Search bioRxiv⌕ Search

Biology subjects

Courtin, A. S.

Publications and source records attributed to Courtin, A. S..

11 recordsLinked to original sources

Perceiving less or perceiving unreliably? Disentangling thermosensory sensitivity and precision in the contexts of ageing and neuropathy

Thermal perception is determined not only by sensitivity but also by precision. Yet, the latter is often overlooked in thermosensation and pain research. This study examined how ageing and diabetic polyneuropathy (DPN) affect these parameters and whether assessing both sensitivity and precision can aid in distinguishing patients from healthy controls. Using Bayesian hierarchical models, we estimated psychometric function thresholds (sensitivity) and slopes (precision) for cold detection, warm detection, cold pain, and heat pain stimuli delivered at the volar forearm, in a cross-sectional sample of 75 healthy adults (aged 21-80) and 33 patients with DPN. We also estimated these parameters separately for each participant and used the resulting estimates in classification analyses. Ageing was associated with elevated cold and warm detection thresholds, elevated cold pain thresholds, and reduced cold detection slope. Patients with DPN showed similar patterns: higher detection thresholds and lower cold detection slopes while pain-related parameters were largely unaffected. These findings indicate that ageing and neuropathy produce qualitatively similar changes in thermosensory function, particularly affecting cold detection. Classification based on single parameters successfully discriminated patients from controls, except when warm detection or heat pain slopes were used. Combining threshold and slope parameters for a given modality did not significantly improve classification accuracy but combining all parameters across all modalities led to the best performance, with excellent accuracy (AUROCC: .84, 95% CI [.75.91]). Modelling both thresholds and slopes provides a more comprehensive view of sensory decline and may enhance the detection of early or subtle sensory dysfunction. PerspectiveThis study shows that ageing and diabetic polyneuropathy produce strikingly similar thermosensory changes, affecting cold detection sensitivity and precision as well as warm detection sensitivity while largely sparing pain-related measures.

neuroscience↗

Hierarchical Bayesian Modelling of Interoceptive Psychophysics

Interoception, the capacity to sense, perceive, and metacognitively appraise viscerosensory and homeostatic signals, is a growing focus in psychology and psychiatry. Adaptive psychophysical tasks now allow quantification of perceptual sensitivity, bias, and precision in cardiac and respiratory domains. However, accurately estimating these parameters often requires large numbers of trials or participants, posing practical challenges, especially in clinical research where participant availability and tolerance are limited. One approach to reduce participant burden while maintaining statistical rigour is to optimise data analysis. Here, we present hierarchical Bayesian models tailored for cardiac and respiratory interoceptive psychophysics that efficiently estimate sensitivity, bias, and precision at both individual and group levels. Using simulations and empirical data, we validate these models and demonstrate that they allow enhanced inference relative to conventional approaches. To support adoption, we provide openly-accessible resources, including a tutorial on how to implement and fit these models in R (written with researchers without modelling expertise in mind) and an app for sample-size justification. These tools facilitate robust, efficient, and generalisable modelling of interoceptive performance, enabling rigorous studies even with limited trials or participant availability.

neuroscience↗

Modelling perceptual uncertainty in a thermosensory illusion across the lifespan

Most studies of perceptual illusions rely on explicit reports alone, offering a limited view into the computations that underlie ambiguous sensory experiences. Here, we introduce a multivariate computational approach to model paradoxical heat sensation (PHS), a thermosensory illusion in which skin cooling evokes sensations of warmth, as an individual-specific process. We tested 75 healthy adults (aged 21-80) using a perceptual decision-making task with stimuli designed to elicit PHS. Binary perceptual choices, response times and confidence ratings were jointly analysed using hierarchical multivariate Bayesian modelling to characterise PHS at both the population and individual levels across the lifespan. We tested two distinct perceptual profiles: "true perceivers", who experience PHS similarly to a veridical warm percept; and "unsure perceivers", who perceive PHS as an ambiguous experience. At the group level, behaviour was best explained by the unsure perceiver model, suggesting that PHS is often an uncertain experience, rather than a categorical misperception. At the individual level, however, both profiles were represented, with considerable inter-individual variability in model fit. Older participants were more likely to report PHS and did so at lower levels of thermal contrast, but we observed no correlation between age and perceptual profile. This suggests that while ageing increases the likelihood of experiencing PHS, it does not alter the qualitative nature of its perception. These findings also show how multivariate modelling of perceptual, decisional and metacognitive responses can reveal distinct, subjective profiles and their variation across individuals and age.

