Biology subjects

Mitchell, A. G.

Publications and source records attributed to Mitchell, A. G..

6 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2025

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↗

bioRxiv2024

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↗

bioRxiv2024

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↗

bioRxiv2023

Disentangling the spinal mechanisms of illusory heat and burning sensations in the Thermal Grill Illusion

The Thermal Grill Illusion (TGI), a phenomenon in which the juxtaposition of innocuous warm and cold temperatures on the skin elicits a burning sensation, offers a unique perspective to how pain occurs in response to harmless stimuli. We investigated the role of the spinal cord in the generation of the TGI across two experiments (total n = 80). We applied heat and cold stimuli to dermatomes, areas of skin innervated by a single spinal nerve, that mapped onto adjacent or nonadjacent spinal segments. Enhanced warm and burning ratings during the TGI were observed when cold and warm stimuli were confined within the same dermatome. Further, we found the spatial organisation of warm and cold stimuli within and across dermatomes affected TGI perception. Perceived warmth and burning intensity increased when the cold stimulus projected to the segment more caudal to the warm stimulus, whilst perceived cold during the TGI decreased, compared to the opposite spatial arrangement. This suggests the perception of TGI is enhanced when cold afferents are projected to spinal segments positioned caudally in relation to those receiving warm afferents. Our results indicate distinct interaction of sensory pathways based on the segmental arrangement of afferent fibres and are consistent with current interpretations of the spread and integration of thermosensory information along the spinal cord.

neuroscience↗

bioRxiv2023

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↗