Peripheral Sensory Stimulation Research Articles

Beneficial Effects of Acupuncture for Depression-A Possible Mediation of Peripheral Sensory Stimulation and Central Oxytocin Release

In modern society, depression is one of the most common mental disorders. It is generally thought that depression is due to the disorders of neuronal circuits and chemical balance in the brain. Patients with depression often receive treatment with selective serotonin reuptake inhibitors (SSRIs). However, recent studies suggest that the magnitude of benefit of pharmacological treatment is quite limited for these patients. Although recent studies propose acupuncture as a non-pharmacological approach to managing depression, the mechanism of its beneficial effects is not well understood. Somatosensory pathways stimulated by acupuncture relay to the central nervous system (CNS). In animal studies, acupuncture has demonstrated the potential to ameliorate neural abnormalities associated with depression. As complex daily life stress is highly associated with depression, the procedure that suppresses stress responses would be a good candidate to treat depression. Oxytocin (OXT) is a hormone produced at the hypothalamus and mediates social bonding and stress reduction. OXT inhibits stress-induced corticotropin-releasing factor (CRF) expression at the hypothalamus, resulting in anti-stress and anti-anxiety effects. Research has demonstrated that acupuncture stimulates the release of hypothalamic OXT through somatosensory stimulation. Thus, stress-related mental disorders can be treated, at least in part, by acupuncture. It is proposed that somatosensory stimulations induced by acupuncture are a possible candidate as a non-pharmacological approach for depression.

Peripheral Sensory Stimulation for Neurological Disorders. A Novel, Non-invasive Therapeutic Option. Review Article

Peripheral sensory stimulation (PSS) represents a new area of therapy for patients with neurological disorders. Grounded in strong basic science research, PSS carries potential promise in the management of multiple diseases. We reviewed the literature regarding those conditions that represent reasonable targets for treatment with PSS including stroke, Parkinson’s disease, traumatic brain injury, and auto-immune, inflammatory illness. Potential mechanisms of action are discussed, and future avenues of investigation are described.

Astrocytes adjust the dynamic range of cortical network activity to control modality-specific sensory information processing

Cortical neuron-astrocyte communication in response to peripheral sensory stimulation occurs in a topographic-, frequency-, and intensity-dependent manner. However, the contribution of this functional interaction to the processing of sensory inputs and consequent behavior remains unclear. We investigate the role of astrocytes in sensory information processing at circuit and behavioral levels by monitoring and manipulating astrocytic activity invivo. We show that astrocytes control the dynamic range of the cortical network activity, optimizing its responsiveness to incoming sensory inputs. The astrocytic modulation of sensory processing contributes to setting the detection threshold for tactile and thermal behavior responses. The mechanism of such astrocytic control is mediated through modulation of inhibitory transmission to adjust the gain and sensitivity of responding networks. These results uncover a role for astrocytes in maintaining the cortical network activity in an optimal range to control behavior associated with specific sensory modalities.

The Effects of Subthreshold Vibratory Noise on Cortical Activity During Motor Imagery.

Previous studies have demonstrated that both visual and proprioceptive feedback play vital roles in mental practice of movements. Tactile sensation has been shown to improve with peripheral sensory stimulation via imperceptible vibratory noise by stimulating the sensorimotor cortex. With both proprioception and tactile sensation sharing the same population of posterior parietal neurons encoding within high-level spatial representations, the effect of imperceptible vibratory noise on motor imagery-based brain-computer interface is unknown. The objective of this study was to investigate the effects of this sensory stimulation via imperceptible vibratory noise applied to the index fingertip in improving motor imagery-based brain-computer interface performance. Fifteen healthy adults (nine males and six females) were studied. Each subject performed three motor imagery tasks, namely drinking, grabbing, and flexion-extension of the wrist, with and without sensory stimulation while being presented a rich immersive visual scenario through a virtual reality headset. Results showed that vibratory noise increased event-related desynchronization during motor imagery compared with no vibration. Furthermore, the task classification percentage was higher with vibration when the tasks were discriminated using a machine learning algorithm. In conclusion, subthreshold random frequency vibration affected motor imagery-related event-related desynchronization and improved task classification performance.

Post-ischemic reorganization of sensory responses in cerebral cortex.

Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats' forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation in RFA modulated and disrupted the sensory response in sensory cortex. The presence of a sensory response in RFA and the sensitivity of S1 to modulation by intracortical stimulation provides additional evidence for functional connectivity between premotor and somatosensory cortex. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.

