Sensory electrical stimulation and postural balance: a comprehensive review.

PURPOSE: Sensory electrical stimulation (SES)-i.e., low-intensity electrical currents below, at, or just above the sensory threshold but below the motor threshold-is mainly used to restore/improve postural balance in pathological and healthy subjects. However, the ins and outs of its application as well as the neurophysiological effects induced are not yet well known. Hence, the aim of this paper was to address the effects of SES on postural balance based on these considerations. METHOD: The immediate/concurrent effects (SES applied during postural balance measurements), the acute effects (SES durably applied before measuring postural balance) and the chronic effects (SES included in training/rehabilitation programs, i.e., measurements performed before and after the programs) were analysed with a comprehensive review. RESULT: SES can lead to the improvement of postural balance using any of the three applications (immediate/concurrent, acute and chronic), notably in pathological subjects. The beneficial effects of SES can take place at the peripheral (sensory receptors sensitivity), spinal (spinal motoneural excitablity) and supra-spinal (cortex reorganisation or adaptation) levels. In healthy subjects, SES appears interesting, but too few studies have been conducted with this population to report clear results. Moreover, the literature is relatively devoid of comparative studies about the characteristics of the stimulation current (e.g., location, current parameters, duration). CONCLUSION: In practice, SES appears to be particularly useful to reinforce or restore the postural function in the immediate/concurrent, acute or chronic application in pathlogical populations while its effects should be confirmed in healthy sujects by future studies. Moreover, future research should focus on the different characteristics of stimulation.

Clinical Impact of Rectal Hyposensitivity: A Cross-Sectional Study of 2,876 Patients With Refractory Functional Constipation.

INTRODUCTION: Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. METHODS: Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. RESULTS: Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a "functional" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). DISCUSSION: RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).(Equation is included in full-text article.).

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

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

Effects of interphase interval during neuromuscular electrical stimulation of the wrist extensors with maximally tolerated current intensity.

Short interphase intervals (IPIs) within biphasic symmetrical pulses enhance maximal electrically induced isometric contractions (EIC). However, IPI effects have not been previously studied in muscles stimulated at the highest tolerated current intensity. Our aim was to examine IPI effects on the strength of EIC, degree of discomfort, and sensory and motor thresholds on the wrist extensor muscles. Eighteen subjects (mean age 25.5, SD ± 3.97 years) participated in a repeated-measures trial. Five parameter settings were used to stimulate the wrist extensors: monophasic pulses with phase durations (PD) 200 µs, and biphasic pulses with PDs either 200 or 500 µs, applied with/without an IPI of 200 µs duration. Order of settings was randomized, and current was set at the maximum intensity tolerated by each subject. IPIs applied at the maximally tolerated current intensity did not increase the strength of the EICs and did not reduce the degree of discomfort or the sensory and motor thresholds. These findings were not dependent on the PDs. Insertion of an IPI within the biphasic current during stimulation of the wrist muscle yielded no advantage in term of contraction strength or degree of discomfort. These results contradict previous studies indicating stronger contractions when an IPI is inserted during stimulation at a predetermined submaximal current intensity. As some of the clinical applications of neuromuscular electrical stimulation utilize the highest intensity tolerated by the individual, these findings are clinically relevant. Additional studies involving other muscle groups, electrode size and locations, and phase parameters are warranted.

Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa.

PURPOSE: Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue. DESIGN: Case series. PARTICIPANTS: Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis. METHODS: Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model. MAIN OUTCOME MEASURES: Brightness and color of the electrically elicited visual perception reported by the subjects. RESULTS: Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment. CONCLUSIONS: These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

Sensory Sub- and Suprathreshold TENS Exhibit No Immediate Effect on Postural Steadiness in Older Adults with No Balance Impairments.

