Current Stimulation Protocols Research Articles

Targeting the left DLPFC and right VLPFC in unmarried romantic relationship breakup (love trauma syndrome) with intensified electrical stimulation: A randomized, single-blind, parallel-group, sham-controlled study

BackgroundEnding a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables. MethodsIn this randomized, sham-controlled, single-blind parallel trial, we assessed the efficacy of an intensified anodal stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) with two montages (left DLPFC vs right VLPFC) to reduce love trauma symptoms. 36 participants with love trauma syndrome were randomized in three tDCS condition (left DLPFC, right VLPFC, sham stimulation). LTS symptoms, treatment-related outcome variables (depressive state, anxiety, emotion regulation, positive and negative affect), and cognitive functions were assessed before, right after, and one month after intervention. ResultsBoth DLPFC and VLPFC protocols significantly reduced LTS symptoms, and improved depressive state and anxiety after the intervention, as compared to the sham group. The improving effect of the DLPFC protocol on love trauma syndrome was significantly larger than that of the VLPFC protocol. For emotion regulation and positive and negative affect, improved regulation of emotions and positive affect and reduced negative affect were revealed after intervention in the two real stimulation conditions compared to the sham. For cognitive functions, no significant difference was observed between the groups, but again a positive effect of intervention within groups in the real stimulation conditions (DLPFC and VLPFC) was found for most components of the cognitive tasks. ConclusionsEnhancement of left DLPFC and right VLPFC activity with intensified stimulation improves LTS symptoms and treatment-related variables. For LTS symptoms, DLPFC stimulation was more efficient than VLPFC stimulation., For the other variables, no significant difference was observed between these two stimulation groups. These promising results require replication in larger trials.

Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap.

A recent hypothesis characterizes difficulties in multitasking as being the price humans pay for our ability to generalize learning across tasks. The mitigation of these costs through training has been associated with reduced overlap of constituent task representations within frontal, parietal, and subcortical regions. Transcranial direct current stimulation, which can modulate functional brain activity, has shown promise in generalizing performance gains when combined with multitasking training. However, the relationship between combined transcranial direct current stimulation and training protocols with task-associated representational overlap in the brain remains unexplored. Here, we paired prefrontal cortex transcranial direct current stimulation with multitasking training in 178 individuals and collected functional magnetic resonance imaging data pre- and post-training. We found that 1mA transcranial direct current stimulation applied to the prefrontal cortex paired with multitasking training enhanced training transfer to spatial attention, as assessed via a visual search task. Using machine learning to assess the overlap of neural activity related to the training task in task-relevant brain regions, we found that visual search gains were predicted by changes in classification accuracy in frontal, parietal, and cerebellar regions for participants that received left prefrontal cortex stimulation. These findings demonstrate that prefrontal cortex transcranial direct current stimulation may interact with training-related changes to task representations, facilitating the generalization of learning.

High-density transcranial direct current stimulation to improve upper limb motor function following stroke: study protocol for a double-blind randomized clinical trial targeting prefrontal and/or cerebellar cognitive contributions to voluntary motion

