Cutaneous Electrical Stimulation Research Articles

Posttraumatic headache: pain related evoked potentials (PREP) and conditioned pain modulation (CPM) to assess the pain modulatory function

Posttraumatic headache (PTH) is common following traumatic brain injury and impacts quality of life. We investigated descending pain modulation as one possible mechanism for PTH and correlated it to clinical measures. Pain-related evoked potentials (PREP) were recorded in 26 PTH-patients and 20 controls after electrical stimulation at the right hand and forehead with concentric surface electrodes. Conditioned pain modulation (CPM) was assessed using painful cutaneous electric stimulation (PCES) on the right hand as test stimulus and immersion of the left hand into 10 °C-cold water bath as conditioning stimulus based on changes in pain intensity and in amplitudes of PCES-evoked potentials. All participants completed questionnaires assessing depression, anxiety, and pain catastrophising. PTH-patients reported significantly higher pain ratings during PREP-recording in both areas despite similar stimulus intensity at pain threshold. N1P1-amplitudes during PREP and CPM-assessment were lower in patients in both areas, but statistically significant only on the hand. Both, PREP-N1-latencies and CPM-effects (based on the N1P1-amplitudes and pain ratings) were similar in both groups. Patients showed significantly higher ratings for anxiety and depression, which did not correlate with the CPM-effect. Our results indicate generalized hyperalgesia for electrical stimuli in both hand and face in PTH. The lacking correlation between pain ratings and EEG parameters indicates different mechanisms of pain perception and nociception.

A Study of the Effect of Cutaneous Electric Stimulation on the Structure of The Anal Sphincter of Rat After Induction of Anal Muscle Injury

A Study of the Effect of Cutaneous Electric Stimulation on the Structure of The Anal Sphincter of Rat After Induction of Anal Muscle Injury

Long-term bilateral change in pain and sensitivity to high-frequency cutaneous electrical stimulation in healthy subjects depends on stimulus modality: a dermatomal examination.

Contradictory changes in pain and sensitivity at long-term following cutaneous 100 Hz high frequency stimulation (HFS) have been previously observed. Thus, we aimed to document long-lasting changes in multimodal sensitivity following HFS, and factors influencing them. Long-lasting changes were assessed with mechanical [brush, von Frey filament (588.2 mN)] and thermal [heat (40°C)/cold (25°C)] bedside sensory testing, and electrical TS (0.2 ms single electrical stimuli), at the homotopic (ipsilateral C6 dermatome), adjacent heterotopic (ipsilateral C5 and C7 dermatomes) and contralateral (contralateral C6 dermatomes) dermatomal sites in a single testing session. TS were applied before and after application of 100 Hz HFS at the ipsilateral C6 dermatome. Subjects rated their sensation and pain intensity to TS, and completed questionnaires related to pain descriptors and quality of life. Long-lasting changes in mechanical and cold sensitivity was detected up to 45 min after HFS at homotopic C6 dermatome, and a temporary increase in cold sensitivity at 20 min in the contralateral C6 dermatome (p < 0.05). A slow development of bilateral depotentiation to electrical pain TS was also detected from 40 min after HFS (p < 0.05). Higher HFS-induced mechanical and cold sensitivity was identified in women (p < 0.05). Age and quality of life were associated with pain intensity (p < 0.05). Long-term unilateral and bilateral changes in sensation and pain following electrical HFS have been found. These findings may suggest a new insight into the development of persistent pain mechanisms. Further studies are now needed.

