Transcranial Brain Stimulation Research Articles

Photoacoustic: A Versatile Nongenetic Method for High-Precision Neuromodulation.

ConspectusHigh-precision neuromodulation plays a pivotal role in elucidating fundamental principles of neuroscience and treating specific neurological disorders. Optical neuromodulation, enabled by spatial resolution defined by the diffraction limit at the submicrometer scale, is a general strategy to achieve such precision. Optogenetics offers single-neuron spatial resolution with cellular specificity, whereas the requirement of genetic transfection hinders its clinical application. Direct photothermal modulation, an alternative nongenetic optical approach, often associates a large temperature increase with the risk of thermal damage to surrounding tissues.Photoacoustic (also called optoacoustic) neural stimulation is an emerging technology for neural stimulation with the following key features demonstrated. First, the photoacoustic approach demonstrated high efficacy without the need for genetic modification. The generated pulsed ultrasound upon ns laser pulses with energy ranging from a few μJ to tens of μJ is sufficient to activate wild-type neurons. Second, the photoacoustic approach provides sub-100-μm spatial precision. It overcomes the fundamental wave diffraction limit of ultrasound by harnessing the localized ultrasound field generated through light absorption. A spatial precision of 400 μm has been achieved in rodent brains using a fiber-based photoacoustic emitter. Single-cell stimulation in neuronal cultures in vitro and in brain slices ex vivo is achieved using tapered fiber-based photoacoustic emitters. This precision is 10 to 100 times better than for piezo-based low-frequency ultrasound and is essential to pinpoint a specific region or cell population in a living brain. Third, compared to direct photothermal stimulation via temperature increase, photoacoustic stimulation requires a 40 times less laser energy dose to evoke neuron activities and is associated with a minimal temperature increase of less than 1 °C, preventing potential thermal damage to neurons. Fourth, photoacoustics is a versatile approach and can be designed in various platforms aiming at specific applications. Our team has shown the design of fiber-based photoacoustic emitters, photoacoustic nanotransducers, soft biocompatible photoacoustic films, and soft photoacoustic lenses. Since they interact with neurons through ultrasound without the need for direct contact, photoacoustic enables noninvasive transcranial and dura-penetrating brain stimulation without compromising high precision.In this Account, we will first review the basic principles of photoacoustic and discuss the key design elements of PA transducers for neural modulation guided by the principle. We will also highlight how these design goals were achieved from a materials chemistry perspective. The design of different PA interfaces, their unique capability, and their applications in neural systems will be reviewed. In the end, we will discuss the remaining challenges and future perspectives for this technology.

MR imaging of the magnetic fields induced by injected currents can guide improvements of individualized head volume conductor models

Abstract Volume conductor models of the human head are routinely used to estimate the induced electric fields in transcranial brain stimulation (TBS) and for source localization in electro- and magnetoencephalography (EEG and MEG). Magnetic resonance current density imaging (MRCDI) has the potential to act as a non-invasive method for dose control and model validation but requires very sensitive MRI acquisition approaches. A double-echo echo-planar imaging (EPI) method is here introduced. It combines fast and sensitive imaging of the magnetic fields generated by the current flow of transcranial electric stimulation with increased robustness to physiological noise. For validation, noise floor measurements without injected currents were obtained in 5 subjects for an established multi-echo gradient-echo (MGRE) sequence and the new EPI method. In addition, data with current injection was acquired in each subject with a right-left (RL) and anterior-posterior (AP) electrode montage with both sequences to assess the accuracy of subject-specific detailed head models. In line with previous findings, the noise floor measurements showed that the MGRE results suffered from spatial low-frequency noise patterns, which were mostly absent in the EPI data. A recently published approach optimizes the ohmic conductivities of subject-specific head models by minimizing the difference between simulated and measured current-induced magnetic fields. Here, simulations demonstrated that the MGRE noise patterns have a larger negative impact on the optimization results than the EPI noise. For the current injection measurements, a larger discrepancy was found for the RL electrode montage compared with the AP electrode montage consistently for all subjects. This discrepancy remained in part also after optimization of the ohmic conductivities, was similar for the data of the two sequences and larger than the measurement noise and thus demonstrates systematic biases in the volume conductor models. We have shown that EPI-based MRCDI is superior to established techniques by mitigating the effects of previously reported spatial low-frequency noise in MRCDI if limited spatial resolution is acceptable. Additionally, the consistent inter-subject results indicate that MRCDI is capable of picking up inaccuracies in computational head models and will be useful to guide systematic improvements.

