Repetitive Sensory Stimulation Research Articles

Repetitive sensory stimulation potentiates and recruits sensory-evoked cortical population activity.

Sensory experience and learning are thought to be associated with plasticity of neocortical circuits. Repetitive sensory stimulation can induce long-term potentiation (LTP) of cortical excitatory synapses in anesthetized mice; however, it is unclear if these phenomena are associated with sustained changes in activity during wakefulness. Here we used time-lapse, calcium imaging of layer (L) 2/3 neurons in the primary somatosensory cortex (S1), in awake male mice, to assess the effects of a bout of rhythmic whisker stimulation (RWS) at a frequency by which rodents sample objects. We found that RWS induced a 1h-increase in whisker-evoked L2/3 neuronal activity in most cells. This was not observed for whiskers functionally connected to distant cortical columns. We also found that RWS could heterogeneously recruit or suppress whisker-evoked activity in different populations of neurons. Vasoactive intestinal-peptide-expressing (VIP) interneurons, which promote plasticity through disinhibition of pyramidal neurons, were found to exclusively elevate activity during RWS. These findings indicate that cortical neurons' representation of sensory input can be modulated over hours through repetitive sensory stimulation, which may be gated by activation of disinhibitory circuits.Significance statement Sensory experience and learning are thought to be associated with the plasticity of cortical synaptic circuits. Here, we tested how repeated sensory stimulation changes subsequent sensory-evoked responses, using the mouse somatosensory cortex as a model. This cortical area processes, among others, sensory information from the whiskers. We found that rhythmic whisker stimulation potentiated excitatory neuronal activity for an hour, and identified a disinhibitory interneuron-mediated mechanism that could gate this plasticity. This work increases our understanding of sensory learning and experience-dependent plasticity processes by demonstrating that cortical representations of sensory input are dynamic and are effectively modulated by repeated sensory stimulation.

Sensory Stimulation and Robot-Assisted Arm Training After Stroke: A Randomized Controlled Trial.

Functional recovery after stroke is often limited, despite various treatment methods such as robot-assisted therapy. Repetitive sensory stimulation (RSS) might be a promising add-on therapy that is thought to directly drive plasticity processes. First positive effects on sensorimotor function have been shown. However, clinical studies are scarce, and the effect of RSS combined with robot-assisted training has not been evaluated yet. Therefore, our objective was to investigate the feasibility and sensorimotor effects of RSS (compared to a control group receiving sham stimulation) followed by robot-assisted arm therapy. Forty participants in the subacute phase (4.4-23.9weeks) after stroke with a moderate to severe arm paresis were randomized to RSS or control group. Participants received 12 sessions of (sham-) stimulation within 3weeks. Stimulation of the fingertips and the robot-assisted therapy were each applied in 45-min sessions. Motor and sensory outcome assessments (e.g. Fugl-Meyer-Assessment, grip strength) were measured at baseline, post intervention and at a 3-week follow-up. Participants in both groups improved their sensorimotor function from baseline to post and follow-up measurements, as illustrated by most motor and sensory outcome assessments. However, no significant group effects were found for any measures at any time ( P >0.058). Stimulations were well accepted, no safety issues arose. Feasibility of robot-assisted therapy with preceding RSS in persons with moderate to severe paresis was demonstrated. However, RSS preceding robot-assisted training failed to show a preliminary effect compared to the control intervention. Participants might have been too severely affected to identify changes driven by the RSS, or these might have been diluted or more difficult to identify because of the additional robotic training and neurorehabilitation. for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A478 ).

Stability of steady-state visual evoked potential contrast response functions.