Peripheral nerves' function recovery by intratissual electric stimulation

To evaluate the time and quality of peripheral nerves' functions recovery after their suturing and conducting two different methods of electrical stimulation, namely intratissual and cutaneous, in projection of central neurons of damaged spinal nerves in the postoperative period. The basic technical parameters of the method of peripheral nerves' functions recovery in the postoperative period were ptacticed. Postoperative rehabilitation treatment was performed in 77 patients with traumatic peripheral nerves' injuries at the level of the forearm: in 42 with intratissual electrical stimulation, in 35 - using cutaneous one with similar characteristics of electrical current and concomitant pharmacological therapy. The follow-up duration was 2 years. A significant (in 4-6 times) reduction in time of treatment and a greater improvement in qualitative indicators when using intratissual electrical stimulation compared to the use of cutaneous stimulation were obtained. The effectiveness of the restorative therapy was dependent on the number of procedures, and a complete recovery of the damaged peripheral nerves' functions was observed after three courses of intratissual electrical stimulation. The time and degree of recovery of peripheral nerves' functions depends on the functional activity of their central neurons at the level of the spinal cord. The activation of these neurons by low-frequency electrical current allows to activate their trophic function. Thus, the cutaneous electrical stimulation does not cause the necessary level of irritation of the neurons due to the fact that the skin is a barrier to electrical current, which reduces its impact in 200-500 times. The intratissual electrical stimulation allows to solve the problem by supplying the needle-electrode much closer to the «target». The proposed method of intratissual electrical stimulation has shown its advantage over cutaneous electrical stimulation, significantly reducing the duration of the restorative treatment and increasing its qualitative indicators.

ID: 198229 Improved Spasticity With Use of Suprascapular Peripheral Nerve Stimulator in Post-Stroke Shoulder Pain

Spasticity, weakness, and pain of affected extremities is common in post stroke patients. There are several treatment modalities that can target each of these. Treatment of spasticity can be pursued with noninvasive (stretching, casting, medications) or invasive (Botox injections, intrathecal baclofen) options [1]. There is literature supporting effect of cutaneous electrical stimulation on spasticity but there is a lack of literature pertaining to implanted stimulators [2]. SPRINT peripheral nerve stimulation is effective in the treatment of hemiplegic poststroke shoulder pain and is the earliest studied and most widely accepted application for PNS technology [3, 4, 5, 6].

Characterization of vagus nerve stimulation-induced pupillary responses in epileptic patients

BackgroundModulation of the locus coeruleus (LC)-noradrenergic system is a key mechanism of vagus nerve stimulation (VNS). Activation of the LC produces pupil dilation, and the VNS-induced change in pupil diameter was demonstrated in animals as a possible dose-dependent biomarker for treatment titration. ObjectiveThis study aimed to characterize VNS-induced pupillary responses in epileptic patients. MethodsPupil diameter was recorded in ten epileptic patients upon four stimulation conditions: three graded levels of VNS intensity and a somatosensory control stimulation (cutaneous electrical stimulation over the left clavicle). For each block, the patients rated the intensity of stimulation on a numerical scale. We extracted the latency of the peak pupil dilation and the magnitude of the early (0–2.5 s) and late components (2.5–5 s) of the pupil dilation response (PDR). ResultsVNS elicited a peak dilation with longer latency compared to the control condition (p = 0.043). The magnitude of the early PDR was significantly correlated with the intensity of perception (p = 0.046), whereas the late PDR was not (p = 0.19). There was a significant main effect of the VNS level of intensity on the magnitude of the late PDR (p = 0.01) but not on the early PDR (p = 0.2). The relationship between late PDR magnitude and VNS intensity was best fit by a Gaussian model (inverted-U). ConclusionsThe late component of the PDR might reflect specific dose-dependent effects of VNS, as compared to control somatosensory stimulation. The inverted-U relationship of late PDR with VNS intensity might indicate the engagement of antagonist central mechanisms at high stimulation intensities.

Shared mechanisms of auditory and non-auditory vocal learning in the songbird brain.

Songbirds and humans share the ability to adaptively modify their vocalizations based on sensory feedback. Prior studies have focused primarily on the role that auditory feedback plays in shaping vocal output throughout life. In contrast, it is unclear how non-auditory information drives vocal plasticity. Here, we first used a reinforcement learning paradigm to establish that somatosensory feedback (cutaneous electrical stimulation) can drive vocal learning in adult songbirds. We then assessed the role of a songbird basal ganglia thalamocortical pathway critical to auditory vocal learning in this novel form of vocal plasticity. We found that both this circuit and its dopaminergic inputs are necessary for non-auditory vocal learning, demonstrating that this pathway is critical for guiding adaptive vocal changes based on both auditory and somatosensory signals. The ability of this circuit to use both auditory and somatosensory information to guide vocal learning may reflect a general principle for the neural systems that support vocal plasticity across species.

