDCS is dependent on current density and duration of application. Similar results were obtained for stimulation of M1 on the non‐dominant side (P = 0.003). The effects of a‐tDCS reduce significantly after 24 h (P = 0.006). Meta‐analysis also revealed significant reduction in CSE following c‐tDCS (P < 0.001) and significant increases after tRNS (P = 0.03) and tPCS (P = 0.01). However, tACS effects on CSE were only significant when the stimulation frequency was ≥140 Hz. This review provides evidence that tES has substantial effects on CSE in healthy individuals for a range of stimulus parameters. tES has significant effect on corticospinal excitability (CSE) in healthy individuals. Among tES techniques, application of a‐tDCS on non‐dominant side primary motor cortex produces significant effect on CSE. Future studies should focus the effect of tPCS on CSE

The effect of transcranial pulsed current stimulation at 4 and 75 Hz on electroencephalography theta and high gamma band power: A pilot study

Transcranial pulsed current stimulation (tPCS) is an emerging noninvasive brain stimulation technique that has shown significant effects on cortical excitability. To date, electrophysiological measures of the efficiency of monophasic tPCS have not been reported. We aimed to explore the effects of monophasic anodal and cathodal-tPCS (a-tPCS/c-tPCS) at theta (4 Hz) and gamma (75 Hz) frequencies on theta and high gamma electroencephalography (EEG) oscillatory power. In a single-blind, randomized, sham-controlled crossover design, 15 healthy participants were randomly assigned into 5 experimental sessions in which they received a-PCS/c-tPCS at 4 and 75 Hz or sham stimulation over the left primary motor cortex (M1) for 15 min at an intensity of 1.5 mA. Changes in theta and high gamma oscillatory power were recorded at baseline, immediately after, and 30 min after stimulation using EEG at rest with eyes open. a-tPCS at 4 Hz showed a significant increase in theta power compared with sham, whereas c-tPCS at 4 Hz had no significant effect on theta power. a-tPCS at 75 Hz produced no changes in high gamma power compared with sham. Importantly, c-tPCS at 75 Hz led to a significant reduction in high gamma power compared with baseline, as well as compared with c-tPCS at 4 Hz and sham stimulation. The results demonstrate the modulation of oscillatory brain activity by monophasic tPCS, and highlight the need for future studies on a larger scale to confirm these initial findings. Impact statement Transcranial pulsed current stimulation (tPCS) is a novel brain stimulation technique. Recently, tPCS has been introduced to directly modulate brain oscillations by applying pulsatile current over the target brain area. Using both anodal and cathodal monophasic tPCS at theta and gamma frequencies, we demonstrate the ability of the stimulation to modulate brain activity. The present findings are the first direct electroencephalography evidence of an interaction between tPCS and ongoing oscillatory activity in the human motor cortex. Our work recommends tPCS as a tool for investigating human brain oscillations and open more studies in this area

Does medicinal cannabis affect depression, anxiety, and stress in people with cancer? A systematic review and meta-analysis of intervention studies

Introduction: Medicinal cannabis might have a role in supporting the mental health of people with cancer. This systematic review and meta-analysis examined the efficacy and safety of medicinal cannabis, compared with any control, as an intervention for depression, anxiety, and stress symptoms in people living with cancer. A secondary aim was to examine the effect of low versus high Δ9-tetrahydrocannabinol (THC) dose on these outcomes. Methods: Five databases were systematically searched, and complemented with a snowball search from inception to May 2023, for any type of interventional study that included humans of any age with any cancer type. Primary outcomes were incidence and severity of depression, anxiety, and stress symptoms. Secondary outcomes were mood, cognition, quality of life, appetite, nutrition status, gastrointestinal symptoms, and adverse events. Data were pooled using Review Manager. Evidence was appraised using Cochrane risk of bias tools. Confidence in the estimated effect of pooled outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Fifteen studies (n = 11 randomized trials, n = 4 non-randomized trials) of 18 interventions (N = 1898 total participants; 100 % ≥18 years of age) were included. Ten studies examined THC (70 % synthetic), two synthetic cannabidiol with or without THC, and six whole-plant extracts. No clinically significant effects of medicinal cannabis were found on primary outcomes. The likelihood of anxiety events increased with higher-dose synthetic THC compared with a lower dose (OR: 2.0; 95 % CI: 1.4, 2.9; p < 0.001; Confidence: very low). Medicinal cannabis (THC, cannabidiol, and whole-plant extract) increased the likelihood of improved appetite (OR: 12.3; 95 % CI: 3.5, 45.5; p < 0.001; n = 3 interventions; Confidence: moderate) and reduced severity of appetite loss (SMD: −0.4; 95 % CI: −0.8, −0.1; p = 0.009; Confidence: very low). There was very low confidence that higher doses of synthetic THC increased the likelihood of any adverse event (OR: 0.5; 95 % CI: 0.3, 0.7; p < 0.001). Medicinal cannabis had no effect on emotional functioning, mood changes, confusion, disorientation, quality of life, and gastrointestinal symptoms. Confidence in findings was limited by some studies having high or unclear risk of bias and imprecise pooled estimates. Conclusions: There was insufficient evidence to determine the efficacy and safety of medicinal cannabis as a therapeutic intervention for depression, anxiety, or stress in people with active cancer. Further research should explore whether medicinal cannabis might improve and maintain appetite and if high-dose synthetic THC might increase the incidence of side-effects, including anxiety. To inform clinical practice, well-powered and rigorously designed trials are warranted that evaluate the effects of medicinal cannabis prescribed to target anxiety, depression, and stress.</p

Medicinal cannabis for management of pain, sleep, and fatigue in cancer survivors: Systematic review and meta-analysis of randomized controlled trials

IntroductionMedicinal cannabis may assist in managing pain, sleep, and fatigue experienced by many cancer survivors. This study aimed to examine existing evidence on the safety and efficacy of medicinal cannabis, compared to any control, on pain, sleep, and fatigue in cancer survivors.MethodsA systematic review with meta-analysis was conducted. Five databases were searched to October 2022 for randomized controlled trials. Any form of medicinal cannabis, control, cancer type/stage, and participant age were eligible. Pain, sleep, and fatigue were primary outcomes. Secondary outcomes were mental health, quality of life, appetite, nutrition status, and gastrointestinal symptoms. Data were pooled using RevMan. Evidence was appraised using the Cochrane RoB-2 tool and GRADE.ResultsEighteen studies of 23 interventions (total participants: 2263 adults; 0 children) were included; 67% had high or unclear risk of bias. Most studies did not measure all primary outcomes, unvalidated outcome measures, and reported inadequate data for meta-analysis. Pain severity was decreased in adults using medicinal cannabis for any duration compared to placebo (SMD:1.4, 95%CI:0.37-2.43; n=4 interventions; GRADE: Low). The likelihood of pain was reduced by 60% with medicinal cannabis use of short duration (ConclusionsMedicinal cannabis might benefit pain management in adult cancer survivors, but use should be closely monitored. Future well-powered trials that assess pain in conjunction with sleep and fatigue, use validated outcome measures, and report data in full are needed to confirm efficacy and safety