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.     

Individual differences in neuroanatomy and neurophysiology predict effects of transcranial alternating current stimulation

BackgroundNoninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited.ObjectiveWe have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60–80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy.MethodsWe conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 min daily for three days (80 min total; Long Exposure Theta group), 6-Hz tACS for 5.33 min daily (16-min total; Short Exposure Theta group), or 1-Hz tACS for 26.67 min (80 min total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency.ResultsResults indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54%–65% of the variance in tACS-related performance improvements, which sustained for a month.ConclusionThese results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies.     

The efficacy of transcranial random noise stimulation (tRNS) on mood may depend on individual differences including age and trait mood

Objectives

To assess whether changes in brain microstructures associated with ageing and presence of cardiovascular risk factors (CVRF) reduce the efficacy of transcranial electrical stimulation (tES) improving mood in euthymic older adults.

Analgesia induced by anodal tDCS and high-frequency tRNS over the motor cortex: Immediate and sustained effects on pain perception

BackgroundMany studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief.ObjectiveThis study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation.MethodsUsing a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation.ResultsCompared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS.ConclusionsThe analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.     

tACS phase-specifically biases brightness perception of flickering light

BackgroundVisual phenomena like brightness illusions impressively demonstrate the highly constructive nature of perception. In addition to physical illumination, the subjective experience of brightness is related to temporal neural dynamics in visual cortex.ObjectiveHere, we asked whether biasing the temporal pattern of neural excitability in visual cortex by transcranial alternating current stimulation (tACS) modulates brightness perception of concurrent rhythmic visual stimuli.MethodsParticipants performed a brightness discrimination task of two flickering lights, one of which was targeted by same-frequency electrical stimulation at varying phase shifts. tACS was applied with an occipital and a periorbital active control montage, based on simulations of electrical currents using finite element head models.ResultsExperimental results reveal that flicker brightness perception is modulated dependent on the phase shift between sensory and electrical stimulation, solely under occipital tACS. Phase-specific modulatory effects by tACS were dependent on flicker-evoked neural phase stability at the tACS-targeted frequency, recorded prior to electrical stimulation. Further, the optimal timing of tACS application leading to enhanced brightness perception was correlated with the neural phase delay of the cortical flicker response.ConclusionsOur results corroborate the role of temporally coordinated neural activity in visual cortex for brightness perception of rhythmic visual input in humans. Phase-specific behavioral modulations by tACS emphasize its efficacy to transfer perceptually relevant temporal information to the cortex. These findings provide an important step towards understanding the basis of visual perception and further confirm electrical stimulation as a tool for advancing controlled modulations of neural activity and related behavior.     

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.     

Exposure to gamma tACS in Alzheimer’s disease: A randomized,double-blind,sham-controlled,crossover, pilot study

ObjectiveTo assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer’s disease (MCI-AD).MethodsIn this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned to a single 60 min treatment with exposure to γ-tACS over Pz or sham tACS. Each subject underwent a clinical evaluation including assessment of episodic memory pre- and post-γ-tACS or sham stimulation. Indirect measures of cholinergic transmission evaluated using transcranial magnetic stimulation (TMS) pre- and post-γ-tACS or sham tACS were evaluated.ResultsTwenty MCI-AD participants completed the study. No tACS-related side effects were observed, and the intervention was well tolerated in all participants. We observed a significant improvement at the Rey auditory verbal learning (RAVL) test total recall (5.7 [95% CI, 4.0 to 7.4], p < 0.001) and long delayed recall scores (1.3 [95% CI, 0.4 to 2.1], p = 0.007) after γ-tACS but not after sham tACS. Face-name associations scores improved during γ−tACS (4.3 [95% CI, 2.8 to 5.8], p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission evaluated with TMS, increased only after γ-tACS (0.31 [95% CI, 0.24 to 0.38], p < 0.001) but not after sham tACS.Conclusionsexposure to γ-tACS over Pz showed a significant improvement of memory performances, along with restoration of intracortical connectivity measures of cholinergic neurotransmission, compared to sham tACS.     

