A usability study on mobile EMG-guided wrist extension training in subacute stroke patients-MyoGuide.

BACKGROUND: Effective stroke rehabilitation requires high-dose, repetitive-task training, especially during the early recovery phase. However, the usability of upper-limb rehabilitation technology in acute and subacute stroke survivors remains relatively unexplored. In this study, we introduce subacute stroke survivors to MyoGuide, a mobile training platform that employs surface electromyography (sEMG)-guided neurofeedback training that specifically targets wrist extension. Notably, the study emphasizes evaluating the platform's usability within clinical contexts. METHODS: Seven subacute post-stroke patients (1 female, mean age 53.7 years, mean time post-stroke 58.9 days, mean duration per training session 48.9 min) and three therapists (one for eligibility screening, two for conducting training) participated in the study. Participants underwent ten days of supervised one-on-one wrist extension training with MyoGuide, which encompassed calibration, stability assessment, and dynamic tasks. All training records including the Level of Difficulty (LoD) and Stability Assessment Scores were recorded within the application. Usability was assessed through the System Usability Scale (SUS) and participants' willingness to continue home-based training was gauged through a self-developed survey post-training. Therapists also documented the daily performance of participants and the extent of support required. RESULTS: The usability analysis yielded positive results, with a median SUS score of 82.5. Compared to the first session, participants significantly improved their performance at the final session as indicated by both the Stability Assessment Scores (p = 0.010, mean = 229.43, CI = [25.74-433.11]) and the LoD (p < 0.001; mean: 45.43, CI: [25.56-65.29]). The rate of progression differed based on the initial impairment levels of the patient. After training, participants expressed a keen interest in continuing home-based training. However, they also acknowledged challenges related to independently using the Myo armband and software. CONCLUSIONS: This study introduces the MyoGuide training platform and demonstrates its usability in a clinical setting for stroke rehabilitation, with the assistance of a therapist. The findings support the potential of MyoGuide for wrist extension training in patients across a wide range of impairment levels. However, certain usability challenges, such as donning/doffing the armband and navigating the application, need to be addressed to enable independent MyoGuide training requiring only minimal supervision by a therapist.

Self-regulating arousal via pupil-based biofeedback.

The brain's arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus, one of the key regulators of central arousal and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the locus coeruleus and other brainstem structures involved in arousal control. Furthermore, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brain's arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioural and clinical applications across various domains, including stress-related and anxiety disorders.

Movement predictability modulates sensorimotor processing.

Introduction: An important factor for optimal sensorimotor control is how well we are able to predict sensory feedback from internal and external sources during movement. If predictability decreases due to external disturbances, the brain is able to adjust muscle activation and the filtering of incoming sensory inputs. However, little is known about sensorimotor adjustments when predictability is increased by availability of additional internal feedback. In the present study we investigated how modifications of internal and external sensory feedback influence the control of muscle activation and gating of sensory input. Methods: Co-activation of forearm muscles, somatosensory evoked potentials (SEP) and short afferent inhibition (SAI) were assessed during three object manipulation tasks designed to differ in the predictability of sensory feedback. These included manipulation of a shared object with both hands (predictable coupling), manipulation of two independent objects without (uncoupled) and with external interference on one of the objects (unpredictable coupling). Results: We found a task-specific reduction in co-activation during the predictable coupling compared to the other tasks. Less sensory gating, reflected in larger subcortical SEP amplitudes, was observed in the unpredictable coupling task. SAI behavior was closely linked to the subcortical SEP component indicating an important function of subcortical sites in predictability related SEP gating and their direct influence on M1 inhibition. Discussion: Together, these findings suggest that the unpredictable coupling task cannot only rely on predictive forward control and is compensated by enhancing co-activation and increasing the saliency for external stimuli by reducing sensory gating at subcortical level. This behavior might serve as a preparatory step to compensate for external disturbances and to enhance processing and integration of all incoming external stimuli to update the current sensorimotor state. In contrast, predictive forward control is accurate in the predictable coupling task due to the integrated sensory feedback from both hands where sensorimotor resources are economized by reducing muscular co-activation and increasing sensory gating.

Upper limb sensorimotor recovery in Asian stroke survivors: a study protocol for the development and implementation of a Technology-Assisted dIgitaL biOmaRker (TAILOR) platform.