Variability of pulse width in transcranial magnetic stimulation

Objective. There is a high variability in the physiological effects of transcranial magnetic brain stimulation, resulting in limited generalizability of measurements. The cause of the variability is assumed to be primarily based on differences in brain function and structure of the stimulated individuals, while the variability of the physical properties of the magnetic stimulus has so far been largely neglected. Thus, this study is dedicated to the systematic investigation of variability in the pulse width of different TMS pulse sources at different stimulation intensities. Approach. The pulse widths of seven MagVenture® pulse sources were measured at the output of 10%–100% stimulation intensity in 10% increments via Near Field Probe and oscilloscope. The same C-B60 coil was used to deliver biphasic pulses. Pulse widths were compared between pulse sources and stimulation intensities. Main results. The mean sample pulse width was 288.11 ± 0.37 µs, which deviates from the value of 280 µs specified by the manufacturer. The pulse sources and stimulation intensities differ in their average pulse width (p’s < .001). However, the coefficient of variation within the groups (pulse source; stimulation intensity) were moderately low (CV = 0.13%–0.67%). Significance. The technical parameter of pulse width shows deviations from the proposed manufacturer value. According to our data, within a pulse source of the same manufacturer, the pulse width variability is minimal, but varies between pulse sources of the same and other pulse source models. Whether the observed variability in pulse width has potential physiological relevance was tested in a pilot experiment on a single healthy subject, showing no significant difference in motor evoked potential amplitude and significant difference in latencies. Future research should systematically investigate the physiological effects of different pulse lengths. Furthermore, potential hardware ageing effects and pulse amplitude should be investigated.

Unlocking hypnotizability: Transcranial brain stimulation for enhanced impact in chronic pain

Hypnosis provides a therapeutic option for health issues like chronic pain, but individual responsiveness, termed hypnotizability, varies. Faerman etal.'s1 study showed that transcranial magnetic stimulation (TMS) can significantly improve hypnotizability, offering potential for patients with limited response to hypnosis in pain management.

Brain Neuromodulation Effects on Sport and Nutrition: A Narrative Review

Study purpose. At the end of the twentieth century, the development of highly reliable and painless non-invasive transcranial brain stimulation techniques and devices has aroused great scientific and clinical interest in numerous fields. In neuroscience, since the introduction of innovative and non-invasive devices such as the brain stimulator, the investigation of cortical processes and their neural basis has played a fundamental role. Furthermore, neuroscientists are attracted to therapeutic applications for the treatment of food craving. This narrative review is aimed to explain the growing and constant interest of neuroscientific experimentation in the field of non-invasive transcranial stimulation. Material and methods. After an introduction explaining the historical evolution of NIBS, we will try to provide an overview of the two stimulation techniques (TMS and tDCS); we will describe the different types of stimulation that can be performed using these techniques, the excitatory/inhibitory effects, and the various mechanisms of action at the level of brain activity. Results. We will also provide some elucidations regarding the implications of the facilitative/inhibitory effects, and how these stimulation methods can be used to advance knowledge of the neurofunctional organization of the brain. Conclusion. The results of the study showed the effect of brain neuromodulation on sports and nutrition.

The effects of combined transcranial brain stimulation and a 4-week visuomotor stepping training on voluntary step initiation in persons with chronic stroke-a pilot study.

Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS. A total of 10 PCS were randomly assigned to one of two training groups, consisting of either 12 sessions of VST paired with a-tDCS (n = 6) or sham tDCS (s-tDCS, n = 4) over 4 weeks, with step initiation (SI) tests at pre-training, post-training, 1-week and 1-month follow-ups. Primary outcomes were: baseline vertical ground reaction force (B-vGRF), response time (RT) to initiate anticipatory postural adjustment (APA), and the retention of B-VGRF and RT. a-tDCS paired with a 4-week VST program results in a significant increase in paretic weight loading at 1-week follow up. Furthermore, a-tDCS in combination with VST led to significantly greater retention of paretic BWB compared with the sham group at 1 week post-training. The preliminary findings suggest a 4-week VST results in improved paretic limb weight bearing (WB) during SI in PCS. Furthermore, VST combined with a-tDCS may lead to better retention of gait improvements (NCT04437251) (https://classic.clinicaltrials.gov/ct2/show/NCT04437251).

The Effects of Cognitive Interventions in Individuals with Chronic Respiratory Diseases: A Systematic Review

Purpose: To evaluate the effects of cognitive interventions (CIs) on cognitive function, health-related quality of life (HRQoL), self-management, physical activity, physical function, and psychosocial outcomes among individuals with chronic respiratory diseases (CRDs). Methods: The methods adhered to the Cochrane Handbook for Systematic Review of Interventions for data analysis and synthesis guidelines. Additionally, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed for the reporting of data. Database searches were conducted from inception to May 2023 across Medline, Embase, Emcare, PsycINFO, Scopus, and CINAHL. Included studies evaluated the effects of cognitive training, cognitive behavioural therapy, and transcranial brain stimulation in adults with CRDs. Studies were evaluated using the Cochrane Risk of Bias 2 tool, Risk of Bias in Non-Randomized Studies of Interventions, and Grading of Recommendations, Assessment, Development, and Evaluation. Results: Five eligible studies with 347 participants were included and showed very low-quality evidence of inconsistent improvements in cognition and no difference between groups for HRQoL and self-management; low evidence for no difference between groups in physical function; moderate evidence for no difference between groups in physical activity and psychosocial outcomes. Conclusion: The effects of CIs on cognitive function in people with CRDs are inconclusive.

Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments—a randomized cross-over study

BackgroundStroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery.MethodsThis randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale.DiscussionWe hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine.Trial registrationClinicalTrials.gov NCT05479006. Registered on 26 July 2022.

Converging Evidence for Frontopolar Cortex as a Target for Neuromodulation in Addiction Treatment.

Noninvasive brain stimulation technologies such as transcranial electrical and magnetic stimulation (tES and TMS) are emerging neuromodulation therapies that are being used to target the neural substrates of substance use disorders. By the end of 2022, 205 trials of tES or TMS in the treatment of substance use disorders had been published, with heterogeneous results, and there is still no consensus on the optimal target brain region. Recent work may help clarify where and how to apply stimulation, owing to expanding databases of neuroimaging studies, new systematic reviews, and improved methods for causal brain mapping. Whereas most previous clinical trials targeted the dorsolateral prefrontal cortex, accumulating data highlight the frontopolar cortex as a promising therapeutic target for transcranial brain stimulation in substance use disorders. This approach is supported by converging multimodal evidence, including lesion-based maps, functional MRI-based maps, tES studies, TMS studies, and dose-response relationships. This review highlights the importance of targeting the frontopolar area and tailoring the treatment according to interindividual variations in brain state and trait and electric field distribution patterns. This converging evidence supports the potential for treatment optimization through context, target, dose, and timing dimensions to improve clinical outcomes of transcranial brain stimulation in people with substance use disorders in future clinical trials.

A scientometrics analysis of physical activity and transcranial stimulation research.

