Investigation of directional discrimination in the nociceptive system using temperature-controlled laser stimuli.

BACKGROUND: Cutaneous laser stimulation has commonly been employed to investigate the thermal properties of the nociceptive system. The aim of this study was to investigate how a temperature-controlled laser system improves the assessment of directional discrimination in the nociceptive system. METHODS: In total, twenty healthy volunteers participated in this study. To determine the directional discrimination threshold (stimulation length 50% correct, expressed in mm), thermal stimuli were delivered using a diode laser and the laser beam was perpendicularly displaced across the skin to give a linear stimulation in four different directions (distal, proximal, lateral and medial) and displacement lengths (3 for lateral-medial and 5 for distal-proximal). Two temperature control modes were used in the stimulation system, open-loop and closed-loop control. The subjects had to report the perceived stimulus direction, the degree of certainty regarding the perceived direction and the intensity of the perceived stimulus (0-10 numerical rating scale, 3: pain threshold). RESULTS: During closed-loop control, the orientation of stimuli was discriminated significantly more accurately than during open-loop control. During closed-loop control, the directional discrimination threshold was 31.9 and 26.1 mm for distal-proximal and lateral-medial directed stimuli, respectively. A numerical rating scale was significantly higher for the lateral/medial directions. Moreover, the variability of the discrimination threshold is reduced in the closed-loop control system. CONCLUSIONS: The findings show that discrimination ability is better in the lateral-medial directions compared to the distal-proximal directions. This study indicates that using a system enabling closed-loop temperature control, allows more robust probing of the temporo-spatial mechanisms in the nociceptive system. SIGNIFICANCE: This study shows that a newly developed temperature-controlled laser stimulation system enhances the possibilities to investigate the nociceptive temporo-spatial integration, as shown by a less variable directional discrimination threshold. The results also show that different orthogonal directions are discriminated differently. This new method allows a better investigation of the combined temporal and spatial mechanisms in the nociceptive system.

Effects of Background Noise and Linguistic Violations on Frontal Theta Oscillations During Effortful Listening.

OBJECTIVES: Background noise and linguistic violations have been shown to increase the listening effort. The present study aims to examine the effects of the interaction between background noise and linguistic violations on subjective listening effort and frontal theta oscillations during effortful listening. DESIGN: Thirty-two normal-hearing listeners participated in this study. The linguistic violation was operationalized as sentences versus random words (strings). Behavioral and electroencephalography data were collected while participants listened to sentences and strings in background noise at different signal to noise ratios (SNRs) (-9, -6, -3, 0 dB), maintained them in memory for about 3 sec in the presence of background noise, and then chose the correct sequence of words from a base matrix of words. RESULTS: Results showed the interaction effects of SNR and speech type on effort ratings. Although strings were inherently more effortful than sentences, decreasing SNR from 0 to -9 dB (in 3 dB steps), increased effort rating more for sentences than strings in each step, suggesting the more pronounced effect of noise on sentence processing that strings in low SNRs. Results also showed a significant interaction between SNR and speech type on frontal theta event-related synchronization during the retention interval. This interaction indicated that strings exhibited higher frontal theta event-related synchronization than sentences at SNR of 0 dB, suggesting increased verbal working memory demand for strings under challenging listening conditions. CONCLUSIONS: The study demonstrated that the interplay between linguistic violation and background noise shapes perceived effort and cognitive load during speech comprehension under challenging listening conditions. The differential impact of noise on processing sentences versus strings highlights the influential role of context and cognitive resource allocation in the processing of speech.

Validity and reliability of self-reported and neural measures of listening effort.

