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.

Corticospinal and intracortical responses from both motor cortices following unilateral concentric versus eccentric contractions.

Cross-education is the phenomenon where training of one limb can cause neuromuscular adaptations in the opposite untrained limb. This effect has been reported to be greater after eccentric (ECC) than concentric (CON) strength training; however, the underpinning neurophysiological mechanisms remain unclear. Thus, we compared responses to transcranial magnetic stimulation (TMS) in both motor cortices following single sessions of unilateral ECC and CON exercise of the elbow flexors. Fourteen healthy adults performed three sets of 10 ECC and CON right elbow flexor contractions at 75% of respective maximum on separate days. Elbow flexor maximal voluntary isometric contraction (MVIC) torques were measured before and after exercise, and responses to single- and paired-pulse TMS were recorded from the non-exercised left and exercised right biceps brachii. Pre-exercise and post-exercise responses for ECC and CON were compared by repeated measures analyses of variance (ANOVAs). MVIC torque of the exercised arm decreased (p < 0.01) after CON (-30 ± 14%) and ECC (-39 ± 13%) similarly. For the non-exercised left biceps brachii, resting motor threshold (RMT) decreased after CON only (-4.2 ± 3.9% of maximum stimulator output [MSO], p < 0.01), and intracortical facilitation (ICF) decreased (-15.2 ± 20.0%, p = 0.038) after ECC only. For the exercised right biceps, RMT increased after ECC (8.6 ± 6.2% MSO, p = 0.014) but not after CON (6.4 ± 8.1% MSO, p = 0.066). Thus, unilateral ECC and CON elbow flexor exercise modulated excitability differently for the non-exercised hemisphere. These findings suggest that responses after a single bout of exercise may not reflect longer term adaptations.

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.

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.

Effect of fatigue-related group III/IV afferent firing on intracortical inhibition and facilitation in hand muscles.

Fatiguing exercise causes a reduction in motor drive to the muscle. Group III/IV muscle afferent firing is thought to contribute to this process; however, the effect on corticospinal and intracortical networks is poorly understood. In two experiments, participants performed sustained maximal isometric finger abductions of the first dorsal interosseous (FDI) muscle, with postexercise blood flow occlusion (OCC) to maintain the firing of group III/IV afferents or without occlusion (control; CON). Before and after exercise, single- and paired-pulse transcranial magnetic stimulation (TMS) tested motor evoked potentials (MEPs), intracortical facilitation [ICF (12 ms)], and short-interval intracortical inhibition [SICI2 (2 ms), SICI3 (3 ms)]. Ulnar nerve stimulation elicited maximal M waves (MMAX). For experiment 1 (n = 16 participants), TMS intensities were 70% and 120% of resting motor threshold (RMT) for the conditioning and MEP stimuli, respectively. For experiment 2 (n = 16 participants), the MEP was maintained at 1 mV before and after exercise and the conditioning stimulus individualized. In experiment 1, MEP/MMAX was reduced after exercise (~48%, P = 0.007) but was not different between conditions. No changes occurred in ICF or SICI. In experiment 2, MEP/MMAX increased (~27%, P = 0.027) and less inhibition (SICI2: ~21%, P = 0.021) occurred after exercise for both conditions, whereas ICF decreased for CON only (~28%, P = 0.006). MEPs and SICI2 were modulated by fatiguing contractions but not by group III/IV afferent firing, whereas sustained afferent firing appeared to counteract postexercise reductions in ICF in FDI. The findings do not support the idea that actions of group III/IV afferents on motor cortical networks contribute to the reduction in voluntary activation observed in other studies.NEW & NOTEWORTHY This is the first study to investigate, in human hand muscles, the action of fatigue-related group III/IV muscle afferent firing on intracortical facilitation and inhibition. In fatigued and nonexercised hand muscles, intracortical inhibition is reduced after exercise but is not modulated differently by the firing of group III/IV afferents. However, facilitation is maintained for the fatigued muscle when group III/IV afferents fire, but these results are unlikely to explain the reduction in voluntary activation observed in other studies.

Altering brain dynamics with transcranial random noise stimulation.

Random noise can enhance the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). This concept is not only applicable to single threshold systems but can also be applied to dynamical systems with multiple attractor states, such as observed during the phenomenon of binocular rivalry. Binocular rivalry can be characterized by marginally stable attractor states between which the brain switches in a spontaneous, stochastic manner. Here we used a computational model to predict the effect of noise on perceptual dominance durations. Subsequently we compared the model prediction to a series of experiments where we measured binocular rivalry dynamics when noise (zero-mean Gaussian random noise) was added either to the visual stimulus (Exp. 1) or directly to the visual cortex (Exp. 2) by applying transcranial Random Noise Stimulation (tRNS 1 mA, 100-640 Hz zero -mean Gaussian random noise). We found that adding noise significantly reduced the mixed percept duration (Exp. 1 and Exp. 2). Our results are the first to demonstrate that both central and peripheral noise can influence state-switching dynamics of binocular rivalry under specific conditions (e.g. low visual contrast stimuli), in line with a SR-mechanism.

Stochastic resonance enhances the rate of evidence accumulation during combined brain stimulation and perceptual decision-making.