Effect of Self-Directed Home Therapy Adherence Combined with TheraBracelet on Poststroke Hand Recovery: A Pilot Study.

Hand impairment is a common consequence of stroke, resulting in long-term disability and reduced quality of life. Recovery may be augmented through self-directed therapy activities at home, complemented by the use of rehabilitation devices such as peripheral sensory stimulation. The objective of this study was to determine the effect of adherence to self-directed therapy and the use of TheraBracelet (subsensory random-frequency vibratory stimulation) on hand function for stroke survivors. In a double-blind, randomized controlled pilot trial, 12 chronic stroke survivors were assigned to a treatment or control group (n = 6/group). All participants were instructed to perform 200 repetitions of therapeutic hand tasks 5 days/week while wearing a wrist-worn device 8 hours/day for 4 weeks. The treatment group received TheraBracelet vibration from the device, while the control group received no vibration. Home task repetition adherence and device wear logs, as well as hand function assessment (Stroke Impact Scale Hand domain), were obtained weekly. Repetition adherence was comparable between groups but varied among participants. Participants wore the device to a greater extent than adhering to completing repetitions. A linear mixed model analysis showed a significant interaction between repetition and group (p = 0.01), with greater adherence resulting in greater hand function change for the treatment group (r = 0.94; R 2 = 0.88), but not for the control group. Secondary analysis revealed that repetition adherence was greater for those with lower motor capacity and greater self-efficacy at baseline. This pilot study suggests that adherence to self-directed therapy at home combined with subsensory stimulation may affect recovery outcomes in stroke survivors. This trial is registered with NCT04026399.

Low-intensity ultrasound stimulation modulates time-frequency patterns of cerebral blood oxygenation and neurovascular coupling of mouse under peripheral sensory stimulation state

Previous studies have demonstrated that transcranial ultrasound stimulation (TUS) not only modulates cerebral hemodynamics, neural activity, and neurovascular coupling characteristics in resting samples but also exerts a significant inhibitory effect on the neural activity in task samples. However, the effect of TUS on cerebral blood oxygenation and neurovascular coupling in task samples remains to be elucidated. To answer this question, we first used forepaw electrical stimulation of the mice to elicit the corresponding cortical excitation, and then stimulated this cortical region using different modes of TUS, and simultaneously recorded the local field potential using electrophysiological acquisition and hemodynamics using optical intrinsic signal imaging. The results indicate that for the mice under peripheral sensory stimulation state, TUS with a duty cycle of 50% can (1) enhance the amplitude of cerebral blood oxygenation signal, (2) reduce the time-frequency characteristics of evoked potential, (3) reduce the strength of neurovascular coupling in time domain, (4) enhance the strength of neurovascular coupling in frequency domain, and (5) reduce the time-frequency cross-coupling of neurovasculature. The results of this study indicate that TUS can modulate the cerebral blood oxygenation and neurovascular coupling in peripheral sensory stimulation state mice under specific parameters. This study opens up a new area of investigation for potential applicability of TUS in brain diseases related to cerebral blood oxygenation and neurovascular coupling.

Disinhibition of short-latency but not long-latency afferent inhibition of the lower limb during upper-limb muscle contraction.

Research has demonstrated that motor and sensory functions of the lower limbs can be modulated by upper-limb muscle contractions. However, whether sensorimotor integration of the lower limb can be modulated by upper-limb muscle contractions is still unknown. [AQ: NR Original articles do not require structured abstracts. Hence, abstract subsections have been deleted. Please check.]Human sensorimotor integration has been studied using short- or long-latency afferent inhibition (SAI or LAI, respectively), which refers to inhibition of motor-evoked potentials (MEPs) elicited via transcranial magnetic stimulation by preceding peripheral sensory stimulation. In the present study, we aimed to investigate whether upper-limb muscle contractions could modulate the sensorimotor integration of the lower limbs by examining SAI and LAI. Soleus muscle MEPs following electrical tibial nerve stimulation (TSTN) during rest or voluntary wrist flexion were recorded at inter-stimulus intervals (ISIs) of 30 (i.e. SAI), 100, and 200 ms (i.e. LAI). The soleus Hoffman reflex following TSTN was also measured to identify whether MEP modulation occurred at the cortical or the spinal level. Results showed that lower-limb SAI, but not LAI, was disinhibited during voluntary wrist flexion. Furthermore, the soleus Hoffman reflex following TSTN during voluntary wrist flexion was unchanged when compared with that during the resting state at any ISI. Our findings suggest that upper-limb muscle contractions modulate sensorimotor integration of the lower limbs and that disinhibition of lower-limb SAI during upper-limb muscle contractions is cortically based.