Listening effort can be defined as a measure of cognitive resources used by listeners to perform a listening task. Various methods have been proposed to measure this effort, yet their reliability remains unestablished, a crucial step before their application in research or clinical settings. This study encompassed 32 participants undertaking speech-in-noise tasks across two sessions, approximately a week apart. They listened to sentences and word lists at varying signal-to-noise ratios (SNRs) (-9, -6, -3 and 0 dB), then retaining them for roughly 3 s. We evaluated the test-retest reliability of self-reported effort ratings, theta (4-7 Hz) and alpha (8-13 Hz) oscillatory power, suggested previously as neural markers of listening effort. Additionally, we examined the reliability of correct word percentages. Both relative and absolute reliability were assessed using intraclass correlation coefficients (ICC) and Bland-Altman analysis. We also computed the standard error of measurement (SEM) and smallest detectable change (SDC). Our findings indicated heightened frontal midline theta power for word lists compared to sentences during the retention phase under high SNRs (0 dB, -3 dB), likely indicating a greater memory load for word lists. We observed SNR's impact on alpha power in the right central region during the listening phase and frontal theta power during the retention phase in sentences. Overall, the reliability analysis demonstrated satisfactory between-session variability for correct words and effort ratings. However, neural measures (frontal midline theta power and right central alpha power) displayed substantial variability, even though group-level outcomes appeared consistent across sessions.

Phase-locking of Neural Activity to the Envelope of Speech in the Delta Frequency Band Reflects Differences between Word Lists and Sentences.

The envelope of a speech signal is tracked by neural activity in the cerebral cortex. The cortical tracking occurs mainly in two frequency bands, theta (4-8 Hz) and delta (1-4 Hz). Tracking in the faster theta band has been mostly associated with lower-level acoustic processing, such as the parsing of syllables, whereas the slower tracking in the delta band relates to higher-level linguistic information of words and word sequences. However, much regarding the more specific association between cortical tracking and acoustic as well as linguistic processing remains to be uncovered. Here, we recorded EEG responses to both meaningful sentences and random word lists in different levels of signal-to-noise ratios (SNRs) that lead to different levels of speech comprehension as well as listening effort. We then related the neural signals to the acoustic stimuli by computing the phase-locking value (PLV) between the EEG recordings and the speech envelope. We found that the PLV in the delta band increases with increasing SNR for sentences but not for the random word lists, showing that the PLV in this frequency band reflects linguistic information. When attempting to disentangle the effects of SNR, speech comprehension, and listening effort, we observed a trend that the PLV in the delta band might reflect listening effort rather than the other two variables, although the effect was not statistically significant. In summary, our study shows that the PLV in the delta band reflects linguistic information and might be related to listening effort.

A novel temperature-controlled laser system to uniformly activate cutaneous thermal receptors during movable thermal stimulation.

Objective. Laser stimulators have been widely used in pain studies to selectively activate Aδand C nociceptors without coactivation of mechanoreceptors. Temperature-controlled laser systems have been implemented with low-temperature variations during stimulations, however, these systems purely enabled stationary stimulation. This study aimed to implement, test and validate a new laser stimulation system that controls skin temperature by continuously adjusting laser output during stimulus movement to allow accurate investigation of tempo-spatial mechanisms in the nociceptive system.Approach. For validation, laser stimuli were delivered to the right forearm of eight healthy subjects using a diode laser. The laser beam was displaced across the skin to deliver a moving thermal stimulation to the skin surface. To test the function and feasibility of the system, different stimulation parameters were investigated involving two control modes (open-loop and closed-loop), three displacement velocities (5, 10 and 12 mm s-1), two intensities (high 46 °C and low 42 °C), two stimulus lengths (20 and 100 mm) and two directions (distal and proximal).Main results. During closed-loop control, the stimulation error and variation of stimulation temperatures were significantly smaller than during open-loop control. The standard deviation of stimulation temperatures increased significantly with stimulation intensity and displacement length.Significance. This study showed that more accurate, less variable laser stimulations were delivered to the skin using closed-loop control during a movable stimulus. The more uniform skin temperature during stimuli is likely to ensure a more uniform nociceptor activation.

An analytical method to separate modality-specific and nonspecific sensory components of event-related potentials.