Repetitive sensory stimulation has been shown to induce neuroplasticity in sensory cortical circuits, at least under certain conditions. We measured the plasticity-inducing effect of repetitive contrast-reversal-sweep steady-state visual-evoked potential (ssVEP) stimuli, hoping to employ the ssVEP's high signal-to-noise electrophysiological readout in the study of human visual cortical neuroplasticity. Steady-state VEP contrast-sweep responses were measured daily for 4 days (four 20-trial blocks per day, 20 participants). No significant neuroplastic changes in response amplitude were observed either across blocks or across days. Furthermore, response amplitudes were stable within-participant, with measured across-block and across-day coefficients of variation (CV = SD/mean) of 15-20 ± 2% and 22-25 ± 2%, respectively. Steady-state VEP response phase was also highly stable, suggesting that temporal processing delays in the visual system vary by at most 2-3 ms across blocks and days. While we fail to replicate visual stimulation-dependent cortical plasticity, we show that contrast-sweep steady-state VEPs provide a stable human neurophysiological measure well suited for repeated-measures longitudinal studies.

Lack of habituation in migraine patients and Evoked Potential types: Analysis study from EEG signals

Inability of habituation is a phenomenon whereby droop responses of cortical responses to repetitive sensory stimulation where the amplitude is persistently increased, which results in an increase in the stimulation time in migraineurs. In contrast, in healthy subjects, the cortical responses to repeated sensory stimuli become progressively lower with respect to the start of the stimulation. This abnormal responsivity to painful or painless stimuli, which becomes visible in the N2P2 in EEG rhythms with repeated stimuli, is a significant feature of migraine patients, so it plays an important role in classifying the phases of migraine (interictal, pre-ictal). The main role of genetics in migraine and its significance in the mechanisms is that it causes altered habits and abnormalities in cortical excitability in both adults and children who are closely related to parent and first-degree relative migraineurs[140-144]. Moreover, habituation and abnormality of cortical excitability increased during the period of hormones in a female who suffers from migraines. In this review, we have tried to outline and discuss the most important research findings over the past twenty years with regard to the habituation deficit in many aspects, such as migraine, its causes, and the role of EEG rhythms in the diagnosis and rehabilitation of migraine patients[144]. The findings of the review indicate that future research may need to create a new classification dependent on EEG recordings which can be used to distinguish between the two types of migraine: with aura (MWA) and without aura (MWoA)[144].

Entrainment of somatosensory beta and gamma oscillations accompany improvement in tactile acuity after periodic and aperiodic repetitive sensory stimulation

Previous research showed that repetitive sensory stimulation entrains neural oscillations at the stimulation rate, facilitates long-term potentiation like perceptual learning, and improves behavioural performance. For example, short-time repetitive tactile stimulation improved tactile acuity measured with two-point or spatial orientation discrimination tests. The behavioural gain was maximal for a stimulation rate of 20 Hz, the same frequency at which repetitive somatosensory stimulation elicits a steady-state response with maximum amplitude. The current study investigated whether sensory stimulation must be strictly periodic to induce perceptual learning and whether the 20-Hz steady-state response plays a crucial role in the neural mechanisms of perceptual learning. In a crossover-designed experiment, young, healthy adults received sensory stimulation to the fingertip on three subsequent days. The stimulation was either periodic or temporally randomized (aperiodic) with the same number of stimuli. Tactile acuity was assessed with a grating orientation discrimination task, and brain activity was measured with magnetoencephalography (MEG). Stimulus type-by-session interactions were found for behavioural and brain data. Tactile acuity improved more after a session with aperiodic than periodic stimulation. Beta-band 20-Hz steady-state responses were localized in the primary somatosensory cortex contralateral to the stimulated finger and had larger amplitudes after periodic than aperiodic stimulation. Both stimulus types also elicited gamma oscillations, which increased in amplitude more with aperiodic than periodic stimulation. Sensory stimuli caused a phase reset of sensorimotor beta oscillations phase-coupled to alpha oscillations. The system of stimulus-related oscillations was discussed as underlying temporal processing. Learning may result from facilitating the temporal code. More pronounced behavioural gain with aperiodic than periodic stimulation suggests beneficial effects of temporal stimulus variability for perceptual learning.

