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.Fil: Völker, Juan Manuel. Aalborg University; DinamarcaFil: Arguissain, Federico Gabriel. Aalborg University; DinamarcaFil: Kæseler Andersen, Ole. Aalborg University; DinamarcaFil: Biurrun Manresa, José Alberto. Aalborg University; Dinamarca. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentin

On the agreement between manual and automated methods for single-trial detection and estimation of features from event-related potentials

The agreement between humans and algorithms on whether an event-related potential (ERP) is present or not and the level of variation in the estimated values of its relevant features are largely unknown. Thus, the aim of this study was to determine the categorical and quantitative agreement between manual and automated methods for single-trial detection and estimation of ERP features. To this end, ERPs were elicited in sixteen healthy volunteers using electrical stimulation at graded intensities below and above the nociceptive withdrawal reflex threshold. Presence/absence of an ERP peak (categorical outcome) and its amplitude and latency (quantitative outcome) in each single-trial were evaluated independently by two human observers and two automated algorithms taken from existing literature. Categorical agreement was assessed using percentage positive and negative agreement and Cohen's κ, whereas quantitative agreement was evaluated using Bland-Altman analysis and the coefficient of variation. Typical values for the categorical agreement between manual and automated methods were derived, as well as reference values for the average and maximum differences that can be expected if one method is used instead of the others. Results showed that the human observers presented the highest categorical and quantitative agreement, and there were significantly large differences between detection and estimation of quantitative features among methods. In conclusion, substantial care should be taken in the selection of the detection/estimation approach, since factors like stimulation intensity and expected number of trials with/without response can play a significant role in the outcome of a study

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.Fil: Jure, Fabricio A.. Aalborg University; DinamarcaFil: Arguissain, Federico G.. Aalborg University; DinamarcaFil: Biurrun Manresa, José Alberto. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Entre Ríos. Universidad Nacional de Entre Ríos. Centro de Investigaciones y Transferencia de Entre Ríos; Argentina. Aalborg University; DinamarcaFil: Graven Nielsen, Thomas. Aalborg University; DinamarcaFil: Andersen, Ole Kæseler. Aalborg University; Dinamarc

Psychophysical and electrophysiological evidence for enhanced pain facilitation and unaltered pain inhibition in acute low back pain patients

The aim of this case-control study was to examine differences in neural correlates of pain facilitatory and inhibitory mechanisms between acute low back pain (LBP) patients and healthy individuals. Pressure pain tolerance, electrical pain detection thresholds, pain ratings to repetitive suprathreshold electrical stimulation (SES) and conditioned pain modulation (CPM) were assessed in 18 patients with acute LBP and 18 healthy control participants. Furthermore, event-related potentials (ERPs) in response to repetitive SES were obtained from high-density electroencephalography. Results showed that the LBP group presented lower pressure pain tolerance and higher pain ratings to SES compared with the control group. Both groups displayed effective CPM, with no differences in CPM magnitude between groups. Both groups presented similar reductions in ERP amplitudes during CPM, but ERP responses to repetitive SES were significantly larger in the LBP group. In conclusion, acute LBP patients presented enhanced pain facilitatory mechanisms, whereas no significant changes in pain inhibitory mechanisms were observed. These results provide new insight into the central mechanisms underlying acute LBP. Perspective: This article present evidence that acute LBP patients show enhanced pain facilitation and unaltered pain inhibition compared with pain-free volunteers. These results provide new insight into the central mechanisms underlying acute LBP.Fil: Vuilleumier, Pascal Henri. University of Bern; SuizaFil: Arguissain, Federico Gabriel. Aalborg University; DinamarcaFil: Biurrun Manresa, José Alberto. Aalborg University; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Entre Rios. Universidad Nacional de Entre Rios. Centro de Investigaciones y Transferencia de Entre Rios; ArgentinaFil: Neziri, Alban Ymer. University of Bern; Suiza. Regional Hospital of Langenthal; SuizaFil: Nirkko, Arto Christian. University of Bern; SuizaFil: Andersen, Ole Kæseler. Aalborg University; DinamarcaFil: Arendt-Nielsen, Lars. Aalborg University; DinamarcaFil: Curatolo, Michele. Aalborg University; Dinamarca. University of Washington; Estados Unido

Social foundations of the mathematics curriculum: a rationale for change

The nature of educational aims as criteria for worthwhile curriculum practice is explored and a cross-section of aims for mathematics education is discussed. An aim for mathematics education which emphasises the social aspect of the subject in its being, its conduct and its applications is identified and epistemological foundations for such a view of the nature of the subject are explored. It is argued that such an epistemological perspective of mathematics would be reflected in the social context of the mathematics classroom, arising from a methodology in which the subject would become more problematic and open to change, investigation and hypothesis. The aims of two major mathematics curriculum development projects (the Nuffield Mathematics Project and the School Mathematics Project) are examined to determine the extent to which their aims may take the 'social' nature of mathematics into account. The probable social context of mathematics classrooms using their materials is postulated in an attempt to characterise the nature of the subject as it is reflected in these materials. A view of the nature of mathematics held by practising teachers and by pupils is then established by drawing upon, and extrapolating from, evidence relating to the social context of mathematics classrooms at primary and secondary level. Conclusions follow, which suggest that fundamental change in mathematics education requires, as a first step, the adoption of a new epistemological perspective of the subject in order that the pursuit of the aim which emphasises the social nature of mathematics is achieved. It is suggested that this, in turn, ultimately could lead to the desired balance in the mathematics curriculum which hitherto has been lacking

Influence of skin type and laser wavelength on laser-evoked potentials

Infrared laser stimulation is a valuable tool in pain research, its primary application being the recording of laser-evoked brain potentials (LEPs). Different types of laser stimulators, varying in their skin penetrance, are likely to have a large influence on the LEPs, when stimulating different skin types. The aim of this study was to investigate how LEPs depend on laser type and skin location. Two different laser stimulators (CO and Nd:YAP) were used to compare LEPs in healthy subjects. Stimuli were delivered to the hand dorsum and palm to investigate the effects of skin type on the evoked responses. Stimulus-evoked brain responses were recorded using EEG and perceived intensity ratings were recorded. Computational modelling was used to investigate the observed differences. LEPs evoked by stimulation of the hairy skin were similar between CO and Nd:YAP stimulation. In contrast, LEPs elicited from the palm were markedly different and barely present for CO stimulation. There was a significant interaction between laser type and skin type (RM-ANOVA, p < 0.05) likely due to smaller CO LEPs in the palm. CO stimuli to the palm also elicited significantly lower perceived intensities. The computational model showed that the observed differences were explainable by the laser absorption characteristics and skin thickness affecting the temperature profile at the dermo-epidermal junction (DEJ). This study shows that LEP elicitation depends on the combination of laser penetrance and skin type. Low penetrance stimuli, from a CO laser, elicited significantly lower LEPs and perceived intensities in the palm. This study showed that the elicitation of laser-evoked potentials in healthy humans greatly depends on the combination of laser stimulator type and skin type. It was shown that high penetrance laser stimuli are capable of eliciting responses in both hairy and glabrous skin, whereas low penetrance stimuli barely elicited responses from the glabrous skin. Computational modelling was used to demonstrate that the results could be fully explained by the combination of laser type and skin thickness