Transcranial electrical stimulation nomenclature

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards.     

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19.ObjectiveTo facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS).MethodsThe present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics.ResultsA model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described.ConclusionThere is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.     

Functional neuroimaging and transcranial electrical stimulation

Transcranial electrical stimulation (tES) is a noninvasive tool for inducing local and widespread neuroplastic changes in brain networks. The combination of tES with various neuroimaging techniques provides whole brain data on the working mechanisms of tES, in particular on the development of large-scale activation patterns of interconnected neuronal regions induced by tES. This review focuses on the combined usage of a noninvasive application of transcranial direct current stimulation and functional magnetic resonance imaging and on magnetic resonance spectroscopy.     

Long-term enhancement of visual responses by repeated transcranial electrical stimulation of the mouse visual cortex

BackgroundTranscranial electrical stimulation (tES) is a popular method to modulate brain activity by sending a weak electric current through the head. Despite its popularity, long-term effects are poorly understood.ObjectiveWe wanted to test if anodal tES immediately changes cerebral responses to visual stimuli, and if repeated sessions of tES produce plasticity in these responses.MethodsWe applied repeated anodal tES, like transcranial direct current stimulation (tDCS), but pulsed (8 s on, 10 s off), to the visual cortex of mice while visually presenting gratings. We measured the responses to these visual stimuli in the visual cortex using the genetically encoded calcium indicator GCaMP3.ResultsWe found an increase in the visual response when concurrently applying tES on the bone without skin (epicranially). This increase was only transient when tES was applied through the skin (transcutaneous). There was no immediate after-effect of tES. However, repeated transcutaneous tES for four sessions at two-day intervals increased the visual response in the visual cortex. This increase was not specific to the grating stimulus coupled to tES and also occurred for an orthogonal grating presented in the same sessions but without concurrent tES. No increase was found in mice that received no tES.ConclusionOur study provides evidence that tES induces long-term changes in the mouse brain. Results in mice do not directly translate to humans, because of differences in stimulation protocols and the way current translates to electric field strength in vastly different heads.     

Clinician Accessible Tools for GUI Computational Models of Transcranial Electrical Stimulation: BONSAI and SPHERES

Computational models of brain current flow during transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), are increasingly used to understand and optimize clinical trials. We propose that broad dissemination requires a simple graphical user interface (GUI) software that allows users to explore and design montages in real-time, based on their own clinical/experimental experience and objectives. We introduce two complimentary open-source platforms for this purpose: BONSAI and SPHERES. BONSAI is a web (cloud) based application (available at neuralengr.com/bonsai) that can be accessed through any flash-supported browser interface. SPHERES (available at neuralengr.com/spheres) is a stand-alone GUI application that allow consideration of arbitrary montages on a concentric sphere model by leveraging an analytical solution. These open-source tES modeling platforms are designed go be upgraded and enhanced. Trade-offs between open-access approaches that balance ease of access, speed, and flexibility are discussed.     

Comparing the efficiency of speech and language therapy and transcranial magnetic stimulation for treating Broca's aphasia

ObjectivesAphasia is an acquired language-cognitive disorder that highly affects an individual's speech, language, and communication skills. Recovery from aphasia requires attentive treatment since it is a long and dynamic process. This study aimed to show interactive benefits of combining classical intervention strategies with new technological approaches and demonstrating their effectiveness.Materials and methodsA total of 40 individuals with Broca's aphasia were included in the study. The participants were divided into Application-1 Speech and Language Therapy, Application-2 Transcranial Magnetic Stimulation, Application-3 (consecutive Transcranial Magnetic Stimulation and Speech and Language Therapy), and Application-4 (Control Group) experimental groups, with 10 participants in each group.ResultsAnalysis indicated that individuals in the group in which Transcranial Magnetic Stimulation and Speech and Language Therapy were applied consecutively had further increases in speech fluency, repetition, and naming scores from pre-test to post-test (p<0.01). Picture naming and quality-of-life communication scores of individuals in the group in which Speech and Language Therapy was performed increased further from pre-test to post-test (p<0.01).ConclusionsThe results of the study showed a positive effect on language skills, naming scores, and participation in social life of Turkish-speaking aphasic individuals with the Speech and Language Therapy and Transcranial Magnetic Stimulation methods. The use of Transcranial Magnetic Stimulation alone is insufficient in this context. Although Speech and Language Therapy alone is effective in naming ability, Transcranial Magnetic Stimulation in addition to Speech and Language Therapy significantly increases the gain obtained with therapies.     