Flexible Conducting Polymer Electrodes for Selective Stimulation of Small Sensory Fibers in Humans

AbstractSmall‐fiber neuropathy (SFN), a pathology caused by severe loss of free‐endings of unmyelinated sensory nerves, is difficult to diagnose and monitor. The use of cutaneous electrical stimulation as a diagnostic tool is hampered by the fact that the injected current penetrates deep into the skin and stimulates many other receptors. Interdigitated electrodes are recently proposed to control the depth of current penetration and selectively address small‐fibers. Here, flexible and adhesive interdigitated electrodes made of Au coated with poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) are developed, that conform comfortably and reliably to human skin. It is shown that the PEDOT:PSS coating improves safety by significantly reducing the voltage required to inject current. The selectivity of the device is assessed by showing that it elicits a significantly slower reaction time than commercial cutaneous electrophysiology electrodes, as it exclusively activates unmyelinated fibers. The device is further evaluated on volunteers that undergo local capsaicin treatment to induce temporary loss of the nerve endings of small‐fibers. Pre‐ and post‐treatment electrical stimulation of the affected area with the device reveals impaired sensory detection that is not observed with commercial cutaneous electrophysiology electrodes. These results represent a significant step towards the use of electrical stimulation as a diagnostic and monitoring tool for SFN.

Location-specific cutaneous electrical stimulation of the footsole modulates corticospinal excitability to the plantarflexors and dorsiflexors during standing.

Non‐noxious electrical stimulation to distinct locations of the foot sole evokes location‐specific cutaneous reflex responses in lower limb muscles. These reflexes occur at latencies that may enable them to be mediated via a transcortical pathway. Corticospinal excitability to the plantarflexors and dorsiflexors was measured in 16 participants using motor evoked potentials (MEPs). Spinal excitability was measured in eight of the original participants using cervicomedullary motor evoked potentials (CMEPs). Measurements were collected with and without preceding cutaneous stimulus to either the heel (HEEL) or metatarsal (MET) locations of the foot sole, and evoked potentials were elicited to coincide with the arrival of the cutaneous volley at either the motor cortex or spinal cord. Plantarflexor MEPs and CMEPs were facilitated with cutaneous stimulation to the HEEL for MEPs (soleus p = 0.04, medial gastrocnemius (MG) p = 0.017) and CMEPs (soleus p = 0.047 and MG p = 0.015), but they were unchanged following MET stimulation for MEPs or CMEPs. Dorsiflexor MEPs were unchanged with cutaneous stimulation at either location, but dorsiflexor CMEPs increased with cutaneous stimulation (p = 0.05). In general, the increase in CMEP amplitudes was larger than the increase in MEP amplitudes, indicating that an increase in spinal excitability likely explains most of the increase in corticospinal excitability. The larger change observed in the CMEP also indicates that excitability from supraspinal sources likely decreased, which could be due to a net change in the excitability of intracortical circuits. This study provides evidence that cutaneous reflexes from foot sole skin are likely influenced by a transcortical pathway.

