Biology subjects

Buechel, C.

Publications and source records attributed to Buechel, C..

11 recordsLinked to original sources

bioRxiv2026

Conditioned pain modulation recruits the descending pain modulatory system to inhibit spinal activity

Conditioned pain modulation (CPM) is a phenomenon where the perception of pain is reduced in the presence of a second painful stimulus. In rodents, a similar phenomenon involves descending control pathways that rely on the brainstem to modulate spinal cord activity while in humans, descending mechanisms including the spinal cord remain elusive. In this study, we applied functional MRI to simultaneously record brain and spinal cord responses during CPM in healthy participants. CPM developed over time and was associated with reduced activity in key pain-related brain regions and the spinal cord dorsal horn. Conversely, regions involved in descending pain modulation showed increased activity during CPM. Functional connectivity analyses revealed reduced coupling during CPM between spinal and descending control regions. Our findings demonstrate that CPM involves both the descending pain control system to inhibit spinal activity and bottom-up pain signalling of attenuated spinal responses.

neuroscience↗

bioRxiv2026

Noninvasive and Objective Near Real-Time Detection of Pain Changes in Fluctuating Pain

Chronic pain involves natural intensity fluctuations that patients cannot control, contributing to learned helplessness and functional impairment. Detecting spontaneous pain decreases could enable precisely timed interventions that enhance perceived control. However, existing research on objective pain assessment has focused primarily on estimating static intensity from short, predictable stimuli rather than detecting moment-to-moment changes in ongoing pain. This study investigated whether pain decreases can be detected objectively using easily obtainable physiological signals during fluctuating pain. We recorded multiple physiological signals (8-channel EEG, electrodermal activity, heart rate, pupil diameter, facial expressions) from 42 healthy participants (Mage = 26.2 years, SD = 5.1) during calibrated tonic noxious heat stimulation on the left forearm with unpredictable intensity fluctuations (0-70 on visual analogue scale; twelve 3-minute trials). Temperature changes lasted 5-20 seconds. Using minimal preprocessing suitable for real-time applications, we trained deep learning models to classify pain decreases versus non-decreases from brief temporal windows, evaluated on a held-out test set (9 participants). Combining electrodermal activity, heart rate, and pupil diameter yielded optimal classification performance using a transformer-based architecture (AUROC = 0.854, accuracy = 76.8%). Electrodermal activity emerged as the most informative single predictor. Continuous stream analysis demonstrated median detection latency of 5.75 seconds with 70.4% sensitivity, reducible to 4.25 seconds at the cost of increased false positives. Results indicate that electrodermal activity and heart rate enable straightforward practical deployment, while highly variable signals such as EEG and facial expressions require personalized fine-tuned models. These findings establish a basis for closed-loop interventions targeting spontaneous pain changes. SummaryDeep learning models detect pain decreases using electrodermal activity, heart rate, and pupil diameter (AUROC=0.854, 5.75s latency), facilitating precisely timed interventions for fluctuating tonic pain.

neuroscience↗

bioRxiv2024

Exercise-induced pain modulation is sex, opioid, and fitness-dependent and mediated by the medial frontal cortex

Exercise might lead to a release of endogenous opioids, potentially resulting in pain relief. However, the neurobiological underpinnings of this effect remain unclear. Using a pharmacological within-subject fMRI study with the opioid antagonist naloxone and different levels of aerobic exercise and pain we investigated exercise-induced hypoalgesia (N = 39, 21 female). Overall, high-intensity aerobic exercise did not reduce pain as compared to low-intensity aerobic exercise. Accordingly, we observed no significant changes in the descending pain modulatory system. The {micro}-opioid antagonist naloxone significantly increased overall pain ratings but showed no interaction with exercise intensity. An exploratory analysis suggested an influence of fitness level (as indicated by the functional threshold power) and sex where males showed greater hypoalgesia after high-intensity exercise with increasing fitness levels. This effect was attenuated by naloxone and mirrored by fMRI signal changes in the medial frontal cortex, where activation also varied with fitness level and sex, and was reversed by naloxone. These results indicate that different aerobic exercise intensities have no differential effect on pain in a mixed population sample, but individual factors such as fitness level and sex might play a role. The current study underscores the need for personalised exercise interventions to enhance pain relief in healthy as well as chronic pain populations taking into account the sex and fitness status as well as the necessity to further investigate the opioidergic involvement in exercise-induced pain modulation.

neuroscience↗

bioRxiv2024

Molecular events accompanying aggregation-induced energy quenching in Fucoxanthin-Chlorophyll Proteins

