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.

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.

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.

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.

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.

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.

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.

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.

From Perception Threshold to Ion Channels-A Computational Study.

Small-surface-area electrodes have successfully been used to preferentially activate cutaneous nociceptors, unlike conventional large area-electrodes, which preferentially activate large non-nociceptor fibers. Assessments of the strength-duration relationship, threshold electrotonus, and slowly increasing pulse forms have displayed different perception thresholds between large and small surface electrodes, which may indicate different excitability properties of the activated cutaneous nerves. In this study, the origin of the differences in perception thresholds between the two electrodes was investigated. It was hypothesized that different perception thresholds could be explained by the varying distributions of voltage-gated ion channels and by morphological differences between peripheral nerve endings of small and large fibers. A two-part computational model was developed to study activation of peripheral nerve fibers by different cutaneous electrodes. The first part of the model was a finite-element model, which calculated the extracellular field delivered by the cutaneous electrodes. The second part of the model was a detailed multicompartment model of an Aδ-axon as well as an Aß-axon. The axon models included a wide range of voltage-gated ion channels: NaTTXs, NaTTXr, Nap, Kdr, KM, KA, and HCN channel. The computational model reproduced the experimentally assessed perception thresholds for the three protocols, the strength-duration relationship, the threshold electrotonus, and the slowly increasing pulse forms. The results support the hypothesis that voltage-gated ion channel distributions and morphology differences between small and large fibers were sufficient to explain the difference in perception thresholds between the two electrodes. In conclusion, assessments of perception thresholds using the three protocols may be an indirect measurement of the membrane excitability, and computational models may have the possibility to link voltage-gated ion channel activation to perception threshold measurements.

Investigating stimulation parameters for preferential small-fiber activation using exponentially rising electrical currents.

Electrical stimulation is widely used in pain research and profiling, but current technologies lack selectivity toward small sensory fibers. Pin electrodes deliver high current density in upper skin layers, and it has been proposed that slowly rising exponential pulses can elevate large-fiber activation threshold and thereby increase preferential small-fiber activation. Optimal stimulation parameters for the combined pin electrode and exponential pulse stimulation have so far not been established, which is the aim of this study. Perception thresholds were compared between pin and patch electrodes using single 1- to 100-ms exponential and rectangular pulses. Stimulus-response functions were evaluated for both pulse shapes delivered as single pulses and pulse trains of 10 Hz using intensities from 0.1 to 20 times perception threshold. Perception thresholds (mA) decreased when duration was increased for both electrodes with rectangular pulses and the pin electrode with exponential pulses. For the patch electrode, perception thresholds for exponential pulses decreased for durations ≤10 ms but increased for durations ≥15 ms, indicating accommodation of large fibers. Stimulus-response curves for single pulses were similar for the two pulse shapes. For pulse trains, the slope of the curve was higher for rectangular pulses. Maximal large-fiber accommodation to exponential pulses was observed for 100-ms pulses, indicating that 100-ms exponential pulses should be applied for preferential small-fiber activation. Intensity of 10 times perception threshold was sufficient to cause maximal pain ratings. The developed methodology may open new opportunities for using electrical stimulation paradigms for small-fiber stimulation and diagnostics.NEW & NOTEWORTHY Selective activation of small cutaneous nerve fibers is pivotal for investigations of the pain system. The present study demonstrated that patch electrode perception thresholds increase with increased duration of exponential currents from 20 to 100 ms. This is likely caused by large-fiber accommodation, which can be utilized to activate small fibers preferentially through small-diameter pin electrodes. This finding may be utilized in studies of fundamental pain mechanisms and, for example, in small-fiber neuropathy.

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.

Cognitive Processing for Step Precision Increases Beta and Gamma Band Modulation During Overground Walking.

The aim of this study was to investigate whether cognitive processing for defining step precision during walking could induce changes in electrocortical activity. Ten healthy adults (21-36 years) were asked to walk overground in three different conditions: (1) normal walking in a straight path (NW); (2) walking in a pre-defined pathway forcing variation in step width and length by stepping on green marks on the floor (only one color: W1C), and (3) walking in the same pre-defined W1C pathway while evaluating different combinations among the colors green, yellow and red, in which only one color was the footfall target (evaluating two colors: W2C). Walking speed, stride duration and scalp electroencephalography (EEG) were recorded from all conditions. Event-related spectral perturbation was calculated for channels Fz, Cz, C3, C4, Pz and Oz in each condition, which were all time-normalized in relation to the gait cycle. The results showed that walking speed was reduced and stride duration was increased for W2C when compared to both NW and W1C (p < 0.01). Moreover, Event-related spectral perturbation analysis revealed significant changes (p < 0.05) during mid-stance in the frontal lobe and motor/sensorimotor regions, a phase in the gait cycle in which participants define the correct foot placement for the next step. These results suggest that greater cognitive demands during precision stepping influences electrocortical dynamics especially towards step transitions. Therefore, increased electrocortical activity in cognitive, motor and sensorimotor areas may be relevant to produce patterned and safe locomotion through challenging paths.

Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans.

Spinal nociceptive long-term potentiation (LTP) can be induced by high- or low-frequency conditioning electrical stimulation (CES) in rodent preparations in vitro. However, there is still sparse information on the effect of different conditioning frequencies inducing LTP-like pain amplification in humans. In this study, we tested two other paradigms aiming to explore the CES frequency effect inducing pain amplification in healthy humans. Cutaneous LTP-like pain amplification induced by three different paradigms (10, 100, and 200 Hz CES) was assessed in fifteen volunteers in a crossover design. Perceptual intensity ratings to single electrical stimulation at the conditioned site and to mechanical stimuli (pinprick and light stroking) in the immediate vicinity were recorded; superficial blood flow was also measured. The short form of the McGill Pain Questionnaire (SF-MPQ) was used for characterizing the perception induced by CES. Compared with the control session, pain perception to pinprick stimuli and area of allodynia significantly increased after all three CES paradigms. In the 10 and 200 Hz sessions, the superficial blood flow 10 min after CES was significantly higher than in the control session reaching a plateau after 20 and 10 min, respectively; for the 100 Hz paradigm, a stable level was found without significant differences compared with CES and control sessions. 10 Hz CES caused a lower SF-MPQ score than 100 Hz. High-frequency (200 Hz) and low-frequency (10 Hz) paradigms can induce heterotopic pain amplification similar to the traditional 100 Hz paradigm. The 10 Hz paradigm can be an appealing alternative paradigm in future studies due to its specific association with low-level discharging of C-fibers during inflammation.

Rehabilitation of the hemiparetic gait by nociceptive withdrawal reflex-based functional electrical therapy: a randomized, single-blinded study.

BACKGROUND: Gait deficits are very common after stroke and improved therapeutic interventions are needed. The objective of this study was therefore to investigate the therapeutic use of the nociceptive withdrawal reflex to support gait training in the subacute post-stroke phase. METHODS: Individuals were randomly allocated to a treatment group that received physiotherapy-based gait training supported by withdrawal reflex stimulation and a control group that received physiotherapy-based gait training alone. Electrical stimuli delivered to the arch of the foot elicited the withdrawal reflex at heel-off with the purpose of facilitating the initiation and execution of the swing phase. Gait was assessed before and immediately after finishing treatment, and one month and six months after finishing treatment. Assessments included the Functional Ambulation Category (FAC) test, the preferred and maximum gait velocities, the duration of the stance phase in the hemiparetic side, the duration of the gait cycle, and the stance time symmetry ratio. RESULTS: The treatment group showed an improved post treatment preferred walking velocity (p < 0.001) and fast walking velocity (p < 0.001) compared to the control group. Furthermore, subjects in the treatment group with severe walking impairment at inclusion time showed the best improvement as assessed by a longer duration of the stance phase in the hemiparetic side (p < 0.002) and a shorter duration of the gait cycle (p < 0.002). The stance time symmetry ratio was significantly better for the treatment than the control group after finishing training (p < 0.02). No differences between groups were detected with the FAC test after finishing training (p = 0.09). CONCLUSION: Withdrawal reflex-based functional electrical therapy was useful in the rehabilitation of the hemiparetic gait of severely impaired patients.

Mathematical model of nerve fiber activation during low back peripheral nerve field stimulation: analysis of electrode implant depth.

OBJECTIVES: The lower back is the most common location of pain experienced by one-fifth of the European population reporting chronic pain. A peripheral nerve field stimulation system, which involves electrodes implanted subcutaneously in the painful area, has been shown to be efficacious for low back pain. Moreover, the predominant analgesic mechanism of action is thought to be via activation of peripheral Aß fibers. Unfortunately, electrical stimulation also might coactivate Aδ fibers, causing pain or unpleasantness itself. The aim of this study was to investigate at which implant depth Aß-fiber stimulation is maximized, and Aδ-fiber minimized, which in turn should lead to therapy optimization. MATERIALS AND METHODS: A finite element model was used to estimate the electrical potential generated by a bipolar single-lead electrode implanted in the subcutaneous adipose tissue at depths of 5 mm to 30 mm below the skin surface. The model includes low back tissue; the epidermis, dermis, adipose, and muscle layers, and nerve fibers, which were programmed to branch randomly in the model in a fiber type-specific manner. Likewise, activation thresholds were specific to Aß- and Aδ-fiber types and were estimated using a passive cable model. RESULTS: The stimulus-response functions showed that the skin area covered by Aß-fiber activation was larger than the area covered by Aδ-fiber activation at all depths and all intensities. The skin area covered by Aδ-fiber activation was largest when the electrode was modeled to have a superficial location (5 mm below the skin surface), while the skin area covered by Aß-fiber activation was largest at lower depths. CONCLUSIONS: The present mathematical model predicts an optimal implantation depth of 10 to 15 mm below the skin surface to achieve activation of the greatest area of Aß fibers and the smallest area of Aδ fibers. This finding may act as a guide for peripheral nerve field stimulation implant depth to treat low back pain.