neuroscience↗

Sensory-evoked perturbational complexity in human EEG: Effects of stimulus temperature and peripheral sensitisation in nociceptive processing

While painful and non-painful thermal stimuli elicit a rich dynamical pattern of brain activity, canonical event related potentials (ERP) analyses quantify only limited aspects of this pattern. In this study, we complement the conventional ERP approach by quantifying the spatial and temporal differentiation of EEG responses to thermal stimulation using the perturbational complexity index (PCI), a complexity metric grounded in systems dynamic and information theory. Using two publicly available datasets, we computed state-transition PCI from thermal-evoked responses recorded over 32-64 scalp channels. Dataset 1 combined three stimulus intensities (10 {degrees}C, 42 {degrees}C, 60 {degrees}C) with topical application of thermosensitive TRP-channel agonists (menthol 20 %, capsaicin 1 %) or vehicle; Dataset 2 manipulated the block-wise transition probability of receiving cold ({approx} 15 {degrees}C) or hot ({approx} 58 {degrees}C) stimulation. PCI scaled non-linearly with temperature, being lowest at the intermediate 42 {degrees}C and highest at the cold and hot extremes (Datasets 1 and 2). PCI was sensitive both to peripheral sensitisation, as topical menthol and capsaicin selectively reduced PCI during cold stimulation (Dataset 1), and to changes in block-wise stimulus probability (Dataset 2). Across all analyses, canonical ERP peak measures (N2-P2 amplitude/latency) failed to account for PCI variance. These findings demonstrate that PCI reflects the brains response to exogenous, sensory-driven thermal perturbations, quantifying changes in neural complexity associated with both stimulus intensity, peripheral sensitisation and probabilistic manipulations. This supports its applicability as a measure of temporal and spatial differentiation in EEG responses relevant to pain neuroscience. SummaryThis study quantified the spatio-temporal complexity of electroencephalographic responses to thermal and pain stimuli. Complexity was sensitive to simulation temperature, chemical sensitization and probabilistic manipulations.

neuroscience↗

Interindividual variations in peak alpha frequency do not predict the magnitude or extent of secondary hyperalgesia induced by high-frequency stimulation

BackgroundPrevious studies have shown an association between interindividual variations in the frequency of alpha-band EEG oscillations such as estimates of peak alpha frequency (PAF) and pain sensitivity. Whether differences in PAF also influence the susceptibility to develop central sensitization (CS) is unknown. ObjectiveThis study aimed to determine if the PAF of vision- and sensorimotor-related alpha-band activity is associated with the magnitude and extent of secondary mechanical hyperalgesia induced by high-frequency stimulation (HFS) of the skin, a surrogate marker of CS. MethodsThe EEG was recorded in 32 healthy participants at rest during eyes open and eyes closed conditions, and during bilateral finger movements. Two methods were used to isolate vision- and sensorimotor-related alpha-band activity based on sensitivity to eye closure and movement: one based on an independent component analysis, the other on spectral subtraction. PAF was assessed using a center-of-gravity approach or the Fitting Oscillations and One-Over-F (FOOOF) method, accounting for the aperiodic EEG component. HFS was applied to the right forearm, and pinprick sensitivity was assessed at both forearms, before and 40 minutes after HFS. ResultsNeither sensorimotor-nor vision-related PAF were significantly correlated with the magnitude or extent of HFS-induced secondary hyperalgesia. Interestingly, at the non-sensitized forearm, participants with a higher vision-related PAF exhibited greater habituation to pinprick stimuli, suggesting that variations in PAF may relate to variations in sensory habituation. ConclusionInterindividual variations of PAF were not significantly associated with the susceptibility to develop HFS-induced secondary hyperalgesia. New and NoteworthyUsing several methods to estimate vision- and sensorimotor-related peak alpha frequency (PAF) in the EEG frequency spectrum, we found no significant association between interindividual variations in PAF and the susceptibility to develop secondary hyperalgesia following high-frequency stimulation (HFS) of the skin in healthy participants.