In high light, the antenna system in oxygenic photosynthetic organisms switches to a photoprotective mode, dissipating excess energy in a process called non-photochemical quenching (NPQ). Diatoms exhibit very efficient NPQ, accompanied by a xanthophyll cycle in which diadinoxanthin is de-epoxidized into diatoxanthin. Diatoms accumulate pigments from this cycle in high light, and exhibit faster and more pronounced NPQ. The mechanisms underlying NPQ in diatoms remain unclear, but it can be mimicked by aggregation of their isolated light-harvesting complexes, FCP (fucoxanthin chlorophyll-a/c protein). We assess this model system by resonance Raman measurements of two peripheral FCPs, trimeric FCPa and nonameric FCPb, isolated from high- and low-light-adapted cells (LL, HL). Quenching is associated with a reorganisation of these proteins, affecting the conformation of their bound carotenoids, and in a manner which is highly dependent on the protein considered. FCPa from LL diatoms exhibits significant changes in diadinoxanthin structure, together with a smaller conformational change of at least one fucoxanthin. For these LL-FCPa, quenching is associated with consecutive events, displaying distinct spectral signatures, and its amplitude correlates with the planarity of the diadinoxanthin structure. HL-FCPa aggregation is associated with a change in planarity of a 515-nm-absorbing fucoxanthin, and, to a lesser extent, of diadinoxanthin. Finally, in FCPb, a blue-absorbing fucoxanthin is primarily affected. FCPs thus possess a plastic structure, undergoing several conformational changes upon aggregation, dependent upon their precise composition and structure. NPQ in diatoms may therefore arise from a combination of structural changes, dependent on the environment the cells are adapted to.

biophysics↗

bioRxiv2023

Expectation of mood improvement entails resource-dependent downregulation of negative inputs

BackgroundClinical trials of antidepressants show improvements in placebo groups of up to 80% compared to the real treatment arm. The mechanism underlying this clinically important effect has been linked to expectation induced goal-directed control. Here, we investigated how cognitive resources influence the effects of positive expectations on emotional processing. MethodsForty-nine healthy volunteers participated in a cross-over fMRI study, in which expectancy of positive emotional changes was induced by an alleged oxytocin nasal spray combined with verbal instruction. Participants performed a spatial cueing paradigm that manipulated the attention to emotional face distractors in the scanner and were characterized regarding their general ability to control attention. ResultsBehavioral findings showed placebo treatment to improve mood and to reduce distractibility by fearful over happy faces, specifically when more attentional resources were available to process faces. This aligned with neural changes in activation and functional coupling in lateral prefrontal-limbic networks indicating an expectation induced top-down regulation of aversive inputs. In addition, behavioral effects and prefrontal-parietal engagement directly correlated with trait ability to control attention. ConclusionsOur data show that placebo treatment combined with verbal instruction alone can improve mood and recruit top-down attentional selection. Changes in emotional processing critically depended on attentional context and individual control ability (i.e., contextual and general resources). These findings may be particularly relevant in patients with major depressive disorder, who often demonstrate a negativity bias and in whom placebo effects by verbal instructions alone may be limited due to reduced cognitive control capacity.

neuroscience↗

bioRxiv2023

Improving fMRI-based prediction of individual pain ratings accounting for interindividual variance

We challenge the pessimistic conclusion of a recently published paper by Hoeppli et al that fMRI-BOLD measures are useless in predicting interindividual differences in pain perception. By conducting a re-analysis of publicly available data of their study, we propose an alternative analysis approach that addresses the issue of interindividual variance differences in BOLD readouts, aiming to enhance the predictive power of fMRI-based measures. Instead of using absolute values of both, pain ratings and BOLD measures, we make use of robust intraindividual differences between the two experimental conditions in their study. Our findings demonstrate a statistically significant positive linear relationship between the neurologic pain signature (NPS) score, a multivariate pain classifier based on BOLD fMRI, and individual differences in perceived pain ratings. This relationship is driven by individuals that report pain sensitivity to both experimental conditions and can clearly distinguish between the two. Our results provide evidence for the potential of fMRI-BOLD measures in predicting interindividual differences in pain perception and allow for a more optimistic conclusion regarding the ongoing debate whether fMRI can be used as an objective measure for pain perception. ARISING FROMHoeppli, M.E., Nahman-Averbuch, H., Hinkle, W.A. et al. Dissociation between individual differences in self-reported pain intensity and underlying fMRI brain activation. Nat Commun 13, 3569 (2022). https://doi.org/10.1038/s41467-022-31039-3

neuroscience↗

bioRxiv2022

Large-Scale Circuit Configuration for Flexible Sensory-Motor Decisions

Humans and non-human primates can flexibly switch between different arbitrary mappings from sensation to action to solve a cognitive task. It has remained unknown how the brain implements such flexible sensory-motor mapping rules. Here, we uncovered a dynamic reconfiguration of task-specific correlated variability between sensory and motor brain regions. Human participants switched between two rules for reporting visual orientation judgments during fMRI recordings. Rule switches were either signaled explicitly or inferred by the participants from ambiguous cues. We used behavioral modeling to reconstruct the time course of their belief about the active rule. In both contexts, the patterns of correlations between ongoing fluctuations in stimulus- and action-selective activity across visual and action-related brain regions tracked participants belief about the active rule. The rule-specific correlation patterns broke down around the time of behavioral errors. We conclude that internal beliefs about task state are instantiated in brain-wide, selective patterns of correlated variability.

