Transcranial Electrical Brain Stimulation Research Articles

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.

Transcranial magnetic stimulation for tinnitus treatment

High prevalence of tinnitus, its negative influence on the quality of life and psychoemotional status of patients support need and extreme urgency of further research of various treatment methods. Rhythmic transcranial magnetic stimulation (rTMS) is an effective method of therapy in patients with chronic tinnitus. The optimal protocol for rhythmic stimulation is low-frequency (1 Hz) rTMS with low-intensity stimuli (below 110% of the motor threshold) with a limited number of stimuli per series. There is evidence that high-frequency rTMS in the area of relatively thin temporal bones can lead to excessive stimulation of the neural structures of the auditory cortex, which is undesirable considering the pathogenesis of this condition. The use of navigation technology in rTMS has no advantage in chronic tinnitus therapy, whereas the combined use of rTMS and transcranial electrical brain stimulation to increase the treatment efficacy is under active study. Considering the attributable favorable clinical safety profile of rTMS, as well as its known positive effects on anxiety and depression that are often seen in patients with tinnitus, we can recommend more widespread use of this method in real-world settings.

Update on the Use of Transcranial Electrical Brain Stimulation to Manage Acute and Chronic COVID-19 Symptoms.

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, we summarize the rationale for using tES techniques, specifically transcranial Direct Current Stimulation (tDCS), across the COVID-19 clinical course, and index ongoing efforts to evaluate the inclusion of tES optimal clinical care.

Post-stroke speech disorders: modern approaches to the treatment of aphasia

The review discusses recent advances in neurobiological research, the treatment of post-stroke speech disorders, and improved patient management. It proves the effectiveness of transcranial magnetic and electrical brain stimulation methods in relation to the restoration of speech functions in aphasia. The possibilities and prospects of cell therapy of post-stroke speech disorders area also considered.

Transorbital alternating current stimulation modifies BOLD activity in healthy subjects and in a stroke patient with hemianopia: A 7 Tesla fMRI feasibility study

BackgroundModifying brain activity using non-invasive, low intensity transcranial electrical brain stimulation (TES) has rapidly increased during the past 20 years. Alternating current stimulation (ACS), for example, has been shown to alter brain rhythm activities and modify neuronal functioning in the visual system. Daily application of transorbital ACS to patients with optic nerve damage induces functional connectivity reorganization, and partially restores vision. While ACS is thought to mainly modify neuronal mechanisms, e.g. changes in brain oscillations that can be detected by EEG, it is still an open question, whether and how it may alter BOLD activity. ObjectiveWe evaluated whether transorbital ACS modulates BOLD activity in early visual cortex using high-resolution 7 Tesla functional magnetic resonance imaging (fMRI). MethodsIn this feasibility study transorbital ACS in the alpha range and sham ACS was applied in a random block design in five healthy subjects for 20 min at 1 mA. Brain activation in the visual areas V1, V2 and V3 were measured using 7 Tesla fMRI-based retinotopic mapping at the time points before (baseline) and after stimulation. In addition, we collected data from one hemianopic stroke patient with visual cortex damage after ten daily sessions with 25–50 min stimulation duration. ResultsIn healthy subjects transorbital ACS increased the activated cortical surface area, decreased the fMRI response amplitude and increased coherence in the visual cortex, which was most prominent in the full field task. In the patient, stimulation improved contrast sensitivity in the central visual field. BOLD amplitudes and coherence values were increased in most early visual areas in both hemispheres, with the most pronounced activation detected during eccentricity testing in retinotopic mapping. ConclusionsThis feasibility study showed that transorbital ACS modifies BOLD activity to visual stimulation, which outlasts the duration of the AC stimulation. This is in line with earlier neurophysiological findings of increased power in EEG recordings and functional connectivity reorganization in patients with impaired vision. Accordingly, the larger BOLD response area after stimulation can be explained by more coherent activation and lower variability in the activation. Alternatively, increased neuronal activity can also be taken into account. Controlled trials are needed to systematically evaluate the potential of repetitive transorbital ACS to improve visual function after visual pathway stroke and to determine the cause-effect relationship between neural and BOLD activity changes.