The search for alternatives to improve physical performance is rising, and in recent years has been focused on the brain. No bibliometric study analyzing research on physical activity (PA) and transcranial stimulation has been found in the scientific literature. Aims: To provide an overview of the existing scientific research on PA and transcranial brain stimulation in healthy and sports participants, using a bibliometric analysis and graphic mapping of the references in the field. To do this, we analyze annual publication trends in this area, identifying the most productive and cited authors, journals and countries with the highest number of publications, and the most cited documents and keywords. Those publications related to this area, published in journals indexed in the web of science main collection were retrieved and analyzed using the traditional laws of bibliometrics. A total of 305 documents were found. Annual publications followed an exponential growth trend (R2 = 94.2%); with A. J. Pearce (9 documents) is the most productive coauthor and M.C. Ridding, H. Theoret and M. Lassonde as the most prominent (with 5 most cited papers). The USA (67 papers) and the journal Frontiers in Human Neuroscience (12 papers) were the most productive country and journal respectively. The paper "Action anticipation and motor resonance in elite basketball players" was the most cited paper and "transcranial magnetic stimulation" was the most used keyword. There are extensive research networks throughout the world, with the USA leading the production. Publications on the issue are of high interest in the scientific community as an exponential increase in publications over the last few years was found. The contribution of these findings is to offer a complete picture of the relationship between PA and transcranial brain stimulation in healthy individuals and athletes. Therefore, this comprehensive analysis provides fruitful information for sports researchers and policymakers to make future correct decisions about how to better design and implement training interventions in these groups of individuals.

Somatosensory evoked potentials amplitude is enhanced after non-invasive brain stimulation in chronic ischemic stroke: Preliminary results from a randomised control trial

ObjectiveTo investigate the effects of transcranial electrical and magnetic non-invasive brain stimulation (NIBS) protocols on somatosensory evoked potential (SEP) in chronic ischemic stroke. Methods33 patients were randomly assigned to one of the four treatment groups of the transcranial direct current stimulation (tDCS) and/or repetitive transcranial magnetic stimulation (rTMS) protocol. SEP parameters were recorded before and after ten days of the treatment session. All the statistical analyses were carried out using SPSS version 19. ResultsIt was found that there is a statistically significant improvement in the N20-P22 mean amplitude after treatment sessions in all groups except the group where tDCS and rTMS groups were sham. On paired t-tests, the difference betweeen post and pre-stimulation SEP amplitudes for the real tDCS and real rTMS coupled group was 1.045 ± 0.732 (p value = 0.005). For sham tDCS+real rTMS group, 1.05 ± 0.96 (P = 0.04); for real tDCS+sham rTMS 0.543 ± 0.332 (P = 0.01) and for double sham stimulation, 0.204 ± 0.648 (P = 0.4) respectively ConclusionIn ischemic stroke patients, either or coupled true transcranial tDCS and rTMS was found to be safe and significantly enhanced the amplitude of cortical somatosensory potentials when combined with standard physiotherapy, in the interim analysis of an ongoing randomised controlled trial. Clinical Trial Registry of IndiaCTRI/2019/11/022009 SignificanceThe results of this research indicates the importance of RCTs in developing robust improved NIBS protocols coupled to physiotherapy to enhance the sensory-motor functional recovery following ischemic stroke.

Cognitive Interventions in Individuals With Chronic Respiratory Diseases: Protocol for a Systematic Review.