Abstract P316: Lower Mortality From Ischemic Heart Disease Associated With Attenuation of Autonomic Dysfunction is Related to Reduction of Sensitivity to Pain at the Chest Bone

Introduction: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD) and has been found also to be related to elevated measures of sensitivity to pain from pressure (PPS) at the sternum. Previously, we found that non-pharmacological intervention by peripheral sensory nerve stimulation, monitored by repeated home-based PPS measurements, consistently was associated with lowered PPS measures. Compared to the general Danish population, the intervention reduced the all-cause mortality in two prospective observations, one of 103 patients with IHD followed for 3 years, and one of 73 patients with stroke followed for 4.5 years. Here, we test if we can reproduce lower all-cause mortality associated with lowered PPS measures in a randomized controlled trial (RCT). Methods: Of 361 consecutively followed patients with stable IHD, 65% had elevated PPS, suggestive of ANSD. Of these, 213 participated in a randomized controlled trial (RCT) with active (n=106) or passive intervention (n=107). We compared the 5-year all-cause mortality of both groups with two corresponding subsections of approximately 35.000 members of the general population of Denmark, matching patients for gender, age, and observation period with data from Statistics Denmark, and we compared the 5-year mortality of the two RCT groups. In separate analyses, we pooled mortality data from the active group of the RCT with data from two observational studies. We registered the pooled active intervention mortality of 1.168 person-years, compared to approximately 40 million person-years of the pooled general population. Results: We observed fewer than three deaths in the active RCT group (exact number and 95% CI not available according to GDRP rules), compared to eight deaths of passive RCT group members (P=0.035). Based on the predicted mortality from the general population of eight deaths in both groups, the result is consistent with significantly reduced mortality of recipients of active intervention (P=0.011). The separate analyses of pooled data from three consecutive studies demonstrated a mean reduction of the 4.2-year all-cause mortality of 50% (P<0.00005). Conclusions: The predicted attenuation of ANSD associated with lowering of elevated PPS matched the lower all-cause mortality of patients with IHD.

Effect of Using TheraBracelet on Grasping versus Reaching in Poststroke Rehabilitation.

A peripheral sensory stimulation named TheraBracelet has recently been shown to have a potential to improve gross manual dexterity following stroke. Upper limb function requires both reach and grasp. It is unknown whether TheraBracelet affects one more than other. The objective of this study was to determine whether TheraBracelet improves reaching versus grasping. In a pilot randomized controlled trial, persons with stroke received TheraBracelet (treatment) or no stimulation (control) during task practice therapy (n = 6/group). Effects of TheraBracelet on reaching versus grasping were determined using breakdown of movement times in the Box and Block Test video recordings. Improvements in movement times for the treatment compared with control group were more pronounced for grasping than for reaching at both post and follow-up time points. TheraBracelet may be beneficial for persons with grasping deficits. This knowledge can guide clinicians for targeted use of TheraBracelet, resulting in effective implementation of the new treatment.

Exploring the brain with sleep-related injuries, and fixing it.

The focus of my research efforts rests with determining dysfunctional neural systems underlying disorders of sleep, and identifying interventions to overcome those disorders. Aberrant central and physiological control during sleep exerts serious consequences, including disruptions in breathing, motor control, blood pressure, mood, and cognition, and plays a major role in sudden infant death syndrome, congenital central hypoventilation, and sudden unexpected death in epilepsy, among other concerns. The disruptions can be traced to brain structural injury, leading to inappropriate outcomes. Identification of failing systems arose from the assessment of single neuron discharge in intact, freely moving and state-changing human and animal preparations within multiple systems, including serotonergic action and motor control sites. Optical imaging of chemosensitive, blood pressure and other breathing regulatory areas, especially during development, were useful to show integration of regional cellular action in modifying neural output. Identification of damaged neural sites in control and afflicted humans through structural and functional magnetic resonance imaging procedures helped to identify the sources of injury, and the nature of interactions between brain sites that compromise physiological systems and lead to failure. Interventions to overcome flawed regulatory processes were developed, and incorporate noninvasive neuromodulatory means to recruit ancient reflexes or provide peripheral sensory stimulation to assist breathing drive to overcome apnea, reduce the frequency of seizures, and support blood pressure in conditions where a failure to perfuse can lead to death.