BackgroundFocal brain lesions following a stroke of the middle cerebral artery induce large-scale network disarray with a potential to impact multiple cognitive and behavioral domains. Over the last 20 years, non-invasive brain neuromodulation via electrical (tCS) stimulation has shown promise to modulate motor deficits and contribute to recovery. However, weak, inconsistent, or at times heterogeneous outcomes using these techniques have also highlighted the need for novel strategies and the assessment of their efficacy in ad hoc controlled clinical trials.MethodsWe here present a double-blind, sham-controlled, single-center, randomized pilot clinical trial involving participants having suffered a unilateral middle cerebral artery (MCA) stroke resulting in motor paralysis of the contralateral upper limb. Patients will undergo a 10-day regime (5 days a week for 2 consecutive weeks) of a newly designed high-definition transcranial direct current stimulation (HD-tDCS) protocol. Clinical evaluations (e.g., Fugl Meyer, NIHSS), computer-based cognitive assessments (visuo-motor adaptation and AX-CPT attention tasks), and electroencephalography (resting-state and task-evoked EEG) will be carried out at 3 time points: (I) Baseline, (II) Post-tDCS, and (III) Follow-up. The study consists of a four-arm trial comparing the impact on motor recovery of three active anodal tDCS conditions: ipsilesional DLPFC tDCS, contralesional cerebellar tDCS or combined DLPFC + contralesional cerebellar tDCS, and a sham tDCS intervention. The Fugl-Meyer Assessment for the upper extremity (FMA-UE) is selected as the primary outcome measure to quantify motor recovery. In every stimulation session, participants will receive 20 min of high-density tDCS stimulation (HD-tDCS) (up to 0.63 mA/cm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathrm{cm}}^{2}$$\\end{document}) with πcm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathrm{\\pi cm}}^{2}$$\\end{document} electrodes. Electrode scalp positioning relative to the cortical surface (anodes and cathodes) and intensities are based on a biophysical optimization model of current distribution ensuring a 0.25 V/m impact at each of the chosen targets.DiscussionOur trial will gauge the therapeutic potential of accumulative sessions of HD-tDCS to improve upper limb motor and cognitive dysfunctions presented by middle cerebral artery stroke patients. In parallel, we aim at characterizing changes in electroencephalographic (EEG) activity as biomarkers of clinical effects and at identifying potential interactions between tDCS impact and motor performance outcomes. Our work will enrich our mechanistic understanding on prefrontal and cerebellar contributions to motor function and its rehabilitation following brain damage.Trial registrationClinicalTrials.gov NCT05329818. April 15, 2022.

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.

Targeting the insula with transcranial direct current stimulation; A simulation study

Insula is considered an important region of the brain in the generation and maintenance of a wide range of psychiatric symptoms, possibly due to being key in fundamental functions such as interoception and cognition in general. Investigating the possibility of targeting this area using non-invasive brain stimulation techniques can open new possibilities to probe the normal and abnormal functioning of the brain and potentially new treatment protocols to alleviate symptoms of different psychiatric disorders. In the current study, COMETS2, a MATLAB based toolbox was used to simulate the magnitude of the current density and electric field in the brain caused by different transcranial direct current stimulation (tDCS) protocols to find an optimum montage to target the insula and its 6 subregions for three different current intensities, namely 2, 3, and 4 mA. Frontal and occipital regions were found to be optimal candidate regions.. The results of the current study showed that it is viable to reach the insula and its individual subregions using tDCS.

Frontal two-electrode transcranial direct current stimulation protocols may not affect performance on a combined flanker Go/No-Go task

Transcranial direct current stimulation (tDCS) has been tested to modulate cognitive control or response inhibition using various electrode montages. However, electrode montages and current polarities have not been systematically compared when examining tDCS effects on cognitive control and response inhibition. In this randomized, sham-controlled study, 38 healthy volunteers were randomly grouped into receiving one session of sham, anodal, and cathodal each in an electrode montage that targeted either the dorsolateral prefrontal cortex (DLPFC) or the fronto-medial (FM) region. Participants performed a combined flanker Go/No-Go task during stimulation. No effect of tDCS was found in the DLPFC and FM groups neither using anodal nor cathodal stimulation. No major adverse effects of tDCS were identified using either montage or stimulation type and the two groups did not differ in terms of the reported sensations. The present study suggests that single-session tDCS delivered in two two-electrode montages might not affect cognitive control or response inhibition, despite using widely popular stimulation parameters. This is in line with the heterogeneous findings in the field and calls for further systematic research to exclude less reliable methods from those with more pronounced effects, identify the determinants of responsiveness, and develop optimal ways to utilize this technique.

An optimized cultivation method for future in vivo application of γδ T cells.