Chronic respiratory diseases (CRDs) may cause reduced oxygen availability to organs and body tissues, leading to an increased risk for ischemic damage, which can result in brain tissue injury. This damage can lead to a myriad of neurological symptoms contributing to cognitive decline. Cognitive interventions may attenuate cognitive deficits in people with CRDs; however, the effects have not yet been systematically summarized in the literature. The purpose of this systematic review is to assess the effects of cognitive interventions (including cognitive behavioral therapy and transcranial brain stimulation) on cognitive function (primary outcome), HRQL, self-management, symptoms, physical activity, physical function, ability to complete activities of daily living (ADLs), hospital admissions, functional capacity, functional performance, psychological and social outcomes, exacerbations, healthcare utilization, and survival in individuals with CRDs. This review will be conducted in accordance with the Cochrane handbook for systematic reviews of interventions and reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Searches will be performed in MEDLINE, Embase, Emcare, PsycINFO, Scopus, and CINAHL. Articles will be included if they focus on the effects of cognitive interventions on adults with CRDs, are published in peer-reviewed journals, and are written in English, French, or Portuguese. Risk of bias will be evaluated with the Cochrane Risk of Bias 2 tool for randomized controlled trials, and the Risk of Bias in Non-randomized Studies of Interventions tool for nonrandomized studies. Meta-analyses will be performed if at least 2 studies provided sufficient data for a specific outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) assessment will be used to evaluate the overall quality of the evidence. This systematic review was initiated in November 2022 and registered with PROSPERO in February 2023, prior to title and abstract screening. Full-text screening of articles will be completed in June 2023. Data extraction and drafting of the manuscript will occur from July 2023 to August 2023, with expected publication in February 2024. This systematic review will summarize the effects of cognitive interventions on cognitive function in people with CRDs. It will guide health care professionals in selecting evidence-based strategies to enhance cognitive well-being and overall health outcomes for individuals with CRDs. Additionally, it will identify research gaps and highlight areas for future exploration, supporting researchers in advancing knowledge in this field. PROSPERO CRD42023396234; https://tinyurl.com/mwjrfbxv. PRR1-10.2196/48235.

Testing a Novel Wearable Device for Motor Recovery of the Elbow Extensor Triceps Brachii in Chronic Spinal Cord Injury.

After corticospinal tract damage, reticulospinal connections to motoneurons strengthen preferentially to flexor muscles. This could contribute to the disproportionately poor recovery of extensors often seen after spinal cord injury (SCI) and stroke. In this study, we paired electrical stimulation over the triceps muscle with auditory clicks, using a wearable device to deliver stimuli over a prolonged period of time. Healthy human volunteers wore the stimulation device for ∼6 h and a variety of electrophysiological assessments were used to measure changes in triceps motor output. In contrast to previous results in the biceps muscle, paired stimulation: (1) did not increase the StartReact effect; (2) did not decrease the suppression of responses to transcranial magnetic brain stimulation (TMS) following a loud sound; (3) did not enhance muscle responses elicited by a TMS coil oriented to induce anterior-posterior current. In a second study, chronic cervical SCI survivors wore the stimulation device for ∼4 h every day for four weeks; this was compared with a four-week period without wearing the device. Functional and electrophysiological assessments were repeated at week 0, week 4, and week 8. No significant changes were observed in electrophysiological assessments after paired stimulation. Functional measurements such as maximal force and variability and speed of trajectories made during a planar reaching task also remained unchanged. Our results suggest that the triceps muscle shows less potential for plasticity than biceps; pairing clicks with muscle stimulation does not seem beneficial in enhancing triceps recovery after SCI.

Comparison of transcranial brain stimulation approaches: prefrontal theta alternating current stimulation enhances working memory performance.

One of the most important cognitive functions in our everyday life is the working memory (WM). In several neuropsychiatric diseases such as ADHD or schizophrenia WM deficits can be observed, making it an attractive target for non-invasive brain stimulation methods like transcranial electrical stimulation (tES). However, the literature shows rather heterogeneous results of tES effects on WM performance. fMRI meta-analyses have identified a WM network including frontoparietal brain areas such as the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Neurophysiological studies revealed oscillatory activity in the theta band frequency range to be of crucial functional relevance for WM processes. Based on this, transcranial alternating current stimulation (tACS) in the theta frequency range targeting DLPFC and PPC in a spatially optimized way might further improve effects of tES on WM performance. Sixteen healthy subjects were stimulated with varying stimulation settings on four different days in a counterbalanced within-subject design. These setups included the application of (1) tACS with a frequency of 5 Hz (theta frequency range) over the left DLPFC and (2) the right superior parietal cortex, (3) transcranial direct current stimulation (tDCS) of the DLPFC and (4) a sham stimulation condition during the online performance of a visual delayed-match-to-sample task with varying working memory load. We introduce a procedure to calculate an optimal tES model revealing optimized high-density setups for the present study for 3 cathodes and 1 anode and stimulation currents of 1.5 mA. A significant interaction effect of stimulation type and load condition on working memory capacity was found. This was reflected by a significant improvement of WM performance in the high load condition during tACS over the left DLPFC compared with sham stimulation, which was not the case for our parietal tACS or tDCS setup. Working memory performance can be improved with optimized high-definition tACS with a frequency of 5 Hz over the left DLPFC. The conception of different mechanisms underlying transcranial electrical stimulation with alternating and direct currents is supported by these results. Patients suffering from working memory impairments due to neuropsychiatric diseases might potentially benefit from this brain stimulation approach.