Background: Stroke is a leading cause of lifelong disability worldwide, partially driven by a reduced ability to use the upper limb in daily life causing increased dependence on caregivers. However, post-stroke functional impairments have only been investigated using limited clinical scores, during short-term longitudinal studies in relatively small patient cohorts. With the addition of technology-based assessments, we propose to complement clinical assessments with more sensitive and objective measures that could more holistically inform on upper limb impairment recovery after stroke, its impact on upper limb use in daily life, and on overall quality of life. This paper describes a pragmatic, longitudinal, observational study protocol aiming to gather a uniquely rich multimodal database to comprehensively describe the time course of upper limb recovery in a representative cohort of 400 Asian adults after stroke. Particularly, we will characterize the longitudinal relationship between upper limb recovery, common post-stroke impairments, functional independence and quality of life. Methods: Participants with stroke will be tested at up to eight time points, from within a month to 3 years post-stroke, to capture the influence of transitioning from hospital to community settings. We will perform a battery of established clinical assessments to describe the factors most likely to influence upper limb recovery. Further, we will gather digital health biomarkers from robotic or wearable sensing technology-assisted assessments to sensitively characterize motor and somatosensory impairments and upper limb use in daily life. We will also use both quantitative and qualitative measures to understand health-related quality of life. Lastly, we will describe neurophysiological motor status using transcranial magnetic stimulation. Statistics: Descriptive analyses will be first performed to understand post-stroke upper limb impairments and recovery at various time points. The relationships between digital biomarkers and various domains will be explored to inform key aspects of upper limb recovery and its dynamics using correlation matrices. Multiple statistical models will be constructed to characterize the time course of upper limb recovery post-stroke. Subgroups of stroke survivors exhibiting distinct recovery profiles will be identified. Conclusion: This is the first study complementing clinical assessments with technology-assisted digital biomarkers to investigate upper limb sensorimotor recovery in Asian stroke survivors. Overall, this study will yield a multimodal data set that longitudinally characterizes post-stroke upper limb recovery in functional impairments, daily-life upper limb use, and health-related quality of life in a large cohort of Asian stroke survivors. This data set generates valuable information on post-stroke upper limb recovery and potentially allows researchers to identify different recovery profiles of subgroups of Asian stroke survivors. This enables the comparisons between the characteristics and recovery profiles of stroke survivors in different regions. Thus, this study lays out the basis to identify early predictors for upper limb recovery, inform clinical decision-making in Asian stroke survivors and establish tailored therapy programs. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05322837.

Exploring the Feasibility of Computer Vision for Detecting Post-Stroke Compensatory Movements.

Compensatory movements are commonly observed post-stroke and can negatively affect long-term motor recovery. In this context, a system that monitors movement quality and provides feedback would be beneficial. In this study, we aimed to detect compensatory movements during seated reaching using a conventional tablet camera and an open-source markerless body pose tracking algorithm called MediaPipe [1]. We annotated compensatory movements of stroke patients per frame based on the comparison between the paretic and non-paretic arms. We trained a binary classification model using the XGBoost algorithm to detect compensatory movements, which showed an average accuracy of 0.92 (SD 0.07) in leave-one-trial-out cross-validation across four participants. Although we observed good model performance, we also encountered challenges such as missing landmarks and misalignment, when using MediaPipe Pose. This study highlights the feasibility of using near real-time compensatory movement detection with a simple camera system in stroke rehabilitation. More work is necessary to assess the generalizability of our approach across diverse groups of stroke survivors and fully implement near real-time compensatory movement detection on a mobile device.

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions.

Understanding how the brain's macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here, we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit in mice, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial caudate putamen (CPdm). We characterize changes in both the BOLD dynamics of individual cortical and subcortical brain areas, and patterns of inter-regional coupling (functional connectivity) between pairs of areas. Using a classification approach based on a large and diverse set of time-series properties, we found that CPdm neuromodulation alters BOLD dynamics within thalamic subregions that project back to dorsomedial striatum. In the cortex, changes in local dynamics were strongest in unimodal regions (which process information from a single sensory modality) and weakened along a hierarchical gradient towards transmodal regions. In contrast, a decrease in functional connectivity was observed only for cortico-striatal connections after D1 excitation. Our results show that targeted cellular-level manipulations affect local BOLD dynamics at the macroscale, such as by making BOLD dynamics more predictable over time by increasing its self-correlation structure. This contributes to ongoing attempts to understand the influence of structure-function relationships in shaping inter-regional communication at subcortical and cortical levels.

Performing a vibrotactile discrimination task modulates finger representations in primary somatosensory cortex.