Several models have been developed to analyse cortical activity in response to salient events constituted by multiple sensory modalities. In particular, additive models compare event-related potentials (ERPs) in response to stimuli from two or more concomitant sensory modalities with the ERPs evoked by unimodal stimuli, in order to study sensory interactions. In this approach, components that are not specific to a sensory modality are commonly disregarded, although they likely carry information about stimulus expectation and evaluation, attentional orientation and other cognitive processes. In this study, we present an analytical method to assess the contribution of modality-specific and nonspecific components to the ERP. We developed an experimental setup that recorded ERPs in response to four stimulus types (visual, auditory, and two somatosensory modalities to test for stimulus specificity) in three different conditions (unimodal, bimodal and trimodal stimulation) and recorded the saliency of these stimuli relative to the sensory background. Stimuli were delivered in pairs, in order to study the effects of habituation. To this end, spatiotemporal features (peak amplitudes and latencies at different scalp locations) were analysed using linear mixed models. Results showed that saliency relative to the sensory background increased with the number of concomitant stimuli. We also observed that the spatiotemporal features of modality-specific components derived from this method likely reflect the amount and type of sensory input. Furthermore, the nonspecific component reflected habituation occurring for the second stimulus in the pair. In conclusion, this method provides an alternative to study neural mechanisms of responses to multisensory stimulation.

Spinal Nociception is Facilitated during Cognitive Distraction.

The nociceptive withdrawal reflex (NWR) is a behavioral response to protect the body from noxious stimuli. The spatial characteristics of the stimulus modulate the reflex response to prevent damage to the affected tissue. Interneurons in the deep dorsal horn in the spinal cord encode the relationship between stimulus characteristics and the magnitude of the NWR and are also likely integrating spatial information of the nociceptive stimulus. The aim of this study was to use the NWR to investigate whether the spinal spatial integration of a simultaneous stimulus is modulated by shifting the attention of the participant towards (attention) or away from (distraction) the stimulus. We hypothesized that the descending activity shapes the receptive fields of the spinal neurons encoding spatial integration of nociception. Twenty healthy volunteers participated in the study. Single and simultaneous stimuli were delivered through two stimulating electrodes located in the arch and on the lateral side in the sole of the foot. The NWR was quantified by electromyography from the Tibialis Anterior and Biceps Femoris muscles during baseline and active tasks (attention and distraction). During the baseline task, spatial summation of the NWR was evoked during simultaneous stimulation. During the distraction task, the NWR was significantly larger compared to baseline, regardless of the sites being stimulated (single and simultaneous stimuli). In contrast, the NWR recorded during the attention task did not differ from baseline. These results further support that the spinal NWR pathway is under descending control which can be modulated by cognitive processes. The NWRs recorded over both proximal and distal muscles were similarly affected by the tasks, suggesting that the descending control affects the lower leg spinal system, with no discrimination between spinal segments.

Priming of central and peripheral mechanisms with heat and cutaneous capsaicin facilitates secondary hyperalgesia to high-frequency electrical stimulation.

Heat/capsaicin sensitization and electrical high-frequency stimulation (HFS) are well-known models of secondary hyperalgesia, a phenomenon related to chronic pain conditions. This study investigated whether priming with heat/capsaicin would facilitate hyperalgesia to HFS in healthy subjects. Heat/capsaicin priming consisted of a 45°C heat stimulation for 5 min followed by a topical capsaicin patch (4 × 4 cm) for 30 min on the volar forearm of 20 subjects. HFS (100 Hz, 5 times 1 s, minimum 1.5 mA) was subsequently delivered through a transcutaneous pin electrode approximately 1.5 cm proximal to the heat/capsaicin application. Two sessions were applied in a crossover design; traditional HFS (HFS) and heat/capsaicin sensitization followed by HFS (HFS + HEAT/CAPS). Heat pain threshold (HPT), mechanical pain sensitivity (MPS), and superficial blood perfusion were assessed at baseline, after capsaicin removal, and up to 40 min after HFS. MPS was assessed with pin-prick stimulation (128 mN and 256 mN) in the area adjacent to both HFS and heat/capsaicin, distal but adjacent to heat/capsaicin and in a distal control area. HPT was assessed in the area of heat/capsaicin. Higher sensitivity to 128 mN pin-prick stimulation (difference from baseline and control area) was observed in the HFS + HEAT/CAPS session than in the HFS session 20 and 30 min after HFS. Furthermore, sensitivity was increased after HFS + HEAT/CAPS compared with after heat/capsaicin in the area adjacent to both paradigms, but not in the area distal to heat/capsaicin. Results indicate that heat/capsaicin causes priming of the central and peripheral nervous system, which facilitates secondary mechanical hyperalgesia to HFS.NEW & NOTEWORTHY High-frequency electrical stimulation (HFS) and heat/capsaicin sensitization are well-known models of secondary hyperalgesia. The results from the current study indicate that increased sensitivity to 128 mN pin-prick stimulation can be obtained when HFS is delivered following an already established heightened central hyperexcitability provoked by heat/capsaicin sensitization.

