Biology subjects

Fardo, F.

Publications and source records attributed to Fardo, F..

16 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

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.

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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.

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bioRxiv2025

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.

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bioRxiv2025

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.

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bioRxiv2024

Body-wandering reveals an embodied dimension of thought with distinct affective and neural signatures

When at rest, the mind becomes preoccupied with self-generated thoughts, commonly known as mind-wandering. While the social, autobiographical, and temporal features of these thoughts have been extensively studied, little is known about how frequently the wandering mind turns towards the interoceptive and somatic body. To map this under-explored component of "body-wandering," we conducted a large-scale neuroimaging study in 536 healthy participants, expanding a retrospective multidimensional experience sampling approach to include probes targeting visceral and somatomotor thoughts. Our findings reveal a robust inter-individual dimension of body-wandering characterized by negative affect, high autonomic arousal, and a reduction in socially oriented thoughts. Despite this negative tone, individual differences in the propensity for body-wandering were associated with lower self-reported symptoms of ADHD and depression. Multivariate functional connectivity analyses further revealed that affective, body-oriented thoughts are related to a pattern of thalamocortical connectivity interlinking somatomotor and interoceptive-allostatic cortical networks. Collectively, these results demonstrate that self-generated thoughts exhibit core embodied features which are linked to the ongoing physical and emotional milieu of the visceral body. Significance statementNeuroimaging studies often treat the resting state as a purely cognitive baseline, overlooking the participants embodied experience within the scanner. Here we show that individuals robustly vary in their degree of body-wandering, such that a more somatically focused stream of thought is associated with negative affect, higher arousal, and increased thalamocortical-somatomotor connectivity. Paradoxically, while this state is experienced negatively in the moment, the propensity for embodied mind-wandering correlates with reduced trait level symptoms of depression and ADHD. Collectively, these findings indicate that we must account for the embodied nature of the resting mind to fully understand the neural and clinical mechanisms of self-generated thought.

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bioRxiv2024

Microstructural Brain Correlates of Inter-individual Differences in Respiratory Interoception

Interoception, the perception and integration of physiological signals, is a fundamental aspect of self-awareness and homeostasis. While previous work has explored interoceptive processing in relation to the cardiac system, research in the respiratory domain, particularly in relation to brain structure and function, is limited. To address this gap, we utilised a Bayesian psychophysical model to quantify perceptual, metacognitive, and affective dimensions of respiratory interoception in a sample of 207 healthy participants. We also measured individual whole-brain microstructural indices of myelination, myeloarchitecture, and cortical iron using quantitative brain imaging. Voxel-based quantification analyses revealed distinct patterns of cortical microstructure in the insular, cingulate, and primary sensory cortices, which underpin interoceptive perceptual sensitivity and precision. In addition, metacognitive bias was associated with increased myelination of the cingulate cortex and periaqueductal grey, while metacognitive sensitivity correlated with myelination of the midline prefrontal cortex. At an affective level, sensitivity to respiratory resistance was related to the myelination of the primary somatosensory cortex. By revealing specific histological brain patterns tied to individual differences in respiratory interoception, our results uncover the neural pathways that govern perceptual, metacognitive, and emotional facets of interoceptive processing.

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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.

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bioRxiv2024

The respiratory cycle modulates distinct dynamics of affective and perceptual decision-making

Respiratory rhythms play a critical role not only in homeostatic survival, but also in modulating other non-interoceptive perceptual and affective processes. Recent evidence from both human and rodent models indicates that neural and behavioural oscillations are influenced by respiratory state as breathing cycles from inspiration to expiration. To explore the mechanisms behind these effects, we carried out a psychophysical experiment where 41 participants categorised dot motion and facial emotion stimuli in a standardised discrimination task. When comparing behaviour across respiratory states, we found that inspiration accelerated responses in both domains. We applied a hierarchical evidence accumulation model to determine which aspects of the latent decision process best explained this acceleration. Computational modelling showed that inspiration reduced evidential decision boundaries, such that participants prioritised speed over accuracy in the motion task. In contrast, inspiration shifted the starting point of affective evidence accumulation, inducing a bias towards categorising facial expressions as more positive. These findings provide a novel computational account of how respiratory rhythms modulate distinct aspects of perceptual and affective decision-dynamics.

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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.

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bioRxiv2024

Supramodal neural information supports stimulus-driven attention across cortical levels