A study of flex miniaturized coils for focal nerve magnetic stimulation.

Peripheral magnetic stimulation (PMS) is emerging as a complement to standard electrical stimulation (ES) of the peripheral nervous system (PNS). PMS may stimulate sensory and motor nerve fibers without the discomfort associated with the ES used for standard nerve conduction studies. The PMS coils are the same ones used in transcranial magnetic stimulation (TMS) and lack focality and selectiveness in the stimulation. This study presents a novel coil for PMS, developed using Flexible technologies, and characterized by reduced dimensions for a precise and controlled targeting of peripheral nerves. We performed hybrid electromagnetic (EM) and electrophysiological simulations to study the EM exposure induced by a novel miniaturized coil (or mcoil) in and around the radial nerve of the neuro-functionalized virtual human body model Yoon-Sun, and to estimate the current threshold to induce magnetic stimulation (MS) of the radial nerve. Eleven healthy subjects were studied with the mcoil, which consisted of two 15mm diameter coils in a figure-of-eight configuration, each with a hundred turns of a 25μm copper-clad four-layer foil. Sensory nerve action potentials (SNAPs) were measured in each subject using two electrodes and compared with those obtained from standard ES. The SNAPs conduction velocities were estimated as a performance metric. The induced electric field was estimated numerically to peak at a maximum intensity of 39V/m underneath the mcoil fed by 70A currents. In such conditions, the electrophysiological simulations suggested that the mcoil elicits SNAPs originating at 7mm from the center of the mcoil. Furthermore, the numerically estimated latencies and waveforms agreed with those obtained during the PMS experiments on healthy subjects, confirming the ability of the mcoil to stimulate the radial nerve sensory fibers. Hybrid EM-electrophysiological simulations assisted the development of a miniaturized coil with a small diameter and a high number of turns using flexible electronics. The numerical dosimetric analysis predicted the threshold current amplitudes required for a suprathreshold peripheral nerve sensory stimulation, which was experimentally confirmed. The developed and now validated computational pipeline will be used to improve the performances (e.g., focality and minimal currents) of new generations of mcoil designs.

Short-and long-latency afferent inhibition of the human leg motor cortex by H-reflex subthreshold electrical stimulation at the popliteal fossa

In humans, peripheral sensory stimulation inhibits subsequent motor evoked potentials (MEPs) induced by transcranial magnetic stimulation; this process is referred to as short- or long-latency afferent inhibition (SAI or LAI, respectively), depending on the inter-stimulus interval (ISI) length. Although upper limb SAI and LAI have been well studied, lower limb SAI and LAI remain under-investigated. Here, we examined the time course of the soleus (SOL) muscle MEP following electrical tibial nerve (TN) stimulation at the popliteal fossa at ISIs of 20–220 ms. When the conditioning stimulus intensity was three-fold the perceptual threshold, MEP amplitudes were inhibited at an ISI of 220 ms, but not at shorter ISIs. TN stimulation just below the Hoffman (H)-reflex threshold intensity inhibited MEP amplitudes at ISIs of 30, 35, 100, 180 and 200 ms. However, the relationship between MEP inhibition and the P30 latency of somatosensory evoked potentials (SEPs) did not show corresponding ISIs at the SEP P30 latency that maximizes MEP inhibition. To clarify whether the site of afferent-induced MEP inhibition occurs at the cortical or spinal level, we examined the time course of SOL H-reflex following TN stimulation. H-reflex amplitudes were not significantly inhibited at ISIs where MEP inhibition occurred but at an ISI of 120 ms. Our findings indicate that stronger peripheral sensory stimulation is required for lower limb than for upper limb SAI and LAI and that lower limb SAI and LAI are of cortical origin. Moreover, the direct pathway from the periphery to the primary motor cortex may contribute to lower limb SAI.

Difference between the Effects of Peripheral Sensory Nerve Electrical Stimulation on the Excitability of the Primary Motor Cortex: Examination of the Combinations of Stimulus Frequency and Duration.