Effects of tactile stimulation on the sensory, motor and cognitive function in people with multiple sclerosis

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease that causes demyelination in the brain and spinal cord. Repetitive sensory stimulation (RSS) can enhance sensory perception and motor function, improve inappropriate synaptic connections and adaptable malformations, and increase cognitive function. The purpose of this study was to specify the effect of RSS on the sensory, motor, and cognitive function in people with MS. MethodsRSS was applied to 50 people with MS. In this study, the following tests were used: two-point discrimination, 9-Hole Peg Test (9-HPT), Box and Block Test (BBT), hand mental rotation (HMR), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test (SDMT). The tests were performed before and after the intervention. ResultsThe results of this study showed significant difference before and after the stimulation in intervention and control groups two-point discrimination threshold (both groups= 0.001), BBT score (both groups: P < 0.001) and 9-HPT score (both groups: P < 0.001), HMR ability (reaction time: both groups: P = 0.003; accuracy rate: intervention: P = 0.004, control: P < 0.001), PASAT score (intervention: P < 0.001, control: P = 0.012) and SDMT score (intervention: P = 0.008, control: P < 0.001), but there was no statistical difference observed between the two groups before and after the intervention in terms of the mentioned variables (P > 0.05). ConclusionThe application of 30 min of RSS in the right index finger of people with MS could not improve the two-point discrimination threshold and the manual dexterity. In addition, this intervention did not improve cognitive function.

Long-lasting changes in muscle activation and step cycle variables induced by repetitive sensory stimulation to discrete areas of the foot sole during walking.

We examined whether repetitive electrical stimulation to discrete foot sole regions that are phase-locked to the step cycle modulates activity patterns of ankle muscles and induces neuronal adaptation during human walking. Nonnoxious repetitive foot sole stimulation (STIM; 67 pulses at 333 Hz) was given to the medial forefoot (f-M) or heel (HL) regions at 1) the stance-to-swing transition, 2) swing-to-stance transition, or 3) midstance, during every step cycle for 10 min. Stance, but not swing, durations were prolonged with f-M STIM delivered at stance-to-swing transition, and these changes remained for up to 20-30 min after the intervention. Electromyographic (EMG) burst durations and amplitudes in the ankle extensors were also prolonged and persisted for 20 min after the intervention. Interestingly, STIM to HL was ineffective at inducing modulation, suggesting stimulation location-specific adaptation. In contrast, STIM to HL (but not f-M), at the swing-to-stance phase transition, shortened the step cycle by premature termination of swing. Furthermore, the onset of EMG bursts in the ankle extensors appeared earlier than in the control condition. STIM delivered during the midstance phase was ineffective at modulating the step cycle, highlighting phase-dependent adaptation. These effects were absent when STIM was applied while mimicking static postures for each walking phase during standing. Our findings suggest that the combination of walking-related neuronal activity with repetitive sensory inputs from the foot can generate short-term adaptation that is phase-dependent and localized to the site of STIM.NEW & NOTEWORTHY Repetitive (∼10 min) long (200 ms) trains of sensory stimulation to discrete areas of the foot sole produce persistent changes in muscle activity and cycle timing during walking. Interactions between the delivery phase and stimulus location determine the expression of the adaptations. These observations bear striking similarities to those in decerebrate cat experiments and may be usefully translated to improving locomotor function after neurotrauma.

Reversal of Temporal Discrimination in Cervical Dystonia after Low-Frequency Sensory Stimulation.

Somatosensory temporal discrimination is abnormal in dystonia and reflects reduced somatosensory inhibition. In healthy individuals, both the latter are enhanced by high-frequency repetitive somatosensory stimulation, whereas opposite effects are observed in patients with cervical dystonia. We tested whether low-frequency repetitive sensory stimulation, which in healthy individuals worsens discrimination, might have the opposite effect in patients with cervical dystonia at the physiological level and, in turn, improve their perceptual performance. Somatosensory temporal discrimination and several electrophysiological measures of sensorimotor inhibition were collected before and after 45 minutes of low-frequency repetitive sensory stimulation. As predicted, and opposite to what happened in controls, low-frequency repetitive sensory stimulation in patients enhanced sensorimotor inhibition and normalized somatosensory temporal discrimination. Patients with cervical dystonia have an abnormal response to repetitive sensory stimulation, which we hypothesize is attributed to abnormally sensitive homeostatic mechanisms of inhibitory circuitry in both sensory and motor systems. © 2020 International Parkinson and Movement Disorder Society.

