Biology subjects

Wiech, K.

Publications and source records attributed to Wiech, K..

8 recordsLinked to original sources

bioRxiv2026

Beyond pain: a brain-based biomarker predicts individual pain relief

Effective pain relief is a central goal of medical care, yet objective biomarkers of pain relief are lacking. Using task-based functional MRI and a capsaicin-induced tonic heat pain model, we experimentally elicited both pain exacerbation and pain relief within the same individuals. Existing brain-based signatures, including the Neurologic Pain Signature (NPS), reliably detected pain increases, but failed to capture pain relief. We therefore developed the PAin and RElief Signature (PARES), a multivariate brain signature trained to predict bidirectional changes in pain perception in n = 61 healthy controls. PARES robustly predicted both pain increases and relief and generalized to an independent cohort of people with chronic back pain (n = 58), who underwent the same experimental procedures. Together these findings establish a neural signature of pain relief and provide a potential biomarker for treatment stratification and analgesic development.

neuroscience↗

bioRxiv2026

Layer-specific cortical processing dissociates sensory and cognitive influences on pain

Pain arises from the integration of nociceptive input with cognitive and affective processes, yet how these signals are organized within cortical circuits remains unclear. Here, using submillimeter-resolution 7T fMRI, we tested whether bottom-up (BU) and top-down (TD) influences on pain are segregated across cortical layers in human sensory-discriminative regions. Participants underwent a factorial manipulation of nociceptive input and cognitive modulation, enabling dissociation of BU and TD processes. BU processing was strongest in middle cortical layers. In contrast, TD modulation preferentially engaged superficial layers, consistent with cortico-cortical feedback mechanisms. Critically, individual differences in this laminar segregation predicted the magnitude of distraction-induced analgesia, linking circuit-level organization to behavior. These findings provide evidence that cognitive modulation of pain is implemented through layer-specific cortical computations and extend canonical microcircuit models to human pain processing. More generally, they establish laminar fMRI as a powerful approach for linking cortical circuit architecture to subjective experience.

neuroscience↗

bioRxiv2025

Meta-analytic evidence for distinct neural correlates of conditioned vs. verbally induced placebo analgesia

Placebo analgesia demonstrates that belief and expectation can significantly alter pain, even without active treatment. Placebo analgesia can be induced through verbal suggestion, classical conditioning, or their combination, though the role of conditioned neural responses above and beyond effects of verbal instructions remains unclear. We conducted a systematic meta-analysis of individual participant data from 16 within-participant placebo neuroimaging studies (n = 409), employing univariate and multivariate analyses to identify shared and distinct mechanisms of placebo analgesia induced by suggestions alone versus suggestions combined with conditioning. Both techniques increased activity during pain in the dorsolateral prefrontal and inferior parietal cortices and decreased activation in the insula, putamen, and primary sensory areas. Adding conditioning enhanced engagement of regions associated with context representation and pain modulation (e.g., dorsolateral/dorsomedial prefrontal cortices) and decreases in nociceptive regions (e.g., primary sensory and insular areas). Conditioning also strengthened the association between analgesia and nociceptive activity, as reflected in the Neurologic Pain Signature. Combining conditioning with instructions yielded greater analgesia, mediated by increased ventromedial prefrontal and dorsal caudate activity, alongside decreased sensory-nociceptive and cerebellar activity. These findings suggest the two strategies rely on partially distinct mechanisms, which could be combined to optimize placebo analgesias clinical application.

neuroscience↗

bioRxiv2025

Common and distinct neural mechanisms of aversive and appetitive pain-related learning

Appetitive and aversive conditioning are both fundamental to adaptive behaviour, yet there remains limited understanding of how they differ on the behavioural and neural level. We investigated the two processes during acquisition and extinction using functional magnetic resonance imaging and behavioural measures. In a within-subject differential conditioning paradigm (preregistration DRKS00027448), aversive learning was induced by pairing visual cues with a temperature increase (pain rise), while appetitive learning involved a temperature decrease (pain reduction). Valence and contingency ratings confirmed successful learning for both types of learning, though only the appetitive condition showed a return to baseline ratings during extinction, suggesting incomplete extinction in the aversive condition. On the neural level, both engaged the visual cortex during acquisition (with increased functional connectivity with the right frontal operculum) and the ventromedial prefrontal cortex (vmPFC) during extinction. However, aversive learning showed a stronger activation increase in the mediodorsal thalamus with heightened connectivity with the locus coeruleus during acquisition, as well as sustained parahippocampal activity during extinction. Moreover, incomplete extinction in the aversive condition (as indicated by contingency ratings) was associated with sustained activity in the visual cortex during pain anticipation. These results suggest that while appetitive and aversive learning share activation in regions involved in sensory processing (occipital lobe) and learning (vmPFC), aversive learning uniquely engages areas promoting rapid acquisition (mediodorsal thalamus and locus coeruleus) and cautious unlearning, in line with the notion of a better-safe-than-sorry strategy.