Transcutaneous electrical nerve stimulation (TENS) has been reported to attenuate postural sway; however, the results are inconclusive, with some indicating the effect and others not. The study aimed to evaluate the effect of sensory sub- and suprathreshold low-frequency TENS applied through the plantar surface and posterior aspect of shanks on postural sway. In a group of healthy community-dwelling older adults, TENS was delivered with two different current intensities: (1) subsensory which is below conscious perception and (2) suprasensory threshold which is within the range of conscious perception. Frequencies of the TENS stimulation were sweeping from 5 to 180 Hz and were delivered through the plantar surface and posterior shanks of both legs. Postural sway was measured with a force platform in eyes-open and eyes-closed conditions. To evaluate potential fast adaptability to TENS stimuli, the results were evaluated in two time intervals: 30 seconds and 60 seconds. The results indicated that TENS with the chosen frequencies and electrode placement did not affect postural sway in both the sub- and suprathreshold intensities of TENS, in eyes-open and eyes-closed conditions, and in 30-second and 60-second time intervals. In conclusion, given that in this study sub- and suprathreshold TENS applied via the plantar surface of the feet did not attenuate postural sway, it would be easy to conclude that this type of electrical stimuli is ineffective and no further research is required. We must caution against this, given the specificity of the electrode placements. We recommend that future research be performed consisting of individuals with balance impairments and with different positions of electrodes.

20-kHz alternating current stimulation: effects on motor and somatosensory thresholds.

BACKGROUND: High frequency alternating current (HFAC) stimulation have been shown to produce a peripheral nerve conduction block. Currently, all the studies applying HFAC stimulation in clinical studies, have employed frequencies below 10 kHz. The main aim of this work was to investigate the neuromodulatory effect of transcutaneous 20 kHz stimulation on somatosensory and pain thresholds, and maximal handgrip strength. METHODS: A randomized, crossover, single-blinded, placebo-controlled trial was conducted following recruitment of fourteen healthy volunteers. Transcutaneous stimulation at 20 kHz and sham stimulation were applied over the ulnar and median nerves of fourteen healthy volunteers for 20 min. Maximal handgrip strength (MHS), mechanical detection threshold (MDT) and pressure pain threshold (PPT) were registered prior to, during (15 min), immediately after the end (20 min), and 10 min following stimulation. RESULTS: The 20 kHz stimulation showed a lower MHS during the stimulation at the 15 min (30.1 kgs SE 2.8) and at 20 min (31.8 kgs, SE 2.8) when compared to sham stimulation (35.1 kgs, SE 3.4; p < 0.001 and 34.2 kgs, SE 3.4; p = 0.03, respectively). The 20 kHz stimulation resulted in a slight increase in MDT at 15 min (0.25 mN; 0.25-2.00) when compared to the sham stimulation (0.25 mN; 0.25-0.25; p = 0.02), and no effects were showed for PPT. CONCLUSIONS: High-frequency stimulation at 20 kHz suggests a partial block of nerve activity. Studies in subjects with neurological disorders characterized by nerve hyperactivity are needed to confirm the clinical impact of this non-invasive electrical stimulation technique. TRIAL REGISTRATION: NCT, NCT02837458. Registered on 12 April 2017.

Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. RESULTS: Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. CONCLUSION: Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.

Enhancing sensorimotor BCI performance with assistive afferent activity: An online evaluation.

An important goal in Brain-Computer Interfacing (BCI) is to find and enhance procedural strategies for users for whom BCI control is not sufficiently accurate. To address this challenge, we conducted offline analyses and online experiments to test whether the classification of different types of motor imagery could be improved when the training of the classifier was performed on the data obtained with the assistive muscular stimulation below the motor threshold. 10 healthy participants underwent three different types of experimental conditions: a) Motor imagery (MI) of hands and feet b) sensory threshold neuromuscular electrical stimulation (STM) of hands and feet while resting and c) sensory threshold neuromuscular electrical stimulation during performance of motor imagery (BOTH). Also, another group of 10 participants underwent conditions a) and c). Then, online experiments with 15 users were performed. These subjects received neurofeedback during MI using classifiers calibrated either on MI or BOTH data recorded in the same experiment. Offline analyses showed that decoding MI alone using a classifier based on BOTH resulted in a better BCI accuracy compared to using a classifier based on MI alone. Online experiments confirmed accuracy improvement of MI alone being decoded with the classifier trained on BOTH data. In addition, we observed that the performance in MI condition could be predicted on the basis of a more pronounced connectivity within sensorimotor areas in the frequency bands providing the best performance in BOTH. These finding might offer a new avenue for training SMR-based BCI systems particularly for users having difficulties to achieve efficient BCI control. It might also be an alternative strategy for users who cannot perform real movements but still have remaining afferent pathways (e.g., ALS and stroke patients).