Novel surface electrode design for preferential activation of cutaneous nociceptors.

Objective.Small area electrodes enable preferential activation of nociceptive fibers. It is debated, however, whether co-activation of large fibers still occurs for the existing electrode designs. Moreover, existing electrodes are limited to low stimulation intensities, for which behavioral and physiological responses may be considered less reliable. A recent optimization study showed that there is a potential for improving electrode performance and increase the range of possible stimulation intensities. Based on those results, the present study introduces and tests a novel planar concentric array electrode design for small fiber activation in healthy volunteers.Approach.Volunteers received electrical stimulation with the planar concentric array electrode and a regular patch electrode. Perception thresholds (PT) were estimated at the beginning and the end of the experiment. Evoked cortical potentials were recorded in blocks of 30 stimuli. For the patch, stimulation current intensity was set to two times PT, while three intensities, two, five, and ten times PT, were applied with the planar concentric array electrode. Sensation quality, numerical-rating scores, and reaction times were obtained for each PT estimation and during each block of evoked potential recordings.Main results.Stimulation with the patch electrode was characterized as dull, while stimulation with the planar concentric array electrode was characterized as sharp, with increased sharpness for increasing stimulus current intensity. Likewise, scores of the numerical rating scale were higher for the planar concentric array electrode compared to the patch and increased with increasing stimulation current intensity. Reaction times and ERP latencies were longer for the planar concentric array electrode compared to the patch.Significance.The presented novel planar concentric array electrode is a small, non-invasive, and single-use electrode that has the potential to investigate small fiber neuropathy and pain mechanisms, as it is small fiber preferential for a wide range of stimulation intensities.

Evaluation of rest-activity cycles in patients with severe acquired brain injury: an observational study.

BACKGROUND: There is little knowledge about rest-activity cycles (RAC) in patients with severe-acquired brain injury (sABI) during early in-hospital rehabilitation. This study aimed to investigate if patients with sABI displayed unconsolidated RACs at the beginning of in-hospital rehabilitation, and how these changed over time. METHODS: This study was a prospective observational study. All patients consecutively admitted to one ward were screened for eligibility. We recorded accelerometric activity for 20 days. The Daytime Activity Ratio (DAR) of activity between daytime (7-22) and the total activity during the entire day was calculated and used to estimate consolidation. RESULTS: Fifty-five patients were screened and 20 patients were included. Complete day 1 & 2 data was obtained on 18 patients. Fifty-six percentage of these had a consolidated RAC at the beginning of rehabilitation. On day 19 & 20, complete data could be obtained from 15 patients, 80% of these had consolidation of RAC. When comparing these a significant mean increase of 5.8% 95%CI(0.52; 11.01) in DAR was found p < .05, and the model of all data also showed a significant increase in median DAR over time p < .01. CONCLUSION: RAC consolidation improves over time in patients admitted for in-hospital early neurorehabilitation.

Tempo-spatial integration of nociceptive stimuli assessed via the nociceptive withdrawal reflex in healthy humans.