Brain‐oscillation-synchronized stimulation to enhance motor recovery in early subacute stroke: a randomized controlled double‐blind three‐ arm parallel‐group exploratory trial comparing personalized, non‐ personalized and sham repetitive transcranial magnetic stimulation (Acronym: BOSS-STROKE)

BackgroundStroke is a major cause of death and the most frequent cause of permanent disability in western countries. Repetitive transcranial brain stimulation (rTMS) has been used to enhance neuronal plasticity after stroke, yet with only moderate effect sizes. Here we will apply a highly innovative technology that synchronizes rTMS to specific brain states identified by real-time analysis of electroencephalography.MethodsOne hundred forty-four patients with early subacute ischemic motor stroke will be included in a multicenter 3-arm parallel, randomized, double-blind, standard rTMS and sham rTMS-controlled exploratory trial in Germany. In the experimental condition, rTMS will be synchronized to the trough of the sensorimotor µ-oscillation, a high-excitability state, over ipsilesional motor cortex. In the standard rTMS control condition the identical protocol will be applied, but non-synchronized to the ongoing µ-oscillation. In the sham condition, the same µ-oscillation-synchronized protocol as in experimental condition will be applied, but with ineffective rTMS, using the sham side of an active/placebo TMS coil. The treatment will be performed over five consecutive work days (1,200 pulses per day, 6,000 pulses total). The primary endpoint will be motor performance after the last treatment session as measured by the Fugl-Meyer Assessment Upper Extremity.DiscussionThis study investigates, for the first time, the therapeutic efficacy of personalized, brain-state-dependent rTMS. We hypothesize that synchronization of rTMS with a high-excitability state will lead to significantly stronger improvement of paretic upper extremity motor function than standard or sham rTMS. Positive results may catalyze a paradigm-shift towards personalized brain-state-dependent stimulation therapies.Trial registrationThis study was registered at ClinicalTrials.gov (NCT05600374) on 10–21-2022.

Cerebellar Transcranial Alternating Current Stimulation in Essential Tremor Patients with Thalamic Stimulation: A Proof-of-Concept Study.

Essential tremor (ET) is a disabling condition resulting from a dysfunction of cerebello-thalamo-cortical circuitry. Deep brain stimulation (DBS) or lesion of the ventral-intermediate thalamic nucleus (VIM) is an effective treatment for severe ET. Transcranial cerebellar brain stimulation has recently emerged as a non-invasive potential therapeutic option. Here, we aim to investigate the effects of high-frequency non-invasive cerebellar transcranial alternating current stimulation (tACS) in severe ET patients already operated for VIM-DBS. Eleven ET patients with VIM-DBS, and 10 ET patients without VIM-DBS and matched for tremor severity, were included in this double-blind proof-of-concept controlled study. All patients received unilateral cerebellar sham-tACS and active-tACS for 10min. Tremor severity was blindly assessed at baseline, without VIM-DBS, during sham-tACS, during and at 0, 20, 40min after active-tACS, using kinetic recordings during holding posture and action ('nose-to-target') task and videorecorded Fahn-Tolosa-Marin (FTM) clinical scales. In the VIM-DBS group, active-tACS significantly improved both postural and action tremor amplitude and clinical (FTM scales) severity, relative to baseline, whereas sham-tACS did not, with a predominant effect for the ipsilateral arm. Tremor amplitude and clinical severity were also not significantly different between ON VIM-DBS and active-tACS conditions. In the non-VIM-DBS group, we also observed significant improvements in ipsilateral action tremor amplitude, and clinical severity after cerebellar active-tACS, with a trend for improved postural tremor amplitude. In non-VIM-DBS group, sham- active-tACS also decreased clinical scores. These data support the safety and potential efficacy of high-frequency cerebellar-tACS to reduce ET amplitude and severity.