Modulating fluid intelligence performance through combined cognitive training and brain stimulation

It is debated whether cognitive training of specific executive functions leads to far transfer effects, such as improvements in fluid intelligence (Gf). Within this context, transcranial direct current stimulation and recently also novel protocols such as transcranial random noise and alternating current stimulation are being investigated with regards to their ability to enhance cognitive training outcomes.We compared the effects of four different transcranial electrical brain stimulation protocols in combination with nine daily computerized training sessions on Gf.82 participants were randomly assigned to receive transcranial direct current stimulation (tDCS), random noise stimulation (tRNS), multifocal alternating current stimulation at 40 Hz (mftACS), or multifocal tDCS (mftDCS) in combination with an adaptive and synergistic executive function (EF) training, or to a no-contact control group. EF training consisted of gamified tasks drawing on isolated as well as integrated executive functions (working memory, inhibition, cognitive flexibility). Transfer was assessed with a combined measure of Gf including three established tests (Bochumer Matrizentest - BOMAT, Raven's Advanced Progressive Matrices - RAPM, and Sandia Matrices). We found significant improvements in Gf for the tDCS, mftDCS, and tRNS groups when compared with the no-contact group. In contrast, the mftACS group did not improve significantly and showed a similar pattern as the no-contact group. Mediation analyses indicated that the improvement in Gf was mediated through game progression in the mftDCS and tRNS group. Electrical brain stimulation in combination with sustained EF training can lead to transfer effects in Gf, which are mediated by training progression.

Investigate the effect of HD-tDCS on the prefrontal cortex using fNIRS for neurorehabilitation

Investigate the effect of HD-tDCS on the prefrontal cortex using fNIRS for neurorehabilitation

Transcranial Electrical Brain Stimulation in Alert Rodents.

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

P194 Withdrawal symptoms of electrical brain stimulation in a probabilistic decision making task

Question It has been shown that transcranial electrical brain stimulation (TES) can improve many aspects of cognition, including decision making and learning. However, it has not been studied whether brain is capable of adapting itself to perform at least equally well without TES, after initially learning the task under influence of TES. We used a probabilistic learning task to investigate this question. Methods Participants ( n = 10) took part in two groups of active ( n = 5) and sham ( n = 5) transcranial direct current stimulation (tDCS). Each participant attended two experimental sessions. In both sessions participants were asked to perform a probabilistic decision making task. In this task participants adapted to changes in reward contingencies. Participants were presented with two options of which one of them was designated as the better one, leading to higher possibility of rewarding than punishing feedback. Participants were asked to maximise their gain by choosing the better option. The contingencies changed over the course of the trials. Consequently participants had to adjust to the changes in the environment. In the first session, participants in the active and sham tDCS groups, received 15 min and 16 s of anodal tDCS over their left dorsolateral prefrontal cortex, respectively. For all participants sham stimulation was administered in the second session. Number of rewards in both sessions was recorded and their difference was considered for analysis. Results Comparison of difference of acquired rewards between the two sessions showed that participants in the active group tend to perform worse than those in the sham group. Conclusions This result shows that learning under the influence of TES leads to adaptation which induces changes that might not be efficient without TES in a later phase. In more general terms, this result indicates that learning a task under the influence of TES leads to creation of a model which might not be valid anymore without TES.

An experience of neurophysiological monitoring in neurosurgery

To evaluate the efficacy of neuromonitoring methods in prevention of postoperative neurological complications and estimation of predictive power of intraoperative changes in monitored characteristics. Retrospective study examined 240 patients, operated in the years 2014-2015 using intraoperative neurophysiological monitoring. One hundred and seventy-three patients suffered from hemispheric lesions and 67 had lesions located in or near the brainstem. Somatosensory evoked potentials (SSEP) were monitored in 152 cases, visual in 32, brainstem acoustic in 22, transcranial motor in 36; stimulation mapping of motor cortex was performed in 69 surgeries, and cranial nerves identification in 27. EEG was recorded in 7 patients, and 3 of them were woke up during the surgery for speech mapping. The sensitivity of the SSEP in motor dysfunction detection was low (33%), while the specificity was relatively high (82%). These characteristics for visual and motor evoked potentials were close to 100% provided that the parameters of anesthesia met the corresponding requirements. The most effective methods in respect of prevention of postoperative dysfunctions were the stimulation mapping of functionally significant areas (motor and speech) and motor pathways mapping. Intraoperative neuromonitoring reduces a number of neurological complications after neurosurgical operations. The SSEP method is not sensitive enough in surgeries that could affect motor centers and/or pathways, and multimodal monitoring combining SSEP and motor responses recording during transcranial and/or direct electrical brain stimulation. Successful monitoring requires highly coordinated actions between neurophysiologists, neurosurgeons and anesthesiologists.