Diagnosis and management of sensory polyneuropathy.

Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.

Evoked Haptic Sensation in the Hand With Concurrent Non-Invasive Nerve Stimulation.

OBJECTIVE: Haptic perception is critical for prosthetic users to control their prosthetic hand intuitively. In this study, we seek to evaluate the haptic perception evoked from concurrent stimulation trains through multiple channels using transcutaneous nerve stimulation. METHODS: A 2 × 8 electrode grid was used to deliver current to the median and ulnar nerves in the upper arm. Different electrodes were first selected to activate the sensory axons, which can elicit sensations at different locations of the hand. Charge-balanced bipolar stimulation was then delivered to two sets of electrodes concurrently with a phase delay (dual stimulation) to determine whether the evoked sensation can be constructed from sensations of single stimulation delivered separately at different locations (single stimulation) along the electrode grid. The temporal delay between the two stimulation trains was altered to evaluate potential interference. The short-term stability of the haptic sensation within a testing session was also evaluated. RESULTS: The evoked sensation during dual stimulation was largely a direct summation of the sensation from single stimulations. The delay between the two stimulation locations had minimal effect on the evoked sensations, which was also stable over repeated testing within a session. CONCLUSION: Our results indicated that the haptic sensations at different regions of the hand can be constructed by combining the response from multiple stimulation trains directly. The interference between stimulations were minimal. SIGNIFICANCE: The outcomes will allow us to construct specific haptic sensation patterns when the prosthesis interacts with different objects, which may help improve user embodiment of the prosthesis.

Does Studying Veterinary Medicine Improve Students' Haptic Perception Ability? A Pilot Study With Two Age-Groups.

Haptic perception is an important tool for veterinarians. The present study analyzed the association between the haptic perception threshold of veterinary students and their palpatory experience. To approach this goal, 35 female students of veterinary medicine were divided into two groups with different levels of experience: (a) students with little practical experience, at the beginning of their studies (first year), and (b) students close to the end of their theoretical training (fourth year). To thoroughly evaluate the students' sense of touch, three different test procedures were used: the Haptic Threshold Test (HTT), the Haptic Figures Test (HFT), and tactile acuity. Contrary to our expectations, we found worse mean haptic perception thresholds (HTT) in the more experienced students than in the less experienced group. This effect was significantly correlated with age. Furthermore, we found that longer exploration times were not sufficient to compensate for shortcomings in haptic perception. We also found large interindividual differences. Future studies should investigate whether and to what extend these effects have an impact on students' palpation performance on simulators and live animals. Moreover, which beneficial effects may be achieved through an additional haptic training for students with inferior haptic thresholds should be investigated. Improving haptic perception abilities in veterinary students could be one important step toward achieving satisfactory Day One Competences in university graduates.

Repeatability of tools to assist in the follow up and troubleshooting of sacral neuromodulation patients using the sensory response.

PURPOSE: Sacral neuromodulation (SNM) is an established minimally invasive therapy for functional disorders of the pelvic organs in which electrodes are stimulated in proximity of the sacral spinal nerves. Reprogramming of the electrodes is regularly required and is based on the sensory response. This study assesses the repeatability of a pelvic chart and grading system to enable a more objective assessment of the sensory response upon electrode stimulation. MATERIAL AND METHODS: In 26 SNM patients, with OAB or NOUR, assessment of the sensory response was done using the sensory threshold (ST) and a pelvic chart with 1 cm2 coordinates, each coordinate corresponding with a dermatome and location of sensation (LoS). A grading system was developed based upon the ST and LoS. Repeatability of ST was assessed using a two-way mixed effects, absolute agreement, single rater/measurement intraclass correlation coefficient (ICC), and displayed using a correlation and Bland Altman plot. Repeatability of dermatomes, LoS, and grading system was assessed using kappa correlation coefficient. RESULTS: On average, 1.55 ± 0.85 coordinates were used to point out the area where the stimulation was perceived. The mean amount of coordinates between the area pointed at during the first and second measurement was 0.47 ± 0.74. ST showed excellent repeatability (ICC 0.93, 95%CI 0.90-0.94, P < 0.001). Dermatomes, LoS and grading system showed a substantial to almost perfect agreement (κ = 0.740-0.833, P < 0.001). CONCLUSIONS: The pelvic chart and grading system, using the sensory response upon electrode stimulation, are repeatable tools and can be used to assist in follow up and troubleshooting of SNM patients.