It is well established that vibrotactile stimuli are represented in somatotopic maps. However, less is known about whether these somatotopic representations are modulated by task demands and maybe even in the absence of tactile input. Here, we used a vibrotactile discrimination task as a tool to investigate these questions in further detail. Participants were required to actively perceive and process tactile stimuli in comparison to a no-task control condition where identical stimuli were passively perceived (no-memory condition). Importantly, both vibrotactile stimuli were either applied to the right index or little finger, allowing us to investigate whether cognitive task demands shape finger representations in primary somatosensory cortex (S1). Using multivoxel pattern analysis and representational similarity analysis, we found that S1 finger representations were more distinct during the memory than the no-memory condition. Interestingly, this effect was not only observed while tactile stimuli were presented but also during the delay period (i.e., in the absence of tactile stimulation). Our findings imply that when individuals are required to focus on tactile stimuli, retain them in their memory, and engage in active processing of distinctive stimulus features, this exerts a modulatory effect on the finger representations present in S1.NEW & NOTEWORTHY Using multivoxel pattern analysis, we found that discrimination task demands shape finger representations in the contralateral primary somatosensory cortex (S1), and that somatotopic representations are modulated by task demands not only during tactile stimulation but also to a certain extent in the absence of tactile input.

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.

Physical inference of falling objects involves simulation of occluded trajectories in early visual areas.

Humans possess an intuitive understanding of the environment's physical properties and dynamics, which allows them to predict the outcomes of physical scenarios and successfully interact with the physical world. This predictive ability is thought to rely on mental simulations and has been shown to involve frontoparietal areas. Here, we investigate whether such mental simulations may be accompanied by visual imagery of the predicted physical scene. We designed an intuitive physical inference task requiring participants to infer the parabolic trajectory of an occluded ball falling in accordance with Newtonian physics. Participants underwent fMRI while (i) performing the physical inference task alternately with a visually matched control task, and (ii) passively observing falling balls depicting the trajectories that had to be inferred during the physical inference task. We found that performing the physical inference task activates early visual areas together with a frontoparietal network when compared with the control task. Using multivariate pattern analysis, we show that these regions contain information specific to the trajectory of the occluded ball (i.e., fall direction), despite the absence of visual inputs. Using a cross-classification approach, we further show that in early visual areas, trajectory-specific activity patterns evoked by the physical inference task resemble those evoked by the passive observation of falling balls. Together, our findings suggest that participants simulated the ball trajectory when solving the task, and that the outcome of these simulations may be represented in form of the perceivable sensory consequences in early visual areas.

A single bout of moderate-intensity aerobic exercise improves motor learning in premanifest and early Huntington's disease.

Introduction: Cardiorespiratory exercise has emerged as a promising candidate to modify disease progression in Huntington's disease (HD). In animal models, exercise has been found to alter biomarkers of neuroplasticity and delay evidence of disease, and some interventions-including exercise-have shown benefits in human HD patients. In healthy human populations, increasing evidence suggests that even a single bout of exercise can improve motor learning. In this pilot study, we investigated the effect of a single bout of moderate intensity aerobic exercise on motor skill learning in presymptomatic and early manifest HD patients. Methods: Participants were allocated to either an exercise (n = 10) or control (n = 10) group. They performed either 20 min of moderate intensity cycling or rest before practicing a novel motor task, the sequential visual isometric pinch force task (SVIPT). After 1 week, the retention of the SVIPT was measured in both groups. Results: We found that the exercise group performed significantly better during initial task acquisition. There were no significant differences in offline memory consolidation between groups, but total skill gain across both acquisition and retention sessions was greater in the group who exercised. The better performance of the exercise group was driven by improvements in accuracy, rather than speed. Discussion: We have shown that a single bout of moderate intensity aerobic exercise can facilitate motor skill learning in people with HD gene-expansion. More research is needed to investigate the underlying neural mechanisms and to further explore the potential for neurocognitive and functional benefits of exercise for people with HD.

Hand and face somatotopy shown using MRI-safe vibrotactile stimulation with a novel soft pneumatic actuator (SPA)-skin interface.