GABA Modulates Frequency-Dependent Plasticity in Humans.

SummaryFrequency-dependent reorganization of the primary somatosensory cortex, together with perceptual changes, arises following repetitive sensory stimulation. Here, we investigate the role of GABA in this process. We co-stimulated two finger tips and measured GABA and Glx using magnetic resonance (MR) spectroscopy at the beginning and end of the stimulation. Participants performed a perceptual learning task before and after stimulation. There were 2 sessions with stimulation frequency either at or above the resonance frequency of the primary somatosensory cortex (23 and 39 Hz, respectively). Perceptual learning occurred following above resonance stimulation only, while GABA reduced during this condition. Lower levels of early GABA were associated with greater perceptual learning. One possible mechanism underlying this finding is that cortical disinhibition “unmasks” lateral connections within the cortex to permit adaptation to the sensory environment. These results provide evidence in humans for a frequency-dependent inhibitory mechanism underlying learning and suggest a mechanism-based approach for optimizing neurostimulation frequency.

20 Hz Steady-State Response in Somatosensory Cortex During Induction of Tactile Perceptual Learning Through LTP-Like Sensory Stimulation.

The induction of synaptic plasticity requires the presence of temporally patterned neural activity. Numerous cellular studies in animals and brain slices have demonstrated that long-term potentiation (LTP) enhances synaptic transmission, which can be evoked by high-frequency intermittent stimulation. In humans, plasticity processes underlying perceptual learning can be reliably induced by repetitive, LTP-like sensory stimulation. These protocols lead to improvement of perceptual abilities parallel to widespread remodeling of cortical processing. However, whether maintained rhythmic cortical activation induced by the LTP-like stimulation is also present during human perceptual learning experiments, remains elusive. To address this question, we here applied a 20 Hz intermittent stimulation protocol for 40 min to the index-, middle- and ring-fingers of the right hand, while continuously recording EEG over the hand representation in primary somatosensory cortex in young adult participants. We find that each train of stimulation initiates a transient series of sensory-evoked potentials which accumulate after about 500 ms into a 20 Hz steady-state response persisting over the entire period of the 2-s-train. During the inter-train interval, no consistent evoked activity can be detected. This response behavior is maintained over the whole 40 min of stimulation without any indication of habituation. However, the early stimulation evoked potentials (SEPs) and the event-related desynchronization (ERD) during the steady-state response change over the 40 min of stimulation. In a second experiment, we demonstrate in a separate cohort of participants that the here-applied pneumatic type of stimulation results in improvement of tactile acuity as typically observed for electrically applied 20 Hz intermittent stimulation. Our data demonstrate that repetitive stimulation using a 20 Hz protocol drives rhythmic activation in the hand representation of somatosensory cortex, which is sustained during the entire stimulation period. At the same time, cortical excitability increases as indicated by altered ERD and SEP amplitudes. Our results, together with previous data underlining the dependence of repetitive sensory stimulation effects on NMDA-receptor activation, support the view that repetitive sensory stimulation elicits LTP-like processes in the cortex, thereby facilitating perceptual learning processes.

A Mechanical Stimulation Glove to Induce Hebbian Plasticity at the Fingertip

Repetitive sensory stimulation of the fingertip induces Hebbian plasticity in the sensorimotor cortex that benefits the tactile and motor behavior of the hand in healthy younger adults, older adults, and patients. To use this method outside the laboratory, robust and portable stimulation systems are needed that allow prolonged stimulation phases over several hours without compromising on signal intensity or personal mobility. Here, we introduce two stimulation gloves that apply finger- and frequency-specific mechanical stimulation to individual fingertips over prolonged periods. The stimulators are built into commercially available cotton gloves and apply stimulation either via loudspeaker membranes or via linear resonant actuators (LRAs). We tested the efficiency of both gloves to induce Hebbian plasticity in younger adults by using two established measures of tactile performance, the grating orientation task (GOT), and the two-point discrimination task (2PDT). Both tests were performed before and after 3 h of sensory finger stimulation using one of either glove system. As a control condition, a non-stimulated finger was tested in both tasks before and after stimulation. The results show no significant effect of sensory stimulation on GOT thresholds, but a significant decrease in the 2PDT thresholds after compared to before the training at the stimulated finger only. The loudspeaker membrane improved performance in the 2PDT in 10/16 participants, whereas the LRA improved performance in the 2PDT in 13/16 participants. Stimulation gloves with built-in modules may be used in future larger-scale cohort studies on sensorimotor plasticity, rehabilitation, and learning.