γδ T cells, with their properties of both the innate and acquired immune systems, are suitable candidates for cellular immunotherapy in cancer. Because of their non-major histocompatibility complex (MHC) binding T cell receptor, allogenic transfer is feasible without relevant graft versus host reactions. In recent years, much experience has been gained with ex vivo expansion and stimulation of γδ T cells using bisphosphonates and Interleukin 2. Unfortunately, many current stimulation protocols are based on the use of xenogenic materials and other potentially hazardous supplements, which conflicts with basic principles of Good Manufacturing Practice (GMP). Adherence to the concept and current guidelines of GMP is state of the art for production of Advanced Therapy Medicinal Products (ATMP) like cell therapeutics and a necessity for clinical use under a regulatory perspective. In this study, we developed a new stimulation protocol that induces a marked increase of γδ T cell counts and allows for an easier transition from research to clinical applications with minimized regulatory workload. It reliably leads to a cell product with a purity of more than 90% γδ T cells and improved in vitro anti-tumor activity compared to our previous standard procedure. Furthermore, by investigating correlations between properties of unstimulated γδ T cells and proliferation rate as well as degranulation ability of stimulated γδ T cells, we can draw conclusions about suitable donors. Finally, we examined if expansion can be improved by pulsing zoledronate and/or using Interleukin 15 with or without Interleukin 2. Significant improvements can be achieved with respect to intrinsic and antibody-dependent cell-mediated cytotoxicity. Our results demonstrate that the stimulation protocol presented here leads to an improved γδ T cell product for future clinical applications.

Using a Pulse Protocol to Fix the Individual Dosage of Transcranial and Transspinal Direct Current Electrical Stimulation.

The non-invasive current stimulation protocol differs significantly between the brain and spinal cord, such that when comparing the two, there is a clear predominance of protocols using transcranial direct current stimulation (tDCS) for the brain and of protocols using pulsed stimulation for the spinal cord (psSC). These protocols differ in their effects on the central nervous system and in such important parameters as stimulation intensity. In most cases, tDCS has a fixed amplitude for all subjects/patients, while psSC is usually chosen on a case-by-case basis, according to the thresholds of muscle responses. In our opinion, it is possible to use the experience of identifying thresholds during psSC to adjust the dose of the direct current for transcranial and transspinal electrical stimulation, an approach that may provide more homogeneous tDCS data.

Sustained and potent analgesia with negligible side effects enabled by adaptive individualized granular stimulation in rat brainstem

Objectives. To clarify if an adaptive current stimulation protocol, in which current amplitude is modulated during continuous stimulation, provides better efficacy than constant current stimulation protocol with respect to analgesia caused by individualized stimulation in rat periaqueductal gray matter (PAG) /dorsal raphe nuclei (DRN). Approach. Ultrathin microelectrodes adapted for recording (n = 6) and stimulation (n = 16) were implanted in rat primary somatosensory cortex and PAG/DRN, respectively. In each animal included (n = 12), a subset of PAG/DRN microelectrodes (n = 1–3 per animal) was selected that on simultaneous stimulation blocked nociceptive withdrawal reflexes in awake unrestrained animals without noticeable side effects. Analgesic effects were subsequently assessed from both nociceptive withdrawal reflexes and intracortical pain-related responses on CO2 laser hind paw stimulation. The analgesic effects of adaptive current PAG/DRN stimulation comprising incremental increases of 5 μA/microelectrode (initial median current 30 μA/microelectrode) when effects declined were compared to the effects of constant current stimulation. Behavioral effects and brain state related changes were analyzed using quantitative movement analysis and electrocorticography (recorded on top of the dura mater), respectively. Tissue reactions and probe placement in PAG/DRN were assessed with immunohistochemistry. Main results. Powerful and sustained (4 h) analgesia was achieved with the adaptive current protocol within a rather wide area of PAG/DRN. Analgesic after-effects were seen for up to 30 min. Behavioral and brain state related side effects were minimal. Moreover, 6 weeks after implantation, there were no traces of bleedings, only small glial reactions and small but not statistically significant loss of neurons nearby indicating that the microelectrode stimulation employed is biocompatible. Significance. The results indicate that sustained and powerful analgesia with minimal side effects can be achieved by granular and individualized stimulation in PAG/DRN using an adaptive current stimulation protocol. This microelectrode technology and stimulation paradigm thus has the potential of providing a highly efficient and safe pain therapy.