P 17 Posttraumatic Headache – Pain Related Evoked Potentials (PREP) and Conditioned Pain Modulation (CPM) as possible biomarkers for identification of risk patients

Introduction : Posttraumatic headache (PTH) is one of the most common complications following traumatic brain injury (TBI)[1], though its underlying pathomechanisms have not been fully understood yet. An altered descending pain modulation seems to contribute to its development and persistence[2]. The aim of our study was to examine the pain processing in PTH-patients using pain-related evoked potentials after electrical stimulation (PREP) and conditioned pain modulation (CPM), based on their N1P1-amplitude as an objective readout. We chose a longitudinal design to analyse if PREP and CPM can be used as biomarkers for persisting PTH. Methods : We plan to recruit 30 patients with PTH and 20 healthy control subjects. Currently (October 2021) we have recruited 21 PTH-patients and 19 healthy control subjects. The patients were invited for follow-up sessions at 3 and 6 months after inclusion. The painful stimuli were applied at the dorsum of the right hand and above the right eyebrow with a concentric surface electrode while PREP were recorded over Cz and evoked pain was assessed on the numerical rating scale (NRS), as previously described [3]. For CPM we used the same electrode for painful cutaneous electric stimulation on the right hand as the test stimulus and the immersion of the left hand in a 10°C cold water bath as the conditioning stimulus. With the assessed data we calculated early and late CPM-effects for the subjective pain ratings and the objective N1-P1-amplitudes in the EEG, as recently reported[4]. Results : PTH-patients were on average 41.3 (± 10.7) years old, had a mean headache duration of 103 (± 265) weeks and a mean headache intensity of 5.9 (± 1.9) on the NRS (0-10). We currently present data at baseline. PREP parameters in both regions did not differ between PTH-patients and age-matched controls. The early CPM-effect based on PREP-amplitudes and the late CPM effect based on pain-rating were significantly less pronounced in patients than in controls. The early and late CPM effect for pain and amplitudes correlated significantly in both groups, but no significant correlation comparing CPM effects based on pain with the CPM effects based on amplitudes could be detected. Conclusions : Our preliminary results display a deficient endogenous pain modulation in PTH-patients also based on PREP-amplitude as an objective readout. The missing correlation between CPM-effects based on subjective pain ratings and PREP-amplitudes indicate different pathways involved in nociception and subjective pain perception. Further analysis of subgroups is planned after complete recruitment.

Distraction by a cognitive task has a higher impact on electrophysiological measures compared with conditioned pain modulation

BackgroundConditioned pain modulation (CPM) evaluates the effect of a painful conditioning stimulus (CS) on a painful test stimulus (TS). Using painful cutaneous electrical stimulation (PCES) as TS and painful cold water as CS, the pain relief was paralleled by a decrease in evoked potentials (PCES-EPs). We now aimed to compare the effect of CPM with cognitive distraction on PCES-induced pain and PCES-EP amplitudes.MethodsPCES was performed using surface electrodes inducing a painful sensation of 60 (NRS 0–100) on one hand. In a crossover design healthy subjects (included: n = 38, analyzed: n = 23) immersed the contralateral hand into 10 °C cold water (CS) for CPM evaluation and performed the 1-back task for cognitive distraction. Before and during the CS and 1-back task, respectively, subjects rated the pain intensity of PCES and simultaneously cortical evoked potentials were recorded.ResultsBoth CPM and cognitive distraction significantly reduced PCES-EP amplitudes (CPM: 27.6 ± 12.0 μV to 20.2 ± 9.5 μV, cognitive distraction: 30.3 ± 14.2 µV to 13.6 ± 5.2 μV, p < 0.001) and PCES-induced pain (on a 0–100 numerical rating scale: CPM: 58 ± 4 to 41.1 ± 12.3, cognitive distraction: 58.3 ± 4.4 to 38.0 ± 13.0, p < 0.001), though the changes in pain intensity and PCES-amplitude did not correlate. The changes of the PCES-EP amplitudes during cognitive distraction were more pronounced than during CPM (p = 0.001).ConclusionsCPM and cognitive distraction reduced the PCES-induced pain to a similar extent. The more pronounced decrease of PCES-EP amplitudes after distraction by a cognitive task implies that both conditions might not represent the general pain modulatory capacity of individuals, but may underlie different neuronal mechanisms with the final common pathway of perceived pain reduction.

Painful Cutaneous Electrical Stimulation vs. Heat Pain as Test Stimuli in Conditioned Pain Modulation.