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.

Topical capsaicin modulates the two-point discrimination threshold-Modulation depends on stimulation modality and intensity.

BACKGROUND: Spatial acuity concerns the ability to localize and discriminate sensory input and is often tested using the two-point discrimination threshold (2PDT). Sensitization of the pain system can affect the spatial acuity, but it is unclear how 2PDTs of different testing modalities are affected. The aim was to investigate if the 2PDTs for mechanical and heat stimulation at different intensities were modulated by topical capsaicin sensitization. METHODS: 30 healthy subjects were divided into either a capsaicin or a placebo group. The 2PDT was tested using two different modalities, mechanical and thermal (laser) delivered at innocuous and noxious intensities. The 2PDT were determined at baseline and re-assessed 48 h later. In the follow-up session, the subjects either had a capsaicin patch (8%) or placebo patch placed in the testing area for 30 min before re-testing the 2PDT. RESULTS: The 2PDT was highly dependent on stimulation modality and intensity. The lowest 2PDT was found for innocuous mechanical stimuli (40.0 mm, 95% CI 38.1-41.9 mm), and the highest 2PDT was found for innocuous thermal stimuli (81.7 mm, 95% CI 73.9-89.5 mm). Topical capsaicin generally increased the 2PDT, but this was only significant for innocuous mechanical stimuli. The perceived intensity of the stimuli was increased following capsaicin and was generally higher for noxious stimuli than for innocuous stimuli (ANOVA, p < 0.001). CONCLUSIONS: This study showed that capsaicin provoked pain sensitization increased the 2PDT. The 2PDT tested using innocuous mechanical stimuli showed less variable results indicating that this test is most suitable to detect this aspect of spatial acuity. SIGNIFICANCE STATEMENT: This study investigated how the two-point discrimination threshold (2PDT) can be modulated by topical capsaicin. The 2PDT was assessed for two different modalities (thermal and mechanical) and for two different intensities (innocuous and noxious) before and after capsaicin. The results showed that the 2PDT was generally impaired following capsaicin, but this was only significant for mechanical innocuous stimuli. Furthermore, it was shown that mechanical innocuous stimuli assessed the 2PDT with lower variability than other combinations.

Spatiotemporal characterization of an experimental model of muscle pain in humans based on short-wave diathermy.

BACKGROUND: Commonly used models for eliciting muscle pain involve the injection of algesic substances or the induction of delayed onset muscle soreness. The former require invasive procedures, and the time frame for pain induction and subsidence in the latter can be inconvenient. This study presents a detailed spatiotemporal characterization of a new experimental model of muscle pain based on short-wave diathermy (SWD), developed to overcome the limitations of existing models. METHODS: The shoulder was selected as target site and the effects of the model were tested in two sessions to assess its reliability. Pain intensity profiles were recorded during the application of SWD, and changes in pressure pain threshold (PPT) in the infraspinatus muscle, together with pain intensity, duration, and quality were assessed 30 min after induction. RESULTS: SWD-induced pain intensity scores averaged 4 points on a visual analogue scale, whereas PPT showed a consistent decrease of about 25% relative to baseline values. Pain was localized in the shoulder area, and was described as continuous, dull, well-delimited, heavy, and bearable. Pain lasted for an average of 145 min without requiring reinduction and was reliably elicited in both experimental sessions. CONCLUSION: SWD can be used to elicit experimental muscle pain in a non-invasive, long-lasting, and reliable way and allows for repeated within- and between-session testing in the shoulder. SIGNIFICANCE STATEMENT: SWD produces deep heating in muscles by converting electromagnetic energy to thermal energy. It was previously shown that it can be used to elicit experimental pain in the forearm muscles, and the present study demonstrates that this can be reliably generalized to other body sites, such as the shoulder. Furthermore, SWD application is non-invasive and presents a convenient time frame for pain induction and subsidence, thus overcoming limitations associated with traditional muscle pain models.