Neuromodulation using cross-frequency coupling tACS: preliminary data

Abstract Non-invasive brain stimulation (NIBS) techniques are widely used in both clinical and experimental settings because they can modulate and provide information about ongoing cortical activity. It is well known that our brain works in networks and that frequency changes probably sustain communication among different cortical areas. In particular, the cross-frequency coupling (CFC) phenomenon is thought to mediate large-scale integration and communication by synchronizing the discharge frequencies of other neuronal populations in time. Based on the CFC hypothesis, this study aimed to interfere with the spontaneous cortical activity of primary motor cortices (M1) using an innovative transcranial alternating current stimulation (tACS) protocol. Seven healthy subjects underwent two experimental sessions in which we applied either 20 minutes of theta-gamma tACS (θ-γ tACS) or 20 minutes of sham tACS (s-tACS). To assess the aftereffects induced with this protocol, we used transcranial magnetic stimulation (TMS) over left M1 to evaluate cortical changes in different intracortical circuits before and after the intervention. In particular, we tested motor evoked potentials (MEP), Short Intracortical Facilitation (SICF), and Short Intracortical Inhibition-Intracortical Facilitation (SICI-ICF) before and after the stimulation. We expected there to be a shift in the balance between inhibitory and excitatory activity only following the θ-γ tACS stimulation. The main result of the study is that θ-γ tACS exerted an effect on SICI, leading to a lower inhibition after the stimulation (p < 0.05), whereas no changes were found in the MEP and ICF following stimulation (p > 0.05). Importantly we found no statistically significant differences in any of the neurophysiological measures (i.e. MEP, SICF, SICI-ICF) following the sham condition. These preliminary data suggest that combining different frequencies for tACS interventions may effectively induce changes in cortical activity. Understanding the neural underpinnings of such neuromodulation may shed light on the future therapeutic application in clinical settings. Research Category and Technology and Methods Basic Research: 8. Transcranial Alternating Current Stimulation (tACS) Keywords: tACS, TMS, cross-frequency , neurophysiology

10 Minutes Frontal 40 Hz tACS-Effects on Working Memory Tested by Luck-Vogel Task.

Working memory is a cognitive process that involves short-term active maintenance, flexible updating, and processing of goal- or task-relevant information. All frequency bands are involved in working memory. The activities of the theta and gamma frequency bands in the frontoparietal network are highly involved in working memory processes; theta oscillations play a role in the temporal organization of working memory items, and gamma oscillations influence the maintenance of information in working memory. Transcranial alternating current stimulation (tACS) results in frequency-specific modulation of endogenous oscillations and has shown promising results in cognitive neuroscience. The electrophysiological and behavioral changes induced by the modulation of endogenous gamma frequency in the prefrontal cortex using tACS have not been extensively studied in the context of working memory. Therefore, we aimed to investigate the effects of frontal gamma-tACS on working memory outcomes. We hypothesized that a 10-min gamma tACS administered over the frontal cortex would significantly improve working memory outcomes. Young healthy participants performed Luck-Vogel cognitive behavioral tasks with simultaneous pre- and post-intervention EEG recording (Sham versus 40 Hz tACS). Data from forty-one participants: sham (15 participants) and tACS (26 participants), were used for the statistical and behavioral analysis. The relative changes in behavioral outcomes and EEG due to the intervention were analyzed. The results show that tACS caused an increase in the power spectral density in the high beta and low gamma EEG bands and a decrease in left-right coherence. On the other hand, tACS had no significant effect on success rates and response times. Conclusion: 10 min of frontal 40 Hz tACS was not sufficient to produce detectable behavioral effects on working memory, whereas electrophysiological changes were evident. The limitations of the current stimulation protocol and future directions are discussed in detail in the following sections.

Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation.

The development of technologies to protect or enhance memory in older people is an enduring goal of translational medicine. Here we describe repetitive (4-day) transcranial alternating current stimulation (tACS) protocols for the selective, sustainable enhancement of auditory-verbal working memory and long-term memory in 65-88-year-old people. Modulation of synchronous low-frequency, but not high-frequency, activity in parietal cortex preferentially improved working memory on day 3 and day 4 and 1 month after intervention, whereas modulation of synchronous high-frequency, but not low-frequency, activity in prefrontal cortex preferentially improved long-term memory on days 2-4 and 1 month after intervention. The rate of memory improvements over 4 days predicted the size of memory benefits 1 month later. Individuals with lower baseline cognitive function experienced larger, more enduring memory improvements. Our findings demonstrate that the plasticity of the aging brain can be selectively and sustainably exploited using repetitive and highly focalized neuromodulation grounded in spatiospectral parameters of memory-specific cortical circuitry.

Alpha rhythm of electroencephalography was modulated differently by three transcranial direct current stimulation protocols in patients with ischemic stroke

The heterogeneity of transcranial direct current stimulation (tDCS) protocols and clinical profiles may explain variable results in modulating excitability in the motor cortex after stroke. However, the cortical electrical effects induced by different tDCS protocols remain unclear. Here, we aimed to compare rhythm changes in electroencephalography (EEG) induced by three tDCS position protocols and the association between tDCS effects and clinical factors in stroke. Nineteen patients with chronic ischemic stroke underwent four experimental sessions with three tDCS protocols [anodal (atDCS), cathodal (ctDCS), and bilateral (bi-tDCS)] and a sham protocol, according to a single-blind randomized crossover design. Resting-state EEG was acquired before and after each protocol. First, a paired-sample t-test was used to examine the difference in spectral power between pre- and post-stimulation. Then, linear and quadratic regression models were used separately to describe the association between the clinical factors of stroke and changes in spectral power which was significantly different between pre- and post-tDCS. Finally, repeated measures analysis of variance with lesion hemisphere, stimulation protocol, and the location was performed to investigate the effects of tDCS over time. The induced effect of tDCS was mainly reflected in the alpha rhythms. The alpha power was increased by atDCS, especially low-alpha (8–10 Hz), in localized areas of the central and distant areas of the frontal and parietal lobes. Bi-tDCS also affected alpha power but in a smaller area that mainly focused on high-alpha rhythms (10–13 Hz). However, ctDCS and sham had no significant effects on any EEG rhythm. The clinical factors of time since stroke and motor impairment level were related to the change in high-alpha induced by atDCS and bi-tDCS following quadratic regression models. The above-mentioned modulation effect lasted for 20 min without attenuation. In conclusion, our findings provide evidence that the alpha rhythm of EEG is modulated differently by different tDCS protocols and that high alpha is affected by clinical characteristics such as post-stroke time and motor deficits, which is of great significance for understanding the modulation effect of different tDCS protocols on stroke and the guidance of protocols to promote motor recovery following stroke.

Multidimensional Assessment of Electroencephalography in the Neuromodulation of Disorders of Consciousness.