Spatial information of nociceptive stimuli applied in the skin of healthy humans is integrated in the spinal cord to determine the appropriate withdrawal reflex response. Double-simultaneous stimulus applied in different skin sites are integrated, eliciting a larger reflex response. The temporal characteristics of the stimuli also modulate the reflex, e.g., by temporal summation. The primary aim of this study was to investigate how the combined tempo-spatial aspects of two stimuli are integrated in the nociceptive system. This was investigated by delivering single- and double-simultaneous stimulation and sequential stimulation with different interstimulus intervals (ISIs ranging 30-500 ms) to the sole of the foot of 15 healthy subjects. The primary outcome measure was the size of the nociceptive withdrawal reflex (NWR) recorded from the tibialis anterior (TA) and biceps femoris (BF) muscles. Pain intensity was measured using a numerical rating scale (NRS) scale. Results showed spatial summation in both TA and BF when delivering simultaneous stimulation. Simultaneous stimulation provoked larger reflexes than sequential stimulation in TA, but not in BF. Larger ISIs elicited significantly larger reflexes in TA, whereas the opposite pattern occurred in BF. This differential modulation between proximal and distal muscles suggests the presence of spinal circuits eliciting a functional reflex response based on the specific tempo-spatial characteristics of a noxious stimulus. No modulation was observed in pain intensity ratings across ISIs. Absence of modulation in the pain intensity ratings argues for an integrative mechanism located within the spinal cord governed by a need for efficient withdrawal from a potentially harmful stimulus.NEW & NOTEWORTHY Tempo-spatial integration of electrical noxious stimuli was studied using the nociceptive withdrawal reflex and a perceived intensity. Tibialis anterior and biceps femoris muscles were differentially modulated by the temporal characteristics of the stimuli and stimulated sites. These findings suggest that spinal neurons are playing an important role in the tempo-spatial integration of nociceptive information, leading to a reflex response that is distributed across multiple spinal cord segments and governed by an efficient defensive withdrawal strategy.

Variability and effect sizes of intracranial current source density estimations during pain: Systematic review, experimental findings, and future perspectives.

Pain arises from the integration of sensory and cognitive processes in the brain, resulting in specific patterns of neural oscillations that can be characterized by measuring electrical brain activity. Current source density (CSD) estimation from low-resolution brain electromagnetic tomography (LORETA) and its standardized (sLORETA) and exact (eLORETA) variants, is a common approach to identify the spatiotemporal dynamics of the brain sources in physiological and pathological pain-related conditions. However, there is no consensus on the magnitude and variability of clinically or experimentally relevant effects for CSD estimations. Here, we systematically examined reports of sample size calculations and effect size estimations in all studies that included the keywords pain, and LORETA, sLORETA, or eLORETA in Scopus and PubMed. We also assessed the reliability of LORETA CSD estimations during non-painful and painful conditions to estimate hypothetical sample sizes for future experiments using CSD estimations. We found that none of the studies included in the systematic review reported sample size calculations, and less than 20% reported measures of central tendency and dispersion, which are necessary to estimate effect sizes. Based on these data and our experimental results, we determined that sample sizes commonly used in pain studies using CSD estimations are suitable to detect medium and large effect sizes in crossover designs and only large effects in parallel designs. These results provide a comprehensive summary of the effect sizes observed using LORETA in pain research, and this information can be used by clinicians and researchers to improve settings and designs of future pain studies.

Characterization of Source-Localized EEG Activity During Sustained Deep-Tissue Pain.