Peripheral sensory nerve electrical stimulation (PES) excites the primary motor cortex and is expected to improve motor dysfunction post-stroke. However, previous studies have reported a variety of stimulus frequencies and stimulus duration settings, and the effects of these different combinations on primary motor cortex excitability are not clear. We aimed to clarify the effects of different combinations of stimulus frequency and stimulus duration of PES on the excitation of primary motor cortex. Twenty-one healthy individuals (aged > 18 years, right-handed, and without a history of neurological or orthopedic disorders) were included. Each participant experienced three different stimulation frequencies (1, 10 and 50 Hz) and durations (20, 40 and 60 min). Motor-evoked potentials (MEPs) were recorded pre- and post-PES. The outcome measure was the change in primary motor cortex excitability using the MEP ratio. We used a D-optimal design of experiments and response surface analysis to define the optimal combination within nine different settings inducing more satisfying responses. The combination of stimulation frequency and stimulation time that maximized the desirability value was 10 Hz and 40 min, respectively. The results of this study may provide fundamental data for more minimally invasive and effective implementation of PES in patients with stroke.

Multimodal Noninvasive Functional Neurophotonic Imaging of Murine Brain-Wide Sensory Responses.

Modern optical neuroimaging approaches are expanding the ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single‐modality functional neuroimaging readings. A hybrid fluorescence optoacoustic tomography platform combined with a custom data processing pipeline based on statistical parametric mapping is devised, attaining the first noninvasive observation of simultaneous calcium and hemodynamic activation patterns using optical contrasts. Correlated changes in the oxy‐ and deoxygenated hemoglobin, total hemoglobin, oxygen saturation, and rapid GCaMP6f fluorescence signals are observed in response to peripheral sensory stimulation. While the concurrent epifluorescence serves to corroborate and complement the functional optoacoustic observations, the latter further aids in decoupling the rapid calcium responses from the slowly varying background in the fluorescence recordings mediated by hemodynamic changes. The hybrid imaging platform expands the capabilities of conventional neuroimaging methods to provide more comprehensive functional readings for studying neurovascular and neurometabolic coupling mechanisms and related diseases.

Neuroplasticity after upper-extremity rehabilitation therapy with sensory stimulation in chronic stroke survivors.

This study investigated the effect of using subthreshold vibration as a peripheral sensory stimulation during therapy on cortical activity. Secondary analysis of a pilot triple-blinded randomized controlled trial. Twelve chronic stroke survivors underwent 2-week upper-extremity task-practice therapy. Half received subthreshold vibratory stimulation on their paretic wrist (treatment group) and the other half did not (control). EEG connectivity and event-related de-/resynchronization for the sensorimotor network during hand grip were examined at pre-intervention, post-intervention and follow-up. Statistically significant group by time interactions were observed for both connectivity and event-related spectral perturbation. For the treatment group, connectivity increased at post-intervention and decreased at follow-up. Event-related desynchronization decreased and event-related resynchronization increased at post-intervention, which was maintained at follow-up. The control group had the opposite trend for connectivity and no change in event-related spectral perturbation. The stimulation altered cortical sensorimotor activity. The findings complement the clinical results of the trial in which the treatment group significantly improved gross manual dexterity while the control group did not. Increased connectivity in the treatment group may indicate neuroplasticity for motor learning, while reduced event-related desynchronization and increased event-related resynchronization may indicate lessened effort for grip and improved inhibitory control. EEG may improve understanding of neural processes underlying motor recovery.

Isolating the Neural Substrates of Visually Guided Attention Orienting in Humans.

The neural processes that enable healthy humans to orient attention to sudden visual events are poorly understood because they are tightly intertwined with purely sensory processes. Here we isolated visually guided orienting activity from sensory activity using event-related potentials (ERPs). By recording ERPs to a lateral stimulus and comparing waveforms obtained under conditions of attention and inattention, we identified an early positive deflection over the ipsilateral visual cortex that was associated with the covert orienting of visual attention to the stimulus. Across five experiments with male and female adult participants, this ipsilateral visual orienting activity (VOA) could be distinguished from purely sensory-evoked activity and from other top-down spatial attention effects. The VOA was linked with behavioral measures of orienting, being significantly larger when the stimulus was detected rapidly than when it was detected more slowly, and its presence was independent of saccadic eye movements toward the targets. The VOA appears to be a specific neural index of the visually guided orienting of attention to a stimulus that appears abruptly in an otherwise uncluttered visual field.SIGNIFICANCE STATEMENT The study of visual attention orienting has been an important impetus for the field of cognitive neuroscience. Seminal reaction-time studies demonstrated that a suddenly appearing visual stimulus attracts attention involuntarily, but the neural processes associated with visually guided attention orienting have been difficult to isolate because they are intertwined with sensory processes that trigger the orienting. Here, we disentangled orienting activity from sensory activity using scalp recordings of event-related electrical activity in the human brain. A specific neural index of visually guided attention orienting was identified. Surprisingly, whereas peripheral sensory stimulation is processed initially and predominantly by the contralateral visual cortex, this electrophysiological index of visual orienting was recorded over the cerebral hemisphere that was ipsilateral to the attention-capturing stimulus.