neuroscience↗

bioRxiv2022

Trait anxiety is associated with hidden state inference during aversive reversal learning

Updating beliefs in changing environments can be driven by gradually adapting expectations or by relying on inferred hidden states (i.e., contexts), and changes therein. Previous work suggests that increased reliance on context could underly fear relapse phenomena that hinder clinical treatment of anxiety disorders. We test whether trait anxiety variations in a healthy population influence how much individuals rely on hidden-state inference. In a Pavlovian learning task, participants observed cues that predicted an upcoming electrical shock with repeatedly changing probability, and were asked to provide expectancy ratings on every trial. We show that trait anxiety is associated with steeper expectation switches after contingency reversals and reduced oddball learning. Furthermore, trait anxiety is related to better fit of a state inference compared to a gradual learning model when contingency changes are large. Our findings support previous work suggesting hidden-state inference as a mechanism behind anxiety-related to fear relapse phenomena.

neuroscience↗

bioRxiv2020

Is there a neuropathic-like component to endometriosis-associated pain? Results from a large cohort questionnaire study

BackgroundPain is one of the primary symptoms of endometriosis, a chronic inflammatory condition characterised by the presence of endometrial tissue outside the uterus. Endometriosis-associated pain is commonly considered as nociceptive in nature but its clinical presentation suggests that it might have neuropathic-like properties in a subgroup of patients. MethodsThis is a cross sectional study using an online survey. The survey was distributed by patient support websites. The survey was composed of validated questionnaires assessing pain symptoms, psychological measures and questions about number of surgeries. Main results and the role of chanceWe had 1417 responses which met the inclusion criteria. Using standard painDETECT cut-off scores, we found that pain was classified as neuropathic in 40% of patients and as mixed neuropathic/nociceptive in a further 35%. In line with observations in other neuropathic conditions, the neuropathic subgroup reported higher pain intensities, greater psychological distress and cognitive impairment. Neuropathic pain was also more likely in those with more surgeries to the abdomen and a longer history of pain. As revealed by a cluster analysis, those with a neuropathic pain component could further be divided into two subgroups based on their sensory profile. ConclusionsThe data presented here indicate that endometriosis-associated pain includes a neuropathic-like component in a substantial proportion of women. Although further investigation is required, our finding challenges the current conceptualisation of endometriosis-associated pain as nociceptive and advocates for a new perspective on this type of pain, which is so debilitating to a large number of women.

neuroscience↗

bioRxiv2018

Cortico-brainstem mechanisms of biased perceptual decision-making in the context of pain

Perceptual decision-making is commonly studied using stimuli with different physical properties but of comparable affective value. Here, we investigate neural processes underlying human perceptual decisions in the affectively rich domain of pain using a drift-diffusion model in combination with a probabilistic cueing paradigm. This allowed us to characterize a novel role for the dorsolateral prefrontal cortex (DLPFC), whose anticipatory responses reflecting a decision bias were dependent on the affective value of the stimulus. During intense noxious stimulation, these model-based anticipatory DLPFC responses were linked to an engagement of the periaqueductal gray (PAG), a midbrain region implicated in defensive responses including analgesia. Complementing these findings on biased decision-making, the model parameter reflecting sensory processing predicted subcortical responses (in amygdala and PAG) when expectations were violated. Our findings highlight the importance of taking a broader perspective on perceptual decisions and link decisions about pain with subcortical circuitry implicated in endogenous pain modulation.

neuroscience↗

bioRxiv2017

Treating the lungs via the brain: Mechanisms underpinning improvements in breathlessness with pulmonary rehabilitation.

BackgroundBreathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (\"over-perception\"). Pulmonary rehabilitation has profound effects upon breathlessness, without influencing lung function. Learned associations can influence brain mechanisms of sensory perception. We therefore hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations, reducing \"over-perception\".\n\nMethodsIn 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during learned associations with a word-cue task (using functional magnetic resonance imaging), clinical, and psychological measures of breathlessness.\n\nResultsImprovements in breathlessness and breathlessness-anxiety correlated with reductions in word-cue related activity in the insula and anterior cingulate cortex (ACC) (breathlessness), and increased activations in attention regulation and motor networks (breathlessness-anxiety). Greater baseline (pre-rehabilitation) activity in the insula, ACC and prefrontal cortex correlated with the magnitude of improvement in breathlessness and breathlessness anxiety.\n\nConclusionsPulmonary rehabilitation reduces the influence of learned associations upon neural processes that generate breathlessness. Patients with stronger word-cue related activity at baseline benefitted more from pulmonary rehabilitation. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.

neuroscience↗