The importance of individual beliefs in assessing treatment efficacy.

In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual's subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non-clinical research to start accounting for participants' subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions.

Neuromodulation is a type of intervention that relies on various non-invasive techniques to temporarily stimulate the brain and nervous system. It can be used for the treatment of depression or other medical conditions, as well as the improvement of cognitive abilities such as attention. However, there is conflicting evidence regarding whether this approach has beneficial effects. Most studies aiming to assess the efficiency of a treatment rely on examining the outcomes of people who received the intervention in comparison to participants who undergo a similar procedure with no therapeutic effect (or placebo). However, the influence of other, 'subjective' factors on these results ­ such as the type of intervention participants think they have received ­ remains poorly investigated. To bridge this gap, Fassi and Hochman et al. used statistical modeling to assess how patients' beliefs about their treatment affected the results of four neuromodulation studies on mind wandering, depression and attention deficit hyperactivity disorder symptoms. In two studies, participants' perceptions of their treatment status were more strongly linked to changes in depression scores and mind-wandering than the actual treatment. Results were more nuanced in the other two studies. In one of them, participants who received the real neuromodulation but believed they received the placebo showed the most improvement in depressive symptoms; in the other study, subjective beliefs and objective treatment both explained changes in inattention symptoms. Taken together, the results by Fassi and Hochman et al. suggest that factoring in patients' subjective beliefs about their treatment may be necessary in studies of neuromodulation and other interventions like virtual reality or neurofeedback, where participants are immersed in cutting-edge research settings and might therefore be more susceptible to develop beliefs about treatment efficacy.

Effectiveness of Conventional Dysphagia Therapy (CDT), Neuromuscular Electrical Stimulation (NMES), and Transcranial Direct Current Stimulation (tDCS) in Acute Post-Stroke Dysphagia: A Comparative Evaluation.

This study aims to compare the effectiveness of conventional dysphagia therapy (CDT), neuromuscular electrical stimulation (NMES), and transcranial direct current stimulation (tDCS) in the treatment of post-stroke dysphagia. A single-blind randomized controlled trial was conducted with 40 acute stroke patients - 18 females and 22 males with a mean age of 65.8 ± 11.9. The subjects were grouped into 4, with 10 individuals in each. The procedures administered to groups were as follows: the first group, sham tDCS and sham NMES; the second group, tDCS and sham NMES; the third group, NMES and sham tDCS; and the fourth group, all therapy procedures. CDT was applied to all groups either as a standalone procedure or combined with one or two of the instrumental techniques. Gugging Swallowing Screen (GUSS) and Videofluoroscopic Swallowing Study (VFSS) were employed to determine the severity of dysphagia and the effectiveness of treatment modalities. Additionally, the Penetration Aspiration Scale (PAS), Functional Oral Intake Scale (FOIS), and Dysphagia Severity Rating Scale (DSRS) were administered to interpret VFSS data. Pre- and post-treatment comparisons of all groups have revealed a statistically significant difference for all parameters except for the PAS scores at International Dysphagia Diet Standardization Initiative (IDDSI)-Level 4 consistencies. However, the differences between pre- and post-treatment scores of the fourth group across all parameters were significant - GUSS (p = 0.005), FOIS (p = 0.004), DSRS (p = 0.005), PAS IDDSI-4 (p = 0.027), PAS IDDSI-0 (p = 0.004). Inter-group comparisons, on the other hand, pointed out that the difference between pre- and post-treatment GUSS, FOIS, DSRS, and PAS scores at IDDSI Level-0 consistencies was statistically significant for all groups - GUSS (p = 0,009), FOIS (p = 0,004), DSRS (p = 0,002), PAS IDDSI-0 (p = 0,049). Closer examination of treatment groups indicated that the tDCS + CDT group, the NMES + CDT group, and the group that underwent the combination of three modalities made better progress than the one that was treated with only CDT. Though not statistically significant, the NMES + CDT group achieved better improvement than the tDCS + CDT group. This study has yielded that the group in which NMES, tDCS, and CDT were applied in combination has achieved better results than all the other groups. All treatment modalities applied to accelerate the general recovery process in acute stroke patients with dysphagia were found to be effective for the treatment of post-stroke swallowing disorders. The use of instrumental treatments such as NMES and tDCS enhanced the effectiveness of the treatment and provided more significant progress. Furthermore, combining treatment modalities such as NMES and tDCS was more effective when compared to using only conventional therapy. As a result, the most effective treatment outcomes were obtained by the group receiving CDT, NMES, and tDCS in combination. Therefore, the use of combined approaches has been recommended in appropriate patients; yet the provisional results should be tested in randomized trials with more participants.