Optimized auditory transcranial alternating current stimulation improves individual auditory temporal resolution

Background

Temporal resolution of cortical, auditory processing mechanisms is suggested to be linked to peak frequency of neuronal gamma oscillations in auditory cortex areas (individual gamma frequency, IGF): Individuals with higher IGF tend to have better temporal resolution.

Cutaneous perception thresholds of electrical stimulation methods: Comparison of tDCS and tRNS

Objective

Controlled blinded studies using transcranial electrical stimulation (tES) paradigms need a validated sham stimulation paradigm since an itching or tingling sensation on the skin surface under the electrode can be associated with current flow.

Methods

Here we investigated the skin perception thresholds of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) for current intensities ranging from 200 to 2000 μA and additional non-stimulation trials using a motor cortex–contralateral orbit montage in three different healthy subject groups: subjects naïve to tES methods, subjects with previous experience with these techniques and investigators, who use these methods in their research.

Results

Taking the whole sample into consideration the 50% perception threshold for both tDCS conditions was at 400 μA while this threshold was at 1200 μA in the case of tRNS. Anodal and cathodal tDCS are indistinguishable regarding sites of perception. Experienced investigators show a significantly higher anodal stimulation detection rate when compared to the naïve group, furthermore investigators performed significantly better than naïve subjects in non-stimulation discrimination.

Conclusions

tRNS has the advantage of higher cutaneous perception thresholds and lower response rates in when compared with tDCS. Further investigation in blinding methods (such as placebo itching) is warranted in order to improve sham control.

Significance

As tRNS has been shown to have similar aftereffects as anodal tDCS, this finding points to the application of tRNS as a possible alternative with a better blinding control.     

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.     

Neurovascular-modulation: A review of primary vascular responses to transcranial electrical stimulation as a mechanism of action

BackgroundThe ubiquitous vascular response to transcranial electrical stimulation (tES) has been attributed to the secondary effect of neuronal activity forming the classic neurovascular coupling. However, the current density delivered transcranially concentrates in: A) the cerebrospinal fluid of subarachnoid space where cerebral vasculature resides after reaching the dural and pial surfaces and B) across the blood-brain-barrier after reaching the brain parenchyma. Therefore, it is anticipated that tES has a primary vascular influence.ObjectivesFocused review of studies that demonstrated the direct vascular response to electrical stimulation and studies demonstrating evidence for tES-induced vascular effect in coupled neurovascular systems.ResultstES induces both primary and secondary vascular phenomena originating from four cellular elements; the first two mediating a primary vascular phenomenon mainly in the form of an immediate vasodilatory response and the latter two leading to secondary vascular effects and as parts of classic neurovascular coupling: 1) The perivascular nerves of more superficially located dural and pial arteries and medium-sized arterioles with multilayered smooth muscle cells; and 2) The endothelial lining of all vessels including microvasculature of blood-brain barrier; 3) Astrocytes; and 4) Neurons of neurovascular units.ConclusionA primary vascular effect of tES is highly suggested based on various preclinical and clinical studies. We explain how the nature of vascular response can depend on vessel anatomy (size) and physiology and be controlled by stimulation waveform. Further studies are warranted to investigate the mechanisms underlying the vascular response and its contribution to neural activity in both healthy brain and pathological conditions – recognizing many brain diseases are associated with alteration of cerebral hemodynamics and decoupling of neurovascular units.     

Electroencephalographic Effects of Transcranial Random Noise Stimulation in the Auditory Cortex

BackgroundTranscranial random noise stimulation (tRNS) is an innovative technique of non-invasive electrical stimulation. tRNS over the parietal cortex has improved cognitive function in healthy controls and, applied to the auditory cortex, tRNS has shown beneficial effects on tinnitus.Objective/hypothesisHere we aimed to investigate the effects of tRNS over the auditory cortex on resting state and evoked activity in healthy subjects.MethodsWe used EEG to measure tRNS induced changes in resting state activity and in auditory steady state responses (ASSRs). Stimuli were 1000 Hz carrier frequency tones, amplitude modulated at 20 Hz and 40 Hz and applied in randomized order. Fourteen subjects participated in a placebo-controlled randomized design study; each received 20 min of tRNS applied over auditory cortices with 2 mA, with a one week interval between real and sham stimulation.ResultsWe found a significant increase in the ASSR in response to 40 Hz frequency modulated tone and a non-significant trend toward an increase in mean theta band power and variability of the theta band power for the resting state data.ConclusionsOur finding of tRNS induced increased excitability in the auditory cortex parallels previous findings of tRNS effects on motor cortex excitability and is in line with current concepts of tRNS mechanisms such as increase of stochastic resonance.     