Different paradigms can assess the effect of conditioned pain modulation (CPM). The aim of the present study was to compare heat pain, as an often used test stimulus (TS), to painful cutaneous electrical stimulation (PCES), having the advantage of the additional recording of PCES-related evoked potentials. In 28 healthy subjects we applied heat and PCES at the dominant hand as test stimulus (TS) to compare the CPM-effect elicited by hand immersion into cold water (10 °C) as conditioning stimulus (CS). Subjects rated the pain intensity of TS at baseline, during and 5 min after CS application and additionally of CS, on a numerical rating scale (NRS) (0–100). The ‘early’ (during CS–before CS) and ‘late’ (after CS–before CS) CPM-effects were analyzed. Parallel to the PCES, the related evoked potentials were recorded via Cz to evaluate any changes in PCES-amplitudes. CS reduced significantly the pain intensity of both PCES and heat pain as TS. On a group level, the CPM-effect did not differ significantly between both paradigms. Both early and late CPM-effect based on PCES correlated significantly with the CS pain intensity (r = −0.630 and −0.503, respectively), whereas using heat pain the correlation was not significant. We found a significant reduction of PCES-amplitudes during CS, but this did not correlate with the PCES-induced pain intensity. Correlation with the CS painfulness (r = −0.464) did not achieve the significance level after Bonferroni correction. The extent of the CPM effects was similar in both testing paradigms at group level, despite intraindividual differences. Future studies should further elicit the exact mechanisms explaining the modality of these specific differences.

Effects of transcutaneous electrical nerve stimulation (TENS) on spasticity in patients with hemiplegia.

The effect of afferent cutaneous electrical stimulation on the spasticity of leg muscles was studied in 20 patients with chronic hemiplegia after stroke. Stimulation electrodes were placed over the sural nerve of the affected limb. The standard method of cutaneous stimulation, TENS with impulse frequency of 100 Hz, was applied. The tonus of the leg muscles was measured by means of an electrohydraulic measuring brace. The EMG stretch reflex activity of the tibialis anterior and triceps surae muscles was detected by surface electrodes and recorded simultaneously with the measured biomechanical parameters. In 18 out of 20 patients, a mild but statistically significant decrease in resistive torques at all frequencies of passive ankle movements was recorded following 20 min of TENS application. The decrease in resistive torque was often (but not always) accompanied by a decrease in reflex EMG activity. This effect of TENS persisted up to 45 min after the end of TENS. The results of the study support the hypothesis that TENS applied to the sural nerve may induce short-term post-stimulation inhibitory effects on the abnormally enhanced stretch reflex activity in spasticity of cerebral origin.

Exposure to Odors Increases Pain Threshold in Chronic Low Back Pain Patients.

Structured exposure to odors is an acknowledged therapy in patients with smell loss but has also been shown to be effective in depression. The latter might rely on connections between olfactory and emotional structures, suggesting possible effects of a similar approach in pain patients. Based on neuroanatomy, there are several interfaces between the "pain matrix" and olfactory system, such as the limbic system, hypothalamus, and mediodorsal thalamus. We aimed to investigate whether structured exposure to odors may impact perceived pain in patients with chronic low back pain. Randomized controlled parallel-group design. Subjects were tested on two occasions, at baseline and after four weeks. Ambulatory. Forty-two patients with chronic low back pain. For all patients, olfactory function (using the "Sniffin'Sticks" test kit), detection, and pain thresholds for cutaneous electrical stimuli (applied to the forearm) were tested at baseline and after four weeks. Twenty-eight patients exposed themselves to four odors (rose, vanilla, chocolate, peach) every two hours over a period of four weeks (training group). Control patients (N = 14) underwent no such "olfactory training" (nontraining group). Pain thresholds were significantly increased in patients who performed olfactory training compared with patients who did not train with odors. Detection thresholds and olfactory function remained unchanged. The present results indicate that regular exposure to odors increases pain thresholds in patients with chronic back pain and could be useful for general pain control in these patients. Furthermore, olfactory training in chronic pain patients might help to reduce chronification of pain by desensitization.

