Contrast detection is enhanced by deterministic, high-frequency transcranial alternating current stimulation with triangle and sine waveform.

Stochastic resonance (SR) describes a phenomenon where an additive noise (stochastic carrier-wave) enhances the signal transmission in a nonlinear system. In the nervous system, nonlinear properties are present from the level of single ion channels all the way to perception and appear to support the emergence of SR. For example, SR has been repeatedly demonstrated for visual detection tasks, also by adding noise directly to cortical areas via transcranial random noise stimulation (tRNS). When dealing with nonlinear physical systems, it has been suggested that resonance can be induced not only by adding stochastic signals (i.e., noise) but also by adding a large class of signals that are not stochastic in nature that cause "deterministic amplitude resonance" (DAR). Here, we mathematically show that high-frequency, deterministic, periodic signals can yield resonance-like effects with linear transfer and infinite signal-to-noise ratio at the output. We tested this prediction empirically and investigated whether nonrandom, high-frequency, transcranial alternating current stimulation (tACS) applied to the visual cortex could induce resonance-like effects and enhance the performance of a visual detection task. We demonstrated in 28 participants that applying 80-Hz triangular-waves or sine-waves with tACS reduced the visual contrast detection threshold for optimal brain stimulation intensities. The influence of tACS on contrast sensitivity was equally effective to tRNS-induced modulation, demonstrating that both tACS and tRNS can reduce contrast detection thresholds. Our findings suggest that a resonance-like mechanism can also emerge when deterministic electrical waveforms are applied via tACS.NEW & NOTEWORTHY Our findings extend our understanding of neuromodulation induced by noninvasive electrical stimulation. We provide the first evidence showing acute online benefits of transcranial alternating current stimulation (tACS)triangle and tACSsine targeting the primary visual cortex (V1) on visual contrast detection in accordance with the resonance-like phenomenon. The "deterministic" tACS and "stochastic" high-frequency-transcranial random noise stimulation (tRNS) are equally effective in enhancing visual contrast detection.

Modulation of Visual Contrast Sensitivity with tRNS across the Visual System, Evidence from Stimulation and Simulation.

Transcranial random noise stimulation (tRNS) has been shown to significantly improve visual perception. Previous studies demonstrated that tRNS delivered over cortical areas acutely enhances visual contrast detection of weak stimuli. However, it is currently unknown whether tRNS-induced signal enhancement could be achieved within different neural substrates along the retino-cortical pathway. In three experimental sessions, we tested whether tRNS applied to the primary visual cortex (V1) and/or to the retina improves visual contrast detection. We first measured visual contrast detection threshold (VCT; N = 24, 16 females) during tRNS delivery separately over V1 and over the retina, determined the optimal tRNS intensities for each individual (ind-tRNS), and retested the effects of ind-tRNS within the sessions. We further investigated whether we could reproduce the ind-tRNS-induced modulation on a different session (N = 19, 14 females). Finally, we tested whether the simultaneous application of ind-tRNS to the retina and V1 causes additive effects. Moreover, we present detailed simulations of the induced electric field across the visual system. We found that at the group level tRNS decreases VCT compared with baseline when delivered to the V1. Beneficial effects of ind-tRNS could be replicated when retested within the same experimental session but not when retested in a separate session. Applying tRNS to the retina did not cause a systematic reduction of VCT, regardless of whether the individually optimized intensity was considered or not. We also did not observe consistent additive effects of V1 and retina stimulation. Our findings demonstrate significant tRNS-induced modulation of visual contrast processing in V1 but not in the retina.

Using noise for the better: The effects of transcranial random noise stimulation on the brain and behavior.

Van der Groen, O., Potok, W., Wenderoth, N., Edwards, G., Mattingley, J.B. and Edwards, D. Using noise for the better: The effects of transcranial random noise stimulation on the brain and behavior. NEUROSCI BIOBEHAV REV X (X) XXX-XXX 2021.- Transcranial random noise stimulation (tRNS) is a non-invasive electrical brain stimulation method that is increasingly employed in studies of human brain function and behavior, in health and disease. tRNS is effective in modulating perception acutely and can improve learning. By contrast, its effectiveness for modulating higher cognitive processes is variable. Prolonged stimulation with tRNS, either as one longer application, or multiple shorter applications, may engage plasticity mechanisms that can result in long-term benefits. Here we provide an overview of the current understanding of the effects of tRNS on the brain and behavior and provide some specific recommendations for future research.

Transcranial Random Noise Stimulation Modulates Neural Processing of Sensory and Motor Circuits, from Potential Cellular Mechanisms to Behavior: A Scoping Review.

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurologic patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioral levels, and discuss how this emerging method might be harnessed to augment perceptual and motor functioning of the human nervous system. Online databases were used to identify papers published in 2008-2021 using tRNS in humans, from which we identified 70 publications focusing on sensory and motor function. Additionally, we interpret the existing evidence by referring to articles investigating the effects of noise stimulation in animal and subcellular models. We review physiological and behavioral findings of tRNS-induced offline after-effects and acute online benefits which manifest immediately when tRNS is applied to sensory or motor cortices. We link these results to evidence showing that activity of voltage-gated sodium ion channels might be an important cellular substrate for mediating these tRNS effects. We argue that tRNS might make neural signal transmission and processing within neuronal populations more efficient, which could contribute to both (1) offline after-effects in the form of a prolonged increase in cortical excitability and (2) acute online noise benefits when computations rely on weak inputs.