Motor cortex transcranial direct current stimulation improves non-motor symptoms in early-onset Parkinson's disease: a pilot study.

Early-onset Parkinson's Disease (EOPD) demands tailored treatments. The younger age of patients might account for a higher sensitivity to transcranial direct current stimulation (tDCS) based non-invasive neuromodulation, which may raise as an integrative therapy in the field. Accordingly, here we assessed the safety and efficacy of the primary left motor cortex (M1) anodal tDCS in EOPD. Ten idiopathic EOPD patients received tDCS at 2.0 mA per 20 min for 10 days within a crossover, double-blind, sham-controlled pilot study. The outcome was evaluated by measuring changes in MDS-UPDRS part III, Non-Motor Symptoms Scale (NMSS), PD-cognitive rating scale, and PD Quality of Life Questionnaire-39 scores. We showed that anodal but not sham tDCS significantly reduced the NMSS total and "item 2" (sleep/fatigue) scores. Other parameters were not modified. No adverse events occurred. M1 anodal tDCS might thus evoke plasticity changes in cortical-subcortical circuits involved in non-motor functions, supporting the value as a therapeutic option in EOPD.

The Effects of Transcranial Direct Current Stimulation in Patients with Mild Cognitive Impairment.

Transcranial direct current stimulation (tDCS) came into consideration in recent years as a promising, non-invasive form of neuromodulation for individuals suffering from mild cognitive impairment (MCI). MCI represents a transitional stage between normal cognitive aging and more severe cognitive decline, which appears in neurodegenerative diseases, such as Alzheimer's disease. Numerous studies have shown that tDCS can have several useful effects in patients with MCI. It is believed to enhance cognitive functions, including memory and attention, potentially slowing down the progression of neurodegeneration and cognitive decline. tDCS is believed to work by modulating neuronal activity and promoting synaptic plasticity in the brain regions associated with cognition. Moreover, tDCS is generally considered safe and well-tolerated, making it an attractive option for long-term therapeutic use in MCI. However, further research is needed to determine the optimal stimulation parameters and long-term effects of tDCS in this population, as well as its potential to serve as a complementary therapy alongside other interventions for MCI. In this review, we included 16 randomized clinical trials containing patients with MCI who were treated with tDCS. We aim to provide important evidence for the cognitive enhancement using tDCS in patients with MCI, summarizing the effects and conclusions found in several clinical trials, and discuss its main mechanisms.

Non-invasive brain stimulation for fibromyalgia: current trends and future perspectives.

Fibromyalgia, a common and enduring pain disorder, ranks as the second most prevalent rheumatic disease after osteoarthritis. Recent years have witnessed successful treatment using non-invasive brain stimulation. Transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsion therapy have shown promise in treating chronic pain. This article reviews the literature concerning non-invasive stimulation for fibromyalgia treatment, its mechanisms, and establishes a scientific basis for rehabilitation, and discusses the future directions for research and development prospects of these techniques are discussed.

Individual Differences in Decision Strategy Relate to Neurochemical Excitability and Cortical Thickness.