Clinical Utility of Longitudinal Measurement of Motor Threshold in Wilson's Disease.

This study describes the longitudinal changes of resting motor threshold (RMT) and central motor conduction time (CMCT) in 18 patients with Wilson's disease (WD). The RMT, CMCT, and Global Assessment Scale for Wilson Disease (GAS-WD) were measured at baseline and at follow-up after 12.94 ± 7.23 months. There was a significant decrease in the RMT (72.11 ± 18.62 vs. 63.7 ± 15.52%; p-value = 0.002) and GAS-WD scores (14.38 ± 5.35 vs. 9.77 ± 6.47 ms; p-value = 0.04). CMCT did not improve despite chelation therapy. Hence, RMT may serve as a marker of chelation efficacy in WD.

Factors Affecting and Adjustments for Sex Differences in Current Perception Threshold With Transcutaneous Electrical Stimulation in Healthy Subjects.

OBJECTIVE: Current perception threshold (CPT) measurement is a noninvasive, easy, and semi-objective method for determining sensory function using transcutaneous electrical stimulation. Previous studies have shown that CPT is determined by physical characteristics, such as sex, age, physical sites, and presence of neuropathy. Although the CPT reported in males is clearly higher than that in females, the reason for this difference remains unclear. This study investigates the cause of sex-based differences in CPT and suggests an adjustment method, which may suppress the sex difference in CPT. MATERIALS AND METHODS: Electrical stimulation was applied with PainVision® via five sizes of circular surface electrodes. Seventy healthy participants were examined thrice under each electrode. The relationship among body water percentage, body fat percentage, and CPT was then analyzed. RESULTS: CPT values are higher in males than that in females, with statistically significant sex differences with each electrode pairs (EL 1: p < 0.001; EL 2: p = 0.006; EL 3: p < 0.001; EL 4: p < 0.001; EL 5: p < 0.001). By adjusting for body fat percentage or body water percentage, the log-transformation values (CPT values) no longer exhibit sex differences with any electrode pairs (body fat: p = 0.09; body water: p = 0.08). CONCLUSION: We conclude that sensitivity for perceiving electrical stimulation can be influenced by the subjects' characteristics, such as body fat or body water percentages.

Stochastic resonance stimulation improves balance in children with cerebral palsy: a case control study.

BACKGROUND: Stochastic Resonance (SR) Stimulation has been used to enhance balance in populations with sensory deficits by improving the detection and transmission of afferent information. Despite the potential promise of SR in improving postural control, its use in individuals with cerebral palsy (CP) is novel. The objective of this study was to investigate the immediate effects of electrical SR stimulation when applied in the ankle muscles and ligaments on postural stability in children with CP and their typically developing (TD) peers. METHODS: Ten children with spastic diplegia (GMFCS level I- III) and ten age-matched TD children participated in this study. For each participant the SR sensory threshold was determined. Then, five different SR intensity levels (no stimulation, 25, 50, 75, and 90% of sensory threshold) were used to identify the optimal SR intensity for each subject. The optimal SR and no stimulation condition were tested while children stood on top of 2 force plates with their eyes open and closed. To assess balance, the center of pressure velocity (COPV) in anteroposterior (A/P) and medial-lateral (M/L) direction, 95% COP confidence ellipse area (COPA), and A/P and M/L root mean square (RMS) measures were computed and compared. RESULTS: For the CP group, SR significantly decreased COPV in A/P direction, and COPA measures compared to the no stimulation condition for the eyes open condition. In the eyes closed condition, SR significantly decreased COPV only in M/L direction. Children with CP demonstrated greater reduction in all the COP measures but the RMS in M/L direction during the eyes open condition compared to their TD peers. The only significant difference between groups in the eyes closed condition was in the COPV in M/L direction. CONCLUSIONS: SR electrical stimulation may be an effective stimulation approach for decreasing postural sway and has the potential to be used as a therapeutic tool to improve balance. Applying subject-specific SR stimulation intensities is recommended to maximize balance improvements. Overall, balance rehabilitation interventions in CP might be more effective if sensory facilitation methods, like SR, are utilized by the clinicians. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02456376; 28 May 2015 (Retrospectively registered); https://clinicaltrials.gov/ct2/show/NCT02456376 .