In the present study, we aimed to elucidate changes in electroencephalography (EEG) metrics during recovery of consciousness and to identify possible clinical markers thereof. More specifically, in order to assess changes in multidimensional EEG metrics during neuromodulation, we performed repeated stimulation using a high-density transcranial direct current stimulation (HD-tDCS) protocol in 42 patients with disorders of consciousness (DOC). Coma Recovery Scale-Revised (CRS-R) scores and EEG metrics [brain network indicators, spectral energy, and normalized spatial complexity (NSC)] were obtained before as well as fourteen days after undergoing HD-tDCS stimulation. CRS-R scores increased in the responders (R +) group after HD-tDCS stimulation. The R + group also showed increased spectral energy in the alpha2 and beta1 bands, mainly at the frontal and parietal electrodes. Increased graphical metrics in the alpha1, alpha2, and beta1 bands combined with increased NSC in the beta2 band in the R + group suggested that improved consciousness was associated with a tendency toward stronger integration in the alpha1 band and greater isolation in the beta2 band. Following this, using NSC as a feature to predict responsiveness through machine learning, which yielded a prediction accuracy of 0.929, demonstrated that the NSC of the alpha and gamma bands at baseline successfully predicted improvement in consciousness. According to our findings reported herein, we conclude that neuromodulation of the posterior lobe can lead to an EEG response related to consciousness in DOC, and that the posterior cortex may be one of the key brain areas involved in the formation or maintenance of consciousness.

The Effect of Different Transcranial Direct Current Stimulation (tDCS) Protocols on Drug Craving and Cognitive Functions in Methamphetamine Addicts

Introduction: Drug craving is a major problem in addiction treatment. Neuroimaging research has revealed various areas for drug craving, among which two key areas are the Dorsolateral Prefrontal Cortex (DLPFC) and the cerebellum. The DLPFC is involved in different cognitive tasks, such as inhibitory control over seductive options that promise an immediate reward. The cerebellum is related to cognition and memory and activated by drug-related cues. Therefore, we decided to study the effect of Transcranial Direct Current Stimulation (tDCS) on six different protocols in reducing drug craving and increasing cognitive functions in methamphetamine addicts. Methods: The present study is quasi-experimental, with a pre-test-post-test design and a control group. Based on a simple sampling method, 15 male methamphetamine addicts were recruited from two rehabilitation centers in Tehran City, Iran. The participants were aged 18-65 years with a minimum of 12-month history of methamphetamine dependence. The Visual Analog Scale (VAS), the go/no-go task and the n-back task were administered before and after a single session of tDCS. The tDCS was applied on six protocols: 1) the right DLPFC anodal and the left DLPFC cathodal stimulation, 2) the right DLPFC cathodal and the left DLPFC anodal stimulation, 3) the right DLPFC anodal and the right arm cathodal stimulation, 4) the left DLPFC anodal and the left arm cathodal stimulation, 5) the right cerebellar hemisphere (O2) anodal and the left cerebellar hemisphere (O1) cathodal stimulation, and 6) the right cerebellar hemisphere (O2) cathodal and the left cerebellar hemisphere (O1) anodal stimulation. The data were analyzed by covariance method using SPSS software v. 22. Results: Study results indicated that while single-session tDCS effects on craving were not significant, it increased cognitive inhibition, especially in protocol 2: the right DLPFC cathodal and the left DLPFC anodal stimulation. Conclusion: Single-session tDCS affects craving insignificantly, but it can increase cognitive inhibition significantly. These findings support the results of previous studies on the effects of brain stimulation on reducing drug craving in other drug-type settings.

Double-blind randomized N-of-1 trial of transcranial alternating current stimulation for mal de débarquement syndrome.