Convolutional Neural Networks Using Dynamic Functional Connectivity for EEG-Based Person Identification in Diverse Human States

Highly secure access control requires Swiss-cheese-type multi-layer security protocols. The use of electroencephalogram (EEG) to provide cognitive indicators for human workload and fatigue has created environments where the EEG data are well-integrated into systems, making it readily available for more forms of innovative uses including biometrics. However, most of the existing studies on EEG biometrics rely on resting state signals or require specific and repetitive sensory stimulation, limiting their uses in naturalistic settings. Moreover, the limited discriminatory power of uni-variate measures denies an opportunity to use dependences information inherent in brain regions to design more robust biometric identifiers. In this paper, we proposed a novel model for ongoing EEG biometric identification using EEG collected during a diverse set of tasks. The novelty lies in representing EEG signals as a graph based on within-frequency and cross-frequency functional connectivity estimates, and the use of graph convolutional neural network (GCNN) to automatically capture deep intrinsic structural representations from the EEG graphs for person identification. An extensive investigation was carried out to assess the robustness of the method against diverse human states, including resting states under eye-open and eye-closed conditions and active states drawn during the performance of four different tasks. We compared our method with the state-of-the-art EEG features, classifiers, and models of EEG biometrics. Results show that the representation drawn from EEG functional connectivity graphs demonstrates more robust biometric traits than direct use of uni-variate features. Moreover, the GCNN can effectively and efficiently capture discriminative traits, thus generalizing better over diverse human states.

Passive perceptual learning modulates motor inhibitory control in superior frontal regions.

Response inhibition is of vital importance in the context of controlling inappropriate responses. The role of perceptual processes during inhibitory control has attracted increased interest. Yet, we are far from an understanding of the mechanisms. One candidate mechanism by which perceptual processes may affect response inhibition refers to “gain control” that is closely linked to the signal‐to‐noise ratio of incoming information. A means to modulate the signal‐to‐noise ratio and gain control mechanisms is perceptual learning. In the current study, we examine the impact of perceptual learning (i.e., passive repetitive sensory stimulation) on response inhibition combining EEG signal decomposition with source localization analyses. A tactile GO/NOGO paradigm was conducted to measure action restraint as one subcomponent of response inhibition. We show that passive perceptual learning modulates response inhibition processes. In particular, perceptual learning attenuates the detrimental effect of response automation during inhibitory control. Temporally decomposed EEG data show that stimulus‐related and not response selection processes during conflict monitoring are linked to these effects. The superior and middle frontal gyrus (BA6), as well as the motor cortex (BA4), are associated with the effects of perceptual learning on response inhibition. Reliable neurophysiological effects were not evident on the basis of standard ERPs, which has important methodological implications for perceptual learning research. The results detail how lower level sensory plasticity protocols affect higher‐order cognitive control functions in frontal cortical structures.

PULSE-I - Is rePetitive Upper Limb SEnsory stimulation early after stroke feasible and acceptable? A stratified single-blinded randomised controlled feasibility study