Qualifying tactile sensations evoked by non-steady cutaneous electrical stimulation with electroencephalography features

Purpose This paper aims to investigate whether electroencephalography (EEG) technology is effective in qualifying the tactile sensation evoked by non-steady cutaneous electrical stimulation. EEG is a novel method for electrotactile analysis and has demonstrated the discrimination ability for electrotactile sensation under steady contact conditions in recent years. However, in non-steady contact conditions, it is necessary to test its effectiveness. This study aims to explore an objective analysis method in comparison to psychophysical approach and to provide a methodology for non-steady electrotactile research. Design/methodology/approach With EEG experimentation on 13 volunteers, the authors collected evoked potentials by the predesigned “1” and “0” stimulation events. In addition, with a series of data preprocessing including artifact elimination, band-pass filtering, baseline normalization, data superposition and fast Fourier transform transformation, the authors got the power spectrum of alpha, beta and gamma rhythms. Furthermore, statistics analysis and ANOVA test were adopted for exploring the discrepancy of the spectrum characterizations for different non-steady electrostimulation events. Findings The EEG power spectrum of the central cortical brain is valuable in discriminating the two types of stimulation events. The power of alpha rhythm especially in the central cortical brain evoked by event “1,” whose current level is equal to the threshold, was significantly lower than that evoked by event “0,” whose level is less than the threshold (p &lt; 0.05). Then, the power of the beta rhythm presented counter-change (p &lt; 0.05). This study suggests that EEG may have the potential to qualify non-steady electrotactile sensation for engineering applications. Research limitations/implications Limiting factors of non-steady electrotactile stimulation were considered in this study. Different tapping frequency and contact time should be investigated in future studies. Originality/value This paper fulfills a challenge in qualifying the tactile sensations evoked by non-steady electrical stimulation with EEG characteristics.

The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation.

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n = 5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n = 4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes, and Actinobacteria, which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.

Enhanced somatosensory feedback modulates cutaneous reflexes in arm muscles during self-triggered or prolonged stimulation.

Somatosensory feedback plays important roles in regulating all animal movement. The effects of sensory feedback on spinally mediated neural excitability are widely studied using cutaneous electrical stimulation paradigms. Cutaneous reflex amplitudes are reduced when stimulation is self-triggered instead ofexternally triggered. Altered spinal excitability and motor output are also observed following sustained stimulation with various parameters. Our purpose was to probe for interactions between mode and duration by investigating muscle responses following enhanced cutaneous stimulation. Fifteen neurologically intact participants were recruited. Cutaneous reflexes in the extensor carpi radialis (ECR) were evoked with brief (15ms, 300Hz) or sustained (300ms, 50Hz) stimulation trains. Stimulation was applied to the superficial radial or median nerve at the wrist and triggered by: (1) a computer program (random-triggered); (2) muscle contraction (EMG-triggered); (3) the participant pressing a button themselves (button-triggered). During each condition, isometric contractions were performed with ECR muscle activity maintained at 10, 25, 35, and 50% of maximal voluntary contraction. Stronger inhibitory reflexes were found following brief superficial radial nerve stimulation was EMG-triggered suggesting that modulation of cutaneous reflex excitability is specific to the timing when sensory 'cues' are applied during muscle contraction. No difference was observed following sustained stimulation applied to the superficial radial nerve meaning that brief and sustained stimulation affect the cutaneous pathways differentially. Nerve-specific responses were found between superficial radial and median nerve stimulation, such that greater inhibition was induced by EMG-triggered sustained stimulation to the median nerve. These observations are critical in moving beyond pathway phenomenology toward targeted sensory enhancement and amplified motor output in rehabilitation and training.