Towards causal mechanisms of consciousness through focused transcranial brain stimulation.

Conscious experience represents one of the most elusive problems of empirical science, namely neuroscience. The main objective of empirical studies of consciousness has been to describe the minimal sets of neural events necessary for a specific neuronal state to become consciously experienced. The current state of the art still does not meet this objective but rather consists of highly speculative theories based on correlates of consciousness and an ever-growing list of knowledge gaps. The current state of the art is defined by the limitations of past stimulation techniques and the emphasis on the observational approach. However, looking at the current stimulation technologies that are becoming more accurate, it is time to consider an alternative approach to studying consciousness, which builds on the methodology of causal explanations via causal alterations. The aim of this methodology is to move beyond the correlates of consciousness and focus directly on the mechanisms of consciousness with the help of the currently focused brain stimulation techniques, such as geodesic transcranial electric neuromodulation. This approach not only overcomes the limitations of the correlational methodology but will also become another firm step in the following science of consciousness.

The Impact of Transcranial Brain Stimulation Combined with Cognitive Training on Attention and Working Memory: A Review of Literature

Studies conducted on both normal and abnormal samples have shown transcranial brain stimulation to be effective in improving cognitive functioning. Meanwhile, the behavioral training of cognitive skills has been found to be effective as well. To enhance or rehabilitate core cognitive processes, neuropsychologists and clinicians usually use either one of these or a combination of both. In this study, we reviewed the literature to investigate the effects of brain stimulation alone or combined with cognitive training on attention and working memory. It was concluded that the combined method can be more effective than brain stimulation alone. However, there is no sufficient evidence to make a conclusive statement.

Inhibitory Control Training Enhanced by Transcranial Direct Current Stimulation to Reduce Binge Eating Episodes: Findings from the Randomized Phase II ACCElect Trial

Introduction: Binge eating disorder (BED) is characterized by recurrent binge eating (BE) episodes with loss of control. Inhibitory control impairments, including alterations in dorsolateral prefrontal cortex (dlPFC) functioning, have been described for BED. A targeted modulation of inhibitory control circuits by the combination of inhibitory control training and transcranial brain stimulation could be promising. Objective: The aim of the study was to demonstrate feasibility and clinical effects of a transcranial direct current stimulation (tDCS)-enhanced inhibitory control training to reduce BE episodes and to generate an empirical basis for a confirmatory trial. Methods: We performed a monocentric clinical phase II double-blind randomized trial with two parallel arms. Forty-one adult outpatients with full-syndrome BED according to DSM-5 received six sessions of food-related inhibitory control training, randomly combined with 2 mA verum or sham tDCS of the right dlPFC. The main outcome was BE frequency within a 4-week interval after treatment termination (T8; primary) and at 12-week follow-up (T9; secondary) as compared to baseline. Results: BE frequency was reduced in the sham group from 15.5 to 5.9 (T8) and to 6.8 (T9); in the verum group, the reduction was 18.6 to 4.4 (T8) resp. 3.8 (T9). Poisson regression with the study arm as the factor and baseline BE frequency as the covariate revealed a p value of 0.34 for T8 and 0.026 for T9. Sham and real tDCS differed at T9 in BE frequency. Conclusions: Inhibitory control training enhanced by tDCS is safe in patients with BED and results in a substantial and sustainable reduction in BE frequency which unfolds over several weeks post-treatment. These results constitute the empirical basis for a confirmatory trial.

P-6 Determination of central pain modulation biomarkers to characterize and profile cancer patients with refractory pain and adaptation and validation of a home-based transcranial brain stimulation procedure for their palliative care

P-6 Determination of central pain modulation biomarkers to characterize and profile cancer patients with refractory pain and adaptation and validation of a home-based transcranial brain stimulation procedure for their palliative care