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop

Background

Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities.

Phase-specific manipulation of rhythmic brain activity by transcranial alternating current stimulation

BackgroundOscillatory phase has been proposed as a key parameter defining the spatiotemporal structure of neural activity. To enhance our understanding of brain rhythms and improve clinical outcomes in pathological conditions, modulation of neural activity by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the phase-specificity of tACS effects in humans is still critically debated.ObjectiveHere, we investigated the phase-specificity of tACS on visually evoked steady state responses (SSRs) in 24 healthy human participants.MethodsWe used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. A neural network model served to validate the plausibility of experimental findings.ResultsWe observed a modulation of SSR amplitudes dependent on the phase shift between flicker and tACS. The tACS effect size was negatively correlated with the strength of flicker-evoked activity. Supported by simulations, data suggest that strong network synchronization limits further neuromodulation by tACS. Neural sources of phase-specific effects were localized in the parieto-occipital cortex within flicker-entrained regions. Importantly, the optimal phase shift between flicker and tACS associated with strongest SSRs was correlated with SSR phase delays in the tACS target region.ConclusionsOverall, our data provide electrophysiological evidence for phase-specific modulations of rhythmic brain activity by tACS in humans. As the optimal timing of tACS application was dependent on cortical SSR phase delays, our data suggest that tACS effects were not mediated by retinal co-stimulation. These findings highlight the potential of tACS for controlled, phase-specific modulations of neural activity.     

Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities

BackgroundRecently we have shown that transcranial random noise (tRNS) and 140 Hz transcranial alternating current stimulations (tACS), applied over the primary motor cortex (M1) and using 10 min stimulation duration and 1 mA intensity, significantly increases cortical excitability as measured by motor evoked potentials at rest before and after stimulation.Objective/hypothesisHere, by decreasing the stimulation intensity in 0.2 mA steps from 1.0 mA, we investigate to what extent intensity depends on the induced after-effects.MethodsAll twenty-five subjects participated in two different experimental sessions each. They received tACS using 140 Hz frequency and full spectrum tRNS at five different intensities on separate days. Sham stimulation was used as a control.ResultsInstead of receiving a simple threshold, unexpectedly, in these two independent data sets at threshold intensities of 0.4 mA we found a switch of the already known excitation achieved with an intensity of 1 mA to inhibition. The intermediate intensity ranges of 0.6 and 0.8 mA had no effect at all. Interestingly, the inhibition produced by 140 Hz tACS was stronger than that induced by tRNS.ConclusionsIn summary, we have shown here the possibility of selectively controlling the enhancement or reduction of M1 excitability by applying different intensities of high frequency transcranial electrical stimulation.     

Estimation of individually induced e-field strength during transcranial electric stimulation using the head circumference

BackgroundHead and brain anatomy have been related to e-field strength induced by transcranial electrical stimulation (tES). Individualization based on anatomic factors require high-quality structural magnetic resonance images, which are not always available. Head circumference (HC) can serve as an alternative means, but its linkage to electric field strength has not yet been established.MethodsWe simulated electric fields induced by tES based on individual T1w- and T2w-images of 47 healthy adults, for four conventional (“standard”) and four corresponding focal (”4x1”) electrode montages. Associations of electric field strength with individual HC were calculated using linear mixed models.ResultsLarger HC was associated with lower electric field strength across montages. We provide mathematical equations to estimate individual electric field strength based on the HC.ConclusionHC can be used as an alternative to estimate interindividual differences of the tES-induced electric field strength and to prospectively individualize stimulation dose, e.g., in the clinical context.     

Neurostimulation for Memory Enhancement in Epilepsy

Purpose of Review

Memory is one of the top concerns of epilepsy patients, but there are no known treatments to directly alleviate the memory deficits associated with epilepsy. Neurostimulation may provide new therapeutic tools to enhance memory in epilepsy patients. Here, we critically review recent investigations of memory enhancement using transcranial electrical stimulation (tES), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), chronic intracranial stimulation, and acute intracranial stimulation.