Perceptual decision-making relies on the gradual accumulation of noisy sensory evidence. It is often assumed that such decisions are degraded by adding noise to a stimulus, or to the neural systems involved in the decision making process itself. But it has been suggested that adding an optimal amount of noise can, under appropriate conditions, enhance the quality of subthreshold signals in nonlinear systems, a phenomenon known as stochastic resonance. Here we asked whether perceptual decisions made by human observers obey these stochastic resonance principles, by adding noise directly to the visual cortex using transcranial random noise stimulation (tRNS) while participants judged the direction of coherent motion in random-dot kinematograms presented at the fovea. We found that adding tRNS bilaterally to visual cortex enhanced decision-making when stimuli were just below perceptual threshold, but not when they were well below or above threshold. We modelled the data under a drift diffusion framework, and showed that bilateral tRNS selectively increased the drift rate parameter, which indexes the rate of evidence accumulation. Our study is the first to provide causal evidence that perceptual decision-making is susceptible to a stochastic resonance effect induced by tRNS, and to show that this effect arises from selective enhancement of the rate of evidence accumulation for sub-threshold sensory events.

Transcranial Random Noise Stimulation of Visual Cortex: Stochastic Resonance Enhances Central Mechanisms of Perception.

UNLABELLED: Random noise enhances the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). Though counterintuitive at first, SR has been demonstrated in a variety of naturally occurring processes, including human perception, where it has been shown that adding noise directly to weak visual, tactile, or auditory stimuli enhances detection performance. These results indicate that random noise can push subthreshold receptor potentials across the transfer threshold, causing action potentials in an otherwise silent afference. Despite the wealth of evidence demonstrating SR for noise added to a stimulus, relatively few studies have explored whether or not noise added directly to cortical networks enhances sensory detection. Here we administered transcranial random noise stimulation (tRNS; 100-640 Hz zero-mean Gaussian white noise) to the occipital region of human participants. For increasing tRNS intensities (ranging from 0 to 1.5 mA), the detection accuracy of a visual stimuli changed according to an inverted-U-shaped function, typical of the SR phenomenon. When the optimal level of noise was added to visual cortex, detection performance improved significantly relative to a zero noise condition (9.7 ± 4.6%) and to a similar extent as optimal noise added to the visual stimuli (11.2 ± 4.7%). Our results demonstrate that adding noise to cortical networks can improve human behavior and that tRNS is an appropriate tool to exploit this mechanism. SIGNIFICANCE STATEMENT: Our findings suggest that neural processing at the network level exhibits nonlinear system properties that are sensitive to the stochastic resonance phenomenon and highlight the usefulness of tRNS as a tool to modulate human behavior. Since tRNS can be applied to all cortical areas, exploiting the SR phenomenon is not restricted to the perceptual domain, but can be used for other functions that depend on nonlinear neural dynamics (e.g., decision making, task switching, response inhibition, and many other processes). This will open new avenues for using tRNS to investigate brain function and enhance the behavior of healthy individuals or patients.

Estimating a neutral reference for electroencephalographic recordings: the importance of using a high-density montage and a realistic head model.

OBJECTIVE: In electroencephalography (EEG) measurements, the signal of each recording electrode is contrasted with a reference electrode or a combination of electrodes. The estimation of a neutral reference is a long-standing issue in EEG data analysis, which has motivated the proposal of different re-referencing methods, among which linked-mastoid re-referencing (LMR), average re-referencing (AR) and reference electrode standardization technique (REST). In this study we quantitatively assessed the extent to which the use of a high-density montage and a realistic head model can impact on the optimal estimation of a neutral reference for EEG recordings. APPROACH: Using simulated recordings generated by projecting specific source activity over the sensors, we assessed to what extent AR, REST and LMR may distort the scalp topography. We examined the impact electrode coverage has on AR and REST, and how accurate the REST reconstruction is for realistic and less realistic (three-layer and single-layer spherical) head models, and with possible uncertainty in the electrode positions. We assessed LMR, AR and REST also in the presence of typical EEG artifacts that are mixed in the recordings. Finally, we applied them to real EEG data collected in a target detection experiment to corroborate our findings on simulated data. MAIN RESULTS: Both AR and REST have relatively low reconstruction errors compared to LMR, and that REST is less sensitive than AR and LMR to artifacts mixed in the EEG data. For both AR and REST, high electrode density yields low re-referencing reconstruction errors. A realistic head model is critical for REST, leading to a more accurate estimate of a neutral reference compared to spherical head models. With a low-density montage, REST shows a more reliable reconstruction than AR either with a realistic or a three-layer spherical head model. Conversely, with a high-density montage AR yields better results unless precise information on electrode positions is available. SIGNIFICANCE: Our study is the first to quantitatively assess the performance of EEG re-referencing techniques in relation to the use of a high-density montage and a realistic head model. We hope our study will help researchers in the choice of the most effective re-referencing approach for their EEG studies.

Touch influences visual perception with a tight orientation-tuning.

Stimuli from different sensory modalities are thought to be processed initially in distinct unisensory brain areas prior to convergence in multisensory areas. However, signals in one modality can influence the processing of signals from other modalities and recent studies suggest this cross-modal influence may occur early on, even in 'unisensory' areas. Some recent psychophysical studies have shown specific cross-modal effects between touch and vision during binocular rivalry, but these cannot completely rule out a response bias. To test for genuine cross-modal integration of haptic and visual signals, we investigated whether congruent haptic input could influence visual contrast sensitivity compared to incongruent haptic input in three psychophysical experiments using a two-interval, two-alternative forced-choice method to eliminate response bias. The initial experiment demonstrated that contrast thresholds for a visual grating were lower when exploring a haptic grating that shared the same orientation compared to an orthogonal orientation. Two subsequent experiments mapped the orientation and spatial frequency tunings for the congruent haptic facilitation of vision, finding a clear orientation tuning effect but not a spatial frequency tuning. In addition to an increased contrast sensitivity for iso-oriented visual-haptic gratings, we found a significant loss of sensitivity for orthogonally oriented visual-haptic gratings. We conclude that the tactile influence on vision is a result of a tactile input to orientation-tuned visual areas.