The speed-accuracy trade-off (SAT), whereby faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during the performance of almost all daily tasks. To date, computational modeling has implicated the latent decision variable of response caution (thresholds), the amount of evidence required for a decision to be made, in the SAT. Previous imaging has associated frontal regions, notably the left prefrontal cortex and the presupplementary motor area (pre-SMA), with the setting of such caution levels. In addition, causal brain stimulation studies, using transcranial direct current stimulation (tDCS), have indicated that while both of these regions are involved in the SAT, their role appears to be dissociable. tDCS efficacy to impact decision-making processes has previously been linked with neurochemical concentrations and cortical thickness of stimulated regions. However, to date, it is unknown whether these neurophysiological measures predict individual differences in the SAT, and brain stimulation effects on the SAT. Using ultra-high field (7T) imaging, here we report that instruction-based adjustments in caution are associated with both neurochemical excitability (the balance between GABA+ and glutamate) and cortical thickness across a range of frontal regions in both sexes. In addition, cortical thickness, but not neurochemical concentrations, was associated with the efficacy of left prefrontal and superior medial frontal cortex (SMFC) stimulation to modulate performance. Overall, our findings elucidate key neurophysiological predictors, frontal neural excitation, of individual differences in latent psychological processes and the efficacy of stimulation to modulate these.SIGNIFICANCE STATEMENT The speed-accuracy trade-off (SAT), faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during most daily tasks. The SAT is often investigated by explicitly instructing participants to prioritize speed or accuracy when responding to stimuli. Using ultra-high field (7T) magnetic resonance imaging (MRI), we found that individual differences in the extent to which participants adjust their decision strategies with instruction related to neurochemical excitability (ratio of GABA+ to glutamate) and cortical thickness in the frontal cortex. Moreover, brain stimulation to the left prefrontal cortex and the superior medial frontal cortex (SMFC) modulated performance, with the efficacy specifically related to cortical thickness. This work sheds new light on the neurophysiological basis of decision strategies and brain stimulation.

[Using electricity to combat headache : Electrotherapy and tDCS in the 1870s/1880s and today]. / Mit Strom gegen den Kopfschmerz : Die Elektro- und tDCS-Therapie der 1870er-/1880er-Jahre und von heute.

Headache can be a widespread symptom as well as a disorder in itself. Headache syndromes such as migraine cause a lot of distress, disability and overall socioeconomic costs. Pharmacological treatments are often limited in their efficacy as well as due to side effects. The therapeutic application of electricity for this medical indication was a relevant field of research in the 19th century and-in the form of transcranial direct current stimulation (tDCS)-is still widely studied today. This paper provides an overview of publications from the late 19th century (as the era of discovery and success of electrotherapy) as well as contemporary studies investigating the usage of weak currents for the treatment or prophylaxis of headache. Our results show a large number of highly favorable reports of treatment successes. However, the number of cases analysed is often rather small and the forms of electric stimulation applied were often highly heterogeneous. In summary, electric stimulation appears to be a promising field of research and a possible therapeutic agent for the treatment of headaches; however, further research is necessary, especially into the details of the stimulation techniques applied and the various indications in which it may be of use.

Transcranial electrical stimulation of the prefrontal cortex to boost the hypnosis experience: who benefits most?

Many attempts have been made to enhance hypnotizability. The most recent studies adopted the non-invasive brain stimulation to deactivate the dorsolateral prefrontal cortex (DLPFC) during hypnosis, indicating this as a promising approach. However, it is still no clear whether individual factors can predict the effects of stimulation on hypnotizability. In the present study we adopted the phenomenological consciousness inventory (PCI) to retrospectively assess the mental processes during hypnosis and to predict hypnotizability, here defined as "hypnoidal state." The aim was to investigate the possible role of the hypnotic susceptibility on the efficacy of a validated approach of hypnosis enhancement through cathodal transcranial electrical stimulation (tDCS) of the left DLPFC. Results indicated that the lower hypnoidal state at baseline predicted the greater enhancement after the active tDCS. These findings suggest the subjects with lower hypnotic responsiveness as the best candidates for the tDCS interventions of hypnosis enhancement, at least for the montage targeting the left DLPFC. Neurocognitive underpinnings and clinical implications of the results are discussed.