Recent Findings

Existing literature suggests that transcranial direct current stimulation (tDCS) produces a small enhancement in memory in neuropsychological patients, but transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) have not been found to have an effect on memory. Most studies of transcranial magnetic stimulation (TMS) have found that TMS has no positive effect on memory. Vagus nerve stimulation can acutely enhance memory, while chronic therapy does not appear to alter memory performance. We found that there is the most evidence for significant memory enhancement using intracranial stimulation techniques, especially chronic stimulation of the fornix and task-responsive stimulation of the lateral temporal lobe.

Summary

Presently, there are no existing therapeutic options for directly treating epilepy-related memory deficits. While neurostimulation technologies for memory enhancement are largely still in the experimental phase, neurostimulation appears promising as a future technique for treating epilepsy-related memory deficits.

     

External induction and stabilization of brain oscillations in the human

BackgroundNeural oscillations in the cerebral cortex are associated with a range of cognitive processes and neuropsychiatric disorders. However, non-invasively modulating oscillatory activity remains technically challenging, due to limited strength, duration, or non-synchronization of stimulation waveforms with endogenous rhythms.ObjectiveWe hypothesized that applying controllable phase-synchronized repetitive transcranial magnetic stimulation pulses (rTMS) with alternating currents (tACS) may induce and stabilize neuro-oscillatory resting-state activity at targeted frequencies.MethodsUsing a novel circuit to precisely synchronize rTMS pulses with phase of tACS, we empirically tested whether combined, 10-Hz prefrontal bilateral stimulation could induce and stabilize 10-Hz oscillations in the bilateral prefrontal cortex (PFC). 25 healthy participants took part in a repeated-measures design. Whole-brain resting-state EEG in eyes-open (EO) and eyes-closed (EC) was recorded before (baseline), immediately (1-min), and 15- and 30-min after stimulation. Bilateral, phase-synchronized rTMS aligned to the positive tACS peak was compared with rTMS at tACS trough, with bilateral tACS or rTMS on its own, and to sham.Results10-Hz resting-state PFC power increased significantly with peak-synchronized rTMS + tACS (EO: 44.64%, EC: 46.30%, p < 0.05) compared to each stimulation protocol on its own, and sham, with effects spanning between prefrontal and parietal regions and sustaining throughout 30-min. No effects were observed with the sham protocol. Moreover, rTMS timed to the negative tACS trough did not induce local or global changes in oscillations.ConclusionPhase-synchronizing rTMS with tACS may be a viable approach for inducing and stabilizing neuro-oscillatory activity, particularly in scenarios where endogenous oscillatory tone is attenuated, such as disorders of consciousness or major depression.     

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.     

Input–Output Functions in Human Heads Obtained With Cochlear Implant and Transcranial Electric Stimulation

ObjectivesElectric stimulation is used to treat a number of neurologic disorders such as epilepsy and depression. However, delivering the required current to far-field neural targets is often ineffective because of current spread through low-impedance pathways. Here, the specific aims are to develop an empirical measure for current passing through the human head and to optimize stimulation strategies for targeting deeper structures, including the auditory nerve, by utilizing the cochlear implant (CI).Materials and MethodsOutward input/output (I/O) functions were obtained by CI stimulation and recording scalp potentials in five CI subjects. Conversely, inward I/O functions were obtained by noninvasive transcranial electric stimulation (tES) and recording intracochlear potentials using the onboard recording capability of the CI.ResultsI/O measures indicate substantial current spread, with a maximum of 2.2% gain recorded at the inner ear target during tES (mastoid-to-mastoid electrode configuration). Similarly, CI stimulation produced a maximum of 1.1% gain at the scalp electrode nearest the CI return electrode. Gain varied with electrode montage according to a point source model that accounted for distances between the stimulating and recording electrodes. Within the same electrode montages, current gain patterns varied across subjects suggesting the importance of tissue properties, geometry, and electrode positioning.ConclusionThese results provide a novel objective measure of electric stimulation in the human head, which can help to optimize stimulation parameters that improve neural excitation of deep structures by reducing the influence of current spread.