Predictive coding posits that the brain actively anticipates inputs from different senses, generating prediction errors when incoming information deviates from internal expectations. While much research has focused on prediction errors elicited by violations of single sensory features, natural environments frequently present more complex events deviating across multiple stimulus dimensions and sensory modalities. In this study, we employed a hierarchical oddball paradigm (n=30) manipulating auditory and somatosensory stimuli to violate one or two sensory features while high-density EEG was recorded. Temporal decoding revealed that while both single- and double-deviants evoked sustained supramodal activation patterns, double-deviants uniquely elicited a supramodal response starting at 100 ms after the oddball. Effective connectivity analyses identified shared interhemispheric interactions between inferior frontal gyri across modalities, as well as distinct modality-specific connectivity within early and associative sensory cortices. Our findings demonstrate that multi-feature prediction errors recruit both rapid supramodal integration mechanisms and hierarchically organized modality-specific pathways. These results advance our understanding of how the brain flexibly integrates multiple sensory expectation violations across different levels of cortical processing, providing new insights into the neural architecture supporting predictive perception. Author summaryThe brain constantly generates predictions about incoming sensory information. While many studies focus on simple violations of individual features, real-life events often involve simultaneous deviations across multiple sensory attributes. Our goal was to examine supramodal or modality-specific aspects of multi-feature prediction errors. Considering that the cortex needs to converge individual predictions from multiple pathways for multi-feature prediction, we hypothesised that multi-feature prediction errors rely on a mid-latency supramodal process in the inferior frontal cortex. In a high-density EEG study using a nested oddball paradigm, we examined neural responses to somatosensory and auditory stimulus deviations in one or two dimensions. Using temporal decoding, we revealed an early supramodal short-lived cortical process when double-deviants are detected. We also applied Parametric Empirical Bayes Modelling to show that multi-feature prediction errors not only rely on a common interhemispheric inhibition between inferior frontal gyri but also on various supramodal and modality-specific changes in effective connectivity across associative and modality-specific cortices.

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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.

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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.

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bioRxiv2021

The Respiratory Resistance Sensitivity Task: An Automated Method for Quantifying Respiratory Interoception and Metacognition

The ability to sense, monitor, and control respiration - e.g., respiratory interoception (henceforth, respiroception) is a core homeostatic ability. Beyond the regulation of gas exchange, enhanced awareness of respiratory sensations is directly related to psychiatric symptoms such as panic and anxiety. Indeed, chronic breathlessness (dyspnea) is associated with a fourfold increase in the risk of developing depression and anxiety, and the regulation of the breath is a key aspect of many mindfulness-based approaches to the treatment of mental illness. Physiologically speaking, the ability to accurately monitor respiratory sensations is important for optimizing cardiorespiratory function during athletic exertion, and can be a key indicator of illness. Given the important role of respiroception in mental and physical health, it is unsurprising that there is increased interest in the quantification of respiratory psychophysiology across different perceptual and metacognitive levels of the psychological hierarchy. Compared to other more popular modalities of interoception, such as in the cardiac domain, there are relatively few methods available for measuring aspects of respiroception. Existing inspiratory loading tasks are difficult to administer and frequently require expensive medical equipment, or offer poor granularity in their quantification of respiratory-related perceptual ability. To facilitate the study of respiroception, we here present a new, fully automated and computer-controlled apparatus and psychophysiological method, which can flexibly and easily measure respiratory-related interoceptive sensitivity, bias and metacognition, in as little as 30 minutes of testing, using easy to make 3D printable parts.

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bioRxiv2021

The heart rate discrimination task: a psychophysical method to estimate the accuracy and precision of interoceptive beliefs

Interoception - the physiological sense of our inner bodies - has risen to the forefront of psychological and psychiatric research. Much of this research utilizes tasks that attempt to measure the ability to accurately detect cardiac signals. Unfortunately, these approaches are confounded by well-known issues limiting their validity and interpretation. At the core of this controversy is the role of subjective beliefs about the heart rate in confounding measures of interoceptive accuracy. Here, we recast these beliefs as an important part of the causal machinery of interoception, and offer a novel psychophysical "heart rate discrimination" method to estimate their accuracy and precision. By applying this task in 223 healthy participants, we demonstrate that cardiac interoceptive beliefs are more biased, less precise, and are associated with poorer metacognitive insight relative to an exteroceptive control condition. Our task, provided as an open-source python package, offers a robust approach to quantifying cardiac beliefs. HighlightsO_LICurrent interoception tasks conflate cardiac beliefs with accuracy. C_LIO_LIWe introduce a Bayesian method for estimating cardiac belief accuracy and precision. C_LIO_LIIndividuals underestimate their heart rate by -7 BPM (95% CI [-8.6 -5.3]) on average. C_LIO_LICardiac beliefs are associated with reduced precision and metacognitive insight. C_LIO_LIThe task and modelling tools are provided in the Python Cardioception Package. C_LI

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bioRxiv2020

Emotional Metacognition: Stimulus Valence Modulates Cardiac Arousal and Metamemory

Emotion alters how we feel, see, and experience the world. In the domain of memory, the emotional valence and arousal of memorised stimuli can modulate both the acuity and content of episodic recall. However, no experiment has investigated whether arousal and valence also influence metacognition for memory (i.e., the process of self-monitoring memories). In a pre-registered study, we applied a novel psychophysiological design together with computational models of metacognition to assess the influence of stimulus valence and arousal on the sensitivity, bias, and efficiency of metamemory. To estimate the role of physiological arousal in mediating these effects, we recorded cardiac measures through pulse oximetry. We found that negative valence substantially decreased both memory performance and subjective confidence, in particular for low arousal words. Simultaneously, we found that emotional valence modulated both heart rate and heart-rate variability (HRV) during recognition memory. Exploratory trial-level analyses further revealed that subjective confidence was encoded in instantaneous heart-rate fluctuations and that this relationship was also modulated by emotional valence. Our results demonstrate that recognition memory and metacognition are influenced by the emotional valence of encoded items and that this correlation is in part related to cardiac activity.

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