Verbal Support From a Stranger Reduces the Development of Mechanical Hypersensitivity: Behavioral and Neurophysiological Evidence.

Hand-holding reduces experimentally induced acute pain and buffers against the development of mechanical secondary hypersensitivity, an indirect proxy of central sensitization. Here, we tested if verbal support from a stranger, a common occurrence in clinical contexts, exerts the same effects. In this preregistered study, 44 healthy female participants were assigned to an alone or support group whereby a supportive female stranger encouraged them through the painful procedure leading to secondary mechanical hypersensitivity. Mechanical hypersensitivity was measured via self-reports and by the size of the anteroposterior and mediolateral spread of mechanical hypersensitivity. We investigated the moderating role of attachment style on self-reports and the effects of support on skin conductance level, salivary cortisol, and pinprick-evoked potentials. We also tested whether theta/beta ratio in the resting-state electroencephalogram predicted mechanical hypersensitivity. Self-reported ratings and the late part of the pinprick-evoked potentials were reduced in the support group, but the spread of mechanical hypersensitivity was not. Attachment anxiety and avoidance moderated the self-reported intensity such that individuals with higher attachment anxiety and avoidance scores reported lower intensity ratings in the support group. No significant effect of the verbal support was observed on skin conductance level and salivary cortisol. The theta/beta ratio did not predict the extent of hypersensitivity. Our data indicate that, in women, verbal support during intense pain leading to hypersensitivity is effective on some behavioral outcomes, but altogether the lack of group differences in cortisol, self-reported stress, and skin conductance does not provide strong support for the stress-buffering hypothesis. PERSPECTIVE: Verbal support by a stranger during a painful procedure leading to secondary mechanical hypersensitivity attenuated the development of some measures of mechanical hypersensitivity and associated neural responses in healthy female participants. No evidence was found for the role of stress. DATA AVAILABILITY: The authors will make all data available upon request.

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.

City-scale model for COVID-19 epidemiology with mobility and social activities represented by a set of hidden Markov models.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 emerged by the end of 2019 and became a global pandemic due to its rapid spread. Various outbreaks of the disease in different parts of the world have been studied, and epidemiological analyses of these outbreaks have been useful for developing models with the aim of tracking and predicting the spread of epidemics. In this paper, an agent-based model that predicts the local daily evolution of the number of people hospitalized in intensive care due to COVID-19 is presented. METHODS: An agent-based model has been developed, taking into consideration the most relevant characteristics of the geography and climate of a mid-size city, its population and pathology statistics, and its social customs and mobility, including the state of public transportation. In addition to these inputs, the different phases of isolation and social distancing are also taken into account. By means of a set of hidden Markov models, the system captures and reproduces virus transmission associated with the stochastic nature of people's mobility and activities in the city. The spread of the virus in the host is also simulated by following the stages of the disease and by considering the existence of comorbidities and the proportion of asymptomatic carriers. RESULTS: As a case study, the model was applied to Paraná city (Entre Ríos, Argentina) in the second half of 2020. The model adequately predicts the daily evolution of people hospitalized in intensive care due to COVID-19. This adequacy is reflected by the fact that the prediction of the model (including its dispersion), as with the data reported in the field, never exceeded 90% of the capacity of beds installed in the city. In addition, other epidemiological variables of interest, with discrimination by age range, were also adequately reproduced, such as the number of deaths, reported cases, and asymptomatic individuals. CONCLUSIONS: The model can be used to predict the most likely evolution of the number of cases and hospital bed occupancy in the short term. By adjusting the model to match the data on hospitalizations in intensive care units and deaths due to COVID-19, it is possible to analyze the impact of isolation and social distancing measures on the disease spread dynamics. In addition, it allows for simulating combinations of characteristics that would lead to a potential collapse in the health system due to lack of infrastructure as well as predicting the impact of social events or increases in people's mobility.

Pressure pain threshold mappings of the infraspinatus muscle in chronic unilateral shoulder pain patients do not reflect generalized hypersensitivity.

OBJECTIVES: Increased mechanical sensitivity has been observed on the unaffected side in chronic pain conditions, suggesting generalized or widespread hypersensitivity. However, this cannot be considered as a universal response since this hypersensitivity is inconsistent across muscle pain pathologies. The aim of this study was to assess generalized hypersensitivity in chronic unilateral shoulder pain, using pressure pain threshold (PPT) mappings of the infraspinatus muscle. The proposed evaluation is based on the assessment of PPT on a limited subset of sites, reducing potential habituation or sensitization effects. METHODS: Twenty-nine patients with unilateral shoulder pain (USP) and twenty-seven healthy volunteers were recruited. PPT was assessed using a manual pressure algometer. Six sites distributed over the infraspinatus muscle were assessed, and three repetitions were performed at each site. Mappings were derived using two-dimensional interpolation. RESULTS: Lower PPT values were found in the symptomatic side in comparison with the asymptomatic side at all assessment sites (estimated difference: 1.42 ±â€¯0.10 kgf/cm2, p < 0.001), but there were no differences among the asymptomatic side of USP patients and any of the sides in healthy volunteers (largest estimated difference: 0.17 ±â€¯0.28 kgf/cm2, p = 0.927). Furthermore, the medial region of the infraspinatus muscle showed higher mechanical sensitivity in both healthy volunteers and USP patients. CONCLUSIONS: These results suggest that USP does not induce generalized hypersensitivity, in contrast with previously reported findings. Physiotherapists could take these results into account for the assessment and treatment of patients with USP.