BackgroundReduction in sensorimotor function of the upper limb is a common and persistent impairment after stroke, and less than half of stroke survivors recover even basic function of the upper limb after a year. Previous work in stroke has shown that repetitive sensory stimulation (RSS) of the upper limb may benefit motor function. As yet, there have been no investigations of RSS in the early-acute period despite this being the time window during which the neuroplastic processes underpinning sensorimotor recovery are likely to occur.MethodsA single-blinded, stratified, randomised controlled feasibility study was undertaken at two NHS acute trusts to determine the recruitment rate, intervention adherence, and safety and acceptability of an RSS intervention in the early period after stroke. Participants were recruited within 2 weeks of index stroke. Stratified on arm function, they were randomised to receive either 45 min of daily RSS and usual care or usual care alone (UC) for 2 weeks. Changes from baseline on the primary outcome of the Action Research Arm Test (ARAT) to measurements taken by a blinded assessor were examined after completion of the intervention (2 weeks) and at 3 months from randomisation.ResultsForty patients were recruited and randomised (RSS n = 23; UC n = 17) with a recruitment rate of 9.5% (40/417) of patients admitted with a stroke of which 52 (12.5%) were potentially eligible, with 10 declining to participate for various reasons. Participants found the RSS intervention acceptable and adherence was good. The intervention was safe and there were no serious adverse events.ConclusionsThis study indicates that recruitment to a trial of RSS in the acute period after stroke is feasible. The intervention was well tolerated and appeared to provide additional benefit to usual care. In addition to a definitive trial of efficacy, further work is warranted to examine the effects of varying doses of RSS upon arm function and the mechanism by which RSS induces sensorimotor recovery in the acute period after stroke.Trial registrationISRCTN, registry no: ISRCTN17422343; IRAS Project ID: 215137. Registered on October 2016

High frequency somatosensory stimulation in dystonia: Evidence fordefective inhibitory plasticity.

Apart from motor symptoms, multiple deficits of sensory processing have been demonstrated in dystonia. The most consistent behavioural measure of this is abnormal somatosensory temporal discrimination threshold, which has recently been associated with physiological measures of reduced inhibition within the primary somatosensory area. High-frequency repetitive sensory stimulation is a patterned electric stimulation applied to the skin through surface electrodes that has been recently reported to shorten somatosensory temporal discrimination in healthy subjects and to increase the resting level of excitability in several different types of inhibitory interaction in the somatosensory and even motor areas. We tested whether high-frequency repetitive sensory stimulation could augment cortical inhibition and, in turn, ameliorate somatosensory temporal discrimination in cervical dystonia. Somatosensory temporal discrimination and a number of electrophysiological measures of sensorimotor inhibition and facilitation were measured before and after 45 minutes of high-frequency repetitive sensory stimulation. As compared with a group of healthy volunteers of similar age, in whom high-frequency repetitive sensory stimulation increased inhibition and shortened somatosensory temporal discrimination, patients with cervical dystonia showed a consistent, paradoxical response: they had reduced suppression of paired-pulse somatosensory evoked potentials, as well as reduced high-frequency oscillations, lateral inhibition, and short interval intracortical inhibition. Somatosensory temporal discrimination deteriorated after the stimulation protocol, and correlated with reduced measures of inhibition within the primary somatosensory cortex. We suggest that patients with dystonia have abnormal homeostatic inhibitory plasticity within the sensorimotor cortex and that this is responsible for their paradoxical response to high-frequency repetitive sensory stimulation. © 2018 International Parkinson and Movement Disorder Society.

F64. High frequency somatosensory stimulation in cervical dystonia: Evidence for defective homeostatic plasticity in sensorimotor inhibitory circuits