The exact somatotopy of the human facial representation in the primary somatosensory cortex (S1) remains debated. One reason that progress has been hampered is due to the methodological challenge of how to apply automated vibrotactile stimuli to face areas in a manner that is: (1) reliable despite differences in the curvatures of face locations; and (2) MR-compatible and free of MR-interference artefacts when applied in the MR head-coil. Here we overcome this challenge by using soft pneumatic actuator (SPA) technology. SPAs are made of a soft silicon material and can be in- or deflated by means of airflow, have a small diameter, and are flexible in structure, enabling good skin contact even on curved body surfaces (as on the face). To validate our approach, we first mapped the well-characterised S1 finger layout using this novel device and confirmed that tactile stimulation of the fingers elicited characteristic somatotopic finger activations in S1. We then used the device to automatically and systematically deliver somatosensory stimulation to different face locations. We found that the forehead representation was least distant from the representation of the hand. Within the face representation, we found that the lip representation is most distant from the forehead representation, with the chin represented in between. Together, our results demonstrate that this novel MR compatible device produces robust and clear somatotopic representational patterns using vibrotactile stimulation through SPA-technology.

An optimized protocol for assessing changes in mouse whole-brain activity using opto-fMRI.

Functional magnetic resonance imaging (fMRI) in mouse brain, paired with spatially and temporally defined manipulations, offers a powerful tool to causally explain the effect of specific neuronal activity on brain network dynamics. Here, we present an optimized protocol to measure cell-type-specific contributions to changes in whole-brain dynamics in mice using optogenetics (opto)-fMRI. This protocol details the injection of ChR2-expressing AAV, the implantation of optical fiber, the steps to perform opto-BOLD (blood-oxygenation-level-dependent) fMRI recording, and data analysis. For complete details on the use and execution of this protocol, please refer to Grimm et al. (2021).

Effects of single- and multiple-dose oxytocin treatment on amygdala low-frequency BOLD fluctuations and BOLD spectral dynamics in autism.

Prior neuroimaging clinical trials investigating the neural effects of intranasal administration of the neuropeptide oxytocin demonstrated a key role of the amygdala in oxytocin's neuromodulatory effects. These studies mostly demonstrated the acute effects of single-dose administrations, examining task-dependent effects of oxytocin on brain activity elicited during explicit experimental tasks or stimuli presentations. The increased consideration of oxytocin as a potential ameliorating treatment in autism spectrum disorder (ASD) requires a better understanding of how multiple-dose oxytocin administration affects intrinsic, task-free, amygdala function. In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment. Effects were assessed either after a single-dose administration, consisting of 24 international units, or after multiple-dose treatment, consisting of 4 weeks of once-daily nasal spray administrations. Compared to placebo, oxytocin induced a decrease in intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala (fractional amplitudes of low-frequency fluctuations) and modulated cross-frequency interactions between adjacent BOLD frequency components. The right amygdala showed a pattern of reduced cross-frequency harmonicity, while the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment. Notably, the direction and magnitude of BOLD spectral changes induced after a single-dose were qualitatively similar to treatment effects induced after multiple-dose treatment. Furthermore, the identified spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension, reflecting oxytocin's anxiolytic, stress-reducing neuromodulatory role. The observed effects of oxytocin on amygdalar BOLD spectral characteristics and associated behaviors contribute to a deeper mechanistic understanding of the intrinsic, task-free neuromodulatory dynamics that underlie single- and multiple-dose oxytocin treatment in ASD. European Clinical Trial Registry (Eudract 2014-000586-45).

Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics.

Slow waves, the hallmark feature of deep nonrapid eye movement sleep, do potentially drive restorative effects of sleep on brain and body functions. Sleep modulation techniques to elucidate the functional role of slow waves thus have gained large interest. Auditory slow wave stimulation is a promising tool; however, directly comparing auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included nights and found a large and global increase in slow-wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow-wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA, and thus, our findings provide insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow-wave enhancements translates into a more rested cardiovascular system on a subsequent day.

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

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.

Optogenetic activation of striatal D1R and D2R cells differentially engages downstream connected areas beyond the basal ganglia.

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However, whether they maintain a uniform function across the striatum and what influence they exert outside the BG is unclear. Here, we address these questions by combining optogenetic activation of D1R and D2R cells in the mouse ventrolateral caudoputamen with fMRI. Striatal D1R/D2R stimulation evokes distinct activity within the BG-thalamocortical network and differentially engages cerebellar and prefrontal regions. Computational modeling of effective connectivity confirms that changes in D1R/D2R output drive functional relationships between these regions. Our results suggest a complex functional organization of striatal D1R/D2R cells and hint toward an interconnected fronto-BG-cerebellar network modulated by striatal D1R and D2R cells.