Some experience of neurophysiological monitoring in neurosurgery

<p><strong>Aim.</strong> This retrospective study is aimed at evaluating the efficacy of neuromonitoring methods to prevent postoperative neurological complications and estimating predictive power of intraoperative changes in monitored characteristics.<br /><strong>Methods.</strong> 240 patients operated over a period from 2014 to 2015 underwent intraoperative neurophysiological monitoring. 173 patients suffered from hemispheric lesions and 67 had lesions located in or near the brainstem. Somatosensory evoked potentials (SSEP) were monitored in 152 cases, visual – in 32, brainstem acoustic – in 22 and transcranial motor potentials were controlled in 36 cases. Stimulation mapping of motor cortex was performed in 69 surgeries and cranial nerves identification – in 27. The electrocorticogram was registered in 7 patients, with 3 of them undergoing intraoperative awakening for speech function mapping.<br /><strong>Results.</strong> The sensitivity of SSEP in detection of motor dysfunctions was low (33%), while the specificity tended to be relatively high (82%). These characteristics for visual and motor evoked potentials were close to 100% provided the parameters of the anesthesia met the relevant requirements. As for prevention of postoperative dysfunctions, the most effective methods were stimulation mapping of functionally significant areas (motor and speech ones) and motor pathways mapping.<br /><strong>Conclusion.</strong> Intraoperative neuromonitoring reduces the occurrence rate of neurological complications after neurosurgical operations. The SSEP method is not sensitive enough in surgeries that could affect motor centers and/or pathways, therefore, multimodal monitoring which combines SSEP and motor responses registration during transcranial and/or direct electrical brain stimulation is needed. Successful monitoring requires efficient cooperation of neurophysiologists, neurosurgeons and anesthesiologists.</p><p>Received 7 April 2016. Accepted 6 October 2016.</p><p><strong>Funding:</strong> The study had no sponsorship.<br /><strong>Conflict of interest:</strong> The authors declare no conflict of interest.</p>

Modulation of the pre-supplementary motor area reduces the sense of agency (Commentary on Cavazzana et al.).

