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Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). •We provide a method for optimizing the configuration of multifocal tDCS.•Optimization cortical target maps are based on fMRI, PET or other data.•Algorithm optimizes electrode currents and locations subject to safety constraints.•We highlight clinical applications in stroke and depression.•We discuss the generalization of these methods to tACS.

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered.

Background Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as Eye Movement Desensitization and Reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients, and if its potential is boosted with the addition of MtCS. Methods Ninety-six patients with FM and a history of traumatic events will be randomly allocated to the treatment as usual (TAU) condition, EMDR + active-MtCS condition, or EMDR + sham-MtCS condition. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, wellbeing, self-care, emotional regulation, self-esteem, and cognitive functioning. Discussion This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS. Trial registration number This trial was registered at ClinicalTrials.gov on 2 August 2019, identifier: NCT04084795.

Background Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as eye movement desensitization and reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients and if its potential is boosted with the addition of MtCS. Methods Forty-five patients with FM and a history of traumatic events will be randomly allocated to Waiting List, EMDR + active-MtCS, or EMDR + sham-MtCS. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, and wellbeing. Discussion This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS. Trial registration ClinicalTrials.gov NCT04084795 . Registered on 2 August 2019.

Transcranial direct current stimulation (tDCS) has been reported to enhance explosive strength in lower limb skeletal muscles. Nevertheless, findings regarding the impact of tDCS on jump performance remain inconclusive, potentially due to variations in stimulation montage and current intensity. Therefore, we aimed to elucidate the effects of multifocal tDCS on lower limb jump kinetics and neuromuscular adaptation. Fourteen female collegiate basketball players were enrolled in a randomized, crossover, controlled trial. Each participant underwent three intervention sessions in a randomized sequence: 2 mA tDCS, 4 mA tDCS, and sham tDCS, all targeting the primary motor cortex (M1). After each stimulation session, countermovement jump (CMJ), squat jump (SJ), drop jump (DJ), and surface electromyography (EMG) data were collected. Statistical analysis was performed using one-way repeated measures ANOVA. The 4 mA multifocal tDCS condition produced a significant increase in jump height compared to baseline, sham, and the 2 mA condition. Similarly, the concentric impulse was markedly higher in the 4 mA group relative to all other conditions. Relative peak force was significantly improved in the 4 mA group versus baseline, and relative peak power was significantly greater under 4 mA tDCS compared to sham stimulation. The modified reactive strength index (RSImod) was also enhanced considerably following 4 mA tDCS, relative to both baseline and sham conditions. However, EMG analysis indicated that none of the tDCS interventions significantly affected the root mean square (RMS) values of lower limb muscle activation, including the rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), semitendinosus/semimembranosus (SEM), medial gastrocnemius (MG), lateral gastrocnemius (GL), and tibialis anterior (TA). Multifocal anodal tDCS at an intensity of 4 mA significantly improves lower limb jump performance in female collegiate basketball athletes. Integrating multifocal anodal tDCS into routine training regimens may serve as a practical and effective adjunct for enhancing performance in this population.

Combining non-invasive brain stimulation (NIBS) with resting-state functional magnetic resonance imaging (rs-fMRI) is a promising approach to characterize and potentially optimize the brain networks subtending cognition that changes as a function of age. However, whether multifocal NIBS approaches are able to modulate rs-fMRI brain dynamics in aged populations, and if these NIBS-induced changes are consistent with the simulated electric current distribution on the brain remains largely unknown. In the present investigation, thirty-one cognitively healthy older adults underwent two different multifocal real transcranial direct current stimulation (tDCS) conditions (C1 and C2) and a sham condition in a crossover design during a rs-fMRI acquisition. The real tDCS conditions were designed to electrically induce two distinct complex neural patterns, either targeting generalized frontoparietal cortical overactivity (C1) or a detachment between the frontal areas and the posteromedial cortex (C2). Data revealed that the two tDCS conditions modulated rs-fMRI differently. C1 increased the coactivation of multiple functional couplings as compared to sham, while a smaller number of connections increased in C1 as compared to C2. At the group level, C1-induced changes were topographically consistent with the calculated electric current density distribution. At the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was related with the magnitude of the simulated electric current density estimates. These results highlight that multifocal tDCS procedures can effectively change rs-fMRI neural functioning in advancing age, being the induced modulation consistent with the spatial distribution of the simulated electric current on the brain. Moreover, our data supports that individually tailoring NIBS-based interventions grounded on subject-specific structural data might be crucial to increase tDCS potential in future studies amongst older adults.