Apart from motor symptoms, multiple deficits of sensory processing have been demonstrated in dystonia. The most consistent behavioural measure of this is abnormal somatosensory temporal discrimination threshold (STDT), which has recently been associated with physiological measures of reduced inhibition within the primary somatosensory area, namely paired-pulse somatosensory evoked potentials (pp-SEP) and high-frequency oscillations (HFO). High-frequency repetitive sensory stimulation (HF-RSS) is a patterned electric stimulation that, when applied to the skin through surface electrodes, has been recently reported to shorten STDT in healthy subjects and to increase the resting level of excitability in several different types of inhibitory interactions in the primary somatosensory cortex (S1) and even the primary motor cortex (M1). We asked here whether HF-RSS was able to increase inhibition also in dystonia, where a lack of inhibitory interactions has been previously described. We tested whether HF-RSS could augment cortical inhibition and, in parallel, ameliorate STDT in 12 patients with cervical dystonia. To this aim, STDT and a number of electrophysiological measures of S1 (pp-SEP, HFO, lateral inhibition) and M1 (short intracortical inhibition (SICI)) were measured before and after 45 min of HF-RSS. The results were also compared with those of 12 age-matched healthy controls. Compared with healthy controls, in whom HF-RSS, as expected, shortened STDT and increased S1 and M1 inhibition assessed with the mentioned tests, patients with cervical dystonia showed a consistent, paradoxical response: they had reduced suppression in pp-SEP, a reduced area of HFO, a smaller amount of lateral inhibition and less SICI. STDT deteriorated after HF-RSS, and the change was correlated with those in pp-SEP and HFO. We suggest that patients with dystonia have abnormal homeostatic plasticity in the inhibitory circuitry within S1, and possibly M1, and that this is responsible for their paradoxical response to HF-RSS.

Abstract TP153: Repetitive Peripheral Sensory Stimulation in Stroke: a Systematic Review and Meta-Analysis

Background: Enhancement of sensory input in the form of repetitive peripheral sensory stimulation (RPSS) can enhance excitability of the motor cortex and upper limb performance. Objective: To perform a systematic review and meta-analysis of effects of RPSS compared to control stimulation on improvement of motor impairments in the upper limb of subjects with stroke. Methods: We searched studies published between 1948 until July, 2016 and selected eight studies that applied a specific paradigm of stimulation (trains of 1 millisecond pulses at 10Hz delivered at 1 Hz). Continuous data were analyzed with pooled means of standard deviations of results of active versus control interventions with the Cohen and Hedges formulas. Adverse events were also assessed. Results: There was significant heterogeneity when data from all eight studies that included subjects at early (n=3) or chronic (n=5) stages after stroke were included, but not when only data from studies in the chronic phase were analyzed. There was a statistically significant beneficial effect of RPSS on motor performance in subjects in the chronic phase with an overall small effect size (standard mean difference between active and control RPSS, 0.45; 95% confidence interval, 0.07, 0.84). When data from the three studies that included subjects at an early stage after stroke were added, the effect was no longer statistically significant. No serious adverse events were reported. Conclusions: RPSS is a safe intervention with potential to become an adjuvant tool for upper extremity paresis rehabilitation in subjects with stroke in the chronic phase.

Daily repetitive sensory stimulation of the paretic hand for the treatment of sensorimotor deficits in patients with subacute stroke: RESET, a randomized, sham-controlled trial

BackgroundRepetitive sensory stimulation (RSS) adapts the timing of stimulation protocols used in cellular studies to induce synaptic plasticity. In healthy subjects, RSS leads to widespread sensorimotor cortical reorganization paralleled by improved sensorimotor behavior. Here, we investigated whether RSS reduces sensorimotor upper limb impairment in patients with subacute stroke more effectively than conventional therapy.MethodsA single-blinded sham-controlled clinical trial assessed the effectiveness of RSS in treating sensorimotor deficits of the upper limbs. Patients with subacute unilateral ischemic stroke were randomly assigned to receive standard therapy in combination with RSS or with sham RSS. Patients were masked to treatment allocation. RSS consisted of intermittent 20 Hz electrical stimulation applied on the affected hand for 45 min/day, 5 days per week, for 2 weeks, and was transmitted using custom-made stimulation-gloves with built-in electrodes contacting each fingertip separately. Before and after the intervention, we assessed light-touch and tactile discrimination, proprioception, dexterity, grip force, and subtasks of the Jebsen Taylor hand-function test for the non-affected and the affected hand. Data from these quantitative tests were combined into a total performance index serving as primary outcome measure. In addition, tolerability and side effects of RSS intervention were recorded.ResultsSeventy one eligible patients were enrolled and randomly assigned to receive RSS treatment (n = 35) or sham RSS (n = 36). Data of 25 patients were not completed because they were transferred to another hospital, resulting in n = 23 for each group. Before treatment, sensorimotor performance between groups was balanced (p = 0.237). After 2 weeks of the intervention, patients in the group receiving standard therapy with RSS showed significantly better restored sensorimotor function than the control group (standardized mean difference 0.57; 95% CI -0.013–1.16; p = 0.027) RSS treatment was superior in all domains tested. Repetitive sensory stimulation was well tolerated and accepted, and no adverse events were observed.ConclusionsRehabilitation including RSS enhanced sensorimotor recovery more effectively than standard therapy alone. Rehabilitation outcome between the effects of RSS and standard therapy was largest for sensory and motor improvement; however, the results for proprioception and everyday tasks were encouraging warranting further studies in more severe patients.Trial registrationThe trial was retrospectively registered January 31, 2012 under DRKS00003515 (https://www.drks.de/drks_web/navigate.do;jsessionid=AEE2585CCB82A22A2B285470B37C47C8?navigationId=results).