neuroscience↗

bioRxiv2021

The role of network interactions in opioid analgesia

Opioids are potent analgesic drugs with widespread cortical, subcortical and spinal targets. In particular, the central pain system comprising ascending and descending pain pathways has high opioid receptor densities and is thus crucial for opioid analgesia. Here, we investigated effects of the opioid remifentanil in a large sample (n=78) of healthy male participants using combined cortico-spinal fMRI. This approach offers the possibility to measure BOLD responses simultaneously in the brain and spinal cord allowing us to investigate the role of cortico-spinal coupling in opioid analgesia. Our data show that opioids altered activity in regions involved in pain processing such as somatosensory regions including the spinal cord and pain modulation such as prefrontal regions. Moreover, coupling strength along the descending pain system, i.e. between the medial prefrontal cortex, periaqueductal gray and spinal cord was stronger in participants who reported stronger analgesia during opioid treatment while the reversed pattern was observed in the control group. These results indicate that coupling along the descending pain pathway is a potential mechanism of opioid analgesia and can differentiate between opioid analgesia and unspecific reductions in pain such as habituation.

neuroscience↗

bioRxiv2020

Reactivation of pain-related patterns in the hippocampus from single past episodes relates to successful memory-based decision making

Aversive and rewarding experiences can exert a strong influence on subsequent behavior. While decisions are often supported by the value of single past episodes, most research has focused on the role of well-learned value associations. Recent studies have begun to investigate the influence of reward-associated episodes, but it is unclear if these results generalize to negative experiences such as pain. To investigate whether and how the value of previous aversive experiences modulates behavior and brain activity, in our experiments female and male human participants experienced episodes of high or low pain in conjunction with incidental, trial-unique neutral pictures. In an incentive-compatible surprise test phase, we found that participants avoided pain-paired objects. In a separate fMRI experiment, at test, participants exhibited significant pain value memory. Neurally, when participants were re-exposed to pain-paired objects, we found no evidence for reactivation of pain-related patterns in pain-responsive regions such as the anterior insula. Critically, however, we found significant reactivation of pain-related patterns of activity in the hippocampus, such that activity significantly discriminated high versus low pain episodes. Further, stronger reactivation in the anterior hippocampus was related to improved pain value memory performance. Our results demonstrate that single incidental aversive experiences can build memories that affect decision making and that this influence may be supported by the hippocampus. Significance StatementAversive and rewarding experiences can exert a strong influence on our subsequent behavior. While decisions are often supported by single past negative or positive episodes, most research has focused on the role of well-learned value associations. In experiments using aversive heat pain in conjunction with incidental objects, we found that participants choices were biased by the level of pain associated with the objects. Further, when participants saw the objects again, pain-related neural patterns in the hippocampus were re-expressed and this was related to pain value memory performance. These results suggest a mechanism by which even single negative experiences can guide our later decisions.

neuroscience↗

bioRxiv2018

Learning of distant state predictions by the orbitofrontal cortex in humans

Representations of our future environment are essential for planning and decision making. Previous research in humans has demonstrated that the hippocampus is a critical region for forming and retrieving associations, while the medial orbitofrontal cortex (OFC) is an important region for representing information about recent states. However, it is not clear how the brain acquires predictive representations during goal-directed learning. Here, we show using fMRI that while participants learned to find rewards in multiple different Y-maze environments, hippocampal activity was highest during initial exposure and then decayed across the remaining repetitions of each maze, consistent with a role in rapid encoding. Importantly, multivariate patterns in the OFC-VPFC came to represent predictive information about upcoming states approximately 30 seconds in the future. Our findings provide a mechanism by which the brain can build models of the world that span long-timescales to make predictions.

neuroscience↗

bioRxiv2017

Aversive Learning Changes Face-Viewing Strategies, as Revealed by Model-Based Fixation-Pattern Similarity Analysis

Animals can effortlessly adapt their behavior by generalizing from past experiences, and avoid harm in novel aversive situations. In our current understanding, the perceptual similarity between learning and generalization samples is viewed as one major factor driving aversive generalization. Alternatively, the threat-prediction account proposes that perceptual similarity should lead to generalization to the extent it predicts harmful outcomes. We tested these views using a two-dimensional perceptual continuum of faces. During learning, one face is conditioned to predict a harmful event, whereas the most dissimilar face stays neutral; introducing an adversity gradient defined only along one dimension. Learning changed the way how humans sampled information during viewing of faces. These occurred specifically along the adversity gradient leading to an increased dissimilarity of eye-movement patterns along the threat-related dimension. This provides evidence for the threat-prediction account of generalization, which conceives perceptual factors to be relevant to the extent they predict harmful outcomes.

neuroscience↗