Musculoskeletal pain is a clinical condition that is characterized by ongoing pain and discomfort in the deep tissues such as muscle, bones, ligaments, nerves, and tendons. In the last decades, it was subject to extensive research due to its high prevalence. Still, a quantitative description of the electrical brain activity during musculoskeletal pain is lacking. This study aimed to characterize intracranial current source density (CSD) estimations during sustained deep-tissue experimental pain. Twenty-three healthy volunteers received three types of tonic stimuli for three minutes each: computer-controlled cuff pressure (1) below pain threshold (sustained deep-tissue no-pain, SDTnP), (2) above pain threshold (sustained deep-tissue pain, SDTP) and (3) vibrotactile stimulation (VT). The CSD in response to these stimuli was calculated in seven regions of interest (ROIs) likely involved in pain processing: contralateral anterior cingulate cortex, contralateral primary somatosensory cortex, bilateral anterior insula, contralateral dorsolateral prefrontal cortex, posterior parietal cortex and contralateral premotor cortex. Results showed that participants exhibited an overall increase in spectral power during SDTP in all seven ROIs compared to both SDTnP and VT, likely reflecting the differences in the salience of these stimuli. Moreover, we observed a difference is CSD due to the type of stimulus, likely reflecting somatosensory discrimination of stimulus intensity. These results describe the different contributions of neural oscillations within these brain regions in the processing of sustained deep-tissue pain.

Does Threat Enlarge Nociceptive Reflex Receptive Fields?

Threat-induced pain modulation can increase survival by amplifying physiological and behavioral reactions toward danger. Threat can also modulate spinal nociception, suggesting engagement of endogenous top-down circuitry. A unique method to assess spinal nociception is via reflex receptive fields (RRF) associated with the nociceptive withdrawal reflex (NWR, a protective spinally-mediated reflex). The size of nociceptive RRFs can be modulated by top-down circuitry with the enlargement of RRFs related to increased spinal nociception. Threat has been previously shown to enhance pain and spinal nociception, but the relationship between threat and RRFs has not been investigated. The present study investigated this issue in 25 healthy individuals. RRFs were determined from NWRs measured by electromyography of the tibialis anterior following electrocutaneous stimulations. RRFs and pain were assessed during periods in which participants were under threat of unpredictable painful abdominal stimulations and when they were not under threat. Results indicated that threat periods led to significantly higher pain, larger nociceptive RRFs and NWR magnitudes. These findings imply that threat produces changes in protective reflexes related to spinal nociceptive sensitivity and increased pain perception. This is likely mediated by top-down circuitry that enhances dorsal horn nociceptive neurons by enlarging RRFs and amplifying ascending pain signals. PERSPECTIVE: This article presents the enlargement of RRF during periods of threat. The results from this study may help clarify the mechanism underlining emotional modulation of spinal nociception.

Increased preferential activation of small cutaneous nerve fibers by optimization of electrode design parameters.

Objective.Electrical preferential activation of small nociceptive fibers may be achieved with the use of specialized small area electrodes, however, the existing electrodes are limited to low stimulation intensities. As existing electrodes have been developed empirically, the present study aimed to use computational modeling and optimization techniques to investigate if changes in electrode design parameters could improve the preferential activation of small fibers.Approach.Two finite element models; one of a planar concentric and one of an intra-epidermal electrode were combined with two multi-compartmental nerve fiber models of an Aδ-fiber and an Aß-fiber. These two-step hybrid models were used for the optimization of four electrode parameters; anode area, anode-cathode distance, cathode area, and cathode protrusion. Optimization was performed using a gradient-free bounded Nelder-Mead algorithm, to maximize the current activation threshold ratio between the Aß-fiber model and the Aδ-fiber model.Main results.All electrode parameters were optimal at their lower bound, except the cathode protrusion, which was optimal a few micrometers above the location of the Aδ-fiber model. A small cathode area is essential for producing a high current density in the epidermal skin layer enabling activation of small fibers, while a small anode area and anode-cathode distance are important for the minimization of current spread to deeper tissues, making it less likely to activate large fibers. Combining each of the optimized electrode parameters improved the preferential activation of small fibers in comparison to existing electrodes, by increasing the activation threshold ratio between the two nerve fiber types. The maximum increase in the activation threshold ratio was 289% and 595% for the intra-epidermal and planar concentric design, respectively.Significance.The present study showed that electrical preferential small fiber activation can be improved by electrode design. Additionally, the results may be used for the production of an electrode that could potentially be used for clinical assessment of small fiber neuropathy.