In animal studies intravitreal injection of tetrodotoxin (TTX) results in mfERG waveform changes similar to those observed in glaucoma. As TTX blocks amacrine as well as ganglion cells, there is still a question regarding the underlying cell population responsible for these changes in waveform. In an attempt to assess the contribution of the amacrine cells to these changes, a mfERG was obtained from patients with Parkinson's disease as some amacrine cells are mediated by dopamine, a substance lacking in Parkinson's. Eight patients with early Parkinson's disease underwent ophthalmologic examination, testing of contrast sensitivity and electrophysiological examination according to ISCEV standard at least 12 h following their last medication with Dopamine. A slow stimulation mfERG was obtained with a stimulus base interval of 53.3 ms and with a stimulus base interval of 106.6 ms. During MF-ERG recordings 103 hexagons stimulated the central 50 deg of the retina simultaneously and independently (m-sequence 2(13), L(max): 200 cd/m(2), approximately 100% contrast). Contrast sensitivity and ISCEV standard electrophysiological testing was unremarkable. When the mfERG was analyzed, only four patients had an adequate signal-to-noise ratio to allow further data analysis - one of whom was diagnosed with a multi system atrophy in retrospect. The first order response component was analyzed at a filter setting of 10-300 Hz and at 100-300 Hz (OPs) and compared to mfERGs of a control group. On average, in patients, the amplitude of N1P1 was slightly lower in the central and nasal response averages. When the three OPs at a latency of 72-89 ms were analyzed in the 53.3 ms base interval recording, the most marked difference in amplitude was observed in the superior nasal response average of the first OP. Here a mean amplitude of 1.3 nV/deg(2) in patients compared to a mean amplitude of 1.9 nV/deg(2) in the control group (P: 0.08). In contrast to our previous findings in NTG, there was a consistent presence of three OPs. Under the stimulus conditions applied, we did not find an influence of dopaminergic amacrine cells on the mfERG in our patients with moderate stages of Parkinsion's. The difficulties in obtaining an adequate signal-to noise ratio due to e.g. muscle artifacts even in Parkinson patients of moderate disease stages render a success of mfERG recording in patients with more advanced stages unlikely. The question of the influence of dopaminergic amacrine cells on the mfERG could possibly be addressed using MPDT in animal research.

Multifocal transcranial Electrical Stimulation (tES) has emerged as an innovative approach for modulating cognitive functions by concurrently targeting multiple brain regions. Despite its potential, the efficacy and underlying mechanisms of this technique remain unclear. To evaluate the efficacy of multifocal tES in enhancing cognitive function by examining targeted brain regions, stimulation protocols, and behavioral and neurophysiological outcomes. A systematic search of PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science databases was conducted up to February 10, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The inclusion criteria encompassed human studies utilizing concurrent dual-site or multifocal tES with pre- and post-intervention behavioral assessments. Studies on deep brain stimulation, corticocortical paired associative stimulation, sequential stimulation, case reports, and reviews were excluded. Of the 1,453 initial records, 14 met the inclusion criteria. The studies predominantly employed transcranial direct current stimulation/transcranial alternating current stimulation, targeting the frontoparietal network. Neurophysiological data from electroencephalography and functional magnetic resonance imaging revealed network-level modulations. Behavioral outcomes were inconsistent, with some studies reporting improvements in executive function, working memory, and response inhibition, whereas others showed no significant advantages over sham stimulation. Although multifocal tES is a promising modality, clearly determining its efficacy is currently limited by heterogeneous study designs, small sample sizes, and conflicting findings. Future research should prioritize multi-arm trials, incorporate neurophysiological biomarkers, and develop personalized stimulation protocols to optimize the effectiveness of this technique. PROSPERO Registration # CRD420250646196.

Background To identify mechanisms of cortical plasticity of the visual cortex and to quantify their significance, sensitive parameters are warranted. In this context, multifocal visual evoked potentials (mfVEPs) can make a valuable contribution as they are not associated with cancellation artifacts and include also the peripheral visual field. Objective To investigate if occipital repetitive transcranial magnetic stimulation (rTMS) can induce mfVEP changes. Methods 18 healthy participants were included in a single-blind crossover-study receiving sessions of excitatory, occipital 10 Hz rTMS and sham stimulation. MfVEP was performed before and after each rTMS session and changes in amplitude and latency between both sessions were compared using generalized estimation equation models. Results There was no significant difference in amplitude or latency between verum and sham group. Conclusion We conclude that occipital 10 Hz rTMS has no effect on mfVEP measures, which is in line with previous studies using full field VEP.

•We ask how focal attention modulates MEG responses across the visual field•Multifocal visual stimulation was combined with multivariate pattern analysis•Focal spatial attention initially modulates responses broadly in the visual field•Later modulation is constrained in space to the location of the attention target Visual focal attention is both fast and spatially localized, making it challenging to investigate using human neuroimaging paradigms. Here, we used a new multivariate multifocal mapping method with magnetoencephalography (MEG) to study how focal attention in visual space changes stimulus-evoked responses across the visual field. The observer's task was to detect a color change in the target location, or at the central fixation. Simultaneously, 24 regions in visual space were stimulated in parallel using an orthogonal, multifocal mapping stimulus sequence. First, we used univariate analysis to estimate stimulus-evoked responses in each channel. Then we applied multivariate pattern analysis to look for attentional effects on the responses. We found that attention to a target location causes two spatially and temporally separate effects. Initially, attentional modulation is brief, observed at around 60–130 ms post stimulus, and modulates responses not only at the target location but also in adjacent regions. A later modulation was observed from around 200 ms, which was specific to the location of the attentional target. The results support the idea that focal attention employs several processing stages and suggest that early attentional modulation is less spatially specific than late.