Concomitant sensory stimulation during therapy to enhance hand functional recovery post stroke

BackgroundPost-stroke hand impairment is prevalent and persistent even after a full course of rehabilitation. Hand diminishes stroke survivors’ abilities for activities of daily living and independence. One way to improve treatment efficacy is to augment therapy with peripheral sensory stimulation. Recently, a novel sensory stimulation, TheraBracelet, has been developed in which imperceptible vibration is applied during task practice through a wrist-worn device. The objective of this trial is to determine if combining TheraBracelet with hand task practice is superior to hand task practice alone.MethodsA double-blind randomized controlled trial will be used. Chronic stroke survivors will undergo a standardized hand task practice therapy program (3 days/week for 6 weeks) while wearing a device on the paretic wrist. The device will deliver TheraBracelet vibration for the treatment group and no vibration for the control group. The primary outcome is hand function measured by the Wolf Motor Function Test. Other outcomes include the Box and Block Test, Action Research Arm Test, upper extremity use in daily living, biomechanical measure of the sensorimotor grip control, and EEG-based neural communication.DiscussionThis research will determine clinical utility of TheraBracelet to guide future translation. The TheraBracelet stimulation is delivered via a wrist-worn device, does not interfere with hand motion, and can be easily integrated into clinical practice. Enhancing hand function should substantially increase stroke survivors' independence and quality of life and reduce caregiver burden.Trial registrationNCT04569123. Registered on September 29, 2020

Effects of Repetitive Peripheral Sensory Stimulation in the Subacute and Chronic Phases After Stroke: Study Protocol for a Pilot Randomized Trial.

BackgroundRepetitive peripheral nerve sensory stimulation (RPSS) is a potential add-on intervention to motor training for rehabilitation of upper limb paresis after stroke. Benefits of RPSS were reported in subjects in the chronic phase after stroke, but there is limited information about the effects of this intervention within the 1st weeks or months. The primary goal of this study is to compare, in a head-to-head proof-of-principle study, the impact of a single session of suprasensory vs. subsensory RPSS on the upper limb motor performance and learning in subjects at different phases after stroke subacute and chronic phases and mild upper limb motor impairments after stroke. In addition, we examine the effects of RPSS on brain perfusion, functional imaging activation, and γ-aminobutyric acid (GABA) levels. Subjects with mild upper limb motor impairments will be tested with MRI and clinical assessment either at an early (7 days to 3 months post-stroke) or at a chronic (>6 months) stage after stroke.MethodsIn this multicenter, randomized, parallel-group, proof-of-principle clinical trial with blinded assessment of outcomes, we compare the effects of one session of suprasensory or subsensory RPSS in patients with ischemic or hemorrhagic stroke and upper limb paresis. Clinical assessment and MRI will be performed only once in each subject (either at an early or at a chronic stage). The primary outcome is the change in performance in the Jebsen–Taylor test. Secondary outcomes: hand strength, cerebral blood flow assessed with arterial spin labeling, changes in the blood oxygenation level-dependent (BOLD) effect in ipsilesional and contralesional primary motor cortex (M1) on the left and the right hemispheres assessed with functional MRI (fMRI) during a finger-tapping task performed with the paretic hand, and changes in GABA levels in ipsilesional and contralesional M1 evaluated with spectroscopy. The changes in outcomes will be compared in four groups: suprasensory, early; subsensory, early; suprasensory, chronic; and subsensory, chronic.DiscussionThe results of this study are relevant to inform future clinical trials to tailor RPSS to patients more likely to benefit from this intervention.Trial RegistrationNCT03956407.

Interactions of transcranial magnetic stimulation and peripheral sensory stimulation from the human lower limbs

Interactions of transcranial magnetic stimulation and peripheral sensory stimulation from the human lower limbs