Spinal spatial integration of nociception and its functional role assessed via the nociceptive withdrawal reflex and psychophysical measures in healthy humans.

Animal studies have previously shown that deep dorsal horn neurons play a role in the processing of spatial characteristics of nociceptive information in mammals. Human studies have supported the role of the spinal neurons; however, the mechanisms involved, and its significance, remain to be clarified. The aim of this study was to investigate spatial aspects of the spinal integration of concurrent nociceptive electrical stimuli in healthy humans using the Nociceptive Withdrawal Reflex (NWR) as an objective indication of spinal nociceptive processing. Fifteen healthy volunteers participated in the study. Electrical stimuli were delivered, using five electrodes located across the sole of the foot in a mediolateral disposition, as a single or double simultaneous stimuli with varying Inter-Electrode Distances (IEDs). The stimulation intensity was set at 1.5× NWR threshold (TA muscle). The size of the NWR was quantified in the 60-180 ms poststimulus window as a primary outcome measure. Psychophysical measures were secondary outcomes. Single stimulation elicited significantly smaller NWRs and perceived intensity than double stimulation (p < .01), suggesting the presence of spatial summation occurring within the spinal processing. During double stimulation, increasing the inter-electrode distance produced significantly smaller NWR sizes (p < .05) but larger pain intensity ratings (p < .05). By the NWR, spatial summation was shown to affect the nociceptive processing within the spinal cord. The inhibited motor response obtained when simultaneously stimulating the medial and lateral side of the sole of the foot suggests the presence of an inhibitory mechanism with a functional, behaviorally oriented function.

Stimulus predictability moderates the withdrawal strategy in response to repetitive noxious stimulation in humans.

Nociceptive withdrawal reflex (NWR) is a protective reaction to a noxious stimulus, resulting in withdrawal of the affected area and thus preventing potential tissue damage. This involuntary reaction consists of neural circuits, biomechanical strategies, and muscle activity that ensure an optimal withdrawal. Studies of lower limb NWR indicate that the amplitude of the NWR is highly modulated by extrinsic and intrinsic factors, such as stimulation site, intensity, frequency, and supraspinal activity, among others. Whether the predictability of the stimulus has an effect on the biomechanical strategies is still unclear. This study aimed to evaluate how the predictability of impending noxious stimuli modulate the NWR reaction in the lower limb. NWR was evoked on fifteen healthy participants by trains of electrical stimuli on the sole of the foot and was measured in one distal (tibialis anterior) and one proximal (biceps femoris) muscle. The predictability was manipulated by giving participants prior information about the onset of the stimulus trains and the number of delivered stimuli per train. Results showed that the predictability of the incoming stimuli differentially modulates the muscle activity involved in the NWR reaction. For the most unpredictable stimulus train, larger NWR at distal muscles were evoked. Furthermore, the stereotyped temporal summation profile to repeated stimulation was observed when the stimulus train was completely predictable, while it was disrupted in proximal muscles in unpredictable conditions. It is inferred that the reflex response is shaped by descending control, which dynamically tunes the activity of the muscles involved in the resulting reaction.NEW & NOTEWORTHY Innate defensive behaviors such as reflexes are found across all species, constituting preprogrammed responses to external threats that are not anticipated. Previous studies indicated that the excitability of the reflex arcs like spinal nociceptive withdrawal reflex (NWR) pathways in humans are modulated by several cognitive factors. This study assesses how the predictability of a threat affects the biomechanical pattern of the withdrawal response, showing that distal and proximal muscles are differentially modulated by descending control.

Comparison of existing electrode designs for preferential activation of cutaneous nociceptors.