Random noise stimulation improves neuroplasticity in perceptual learning

Perceptual learning is considered a manifestation of neural plasticity in the human brain. We investigated brain plasticity mechanisms in a learning task using noninvasive transcranial electrical stimulation (tES). We hypothesized that different types of tES would have varying actions on the nervous system, which would result in different efficacies of neural plasticity modulation. Thus, the principal goal of the present study was to verify the possibility of inducing differential plasticity effects using two tES approaches [i.e., direct current stimulation (tDCS) and random noise stimulation (tRNS)] during the execution of a visual perceptual learning task.     

皮质刺激治疗脑损伤的研究进展

皮质刺激因其对脑损伤后的康复治疗有良好的效果而被应用于临床，皮质刺激包括重复经颅磁刺激、经颅直流电刺激和直接皮质电刺激，每种方法又各具特点。本文就其应用现状及进展作一综述。     

Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial

BackgroundTranscranial direct current stimulation (tDCS) is a promising intervention for major depression. However, its clinical effects are heterogeneous. We investigated, in a subsample of the randomized, clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECT-TDCS), whether the volumes of left and right prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were associated with prefrontal tDCS response.MethodsBaseline structural T1 weighted MRI data were analyzed from 52 patients (15 males). Patients were randomized to the following conditions: escitalopram 20 mg/day, bifrontal tDCS (2 mA, 30min, 22 sessions), or placebo. Antidepressant outcomes were assessed over a treatment period of 10 weeks. Voxel-based gray matter volumes of PFC and ACC were determined using state-of-the-art parcellation approaches.ResultsAccording to our a priori hypothesis, in the left dorsal PFC, larger gray matter volumes were associated with depression improvement in the tDCS group (n = 15) compared to sham (n = 21) (Cohen's d = 0.3, 95% confidence interval [0.01; 0.6], p = 0.04). Neither right PFC nor ACC volumes were associated with depression improvement. Exploratory analyses of distinct PFC subregions were performed, but no area was associated with tDCS response after correction for multiple comparisons.ConclusionLeft PFC baseline gray matter volume was associated with tDCS antidepressant effects. This brain region and its subdivisions should be investigated further as a potential neurobiological predictor for prefrontal tDCS treatment in depression and might be correlated with tDCS antidepressant mechanisms of action.     

Cranial Electrotherapy Stimulation Review: A Safer Alternative to Psychopharmaceuticals in the Treatment of Depression

ABSTRACT

The use of Cranial Electrotherapy Stimulation (CES) to treat depression and anxiety is reviewed. The data submitted to the Federal Drug Administration (FDA) for approval of medication in the treatment of depression are compared with CES data. Proposed method of action, side-effects, safety factors, and treatment efficacy are discussed. The results suggest there is sufficient data to show that CES technology has equal or greater efficacy for the treatment of depression compared to antidepressant medications, with fewer side effects. A prospective research study should be undertaken to directly compare CES with antidepressant medications and to compare the different CES technologies with each other.     

tDCS changes in motor excitability are specific to orientation of current flow

Background

Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS.

Cutaneous sensation of electrical stimulation waveforms

BackgroundSkin sensation is the primary factor limiting the intensity of transcranial electrical stimulation (tES). It is well established that different waveforms generate different sensations, yet transcranial stimulation has been limited to a relatively small number of prototypical waveforms.ObjectiveWe explore whether alternative stimulation waveforms could substantially reduce skin sensation and thus allow for stronger intensities in tES.MethodsWe systematically tested a range of waveforms in a series of 6 exploratory experiments stimulating human adults on the forearm and in one instance on the head. Subjects were asked to rate skin sensation level on a numerical scale from “none” to “extreme”.ResultsHigh frequency (>1 kHz) monophasic square wave stimulation was found to decrease in sensation with increasing duty cycle, baseline, and frequency, but the sensation was never lower than for constant current stimulation. For the purpose of injecting a net direct current (DC), a constant current is optimal. For stimulation with alternating current (AC), sensation decreased with increasing frequency, consistent with previous reports. Amplitude modulation did not reduce sensation below stimulation with constant AC amplitude, and biphasic square waveforms produced higher sensation levels than biphasic sinusoidal waveforms. Furthermore, for DC stimulation, sensation levels on the arm were similar to those reported on the head.ConclusionOur comparisons of various waveforms for monophasic and biphasic stimulation indicate that conventional DC and AC waveforms may provide the lowest skin sensations levels for transcutaneous electrical stimulation. These results are likely generalizable to tES applications.     