neuroscience↗

Peripheral Beta-Blockade Differentially Enhances Cardiac and Respiratory Interoception

Interoception, the perception of internal visceral states, arises from complex brain-body interactions across the central and peripheral nervous systems. Despite noradrenalines key role in these interactions, its specific contribution to interoceptive processes remains unclear. In a placebo-controlled, randomised, within-subject study, we employed computational modelling of interoceptive psychophysics to determine how pharmacological beta-adrenoceptor antagonism controls interoception across cardiac and respiratory domains. Both cardio-selective bisoprolol and non-selective propranolol improved cardiac perceptual sensitivity, with bisoprolol exerting an enhanced effect on cardiac metacognition. In contrast, both beta-blockers increased respiratory perceptual precision, with no corresponding changes in sensitivity or metacognition. These findings reveal a novel dissociation between central and peripheral beta-adrenergic mechanisms in interoception, highlighting the pivotal role of peripheral noradrenaline in regulating multi-organ brain-body interactions. Our results suggest that beta-blockers may provide promising routes for modulating distinct facets of interoception, potentially opening new avenues for intervention in conditions characterised by disrupted bodily self-awareness.

neuroscience↗

Uncertainty in Thermosensory Expectations Enhances an Illusion of Pain

The human brain has a remarkable ability to learn and update its beliefs about the world. Here, we investigate how thermosensory learning shapes our subjective experience of temperature and the misperception of pain in response to harmless thermal stimuli. Through computational modeling, we demonstrate that the brain uses a probabilistic predictive coding scheme to update beliefs about temperature changes based on their uncertainty. We find that these expectations directly modulate the perception of pain in the thermal grill illusion. Quantitative microstructural brain imaging revealed that the myeloarchitecture and iron content of the somatosensory cortex, the posterior insula and the amygdala reflect inter-individual variability in computational parameters related to learning and the degree to which uncertainty modulates illusory pain perception. Our findings offer a new framework to explain how the brain infers pain from innocuous thermal inputs. Our model has important implications for understanding the etiology of thermosensory symptoms in chronic pain conditions.

neuroscience↗

Assessing Individual Sensitivity to the Thermal Grill Illusion: A Two-Dimensional Adaptive Psychophysical Approach

In the thermal grill illusion (TGI), the spatial alternation of non-noxious warm and cold temperatures elicits burning sensations that resemble the presence of noxious stimuli. Previous research has largely relied on the use of specific temperature values (i.e., 20{degrees}C and 40{degrees}C) to study this phenomenon in both healthy individuals and patient populations. However, this methodology fails to account for inter-individual differences in thermal sensitivity, limiting the precision with which TGI responses can be evaluated across diverse populations. To address this gap, we created a Two-Dimensional Thermal Grill Calibration (2D-TGC) protocol, enabling an efficient and precise estimation of the combinations of warm and cold temperatures needed to elicit burning sensations tailored to each individual. By applying the 2D-TGC protocol in 43 healthy participants, we demonstrated key findings: (1) The TGI can be thresholded using an adaptive psychophysical method. (2) Multiple combinations of warm and cold temperatures can elicit this phenomenon. (3) The protocol facilitated the identification of temperature combinations that elicit TGI with varying levels of probability, intensity, and perceived quality ranging from freezing cold to burning hot. (4) TGI responsivity can be quantified as a continuous variable, moving beyond the conventional classification of individuals as responders vs. non-responders based on arbitrary temperature values. The 2D-TGC offers a comprehensive approach to investigate the TGI across populations with altered thermal sensitivity, and can be integrated with other methods (e.g., neuroimaging) to elucidate the mechanisms responsible for perceptual illusions in the thermo-nociceptive system.

