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.     

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.     

Noninvasive brain stimulation to suppress craving in substance use disorders: Review of human evidence and methodological considerations for future work

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of noninvasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of noninvasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects’ characteristics.     

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.     

Transcranial electric stimulation as a neural interface to gain insight on human brain functions: current knowledge and future perspective

The use of brain stimulation approaches in social and affective science has greatly increased over the last two decades. The interest in social factors has grown along with technological advances in brain research. Transcranial electric stimulation (tES) is a research tool that allows scientists to establish contributory causality between brain functioning and social behaviour, therefore deepening our understanding of the social mind. Preliminary evidence is also starting to demonstrate that tES, either alone or in combination with pharmacological or behavioural interventions, can alleviate the symptomatology of individuals with affective or social cognition disorders. This review offers an overview of the application of tES in the field of social and affective neuroscience. We discuss the issues and challenges related to this application and suggest an avenue for future basic and translational research.     

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.     

The Role of Timing in the Induction of Neuromodulation in Perceptual Learning by Transcranial Electric Stimulation

BackgroundTranscranial electric stimulation (tES) protocols are able to induce neuromodulation, offering important insights to focus and constrain theories of the relationship between brain and behavior. Previous studies have shown that different types of tES (i.e., direct current stimulation – tDCS, and random noise stimulation – tRNS) induce different facilitatory behavioral effects. However to date is not clear which is the optimal timing to apply tES in relation to the induction of robust facilitatory effects.Objective/hypothesisThe goal of this work was to investigate how different types of tES (tDCS and tRNS) can modulate behavioral performance in the healthy adult brain in relation to their timing of application. We applied tES protocols before (offline) or during (online) the execution of a visual perceptual learning (PL) task. PL is a form of implicit memory that is characterized by an improvement in sensory discrimination after repeated exposure to a particular type of stimulus and is considered a manifestation of neural plasticity. Our aim was to understand if the timing of tES is critical for the induction of differential neuromodulatory effects in the primary visual cortex (V1).MethodsWe applied high-frequency tRNS, anodal tDCS and sham tDCS on V1 before or during the execution of an orientation discrimination task. The experimental design was between subjects and performance was measured in terms of d' values.ResultsThe ideal timing of application varied depending on the stimulation type. tRNS facilitated task performance only when it was applied during task execution, whereas anodal tDCS induced a larger facilitation if it was applied before task execution.ConclusionThe main result of this study is the finding that the timing of identical tES protocols yields opposite effects on performance. These results provide important guidelines for designing neuromodulation induction protocols and highlight the different optimal timing of the two excitatory techniques.     

Combining transcranial electrical stimulation with electroencephalography: a multimodal approach

Although numerous studies have been performed using transcranial electrical stimulation (tES), our understanding of tES-induced effects on neural activity remains limited, especially regarding the effects on neural networks. The use of an approach, such as electroencephalography (EEG) in combination with tES, could allow for a more detailed understanding of the neural mechanisms involved in these observed changes. Co-registration of tES and EEG might provide high temporal resolution information regarding tES-induced modifications/modulations to cortical activity that corresponds to different stages of processing. This article aims at presenting new knowledge about this recent and innovative approach that can possibly provide information about the dynamics of human brain functions beyond what is possible by the use of either method alone.     

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.     

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.     

Pulsed transcranial electric brain stimulation enhances speech comprehension

BackgroundOne key mechanism thought to underlie speech processing is the alignment of cortical brain rhythms to the acoustic input, a mechanism termed entrainment. Recent work showed that transcranial electrical stimulation (tES) in speech relevant frequencies or adapted to the speech envelope can in fact enhance speech processing. However, it is unclear whether an oscillatory tES is necessary, or if transients in the stimulation (e.g., peaks in the tES signal) at relevant times are sufficient.ObjectiveIn this study we used a novel pulsed-tES-protocol and tested behaviorally if a transiently pulsed - instead of a persistently oscillating - tES signal, can improve speech processing.MethodsWhile subjects listened to spoken sentences embedded in noise, brief electric direct current pulses aligned to speech transients (syllable onsets) were applied to auditory cortex regions to modulate comprehension. Additionally, we modulated the temporal delay between tES-pulses and speech transients to test for periodic modulations of behavior, indicative of entrainment by tES.ResultsSpeech comprehension was improved when tES-pulses were applied with a delay of 100 ms in respect to the speech transients. Contradictory to previous reports we find no periodic modulation of behavior. However, we find indications that periodic modulations can be spurious results of sampling behavioral data too coarsely.ConclusionsSubject’s speech comprehension benefits from pulsed-tES, yet behavior is not modulated periodically. Thus, pulsed-tES can aid cortical entrainment to speech input, which is especially relevant in a noisy environment. Yet, pulsed-tES does not seem to entrain brain oscillations by itself.     

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.     

Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.     

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.     

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.     

Is it time to replace the Wada test and put awake craniotomy to sleep?

The question we address here is whether the invasive presurgical brain mapping approaches of direct cortical stimulation and of the Wada procedure can be replaced by noninvasive functional neuroimaging methods (functional magnetic resonance imaging [fMRI], magnetoencephalography [MEG], transcranial magnetic stimulation and [TMS]). First, we outline the reasons for contemplating such a replacement. Second, we present evidence to the effect that the efficacy of the invasive and noninvasive methods, while suboptimal, is comparable. Third, we discuss additional advantages of noninvasive presurgical brain mapping and conclude that there are no longer compelling reasons for opting for invasive mapping in many if not most cases provided that the non‐invasive methods are available. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

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.     

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.

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.