Manual praxis and language-production networks, and their links to handedness.

While Liepmann was one of the first researchers to consider a relationship between skilled manual actions (praxis) and language for tasks performed "freely from memory", his primary focus was on the relations between the organization of praxis and left-hemisphere dominance. Subsequent attempts to apply his apraxia model to all cases he studied - including his first patient, a "non-pure right-hander" treated as an exception - left the praxis-handedness issue unresolved. Modern neuropsychological and recent neuroimaging evidence either showed closer associations of praxis and language, than between handedness and any of these two functions, or focused on their dissociations. Yet, present-day developments in neuroimaging and statistics allow us to overcome the limitations of the earlier work on praxis-language-handedness links, and to better quantify their interrelationships. Using functional magnetic resonance imaging (fMRI), we studied tool use pantomimes and subvocal word generation in 125 participants, including righthanders (NRH = 52), ambidextrous individuals (mixedhanders; NMH = 31), and lefthanders (NLH = 42). Laterality indices were calculated both in two critical cytoarchitectonic maps, and 180 multi-modal parcellations of the human cerebral cortex, using voxel count and signal intensity, and the most relevant regions of interest and their networks were further analyzed. We found that atypical organization of praxis was present in all handedness groups (RH = 25.0%, MH = 22.6%; LH = 45.2%), and was about two and a half times as common as atypical organization of language (RH = 3.8%; MH = 6.5%; LH = 26.2%), contingent on ROI selection/LI-calculation method. Despite strong associations of praxis and language, regardless of handedness and typicality, dissociations of atypically represented praxis from typical left-lateralized language were common (~20% of cases), whereas the inverse dissociations of atypically represented language from typical left-lateralized praxis were very rare (in ~2.5% of all cases). The consequences of the existence of such different phenotypes for theoretical accounts of manual praxis, and its links to language and handedness are modeled and discussed.

Transcranial Random Noise Stimulation Acutely Lowers the Response Threshold of Human Motor Circuits.

Transcranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioral effect is stochastic resonance (SR), a mechanism that explains how signal processing in nonlinear systems can benefit from added noise. While acute noise benefits of electrical RNS have been demonstrated at the behavioral level as well as in in vitro preparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Here, we hypothesized that acute tRNS will increase the responsiveness of primary motor cortex (M1) when probed with transcranial magnetic stimulation (TMS). Neural responsiveness was operationalized via the well-known concept of the resting motor threshold (RMT). We showed that tRNS acutely decreases RMT. This effect was small, but it was consistently replicated across four experiments including different cohorts (total N = 81, 46 females, 35 males), two tRNS electrode montages, and different control conditions. Our experiments provide critical neurophysiological evidence that tRNS can acutely generate noise benefits by enhancing the neural population response of human M1.SIGNIFICANCE STATEMENT A hallmark feature of stochastic resonance (SR) is that signal processing can benefit from added noise. This has mainly been demonstrated at the single-cell level in vitro where the neural response to weak input signals can be enhanced by simultaneously applying random noise. Our finding that transcranial random noise stimulation (tRNS) acutely increases the excitability of corticomotor circuits extends the principle of noise benefits to the neural population level in human cortex. Our finding is in line with the notion that tRNS might affect cortical processing via the SR phenomenon. It suggests that enhancing the response of cortical populations to an external stimulus might be one neurophysiological mechanism mediating performance improvements when tRNS is applied to sensory cortex during perception tasks.

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

BACKGROUND: The 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. OBJECTIVE: To 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). METHODS: The 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. RESULTS: A 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. CONCLUSION: There 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.

The temporal involvement of the left supramarginal gyrus in planning functional grasps: A neuronavigated TMS study.

The left supramarginal gyrus (SMG) is a critical structure in tool use actions, including such simple acts as selection of appropriate grasps and, if necessary, their on-line corrections. Yet, its temporal contribution to initial planning of functional grasps of tools is largely unknown. We used MRI-guided, event-related transcranial magnetic stimulation (TMS) to determine the time point when SMG involvement in processing of tools for functional grasp decision was affected most. In Exp. 1, with 15 participants, triple-pulse (10 Hz) TMS was applied to either the left anterior-to-mid SMG (amSMG; subdivisions PFt/PF) or vertex at three different time points: starting from 17 ms (i.e., delivered at 17/117/217 ms), 117 ms (117/217/317 ms) or 217 ms (217/317/417 ms) after stimulus onset. In Exp. 2, with 12 participants, we applied single-pulse TMS to either left amSMG or the left rostral middle frontal gurus (rMFG; area 46) at these same time points relative to stimulus onset. Subject- and item-based analyses of response times (RTs) were performed. Whereas the amSMG and vertex stimulation with triple pulse has revealed differential effects on RTs in general, as well as on tool orientation processing, it gave only vague pointers as to their temporal contributions to the task. Yet, amSMG and rMFG stimulation with single pulse demonstrated that, while the processing in both of these areas can be enhanced at 17 ms and no doubt at 117 ms (as compared to 217 ms), the earliest stimulation facilitated amSMG (vs. rMFG) contribution, and the latest stimulation had the opposite effect, facilitating rMFG (vs. amSMG) contribution to planning functional grasps. These outcomes demonstrate that the critical role of SMG in tool-related actions can be invoked substantially earlier than previously thought.