Effect of citicoline and transcranial direct current stimulation on depressive-like behaviors in mice & quot.

Recent investigations revealed the positive role of transcranial direct current stimulation (tDCS) in the treatment of depressive-like behavior & quot. Citicoline is a dietary supplement. It acts as a neuroprotective factor for the treatment of neurological disorders. The aim of this research was to evaluate a possible interaction between tDCS and citicoline on the modulation of depressive-like behavior s & quot in male mice. For tDCS, an electrode was surgically implanted in the left prefrontal of the brain of male mice & quot. Acute restraint stress was induced by movement restraint for 4 h. Locomotor activity and depressive-like behaviors & quot were examined by open field test (OFT), forced swimming test (FST), and tail suspension test (TST). The results indicated that the intraperitoneal (i.p.) administration of citicoline, left prefrontal anodal tDCS, and co-treatment of citicoline and tDCS had no significant effect on locomotor activity. I.p. injection of citicoline (30 mg/kg) decreased immobility time in the FST and TST, showing an antidepressant-like effect & quot. Moreover, the application of left prefrontal anodal tDCS (0.2 mA) for 20 min induced antidepressant-like effect & quot by reducing immobility time in the FST and TST. Co-administration of citicoline (7 and 15 mg/kg) along with tDCS (0.1 mA) decreased immobility time in the FST and TST, indicating an antidepressant-like effect & quot. Therefore, it can be concluded that administration of citicoline in combination with tDCS enhanced the efficacy of tDCS for remedy of depressive-like behaviors & quot.

Self-perception and anticipated efficacy of the anti-dementia multimodal program in 100 older adults with mild cognitive impairment.

BACKGROUND: Effective and sustainable interventions are clearly needed for mild cognitive impairment (MCI) patients. Despite the clinical importance of the multimodal intervention approach, only one study using a multimodal approach demonstrated promising improvements in memory, attention, and executive functions, which also correlated with functional magnetic resonance imaging (MRI) blood oxygenation level dependent (BOLD) changes in cerebral activation in 50 MCI patients. OBJECTIVE: To investigate the self-perception and anticipated efficacy of each element of the BRAIN-FIT multimodal intervention program (robotic-assisted gait training (RAGT), computerized cognitive therapy, music, light, transcranial direct current stimulation (tDCS), and diaphragmatic breathing exercises) and the correlation between memory, concentration, depression, and sleep in older adults with MCI. METHODS: One hundred participants (mean±standard deviation: 8.63±78.4 years; 47 women) with MCI were recruited from a major university medical center and community dementia relief center. The survey questionnaire comprised four domains with 21 questions, including four pertaining to general demographic characteristics, eight related to exercise and activity, three related to sleep, and nine related to the BRAIN-FIT program. Chi-squared test was used to analyze the Likert scale data. The descriptive frequencies were calculated. Additionally, Spearman's rho statistics measure the rank-order association. The statistical significance was at P < 0.05. RESULTS: A strong correlation was observed between memory and concentration (r = 0.850, P = 0.000), memory and depression (r = 0.540, P = 0.000), memory and sleep (r = 0.502, P = 0.000), concentration and depression (r = 0.602, P = 0.000), concentration and sleep (r = 0.529, P = 0.000) and sleep and depression (r = 0.497, P = 0.000). The correlation between medical services and sleep (r = 0.249, P = 0.012) was moderate. The chi-square test revealed a significant difference in memory and low-intensity duration of exercise (χ2[3,N = 100] = 11.69, P = 0.01), concentration and high-intensity exercise duration (χ2[3,N = 100] = 10.08, P = 0.02), concentration with low-intensity exercise duration (χ2[3,N = 100] = 21.11, P = 0.00), depression with high-intensity (χ2[3,N = 100] = 10.36, P = 0.02), high-intensity duration of exercise (χ2[3,N = 100] = 10.48, P = 0.02); low-intensity (χ2[3,N = 100] = 7.90, P = 0.48), and low-intensity duration of exercise (χ2[3,N = 100] = 9.69, P = 0.02). Additionally, significant differences were observed between sleep and high-intensity (χ2[3, N = 100] = 10.36, P = 0.02), low-intensity (χ2[3, N = 100] = 18.14, P = 0.00), and low-intensity duration of exercise (χ2[3, N = 100] = 18.30, P = 0.00). Among the participants 5% answered RAGT, and 20% responded that they had experienced computerized cognitive therapy. Music therapy (20 %), diaphragmatic breathing exercises (45 %), and light therapy (10 %) were used. No patient had experienced tDCS. Conversely, 11% of the participants answered RAGT for programs they wanted to experience and 21% responded to computerized cognitive therapy. 25% of music therapy, 22% of diaphragmatic breathing exercises, 5% of light therapy, and 16% of tDCS participants said they wanted to experience it. Finally, 63% of the participants wanted to participate in the BRAIN-FIT program. CONCLUSION: The present study's results provide clinical evidence-based insights into the utilization of BRAIN-FIT in MCI to maximize cognitive score improvement of memory, concentration, depression, and sleep. Therefore, when designing the BRAIN-FIT, six intervention items were set in proportion to the preference based on the survey, to reduce participants' feeling of repulsion. The program was configured according to exercise intensity.