Safety and efficacy of sphenopalatine ganglion stimulation for chronic cluster headache: a double-blind, randomised controlled trial

Chronic cluster headache is the most disabling form of cluster headache. The mainstay of treatment is attack prevention, but the available management options have little efficacy and are associated with substantial side-effects. In this study, we aimed to assess the safety and efficacy of sphenopalatine ganglion stimulation for treatment of chronic cluster headache. We did a randomised, sham-controlled, parallel group, double-blind, safety and efficacy study at 21 headache centres in the USA. We recruited patients aged 22 years or older with chronic cluster headache, who reported a minimum of four cluster headache attacks per week that were unsuccessfully controlled by preventive treatments. Participants were randomly assigned (1:1) via an online adaptive randomisation procedure to either stimulation of the sphenopalatine ganglion or a sham control that delivered a cutaneous electrical stimulation. Patients and the clinical evaluator and surgeon were masked to group assignment. The primary efficacy endpoint, which was analysed with weighted generalised estimated equation logistic regression models, was the difference between groups in the proportion of stimulation-treated ipsilateral cluster attacks for which relief from pain was achieved 15 min after the start of stimulation without the use of acute drugs before that timepoint. Efficacy analyses were done in all patients who were implanted with a device and provided data for at least one treated attack during the 4-week experimental phase. Safety was assessed in all patients undergoing an implantation procedure up to the end of the open-label phase of the study, which followed the experimental phase. This trial is registered with ClinicalTrials.gov, number NCT02168764. Between July 9, 2014, and Feb 14, 2017, 93 patients were enrolled and randomly assigned, 45 to the sphenopalatine ganglion stimulation group and 48 to the control group. 36 patients in the sphenopalatine ganglion stimulation group and 40 in the control group had at least one attack during the experimental phase and were included in efficacy analyses. The proportion of attacks for which pain relief was experienced at 15 min was 62·46% (95% CI 49·15-74·12) in the sphenopalatine ganglion stimulation group versus 38·87% (28·60-50·25) in the control group (odds ratio 2·62 [95% CI 1·28-5·34]; p=0·008). Nine serious adverse events were reported by the end of the open-label phase. Three of these serious adverse events were related to the implantation procedure (aspiration during intubation, nausea and vomiting, and venous injury or compromise). A fourth serious adverse event was an infection that was attributed to both the stimulation device and the implantation procedure. The other five serious adverse events were unrelated. There were no unanticipated serious adverse events. Sphenopalatine ganglion stimulation seems efficacious and is well tolerated, and potentially offers an alternative approach to the treatment of chronic cluster headache. Further research is need to clarify its place in clinical practice. Autonomic Technologies.

Distilling the essence of TMS-evoked EEG potentials (TEPs): A call for securing mechanistic specificity and experimental rigor

Distilling the essence of TMS-evoked EEG potentials (TEPs): A call for securing mechanistic specificity and experimental rigor

Motor Action Execution in Reaction-Time Movements: Magnetoencephalographic Study.

Reaction-time movements are internally planned in the brain. Presumably, proactive control in reaction-time movements appears as an inhibitory phase preceding movement execution. We identified the brain activity of reaction-time movements in close proximity to movement onset and compared it with similar self-paced voluntary movements without external command. We recorded 18 healthy participants performing reaction-time and self-paced fast index finger abductions with 306-sensor magnetoencephalography and electromyography. Reaction-time movements were performed as responses to cutaneous electrical stimulation delivered on the hand radial nerve area. Motor field and movement-evoked field 1 corresponding to the sensorimotor cortex activity during motor execution and afferent feedback after the movement were analyzed with Brainstorm's scouts using regions of interest analysis. Primary motor and somato sensory cortices were active before and after movement onset. During reaction-time movements, primary motor and somato sensory cortices showed higher activation compared with self-paced movements. In primary motor cortex, stronger preparatory activity was seen in self-paced than in reaction time task. Both primary motor and somato sensory cortices participated in the movement execution and in the prediction of sensory consequences of movement. Cutaneous stimulation facilitated cortical activation during motor field after reaction-time movements, implying the applicability of cutaneous stimulation in motor rehabilitation.