neuroscience↗

Evidence of interplays between the vascular and nociceptive systems revealed by changes in capsaicin pain caused by limb position change

This experiment aimed at confirming our incidental observation that, when capsaicin is applied on the volar forearm, raising the arm to a vertical position leads to a dramatic increase in capsaicin-evoked pain and to explore possible underlying mechanisms. Twenty healthy volunteers received a 2% capsaicin patch on one forearm and a vehicle patch on the other. Patches were kept in place for 60 minutes. The sensation caused by the patch was assessed repeatedly -in resting position and when the arm was raised vertically-before, during and after patch application. In addition, capsaicin-induced secondary hyperalgesia was assessed using mechanical pinprick stimuli. Half of the participants were seated upright while the other half were lying supine, to assess whether the effect of limb position was due to gravity. After a few minutes of patch application, raising the capsaicin treated arm (but not the vehicle treated arm) led to a strong increase of the pain experienced at the patch. This effect of raising the arm did not differ between participants in the supine and seated groups and is therefore likely related to the position of the arm relative to the ground (gravity) rather than to the body. Mechanical secondary hyperalgesia and the arm raising effect were strongly decorrelated at the last time point after patch removal, indicating different underlying mechanisms. Our results indicate that capsaicin-evoked pain can be strongly modulated by limb posture and that this effect may be caused by an interplay between vascular and nociceptive systems.

neuroscience↗

Exploration of the EEG response to periodic thermal and vibrotactile stimuli

Under certain conditions, a stimulus applied at a given frequency will lead to a periodic variation of neural activity at the same frequency. Taking advantage of this periodicity, it is possible to tag this response in the EEG frequency spectrum. Frequency tagging of sustained periodic noxious heat stimuli led to the recording of phase-locked and non-phase-locked responses whose functional significance remains unclear. This study aimed at assessing whether such responses can also be recorded during the repetitive presentation of brief innocuous cold, noxious heat and vibrotactile stimuli. Comparison between the responses obtained with different stimulation modalities should inform us on the nature of the neural processes underlying these responses (modality aspecific, somatosensory, thermosensory, nociceptive). Comparison between upper and lower limb stimulation should inform us on the somatotopic organization of these responses and, therefore, on their potential sources. Based on our results, on one hand, trains of brief innocuous cold, noxious heat and vibrations can elicit phase-locked and non-phase-locked responses which appear highly similar to those evoked by sustained periodic noxious heat stimuli when frequency tagged. On the other hand, when analysed in the time domain or using time-frequency decomposition, these responses appeared highly similar to those that can be recorded following isolated brief noxious heat or tactile stimuli. These responses consisted in phase-locked activity corresponding to the vertex potential, thought to reflect modality non-specific attentional processes, and in an alpha-to-beta ERD originating in the S1/M1 area contralateral to the stimulated hand, probably reflecting non-specific somatosensory activity.

neuroscience↗

Temporal Contrast Enhancement in Thermosensation: A Framework for Understanding Paradoxical Heat Sensation

Paradoxical Heat Sensation (PHS) is the remarkable feeling of warmth or heat pain while the skin is cooling. Despite its initial documentation over 100 years ago, a unified explanation for this perplexing experience remains elusive. Here we apply contrast enhancement principles, known for their instrumental role in understanding visual illusions, to the domain of thermosensation. Contrast enhancement describes the amplification of two contrasting visual features, such as the enhanced perception of an edge between a light and dark bar. In thermosensation, this encompasses an enhancement of the difference between sequential warming and cooling of the skin, and is defined as the normalised difference between successive temporal warm and cold temperatures. Remarkably, thermal contrast predicts the occurrence of PHS. Our findings reveal compelling evidence supporting the role of thermal contrast in the generation of PHS, shedding light on its underlying mechanism and offering a framework for broader encoding principles in thermosensation and pain.

neuroscience↗