Characteristics of Stimulus Intensity in Transcutaneous Vagus Nerve Stimulation for Chronic Tinnitus.

OBJECTIVES: We aimed to assess the clinical significance of the intensity of transcutaneous vagus nerve stimulation (tVNS) in chronic tinnitus. MATERIALS AND METHODS: Four sessions of tVNS were performed over a 2-week period for 24 patients with unilateral, non-pulsatile chronic tinnitus. The cavum, cymba, and tragus were sequentially stimulated to the maximal sensory thresholds. One month later, after the four sessions, the level of tinnitus distress and changes in stimulus intensity were assessed. RESULTS: The stimulus intensity did not differ according to sex or laterality. However, a moderate positive correlation between tinnitus distress and the initial stimulus intensity was observed. This correlation was not observed during the subsequent sessions. The stimulus intensity at the cavum changed significantly (p=0.018), and notable differences in tinnitus annoyance were observed between the responders and non-responders (p=0.006). CONCLUSION: The effect of stimulus intensity on the treatment outcome seems to be limited. An increasing trend in the stimulus intensity for tinnitus annoyance at the cavum was observed in the responders. Therefore, the cavum may be an optimal stimulation site for tVNS.

Home-based versus office-based biofeedback therapy for constipation with dyssynergic defecation: a randomised controlled trial.

BACKGROUND: Office-based biofeedback therapy is effective for constipation with dyssynergic defecation, but must be performed by skilled staff, is only available in selected centres, and requires multiple visits. The efficacy of home-based biofeedback therapy is unknown. We compared clinical and subjective outcomes with home-based and office-based approaches. METHODS: In this randomised controlled trial, eligible patients were adult outpatients (age 18-80 years) who met the Rome III criteria for functional constipation and who had been referred to a tertiary-care centre after non-response to routine management, and who had dyssynergic defecation. Patients were randomly assigned according to a schedule generated in advance by the study biostatistician, in permuted blocks of four, to receive office-based or home-based biofeedback therapy. Office-based biofeedback comprised therapist-guided pelvic floor training for six sessions over 3 months (visits every 2 weeks). Home-based biofeedback comprised 20 min self-training sessions twice per day, in which a self-inserted probe was used to provide visual feedback via a handheld monitoring device of anal sphincter pressure and push effort. Patients recorded in diaries the time of each defecation attempt, stool consistency, straining effort, feeling of incomplete evacuation, need for digital assistance with stooling, and satisfaction with bowel function, from 1 week before enrolment to the end of follow-up. Treatment responders were defined post hoc as those with normalisation of dyssynergic defecation and an increase in the number of complete spontaneous bowel movements per week by 3 months. Cost outcomes calculated from health-care costs and loss of salary were assessed from hospital billing and medical records and questionnaires. Primary outcome measures were the presence of a dyssynergic pattern during attempted defecation, balloon expulsion time, the number of complete spontaneous bowel movements per week, and satisfaction with bowel function, assessed by intention to treat (non-inferiority) and per protocol. This trial is registered with ClinicalTrials.gov, number NCT03202771. FINDINGS: Of 300 patients screened we enrolled 100, from Jan 7, 2005, to Jan 31, 2010. 83 patients completed training (38 [76%] of 50 in the home-based biofeedback group and 45 [90%] of 50 in the office-based biofeedback group). 34 (68%) patients in the home-based group and 35 (70%) in the office-based group were classified as responders. All primary outcomes improved significantly from baseline in the two treatment groups (all p<0·0001). Home-based biofeedback therapy was non-inferior to office-based therapy for number of complete spontaneous bowel movements per week, satisfaction with bowel function, and balloon expulsion time in the intention-to-treat and per-protocol analyses, and for dyssynergia in the per-protocol analysis. No adverse events were reported. The median cost of home-based biofeedback therapy was significantly lower than that for office-based treatment (US$1081·70, IQR 794·90-1399·30 vs $1942·50, 1621·70-2369·00, p=0·009). INTERPRETATION: Home-based and office-based biofeedback therapy for dyssynergic defecation improved bowel symptoms and physiology with similar efficacy. A home-based programme could substantially broaden the availability and use of this treatment. FUNDING: National Institutes of Health.