Institute of Behavioural Neuroscience (IBN), Department of Experimental Psychology, University College London (UCL), London,UKThe sense of agency is the capacity to control one’s own actions and, through them, events in the outside world (Haggard & Chambon,2012). The proposition ‘I did that’ is an important aspect of our everyday lives. For example, this sense associates a light turning on toone’s action when pressing a switch. Abnormalities in this sense can lead to illnesses such as psychosis (increased sense of agency) anddepression (decreased sense of agency). Despite a large amount of theoretical work on the sense of agency, the neural correlates arepoorly understood. Only a handful of imaging and brain stimulation studies have attempted to investigate how different brain areas con-tribute to the emergence of this feeling. Cavazzana et al. (2015) describe evidence showing that modulation of activity in the pre-supple-mentary motor area (pre-SMA) using transcranial electrical brain stimulation can reduce the sense of agency. This is an important findingas it highlights a possible causal link between the activity of the pre-SMA and one’s sense of agency, and thus could have clinical impli-cations.One way of studying the sense of agency is through ‘explicit agency attribution tasks’. In these tasks a person judges whether they did ordid not cause a specific event. For example, a computer program presents a tone whenever the person presses a button. Immediate presenta-tion of the tone following the participant’s key press creates the sense that they caused the presentation of the tone (e.g. agency). If the toneis presented with a delay the sense of agency is reduced. This suggests that the sense of agency is computed by comparing the prediction ofaction outcome(s) with actual outcomes. Figure 1A is a diagram of how this process might work.In addition to explicit measures of the sense of agency there are also several implicit measures, such as intentional binding. Inten-tional binding refers to the temporal compression between a voluntary action and its sensory effect (Haggard & Tsakiris, 2009). In thetask of Cavazzana et al. (2015), an effect (e.g. a tone) is presented after a certain delay, rather than immediately, subsequent to the par-ticipant’s key press. The participant is then required to report the time on a clock indicating when they pressed the button or when thetone was presented. The sense of agency leads to an overestimation of time of action and an underestimation of time (Haggard & Tsak-iris, 2009). Cavazzana et al. (2014) adapted this task for children and presented a series of letters instead of a clock. Participants wererequired to report the letter presented on the screen at the time of their key press or at the time of the presentation of the tone. Cavazz-ana et al. (2015) used this novel method to test healthy adults in combination with a non-invasive brain stimulation paradigm. Anodaland cathodal transcranial direct current stimulation was used to modulate activity of the pre-SMA. Although it has been shown that ano-dal and cathodal stimulation cause excitation and inhibition of neuronal activity, respectively (Nitsche & Paulus, 2000), the results ofCavazzana et al. (2015) did not differentiate between the polarity of stimulation, i.e. both polarities reduced the sense of agency. Onepossible explanation for this is based on the contribution of the SMA and pre-SMA in the perception of time (Lewis & Miall, 2003;Allman et al., 2014). Transcranial direct current stimulation of the pre-SMA might have changed the expected duration of the delay andconsequently reduced the sense of agency. Figure 1 illustrates this possibility. The strongest sense of agency occurs when sensory feed-back and predicted outcomes match (Fig. 1B). Changes to the outcome prediction lead to a weakening of the sense of agency (Fig. 1C).As illustrated, this effect is not dependent on the direction of change of the predicted outcome. Moore et al. (2010) demonstrated a sim-ilar reduction in the sense of agency by stimulating the pre-SMA using transcranial magnetic stimulation. Their stimulation method,however, prevented them from studying both excitation and inhibition of neuronal activity. Application of transcranial direct current stim-ulation enabled Cavazzana et al. (2015) to extend their findings and show that both anodal and cathodal stimulation both lead to similarbehavioural outcomes. This is important as it shows that, regardless of the direction of the effect of stimulation, modulation of activityof the pre-SMA reduces the sense of agency.In summary, the findings of Cavazzana et al. (2015) constitute considerable progress towards understanding the brain network contributingto the sense of agency and highlight the important role of brain areas involved in time perception. More work, such as dynamic causalmodelling and psychophysiological interaction, will be required to elucidate the brain network(s) involved and also studies using behaviouralmanipulations to disentangle the effects of time perception from the sense of agency.

Modulating Cognition Using Transcranial Direct Current Stimulation of the Cerebellum

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain regions involved in working memory and attention using transcranial electrical brain stimulation. Some researchers now believe the cerebellum supports cognition, possibly via a remote neuromodulatory effect on the prefrontal cortex. This paper describes a procedure for investigating a role for the cerebellum in cognition using transcranial direct current stimulation (tDCS), and a selection of information-processing tasks of varying task difficulty, which have previously been shown to involve working memory, attention and cerebellar functioning. One task is called the Paced Auditory Serial Addition Task (PASAT) and the other a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST). A verb generation task and its two controls (noun and verb reading) were also investigated. All five tasks were performed by three separate groups of participants, before and after the modulation of cortico-cerebellar connectivity using anodal, cathodal or sham tDCS over the right cerebellar cortex. The procedure demonstrates how performance (accuracy, verbal response latency and variability) could be selectively improved after cathodal stimulation, but only during tasks that the participants rated as difficult, and not easy. Performance was unchanged by anodal or sham stimulation. These findings demonstrate a role for the cerebellum in cognition, whereby activity in the left prefrontal cortex is likely dis-inhibited by cathodal tDCS over the right cerebellar cortex. Transcranial brain stimulation is growing in popularity in various labs and clinics. However, the after-effects of tDCS are inconsistent between individuals and not always polarity-specific, and may even be task- or load-specific, all of which requires further study. Future efforts might also be guided towards neuro-enhancement in cerebellar patients presenting with cognitive impairment once a better understanding of brain stimulation mechanisms has emerged.

Modulating cognition using transcranial direct current stimulation of the cerebellum.