Stimulated brains and meditative minds: A systematic review on combining low intensity transcranial electrical stimulation and meditation in humans.

Background: Low intensity transcranial electrical stimulation (tES) and meditation are two promising, yet variable, non-pharmacological interventions. Growing research is investigating combined effects of both techniques on one's cognitive, emotional, and physical health. Objective: This article reviews the current research that combines tES and meditation interventions in healthy and diseased participants. The review considers the intervention parameters and their effects in a well-organized manner. Method: A systematic search for clinical and experimental published studies was conducted in the PubMed, Cochrane, and transcranial direct current stimulation (tDCS) databases using common keywords for tES and for meditation techniques well defined by previous studies. Unpublished ongoing studies were identified with the ClinicalTrials.gov and DRKS.de clinical trial websites. Results: 20 published studies and 13 ongoing studies were included for qualitative analysis. 13 published articles studied patients with chronic pain, psychological disorders, cognitive impairment, and movement disorders. Anodal tDCS was the only tES technique while mindfulness meditation was the most common meditation type. Eight studies had a main group effect, with outcome improvement in the active combined intervention. However, most published studies showed improvements after at least one combined intervention with variable effects. Conclusion: Pairing anodal tDCS with meditation shows promising improvements of the physical, mental, and emotional aspects of daily life. Further studies are required to confirm the relevance of this combination in the clinic.

Neurologic music therapy combined with EEG-tDCS for upper motor extremity performance in patients with corticobasal syndrome: Study protocol for a novel approach.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian disorder that involves degeneration of brain regions associated with motor coordination and sensory processing. Combining transcranial direct current stimulation (tDCS) with rehabilitation training has been shown to improve upper-limb performance in other disease models. Here, we describe the protocol investigating whether tDCS with neurologic music therapy (NMT) (patterned sensory enhancement and therapeutic instrumental music performance) enhances functional arm/hand performance in individuals with CBS. METHODS: Study participants are randomly assigned to six 30-min sessions (twice per week for 3 weeks) of NMT + either sham tDCS or active tDCS. We aim to stimulate the frontoparietal cortex, which is associated with movement execution/coordination and sensory processing. The hemisphere contralateral to the more affected arm is stimulated (total stimulation current of 2 mA from 5 dime-sized electrodes). Individualized NMT sessions designed to exercise the upper limb are provided. Participants undergo gross/fine motor, cognitive and emotional assessments at baseline and follow-up (one month after the final session). To investigate the immediate effects of tDCS and NMT training, gross /fine motor, affective level, and kinematic parameter measurements using motion sensors are collected before and after each session. Electroencephalography is used to collect electrical neurophysiological responses before, during, and after tDCS+NMT sessions. The study participants, neurologic music therapist and outcome assessor are blinded to whether participants are in the sham or active tDCS group. CONCLUSION: This noninvasive and patient-centered clinical trial for CBS may provide insight into rehabilitation options that are sorely lacking in this population.