Technical development of transcutaneous electrical nerve inhibition using medium-frequency alternating current.

BACKGROUND: Innovative technical approaches to controlling undesired sensory and motor activity, such as hyperalgesia or spasticity, may contribute to rehabilitation techniques for improving neural plasticity in patients with neurologic disorders. To date, transcutaneous electrical stimulation has used low frequency pulsed currents for sensory inhibition and muscle activation. Yet, few studies have attempted to achieve motor nerve inhibition using transcutaneous electrical stimulation. This study aimed to develop a technique for transcutaneous electrical nerve inhibition (TENI) using medium-frequency alternating current (MFAC) to suppress both sensory and motor nerve activity in humans. METHODS: Surface electrodes were affixed to the skin of eight young adults to stimulate the median nerve. Stimulation intensity was increased up to 50% and 100% of the pain threshold. To identify changes in sensory perception by transcutaneous MFAC (tMFAC) stimulation, we examined tactile and pressure pain thresholds in the index and middle fingers before and after stimulation at 10 kHz. To demonstrate the effect of tMFAC stimulation on motor inhibition, stimulation was applied while participants produced flexion forces with the index and middle fingers at target forces (50% and 90% of MVC, maximum voluntary contraction). RESULTS: tMFAC stimulation intensity significantly increased tactile and pressure pain thresholds, indicating decreased sensory perception. During the force production task, tMFAC stimulation with the maximum intensity immediately reduced finger forces by ~ 40%. Finger forces recovered immediately after stimulation cessation. The effect on motor inhibition was greater with the higher target force (90% MVC) than with the lower target (50% MVC). Also, higher tMFAC stimulation intensity provided a greater inhibition effect on both sensory and motor nerve activity. CONCLUSION: We found that tMFAC stimulation immediately inhibits sensory and motor activity. This pre-clinical study demonstrates a novel technique for TENI using MFAC stimulation and showed that it can effectively inhibit both sensory perception and motor activity. The proposed technique can be combined with existing rehabilitation devices (e.g., a robotic exoskeleton) to inhibit undesired sensorimotor activities and to accelerate recovery after neurologic injury.

Comparison of Electroacupuncture and Mild-Warm Moxibustion on Brain-Gut Function in Patients with Constipation-Predominant Irritable Bowel Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To compare the effects of electroacupuncture (EA) and mild-warm moxibustion (Mox) therapies for constipation-predominant irritable bowel syndrome (C-IBS) patients. METHODS: Sixty C-IBS patients were assigned to 2 groups by simple randomized method, i.e. EA group (30 cases) and Mox group (30 cases). Both EA and Mox treatments were performed on bilateral Tianshu (ST 25) and Shangjuxu (ST 37) for 30 min each time, 6 times per week, for 4 consecutive weeks. The gastrointestinal symptoms and psychological symptoms of the two groups were scored before and after treatment. The effects on the corresponding functional brain areas, namely the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging (fMRI) before and after treatment. RESULTS: Compared with the Mox group, greater improvements in abdominal distension, defecation frequency, diffificulty in defecation and stool features were observed in the EA group (all P<0.01), both Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores were signifificantly decreased in the EA group (all P<0.01). Finally, decreased activated voxel values were observed in the ACC, right IC and PFC brain regions of EA group with 150 mL colorectal distension stimulation (P<0.05 or P<0.01). CONCLUSIONS: Both EA and Mox could signifificantly improve some of the most intrusive symptoms of C-IBS patients, and EA was more effective than Mox. The therapeutic effect of these two therapies might through modulating of the brain-gut axis function. (Registration No. ChiCTRTRC-11001349).