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain regions involved in working memory and attention using transcranial electrical brain stimulation. Some researchers now believe the cerebellum supports cognition, possibly via a remote neuromodulatory effect on the prefrontal cortex. This paper describes a procedure for investigating a role for the cerebellum in cognition using transcranial direct current stimulation (tDCS), and a selection of information-processing tasks of varying task difficulty, which have previously been shown to involve working memory, attention and cerebellar functioning. One task is called the Paced Auditory Serial Addition Task (PASAT) and the other a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST). A verb generation task and its two controls (noun and verb reading) were also investigated. All five tasks were performed by three separate groups of participants, before and after the modulation of cortico-cerebellar connectivity using anodal, cathodal or sham tDCS over the right cerebellar cortex. The procedure demonstrates how performance (accuracy, verbal response latency and variability) could be selectively improved after cathodal stimulation, but only during tasks that the participants rated as difficult, and not easy. Performance was unchanged by anodal or sham stimulation. These findings demonstrate a role for the cerebellum in cognition, whereby activity in the left prefrontal cortex is likely dis-inhibited by cathodal tDCS over the right cerebellar cortex. Transcranial brain stimulation is growing in popularity in various labs and clinics. However, the after-effects of tDCS are inconsistent between individuals and not always polarity-specific, and may even be task- or load-specific, all of which requires further study. Future efforts might also be guided towards neuro-enhancement in cerebellar patients presenting with cognitive impairment once a better understanding of brain stimulation mechanisms has emerged.

Transcranial electrical brain stimulation modulates neuronal tuning curves in perception of numerosity and duration

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method with many putative applications and reported to effectively modulate behaviour. However, its effects have yet to be considered at a computational level. To address this we modelled the tuning curves underlying the behavioural effects of stimulation in a perceptual task. Participants judged which of the two serially presented images contained more items (numerosity judgement task) or was presented longer (duration judgement task). During presentation of the second image their posterior parietal cortices (PPCs) were stimulated bilaterally with opposite polarities for 1.6s. We also examined the impact of three stimulation conditions on behaviour: anodal right-PPC and cathodal left-PPC (rA-lC), reverse order (lA-rC) and no-stimulation condition. Behavioural results showed that participants were more accurate in numerosity and duration judgement tasks when they were stimulated with lA-rC and rA-lC stimulation conditions respectively. Simultaneously, a decrease in performance on numerosity and duration judgement tasks was observed when the stimulation condition favoured the other task. Thus, our results revealed a double-dissociation of laterality and task. Importantly, we were able to model the effects of stimulation on behaviour. Our computational modelling showed that participants' superior performance was attributable to a narrower tuning curve — smaller standard deviation of detection noise. We believe that this approach may prove useful in understanding the impact of brain stimulation on other cognitive domains.

Restoring Cognitive Functions Using Non-Invasive Brain Stimulation Techniques in Patients with Cerebellar Disorders

Numerous studies have highlighted the possibility of modulating the excitability of cerebro–cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral–lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato–rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro–cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed “non-invasive brain stimulation” as a cognitive rehabilitation tool to modulate cerebro–cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo–cortical disturbances.

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 × 1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4 × 1 montage (4 × cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4 × 1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4 × 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 × 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 × 1-Ring montage for cortically targeted neuromodulation.

A Pioneer Work on Electric Brain Stimulation in Psychotic Patients. Rudolph Gottfried Arndt and his 1870s Studies

BackgroundToday's brain stimulation methods are commonly traced back historically to surgical brain operations. With this one-sided historical approach it is easy to overlook the fact that non-surgical electrical brain-stimulating applications preceded present-day therapies. Objective/HypothesisThe first study on transcranial electrical brain stimulation for the treatment of severe mental diseases in a larger group of patients was carried out in the 1870s. MethodsBetween 1870 and 1878 German psychiatrist Rudolph Gottfried Arndt published the results of his studies in three reports. These are contextualized with contemporary developments of the time, focusing in particular on the (neuro-) sciences. As was common practice at the time, Arndt basically reported individual cases in which electricity was applied to treat severe psychoses with depressive symptoms or even catatonia, hypochondriac delusion and melancholia. Despite their lengthiness, there is frequently a lack of precise physical data on the application of psychological-psychopathological details. Only his 1878 report includes general rules for electrical brain stimulation. ResultsDespite their methodological shortcomings and lack of precise treatment data impeding exact understanding, Arndt's studies are pioneering works in the field of electric brain stimulation with psychoses and its positive impacts. Today's transcranial direct current stimulation, and partly vagus nerve stimulation, can be compared with Arndt's methods. Although Arndt's only tangible results were indications for the application of faradic electricity (for inactivity, stupor, weakness and manic depressions) and galvanic current (for affective disorders and psychoses), a historiography of present-day brain stimulation therapies should no longer neglect studies on electrotherapy published in German and international psychiatric and neurological journals and monographs in the 1870s and 1880s.