Structural changes in brain morphology induced by brief periods of repetitive sensory stimulation

There is a growing interest in identifying the neural mechanisms by which the human brain allows for improving performance. Tactile perceptual measurements, e.g. two-point discrimination (2ptD), can be used to investigate neural mechanisms of perception as well as perceptual improvement. Improvement can be induced in a practice-independent manner, e.g. in the tactile domain through repetitive somatosensory stimulation (rSS). With respect to tactile perception, the role of cortical excitability and activation within the somatosensory cortex has been investigated extensively. However, the role of structural properties, such as regional gray matter (GM) volume, is unknown. Using high resolution imaging and voxel-based morphometry (VBM), we sought to investigate how regional GM volume relates to individual 2ptD performance. Furthermore, we wanted to determine if electrical rSS has an influence on regional GM volume.2ptD thresholds of the index fingers were assessed bilaterally. High-resolution (1 mm3), T1-weighted images were obtained using a 3T scanner pre-and post-stimulation. RSS was applied for 45 min to the dominant right hand, specifically to the fingertips of all fingers.At baseline, performance in the 2ptD task was associated with regional GM volume in the thalamus, primary somatosensory cortex, and primary visual cortex (negative association). After 45 min of rSS, we observed an improvement in 2ptD of the stimulated hand, whereas no improvement in tactile performance was seen on the non-stimulated side. These perceptual changes were accompanied by an increase in GM volume in the left somatosensory cortex and the degree of improvement correlated with GM volume changes in the insular cortex.Our results show that structural changes in the brain, specifically in regions receiving afferent input from the stimulated body site can be induced via a short-term intervention lasting only 45 min. However, the neurobiological correlates of these changes and the dynamics need to be further elucidated.

Recovery of hippocampal functions and modulation of muscarinic response by electroacupuncture in young diabetic rats

The muscarinic receptor response to acetylcholine regulates the hippocampal-related learning, memory, neural plasticity and the production and processing of the pro-nerve growth factor (proNGF) by hippocampal cells. The development and progression of diabetes generate a mild cognitive impairment reducing the functions of the septo-hippocampal cholinergic circuitry, depressing neural plasticity and inducing proNGF accumulation in the brain. Here we demonstrate, in a rat model of early type-1 diabetes, that a physical therapy, the electroacupuncture, counteracts the diabetes-induced deleterious effects on hippocampal physiology by ameliorating hippocampal-related memory functions; recovering the impaired long-term potentiation at the dentate gyrus (DG-LTP) and the lowered expression of the vesicular glutamate transporter 1; normalizing the activity-dependent release of proNGF in diabetic rat hippocampus. Electroacupuncture exerted its therapeutic effects by regulating the expression and activity of M1- and M2-acetylcholine muscarinic receptors subtypes in the dentate gyrus of hippocampus. Our results suggest that a physical therapy based on repetitive sensory stimulation could promote hippocampal neural activity, neuronal metabolism and functions, and conceivably improve the diabetes-induced cognitive impairment. Our data can support the setup of therapeutic protocols based on a better integration between physical therapies and pharmacology for the cure of diabetes-associated neurodegeneration and possibly for Alzheimer’s disease.