Modeling transcranial electrical stimulation in the aging brain

BackgroundVarying treatment outcomes in transcranial electrical stimulation (tES) recipients may depend on the amount of current reaching the brain. Brain atrophy associated with normal aging may affect tES current delivery to the brain. Computational models have been employed to compute predicted tES current inside the brain. This study is the largest study that uses computational models to investigate tES field distribution in healthy older adults.MethodsIndividualized head models from 587 healthy older adults (mean = 73.9years, 51–95 years) were constructed to create field maps. Two electrode montages (F3-F4, M1-SO) with 2 mA input current were modeled using ROAST with modified codes. A customized template of healthy older adults, the UFAB-587, was created from the same dataset and used to warp individual brains into the same space. Warped models were analyzed to determine the relationship between computed field measures, brain atrophy and age.Main resultsComputed field measures were inversely correlated with brain atrophy (R² = 0.0829, p = 1.14e-12). Field pattern showed negative correlation with age in brain sub-regions including part of DLPFC and precentral gyrus. Mediation analysis revealed that the negative correlation between age and current density is partially mediated by brain-to-CSF ratio.ConclusionsComputed field measures showed decreasing amount of tES current reaching the brain with increasing atrophy. Therefore, adjusting current dose by modifying tES stimulation parameters in older adults based on degree of atrophy may be necessary to achieve desired stimulation benefits. Results from this study may inform future tES application in healthy older adults.     

Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta‐analysis

Numerous studies have explored the effects of transcranial electrical stimulation (tES) – including anodal transcranial direct current stimulation (a‐tDCS), cathodal transcranial direct current stimulation (c‐tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) – on corticospinal excitability (CSE) in healthy populations. However, the efficacy of these techniques and their optimal parameters for producing robust results has not been studied. Thus, the aim of this systematic review was to consolidate current knowledge about the effects of various parameters of a‐tDCS, c‐tDCS, tACS, tRNS and tPCS on the CSE of the primary motor cortex (M1) in healthy people. Leading electronic databases were searched for relevant studies published between January 1990 and February 2017; 126 articles were identified, and their results were extracted and analysed using RevMan software. The meta‐analysis showed that a‐tDCS application on the dominant side significantly increases CSE (P < 0.01) and that the efficacy of a‐tDCS is dependent on current density and duration of application. Similar results were obtained for stimulation of M1 on the non‐dominant side (P = 0.003). The effects of a‐tDCS reduce significantly after 24 h (P = 0.006). Meta‐analysis also revealed significant reduction in CSE following c‐tDCS (P < 0.001) and significant increases after tRNS (P = 0.03) and tPCS (P = 0.01). However, tACS effects on CSE were only significant when the stimulation frequency was ≥140 Hz. This review provides evidence that tES has substantial effects on CSE in healthy individuals for a range of stimulus parameters.     

Neurocapillary-Modulation

ObjectivesWe consider two consequences of brain capillary ultrastructure in neuromodulation. First, blood-brain barrier (BBB) polarization as a consequence of current crossing between interstitial space and the blood. Second, interstitial current flow distortion around capillaries impacting neuronal stimulation.Materials and MethodsWe developed computational models of BBB ultrastructure morphologies to first assess electric field amplification at the BBB (principle 1) and neuron polarization amplification by the presence of capillaries (principle 2). We adapt neuron cable theory to develop an analytical solution for maximum BBB polarization sensitivity.ResultsElectrical current crosses between the brain parenchyma (interstitial space) and capillaries, producing BBB electric fields (E_BBB) that are >400x of the average parenchyma electric field (ē_BRAIN), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λ_BBB) and wall thickness (d_th-BBB), the analytical solution for maximal BBB electric field (E^A_BBB) is given as: (ē_BRAIN × λ_BBB)/d_th-BBB. Electrical current in the brain parenchyma is distorted around brain capillaries, amplifying neuronal polarization. Specifically, capillary ultrastructure produces ～50% modulation of the ē_BRAIN over the ～40 μm inter-capillary distance. The divergence of E_BRAIN (Activating function) is thus ～100 kV/m² per unit ē_BRAIN.ConclusionsBBB stimulation by principle 1 suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Whereas the spatial profile of E_BRAIN is traditionally assumed to depend only on macroscopic anatomy, principle 2 suggests a central role for local capillary ultrastructure—which impact forms of neuromodulation including deep brain stimulation (DBS), spinal cord stimulation (SCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and transcranial electrical stimulation (tES)/transcranial direct current stimulation (tDCS).     

Transcranial electrical stimulation improves phoneme processing in developmental dyslexia

BackgroundAbout 10% of the western population suffers from a specific disability in the acquisition of reading and writing skills, known as developmental dyslexia (DD). Even though DD starts in childhood it frequently continuous throughout lifetime. Impaired processing of acoustic features at the phonematic scale based on dysfunctional auditory temporal resolution is considered as one core deficit underlying DD. Recently, the efficacy of transcranial electrical stimulation (tES) to modulate auditory temporal resolution and phoneme processing in healthy individuals has been demonstrated.ObjectiveThe present work aims to investigate online effects of tES on phoneme processing in individuals with DD.MethodUsing an established phoneme-categorization task, we assessed the immediate behavioral and electrophysiological effects of transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) over bilateral auditory cortex in children and adolescents with DD (study 1) and adults with DD (study 2) on auditory phoneme processing acuity.ResultsOur data revealed that tACS improved phoneme categorization in children and adolescents with DD, an effect that was paralleled by an increase in evoked brain response patterns representing low-level sensory processing. In the adult sample we replicated these findings and additionally showed a more pronounced impact of tRNS on phoneme-categorization acuity.ConclusionThese results provide compelling evidence for the potential of both tACS and tRNS to increase temporal precision of the auditory system in DD and suggest transcranial electrical stimulation as potential intervention in DD to foster the effect of standard phonology-based training.     