Insights and Future Directions on the Combined Effects of Mind-Body Therapies with Transcranial Direct Current Stimulation: An Evidence-based Review.

Mind-body therapies (MBTs) use mental abilities to modify electrical neural activity across brain networks. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates neuronal membrane potentials to enhance neuroplasticity. A combination of these treatment strategies may generate synergistic or additive effects, and thus has been more commonly tested in clinical trials, fostering a novel yet promising field of research. We conducted a literature search in four different databases including only randomized clinical trials (RCTs) that tested the combination of MBTs with tDCS. Ten studies (n=461) were included. Combined protocols included meditation/mindfulness (8/10), biofeedback (1/10), and hypnosis (1/10). The RCTs were heterogeneous with regards to population, design, and types of outcomes. Based on the findings of this search, we provide here a content description, methodological and practical insights, and future directions for the field. We hope this review will provide future authors with information to facilitate the development of trials with improved protocols.

Pain reduction in fibromyalgia syndrome through pairing transcranial direct current stimulation and mindfulness meditation: A randomized, double-blinded, sham-controlled pilot clinical trial.

Background: This double-blinded, randomized and sham-controlled pilot clinical trial aimed to investigate the preliminary clinical efficacy and feasibility of combining mindfulness meditation (MM) and transcranial direct current stimulation (tDCS) for pain and associated symptoms in patients with fibromyalgia syndrome (FMS). Methods: Included FMS patients (age: 33 to 70) were randomized to three different groups to receive either ten daily sessions of anodal tDCS over the left primary motor cortex paired with MM for 20 min (active + MM, n = 10), sham tDCS combined with MM (sham + MM, n = 10) or no intervention (NoT, n = 10). Patients in the bimodal therapy groups received a week of training in MM prior to the stimulation. Participants reported pain intensity, the primary outcome, by filling in a pain diary daily throughout the whole study. They were also evaluated for quality of life, pressure pain sensitivity, psychological wellbeing, sleep quality and sleep quantity. Assessments were performed at three time points (baseline, immediately after treatment and one-month follow-up). Results: Participants in the active + MM group did not exhibit reduced pain intensity following the bimodal therapy compared to controls. Patients in active group demonstrated clinically meaningful and significantly higher quality of life following the therapeutic intervention than other groups. There was no significant difference among groups regarding pressure pain sensitivity, sleep parameters and psychological scales. The combined treatment was well tolerated among participants, with no serious adverse effects. Conclusion: This study was the first to pair these two effective non-pharmacological therapies for pain management in FMS. In the light of an underpowered sample size, repetitive anodal tDCS combined with MM did not improve pain or FMS-associated symptoms. However, patients in the active + MM group reported higher quality of life than the control groups. Studies with more participants and longer follow-ups are required to confirm our findings. Clinical trial registration: [www.drks.de], identifier [DRKS00023490].

Treatment efficacy of tDCS and predictors of treatment response in patients with post-traumatic stress disorder.

BACKGROUND: Although transcranial direct stimulation (tDCS) has been proposed as an alternative treatment option for various psychiatric disorders, there is inconsistent information regarding the treatment effects of tDCS for patients with post-traumatic stress disorder (PTSD). This study aimed to investigate the tDCS efficacy and identify predictors of treatment response to tDCS in patients with PTSD. METHOD: Fifty-one patients received 10 sessions of tDCS involving the position of the anode over the F3 area and cathode over the F4 as a condition of 2.0 mA and 20 min duration. Digit span test and 10 questionnaires (Clinician-Administered PTSD Scale (CAPS), Cognitive Emotion Regulation Questionnaire (CERQ), Multidimensional Experiential Avoidance Questionnaire (MEAQ), etc.) were used to measure tDCS effects on PTSD symptoms and identify predictors of response to tDCS. RESULTS: 1) 50.9 % of patients had a significant reduction in the frequency and severity of PTSD symptoms, 2) PTSD-related symptoms such as depression, anxiety, rumination, and quality of life were significantly improved, 3) baseline scores on rumination and digit span test significantly predicted treatment response to tDCS. LIMITATIONS: This study was open design without a sham control group. Also, the patients' medications were not controlled. CONCLUSION: This study highlighted the efficacy of frontal tDCS for the treatment of patients with PTSD and identified rumination and digit span as favorable predictive factors for the outcomes of tDCS.