Investigating Neuroplastic Changes in the Human Brain Induced by Transcranial Direct (tDCS) and Alternating Current (tACS) Stimulation Methods

It has been 211 years since C. Grapengiesser first published a book entitled Galvanism to Cure Some Diseases (original title: Galvanismus zur Heilung einiger Krankheiten) describing the successful use of galvanic currents in treating several patients with pain and strokes. A comparatively short time of slightly more than a decade has passed since tDCS with weak currents in the range of 1 to 2 mA was reintroduced as an additional tool to repetitive transcranial magnetic stimulation (rTMS) for the induction of plastic after-effects in the treatment of brain diseases. Successful quantification of tDCS plasticity-promoting effects by single-pulse TMS has established the usefulness of this non-invasive electrical stimulation method. Generally speaking, applying anodal tDCS to the surface of both the motor and the visual cortex increases cortical excitability, probably by depolarizing pyramidal cell bodies in layer V and thereby increasing the spontaneous firing rates, whereas applying a cathodal current results in the reverse effect by hyperpolarizing cell bodies. Further technical development of transcranial alternating current stimulation (tACS) now permits external interference with the cortical oscillations that play a major role in the temporal coherence between different cortical areas. Transcranial ACS in the ripplefrequency range and a special form of tACS, called highfrequency transcranial random noise stimulation (tRNS), also generate cortical after-effects which, unlike those produced by anodal tDCS, are independent of the direction of current flow. In contrast, inhibition or excitation now may be determined by modulating intensity. What features of electrical stimulation methods may render them superior to rTMS? Both tDCS and tACS, as well as rTMS, produce cortical excitability changes over time. However, tDCS/tACS application is distinctly cheaper since it can be performed with a small low-priced battery-driven portable stimulator also suitable for home use. Furthermore, since it produces less acoustic noise, skin sensation, like itching or tingling, or muscle twitching, it is more suitable for double-blind, sham-controlled studies and for clinical applications. On its own, or in combination with other methods, such as cognitive tasks, pharmacological interventions, functional brain mapping electroencephalography or transcranial electrical brain stimulation, it can also be used to investigate, for example, the location and relative timing of task-related brain activity, excitability changes of neural tissues and circuits, and functional significance of circumscribed and remote brain areas with regard to a given visual, motor, or cognitive task. The induction of relatively long lasting changes in cortical excitability can modify behavior and improve learning, an enduring and exciting challenge for scientists and clinicians. The aim of this issue is to summarize and update research and clinical findings with regard to the application of electrical stimulation methods in combination with other techniques. In the first article, Bikson, Rahman, and Datta describe how computational models can underpin the design and evaluation of stimulation montages and thus contribute to the validation of tDCS. In the second article, Miniussi, Brignani, and Pellicciari summarize recent findings regarding the combination of transcranial electrical stimulation with electroencephalography. Kuo and Nitsche present knowledge gathered about the potential of tDCS and tACS to study and modify cognitive processes in healthy humans, and they discuss options for future research. The review, written by Turi, Paulus, and Antal, focuses on the combined use of a non-invasive application of tDCS and functional magnetic resonance imaging (fMRI) and on MR spectroscopy. Finally, Rothwell summarizes problems facing investigators with regard to the variety of possible paradigms that can be applied within clinical populations. We thank the authors, whose work moves this field along with great enthusiasm, who have taken time from their other activities to contribute to this special issue.

Intraoperative Motor Evoked Potential Monitoring: Overview and Update

Amidst controversy about methodology and safety, intraoperative neurophysiology has entered a new era of increasingly routine transcranial and direct electrical brain stimulation for motor evoked potential (MEP) monitoring. Based on literature review and illustrative clinical experience, this tutorial aims to present a balanced overview for experienced practitioners, surgeons and anesthesiologists as well as those new to the field. It details the physiologic basis, indications and methodology of current MEP monitoring techniques, evaluates their safety, explores interpretive controversies and outlines some applications and results, including aortic aneurysm, intramedullary spinal cord tumor, spinal deformity, posterior fossa tumor, intracranial aneurysm and peri-rolandic brain surgeries. The many advances in motor system assessment achieved in the last two decades undoubtedly improve monitoring efficacy without unduly compromising safety. Future studies and experience will likely clarify existing controversies and bring further advances.