Does feedback based on FES-evoked nociceptive withdrawal reflex condition event-related desynchronization? An exploratory study with brain-computer interfaces.

Introduction.Event-related desynchronization (ERD) is used in brain-computer interfaces (BCI) to detect the user's motor intention (MI) and convert it into a command for an actuator to provide sensory feedback or mobility, for example by means of functional electrical stimulation (FES). Recent studies have proposed to evoke the nociceptive withdrawal reflex (NWR) using FES, in order to evoke synergistic movements of the lower limb and to facilitate the gait rehabilitation of stroke patients. The use of NWR to provide sensorimotor feedback in ERD-based BCI is novel; thererfore, the conditioning effect that nociceptive stimuli might have on MI is still unknown.Objetive.To assess the ERD produced during the MI after FES-evoked NWR, in order to evaluate if nociceptive stimuli condition subsequent ERDs.Methods. Data from 528 electroencephalography trials of 8 healthy volunteers were recorded and analyzed. Volunteers used an ERD-based BCI, which provided two types of feedback: intrisic by the FES-evoked NWR and extrinsic by virtual reality. The electromyogram of the tibialis anterior muscle was also recorded. The main outcome variables were the normalized root mean square of the evoked electromyogram (RMSnorm), the average electroencephalogram amplitude at the ERD frequency during MI (A¯MI) and the percentage decrease ofA¯MIrelative to rest (ERD%) at the first MI subsequent to the activation of the BCI.Results.No evidence of changes of theRMSnormon both theA¯MI(p = 0.663) and theERD%(p = 0.252) of the subsequent MI was detected. A main effect of the type of feedback was found in the subsequentA¯MI(p < 0.001), with intrinsic feedback resulting in a largerA¯MI.Conclusions.No evidence of ERD conditioning was observed using BCI feedback based on FES-evoked NWR .Significance.FES-evoked NWR could constitute a potential feedback modality in an ERD-based BCI to facilitate motor recovery of stroke people.

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.

A new objective method for acquisition and quantification of reflex receptive fields.

The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex correlated with pain perception. Assessment of this objective physiological measure constitutes the core of existing methods for quantification of reflex receptive fields (RRFs), which however still suffer from a certain degree of subjective involvement. This article proposes a strictly objective methodology for RRF quantification based on automated identification of NWR thresholds (NWR-Ts). Nociceptive withdrawal reflex thresholds were determined for 10 individual stimulation sites using an interleaved up-down staircase method. Reflexes were detected from electromyography by evaluation of interval peak z scores and application of conduction velocity analysis. Reflex receptive field areas were quantified from interpolated mappings of NWR-Ts and compared with existing RRF quantifications. A total of 3 repeated measures were performed in 2 different sessions to evaluate the test-retest reliability of the various quantifications, using coefficients of repeatability (CRs) and hypothetical sample sizes. The novel quantifications based on identification of NWR-Ts showed a similar level of reliability within and between sessions, whereas existing quantifications all demonstrated worse between-session than within-session reliability. The NWR-T-based quantifications required a smaller sample size than any of the existing RRF measures to detect a clinically relevant effect in a crossover study design involving more than 1 session. Of all measures, quantification from mapping of inversed NWR-Ts demonstrated superior reliability both within (CR, 0.25) and between sessions (CR, 0.28). The study presents a more reliable and robust quantification of the RRF to be used as biomarker of pain hypersensitivity in clinical and experimental research.

Generalized expansion of nociceptive reflex receptive fields in chronic pain patients.

Widespread central hypersensitivity is present in chronic pain and contributes to pain and disability. According to animal studies, expansion of receptive fields of spinal cord neurons is involved in central hypersensitivity. We recently developed a method to quantify nociceptive receptive fields in humans using spinal withdrawal reflexes. Here we hypothesized that patients with chronic pelvic pain display enlarged reflex receptive fields. Secondary endpoints were subjective pain thresholds and nociceptive withdrawal reflex thresholds after single and repeated (temporal summation) electrical stimulation. 20 patients and 25 pain-free subjects were tested. Electrical stimuli were applied to 10 sites on the foot sole for evoking reflexes in the tibialis anterior muscle. The reflex receptive field was defined as the area of the foot (fraction of the foot sole) from which a muscle contraction was evoked. For the secondary endpoints, the stimuli were applied to the cutaneous innervation area of the sural nerve. Medians (25-75 percentiles) of fraction of the foot sole in patients and controls were 0.48 (0.38-0.54) and 0.33 (0.27-0.39), respectively (P=0.008). Pain and reflex thresholds after sural nerve stimulation were significantly lower in patients than in controls (P<0.001 for all measurements). This study provides for the first time evidence for widespread expansion of reflex receptive fields in chronic pain patients. It thereby identifies a mechanism involved in central hypersensitivity in human chronic pain. Reverting the expansion of nociceptive receptive fields and exploring the prognostic meaning of this phenomenon may become future targets of clinical research.