Transcranial direct current stimulation for balance rehabilitation in neurological disorders: A systematic review and meta-analysis.

Postural instability is common in neurological diseases. Although transcranial direct current stimulation (tDCS) seems to be a promising complementary therapy, emerging evidence indicates mixed results and protocols' characteristics. We conducted a systematic review and meta-analysis on PubMed, EMBASE, Scopus, and Web of Science to synthesize key findings of the effectiveness of single and multiple sessions of tDCS alone and combined with other interventions on balance in adults with neurological disorders. Thirty-seven studies were included in the systematic review and 33 in the meta-analysis. The reviewed studies did not personalize the stimulation protocol to individual needs/characteristics. A random-effects meta-analysis indicated that tDCS alone (SMD = -0.44; 95%CI = -0.69/-0.19; p < 0.001) and combined with another intervention (SMD = -0.31; 95%CI = -0.51/-0.11; p = 0.002) improved balance in adults with neurological disorders (small to moderate effect sizes). Balance improvements were evidenced regardless of the number of sessions and targeted area. In summary, tDCS is a promising therapy for balance rehabilitation in adults with neurological disorders. However, further clinical trials should identify factors that influence responsiveness to tDCS for a more tailored approach, which may optimize the clinical use of tDCS.

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel.

BACKGROUND AND OBJECTIVE: Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. METHODS: Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. RESULTS: In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. CONCLUSIONS: Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.

Transcranial Current Stimulation as a Tool of Neuromodulation of Cognitive Functions in Parkinson's Disease.

Decrease in cognitive function is one of the most common causes of poor life quality and early disability in patients with Parkinson's disease (PD). Existing methods of treatment are aimed at both correction of motor and non-motor symptoms. Methods of adjuvant therapy (or complementary therapy) for maintaining cognitive functions in patients with PD are of interest. A promising subject of research in this regard is the method of transcranial electric current stimulation (tES). Here we reviewed the current understanding of the pathogenesis of cognitive impairment in PD and of the effects of transcranial direct current stimulation and transcranial alternating current stimulation on the cognitive function of patients with PD-MCI (Parkinson's Disease-Mild Cognitive Impairment).

Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review.

BACKGROUND: The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS: We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS: We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION: Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING: None.

Synchronized Auditory Gamma Response to Frontal Transcranial Direct Current Stimulation (tDCS) and its Inter-Individual Variation in Healthy Humans.

In schizophrenia, a disorder associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction, auditory cortical plasticity deficits have been indexed by the synchronized electroencephalographic (EEG) auditory steady-state gamma-band (40-Hz) response (ASSR) and the early auditory evoked gamma-band response (aeGBR), both considered to be target engagement biomarkers for NMDAR function, and potentially amenable to treatment by NMDAR modulators. As transcranial direct current stimulation (tDCS) is likely dependent on NMDAR neurotransmission, this preliminary study, conducted in 30 healthy volunteers, assessed the off-line effects of prefrontal anodal tDCS and sham (placebo) treatment on 40-Hz ASSR and aeGBR. Anodal tDCS failed to alter aeGBR but increased both 40-Hz ASSR power, as measured by event-related spectral perturbations (ERSP), and phase locking, as measured by inter-trial phase consistency (ITPC). Inter-individual differences in tDCS-induced increases in ERSP were negatively related to baseline ERSPs. These findings provide tentative support for further study of tDCS as a potential NMDAR neuromodulatory intervention for synchronized auditory gamma response deficits.