Search bioRxiv⌕ Search

Biology subjects

Keuter, L.

Publications and source records attributed to Keuter, L..

3 recordsLinked to original sources

Withdrawal latency in a human hot plate analog tracks inter-individual differences in pain sensitivity

Pain research relies mainly on self-report in humans and nocifensive behavior in animals. This asymmetry limits cross-species translation and neglects movement as integral to human pain responses. We therefore developed a human analog of the rodent hot plate test and tested whether temporal and kinematic features of nocifensive withdrawal can capture inter-individual differences in pain sensitivity. Ninety-one healthy participants rested their forearm on a thermode that rapidly heated to and held a fixed noxious temperature (46 {degrees}C or 48 {degrees}C) and were instructed to withdraw once the percept reached their pain threshold or tolerance. From wrist accelerometry, we extracted withdrawal latency and peak acceleration, an index of withdrawal vigor, and related both to pain intensity ratings from a separate, temperature-matched task and to calibrated pain sensitivity. Participants withdrew earlier and with higher peak acceleration at 48 {degrees}C than at 46 {degrees}C. Crucially, withdrawal latency tracked inter-individual differences in pain sensitivity: Participants who withdrew earlier reported higher pain in the separate task (48 {degrees}C: r = -.47 and -.50) and showed lower pain thresholds and higher suprathreshold sensitivity during calibration. In contrast, withdrawal vigor showed no such relationship, despite high reliability. Withdrawal latency can thus serve as a behavioral readout of inter-individual differences in pain sensitivity, whereas vigor might reflect intra-individual motor scaling with stimulus intensity. By separating the decision to withdraw from its motor execution, this paradigm offers a behavioral complement to traditional self-report and provides a translational link between human and preclinical pain assays.

neuroscience↗

The pursuit of motivational goals reduces pain through an opioidergic mechanism

Pain promotes protective behavior but can interfere with other biologically important goals. Survival may require overcoming pain to obtain rewards, secure resources or escape danger, yet evidence for pain modulation by competing demands and endogenous modulatory systems during goal pursuit is lacking. We developed a paradigm in which participants chose whether to pursue monetary rewards despite painful heat stimulation during fMRI, under placebo or opioid receptor blockade with naloxone. Actively pursuing motivational goals during painful stimulation reduced perceived pain and increased fMRI signal in pain-modulatory cortical regions, including multiple subregions of the rostral anterior cingulate cortex (rACC) and dorsolateral prefrontal cortex, alongside enhanced rACC-periaqueductal gray coupling, consistent with recruitment of the descending pain modulatory system. Behavioral and neural effects were attenuated by naloxone, supporting a mediating role for endogenous opioids. These findings provide convergent evidence that active goal pursuit engages opioidergic pain modulatory mechanisms to reduce pain in humans.

neuroscience↗

Entorhinal grid-like codes for visual space during memory formation

Eye movements, such as saccades, allow us to gather information about the environment and, in this way, can shape memory. In non-human primates, saccades are associated with the activity of grid cells in the entorhinal cortex. Grid cells are essential for spatial navigation, but whether saccade-based grid-like signals play a role in human memory formation is currently unclear. Here, human participants underwent functional magnetic resonance imaging (fMRI) and continuous eye gaze monitoring while studying scene images. Recognition memory was probed immediately thereafter. Results revealed saccade-based grid-like codes in the left entorhinal cortex while participants studied the scene images, a finding that was replicated with an independent data set reported here. The grid-related effects were time-locked to activation increases in the frontal eye fields. Most importantly, saccade-based grid-like codes were associated with recognition memory, such that grid-like codes were lower the better participants performed in subsequently recognizing the scene images. Collectively, our findings suggest an entorhinal map of visual space that is timed with neural activity in oculomotor regions, supporting memory formation.

neuroscience↗