OBJECTIVE: Over the recent years, several small area electrodes have been introduced as tools for preferential stimulation of small cutaneous nerve fibers. However, the performance of the electrodes is highly debated and have not previously been systematically compared. The electrodes have been developed empirically and little is known about the electrical potential they produce in the skin, and how this influences the nerve fiber activation. The objective of the present study was to develop and validate a computational model to compare the preferential stimulation of small fibers for electrodes of different designs. APPROACH: A finite element model of the skin was developed and coupled with an Aß-fiber and an Aδ-fiber multi-compartmental nerve fiber model, to describe the current spread and consequent nerve fiber activation produced by five different surface electrodes; intra-epidermal, planar concentric, pin, planar array, and patch. The model was validated through experimental assessments of the strength-duration relationship, impedance, and reaction times. MAIN RESULTS: The computational model predicted the intra-epidermal electrode to be the most preferential for small fiber activation. The intra-epidermal electrode was, however, also found to be the most sensitive to positioning relative to nerve fiber location, which may limit the practical use of the electrode. SIGNIFICANCE: The present study highlights the influence of different electrode design features on the current spread and resulting activation of cutaneous nerve fibers. Additionally, the computational model may be used for the optimization of electrode design towards even better preferential stimulation of small fibers.

Development of an individualized asynchronous sensor-based telerehabilitation program for patients undergoing total knee replacement: Participatory design.

Telerehabilitation programs can be employed to establish communication between patients and healthcare professionals and empower patients performing their training remotely. This study aimed to identify patients' requirements after a total knee replacement following a self-training rehabilitation program, leading to the design and development of a telerehabilitation program that can meet the stakeholders' actual needs. System design, development, and testing were conducted in five iterations based on a participatory design approach. Data collection was performed using interviews, observations, prototyping, and questionnaires. It was found that the main barriers facing the existing rehabilitation program were a lack of clear communication, lack of relevant information, and healthcare professional's feedback. The participants emphasized the main themes of communication, information, training, and motivation in the process of design and development. In using the telerehabilitation program, the patients reported a high level of user-friendliness, flexibility, and a sense of security. This study has identified obstacles in the current rehabilitation program and revealed the potential effectiveness of using asynchronous communication and sensor-based technologies by employing participatory design and development. A higher level of portability and flexibility were observed. However, future studies and development are required to investigate the overall usability and reliability of the telerehabilitation program.

Preferential activation of small cutaneous fibers through small pin electrode also depends on the shape of a long duration electrical current.

BACKGROUND: Electrical stimulation is widely used in experimental pain research but it lacks selectivity towards small nociceptive fibers. When using standard surface patch electrodes and rectangular pulses, large fibers are activated at a lower threshold than small fibers. Pin electrodes have been designed for overcoming this problem by providing a higher current density in the upper epidermis where the small nociceptive fibers mainly terminate. At perception threshold level, pin electrode stimuli are rather selectively activating small nerve fibers and are perceived as painful, but for high current intensity, which is usually needed to evoke sufficient pain levels, large fibers are likely co-activated. Long duration current has been shown to elevate the threshold of large fibers by the mechanism of accommodation. However, it remains unclear whether the mechanism of accommodation in large fibers can be utilized to activate small fibers even more selectively by combining pin electrode stimulation with a long duration pulse. RESULTS: In this study, perception thresholds were determined for a patch- and a pin electrode for different pulse shapes of long duration. The perception threshold ratio between the two different electrodes was calculated to estimate the ability of the pulse shapes to preferentially activate small fibers. The perception threshold ratios were compared between stimulation pulses of 5- and 50 ms durations and shapes of: exponential increase, linear increase, bounded exponential, and rectangular. Qualitative pain perception was evaluated for all pulse shapes delivered at 10 times perception threshold. The results showed a higher perception threshold ratio for long duration 50 ms pulses than for 5 ms pulses. The highest perception threshold ratio was found for the 50 ms, bounded exponential pulse shape. Results furthermore revealed different strength-duration relation between the bounded exponential- and rectangular pulse shapes. Pin electrode stimulation at high intensity was mainly described as "stabbing", "shooting", and "sharp". CONCLUSION: These results indicate that long duration pulses with a bounded exponential increase preferentially activate the small nociceptive fibers with a pin electrode and concurrently cause elevated threshold of large non-nociceptive fibers with patch electrodes.