Transcranial electrical stimulation motor threshold can estimate individualized tDCS dosage from reverse-calculation electric-field modeling

BackgroundUnique amongst brain stimulation tools, transcranial direct current stimulation (tDCS) currently lacks an easy or widely implemented method for individualizing dosage.ObjectiveWe developed a method of reverse-calculating electric-field (E-field) models based on Magnetic Resonance Imaging (MRI) scans that can estimate individualized tDCS dose. We also evaluated an MRI-free method of individualizing tDCS dose by measuring transcranial magnetic stimulation (TMS) motor threshold (MT) and single pulse, suprathreshold transcranial electrical stimulation (TES) MT and regressing it against E-field modeling. Key assumptions of reverse-calculation E-field modeling, including the size of region of interest (ROI) analysis and the linearity of multiple E-field models were also tested.MethodsIn 29 healthy adults, we acquired TMS MT, TES MT, and anatomical T1-weighted MPRAGE MRI scans with a fiducial marking the motor hotspot. We then computed a “reverse-calculated tDCS dose” of tDCS applied at the scalp needed to cause a 1.00 V/m E-field at the cortex. Finally, we examined whether the predicted E-field values correlated with each participant’s measured TMS MT or TES MT.ResultsWe were able to determine a reverse-calculated tDCS dose for each participant using a 5 × 5 x 5 voxel grid region of interest (ROI) approach (average = 6.03 mA, SD = 1.44 mA, range = 3.75–9.74 mA). The Transcranial Electrical Stimulation MT, but not the Transcranial Magnetic Stimulation MT, significantly correlated with the ROI-based reverse-calculated tDCS dose determined by E-field modeling (R² = 0.45, p < 0.001).ConclusionsReverse-calculation E-field modeling, alone or regressed against TES MT, shows promise as a method to individualize tDCS dose. The large range of the reverse-calculated tDCS doses between subjects underscores the likely need to individualize tDCS dose. Future research should further examine the use of TES MT to individually dose tDCS as an MRI-free method of dosing tDCS.     

tDCS potentiation provides no evidence for a link between right dorsal–lateral prefrontal cortical activity and empathic responding

Previous studies suggest the dorsolateral prefrontal cortex (DLPFC) is involved in processing of empathic concern. This has not been experimentally tested to date. We tested the hypotheses that electrical potentiation in the right DLPFC would be associated with increased empathic concern and prosocial behavior. Participants were randomly allocated to one of three transcranial Direct Current Stimulation (tDCS) conditions: (a) relative right potentiation, (b) relative left potentiation, and (c) sham. Participants viewed images of African children in distressing circumstances, and completed measures of empathic concern pre- and post-tDCS manipulation. Contrary to our prediction, neither effects, nor interactions of heightened empathic concern were observed. These results conflict with previous studies using this bilateral tDCS montage. Explanations could be that stimulation used in this study had been simply too weak (1.5 mA). Alternatively, the area of the DLPFC involved in emotion regulation is closer to the cortex than the area involved in empathic concern, and more easily potentiated by tDCS. Therefore, the DLPFC potentiation in the present study may have linked empathic concern with adaptive emotion regulation strategies. Future research could examine this possibility using measures of emotion regulation and higher fidelity neurostimulation (e.g., repetitive Transcranial Magnetic Stimulation [rTMS]).     

The physiological basis of transcranial motor cortex stimulation in conscious humans.

Transcranial stimulation of the human motor cortex can evoke several different kinds of descending activity depending on the type of stimulation, the intensity of stimulation and the area of the cortex being stimulated. Thus, transcranial magnetic stimulation preferentially activates different structures than transcranial electrical stimulation. In addition, the response to magnetic stimulation depends on the direction of the induced current in the brain, the waveform of the stimulating current, and the shape of the coil. Stimulation of the lower limb area of motor cortex recruits different elements than stimulation of the upper limb area. These differences occur because different structures in the motor cortex have a differential threshold to the different techniques of stimulation. We have had the opportunity to perform a series of direct recordings of the corticospinal volley evoked by the different techniques of transcranial stimulation from the epidural space of conscious patients with chronically implanted spinal electrodes. These recordings provide insights about the physiological basis of the excitatory and inhibitory phenomena produced by transcranial stimulation.