BackgroundMal de Débarquement Syndrome (MdDS) is a medically refractory neurotological disorder characterized by persistent oscillating vertigo that follows a period of entrainment to oscillating motion such as experienced during sea or air travel. Fronto-occipital hypersynchrony may correlate with MdDS symptom severity.Materials and methodsIndividuals with treatment refractory MdDS lasting at least 6 months received single administrations of three fronto-occipital transcranial alternating current stimulation (tACS) protocols in an “n-of-1” double-blind randomized design: alpha frequency anti-phase, alpha-frequency in-phase, and gamma frequency control. Baseline assessments were made on Day 1. The treatment protocol that led to the most acute reduction in symptoms during a test session on Day 2 was administered for 10–12 stacked sessions given on Days 3 through 5 (20-minutes at 2-4mA). Pre to post symptom changes were assessed on Day 1 and Day 5. Participants who could clearly choose a preferred protocol on Day 2 did better on Day 5 than those who could not make a short-term determination on Day 2 and either chose a protocol based on minimized side effects or were randomized to one of the three protocols. In addition, weekly symptom assessments were made for four baseline and seven post stimulation points for the Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS).ResultsOf 24 participants, 13 chose anti-phase, 7 chose in-phase, and 4 chose control stimulation. Compared to baseline, 10/24 completers noted ≥ 25% reduction, 5/24 ≥50% reduction, and 2/24 ≥75% reduction in oscillating vertigo intensity from Day 1 to Day 5. Stimulating at a frequency slightly higher than the individual alpha frequency (IAF) was better than stimulating at exactly the IAF, and slightly better than stimulating with a strategy of standardized stimulation at 10Hz. A one-way repeated measures ANOVA of weekly DHI, MBRS, and HADS measurements showed significant reductions immediately after treatment with improvement increasing through post-treatment week 6.ConclusionFronto-occipital tACS may be effective in reducing the oscillating vertigo of MdDS and serve as a portable neuromodulation alternative for longer-term treatment. Stimulation frequency relative to the IAF may be important in determining the optimum treatment protocol [ClinicalTrials.gov study NCT02540616. https://clinicaltrials.gov/ct2/show/NCT02540616].

The Effect of Different Transcranial Direct Current Stimulation (tDCS) Protocols on Drug Craving and Cognitive Functions in Methamphetamine Addicts.

Drug craving is a major problem in addiction treatment. Neuroimaging research has revealed various areas for drug craving, among which two key areas are the Dorsolateral Prefrontal Cortex (DLPFC) and the cerebellum. The DLPFC is involved in different cognitive tasks, such as inhibitory control over seductive options that promise an immediate reward. The cerebellum is related to cognition and memory and activated by drug-related cues. Therefore, we decided to study the effect of Transcranial Direct Current Stimulation (tDCS) on six different protocols in reducing drug craving and increasing cognitive functions in methamphetamine addicts. The present study is quasi-experimental, with a pre-test-post-test design and a control group. Based on a simple sampling method, 15 male methamphetamine addicts were recruited from two rehabilitation centers in Tehran City, Iran. The participants were aged 18-65 years with a minimum of 12-month history of methamphetamine dependence. The Visual Analog Scale (VAS), the go/no-go task and the n-back task were administered before and after a single session of tDCS. The tDCS was applied on six protocols: 1) the right DLPFC anodal and the left DLPFC cathodal stimulation, 2) the right DLPFC cathodal and the left DLPFC anodal stimulation, 3) the right DLPFC anodal and the right arm cathodal stimulation, 4) the left DLPFC anodal and the left arm cathodal stimulation, 5) the right cerebellar hemisphere (O2) anodal and the left cerebellar hemisphere (O1) cathodal stimulation, and 6) the right cerebellar hemisphere (O2) cathodal and the left cerebellar hemisphere (O1) anodal stimulation. The data were analyzed by covariance method using SPSS software v. 22. Study results indicated that while single-session tDCS effects on craving were not significant, it increased cognitive inhibition, especially in protocol 2: the right DLPFC cathodal and the left DLPFC anodal stimulation. Single-session tDCS affects craving insignificantly, but it can increase cognitive inhibition significantly. These findings support the results of previous studies on the effects of brain stimulation on reducing drug craving in other drug-type settings. One session of Transcranial Direct Current Stimulation (tDCS) intervention is ineffective for reducing addiction craving in methamphetamine addicts.DCS intervention significantly increases cognitive inhibition.The best results with tDCS intervention in addiction recovery are use of the right DLPFC cathodal stimulation and left DLPFC anodal stimulation protocol. One of the primary concerns in treating addiction is to choose an effective intervention for reducing craving. tDCS is a non-invasive and safe way of reducing craving, which can be used in different ways to decrease addiction craving and treat addiction. While his study founds that one session of tDCS protocols is not effective in reducing the methamphetamine craving, They are effective for increasing cognitive inhibition, which is essential in addiction recovery and saying no to cravings. This effect on the cognitive inhibition ability has important implications for those seeking new and non-invasive addiction recoveries, especially in methamphetamine addiction.

Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis.

Objective:The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review.Methods:We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively.Results:Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges’s g = −0.870, 95% confidence intervals (CI) = [−1.225 to −0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms.Conclusion:tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.

Efficacy of Unilateral and Bilateral Parietal Transcranial Direct Current Stimulation on Right Hemispheric Stroke Patients With Neglect Symptoms: A Proof-of-Principle Study.

Different transcranial direct current stimulation (tDCS) protocols have been tested to improve visuospatial neglect (VSN). So far, methodological heterogenity limits reliable conclusions about optimal stimualtion set-up. With this proof-of-principle study behavioral effects of two promising (uni- vs. bilateral) stimulation protocols were directly compared to gain more data for an appropriate tDCS protocol in subacute neglect patients. Notably, each tDCS set-up was combined with an identical sham condition to improve comparability. In a double-blind sham-controlled cross-over study 11 subacute post-stroke neglect patients received 20 minutes or 30 seconds (sham) tDCS (2 mA, 0.8 A/m2) parallel to neglect therapy randomized in unilateral (anode-reference: P4-Fp2 10-20 electroencephalography [EEG] system) and bilateral manner (anode-cathode: P4-P3) and 48h wash-out in-between. Before and immediately after stimulation performance were measured in cancellation task (bell test), and line bisection (deviation error). Significant difference between active and assigned sham condition was found in line bisection but not cancellation task. Particularly, deviation error was reduced after bilateral tDCS (hedges g* = 0.6) compared to bilateral sham, no such advantage were obtained for unilateral stimulation (hedges g* = 0.2). Using a direct comparison approach findings add further evidence that stimulating both hemispheres (bilateral) is superior in alleviating VSN symptoms than unilateral stimulation in subacute neglect.

The effect of aging on inter-limb coordination: Establishing a novel transcranial alternating current stimulation (tACS) protocol by means of electroencephalography (EEG)

Abstract Healthy aging is a societal challenge with a significant socioeconomic impact. Gaining knowledge about neurodegenerative changes that impact functional independence is thus of high scientific importance. Age-related structural and functional neural changes have consequences for inter-limb coordination, which forms an intrinsic part of everyday life (e.g., driving, buttoning a shirt). Research has demonstrated that transcranial alternating current stimulation (tACS) targeting neural oscillations can alter behavioral performance. Nevertheless, profound understanding of tACS in the context of inter-limb coordination is yet to be achieved. In order to accomplish this, a more thorough understanding of the neural oscillations underlying inter-limb coordination is of utmost importance. The current study used electroencephalography (EEG) in healthy right-handed participants during two inter-limb coordination tasks; the bimanual tracking task (BTT) and the multi-limb reaction time task (MLT). The BTT consists of rotating two dials with both hands in a coordinated fashion. Three conditions were used, differing in left- and right-hand movement frequency. The MLT requires participants to lift multiple limbs in a correct manner. Six conditions were used, differing in required motor response (e.g., lifting right arm and left leg, lifting left arm and both legs). Twenty healthy right-handed young adults (age: 22.3 ± 1.0 (mean ± standard deviation)) and nineteen older adults (age: 70.7 ± 3.0) participated. Laplacian filtered EEG data will be analyzed in the time-frequency domain using morlet wavelet convolution. EEG time-frequency data between 4 and 35 hertz will be analyzed by means of repeated measures ANOVA, investigating differences across conditions and groups for each task respectively. In addition, bivariate channel-level functional connectivity will be analyzed using inter-site phase clustering. Behavioral data will be analyzed with a mixed model approach. These insights will be used to establish novel tACS protocols. If significant differences between young and older adults are present, these findings can lead to age-adapted tACS protocols. Keywords: Electroencephalography, Transcranial alternating current stimulation, Ageing, Functional connectivity