{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:35:15Z","timestamp":1772156115564,"version":"3.50.1"},"reference-count":56,"publisher":"The Royal Society","issue":"2049","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/-\/media\/journals\/author\/Licence-to-Publish-20062019-final.pdf"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Proc. R. Soc. B."],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>Individuals encounter various somatosensory inputs in their daily lives, often in multiple forms at once. When exposed to noxious stimuli, the intensity of these inputs can lead to a complex experience of pain. However, the mechanisms by which these harmful stimuli combine into a unified pain experience remain unclear. Understanding this process is essential for comprehending pain perception in challenging situations. Here, we investigated pain integration through four experiments involving multimodal noxious stimuli\u2014heat, pressure, and electrical inputs\u2014applied to the feet, instructed by perceptual cues. We found that pain integration\u2014rather than somatosensory inputs\u2014significantly enhanced overall pain perception. Notably, this effect was not simply due to the additive nature of the stimuli. Our imaging results indicated that pain integration involved the precuneus cortex, with connectivity between the precuneus and both the angular gyrus and lateral occipital cortex playing a vital role in the integration process. Furthermore, we observed strong similarities between the brain activity in the precuneus and participants\u2019 pain perception, highlighting the unique function of this area during pain integration. These findings provide crucial evidence of how the brain integrates responses to multimodal noxious stimuli, underscoring an important clinical consideration for pain management strategies.<\/jats:p>","DOI":"10.1098\/rspb.2025.1229","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T19:09:45Z","timestamp":1750792185000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pain integration of multimodal noxious stimulation based on the perceptual instruction"],"prefix":"10.1098","volume":"292","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, People\u2019s Republic of China"},{"name":"Department of Psychology, University of the Chinese Academy of Sciences, Beijing 100049, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkang","family":"Zhi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, People\u2019s Republic of China"},{"name":"Department of Psychology, University of the Chinese Academy of Sciences, Beijing 100049, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Applied Psychology, Beijing Forestry University, Beijing 100083, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiushi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, People\u2019s Republic of China"},{"name":"Department of Psychology, University of the Chinese Academy of Sciences, Beijing 100049, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-5032","authenticated-orcid":true,"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, People\u2019s Republic of China"},{"name":"Department of Psychology, University of the Chinese Academy of Sciences, Beijing 100049, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazhuo","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, People\u2019s Republic of China"},{"name":"Department of Psychology, University of the Chinese Academy of Sciences, Beijing 100049, People\u2019s Republic of China"},{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2009.03.012"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2015.11.002"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2009.08.004"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn914"},{"key":"e_1_3_7_6_2","article-title":"Multi-modal signals for analyzing pain responses to thermal and electrical stimuli","volume":"146","author":"Gruss S","year":"2019","unstructured":"Gruss S, Geiger M, Werner P, Wilhelm O, Traue HC, Al-Hamadi A, Walter S. 2019 Multi-modal signals for analyzing pain responses to thermal and electrical stimuli. J. Vis. Exp. 146, e59057. (doi:10.3791\/59057)","journal-title":"J. Vis. Exp."},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.03.007"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00615"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw1297"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/bab.2086"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13753"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.108951"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brat.2023.104252"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00468-2"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2014.10.001"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105707"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2014.00818"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-821343-8.00021-6"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2018.05.002"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2012.01896.x"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10548-013-0291-0"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.844146"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-023-03237-3"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2015.12.009"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116254"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1010211"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afae107"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-020-02173-9"},{"key":"e_1_3_7_29_2","article-title":"Cortico-spinal mechanisms of periphery neuromodulation induced analgesia","author":"Wei Z","year":"2024","unstructured":"Wei Z, Duan Y, Zhu Y, Lin X, Zhang M, Brooks JCW, Liu Y, Hu L, Kong Y. 2024 Cortico-spinal mechanisms of periphery neuromodulation induced analgesia. bioRxiv 579059. (doi:10.1101\/2024.02.06.579059)","journal-title":"bioRxiv"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1361-8415(01)00036-6"},{"key":"e_1_3_7_31_2","unstructured":"Andersson JLR Jenkinson M Smith S. 2007 Non-linear registration aka spatial normalisation. FMRIB Tech. Rep. no. TR07JA2. Oxford UK: FMRIB Centre."},{"key":"e_1_3_7_32_2","unstructured":"Andersson JLR Jenkinson M Smith S. 2007 Non-linear optimisation. FMRIB Tech. Rep. no. TR07JA1. Oxford UK: FMRIB Centre."},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.03.028"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0931"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780192630711.003.0014"},{"key":"e_1_3_7_36_2","first-page":"509","volume-title":"Handbook of behavioral neuroscience","author":"Dimsdale-Zucker HR","year":"2018","unstructured":"Dimsdale-Zucker HR, Ranganath C. 2018 Representational similarity analyses. In Handbook of behavioral neuroscience (ed. D Manahan-Vaughan), pp. 509\u2013525. Amsterdam, The Netherlands: Elsevier."},{"key":"e_1_3_7_37_2","first-page":"249","article-title":"Representational similarity analysis \u2013 connecting the branches of systems neuroscience","volume":"2","author":"Kriegeskorte N","year":"2008","unstructured":"Kriegeskorte N, Mur M, Bandettini PA. 2008 Representational similarity analysis \u2013 connecting the branches of systems neuroscience. Front. Syst. Neurosci. 2, 249. (doi:10.3389\/neuro.06.004.2008)","journal-title":"Front. Syst. Neurosci."},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.07.015"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cognition.2019.02.008"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1377"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-809324-5.23879-0"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.10.005"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.02.003"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnp.12250"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphysparis.2004.03.018"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25401"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-022-02576-w"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102907"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002818"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1177\/1073858412440596"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0539-9"},{"key":"e_1_3_7_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00518-9"},{"key":"e_1_3_7_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.05.015"},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1243-21.2022"},{"key":"e_1_3_7_55_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2021.769228"},{"key":"e_1_3_7_56_2","unstructured":"Zhang Y Zhi Y Zhang Y. 2024 Data & code for: Pain integration of multimodal noxious stimulation based on perceptual cue[DS\/OL]. V1. Science Data Bank 2024[2025-05-29]. (doi:10.57760\/sciencedb.psych.00355)"},{"key":"e_1_3_7_57_2","unstructured":"Zhang Y Zhi Y Li Q Zhang M Kong Y. 2025 Supplementary material from: Pain integration of multimodal noxious stimulation based on the perceptual instruction. Figshare. (doi:10.6084\/m9.figshare.c.7867347)"}],"container-title":["Proceedings of the Royal Society B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rspb.2025.1229","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rspb.2025.1229","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rspb.2025.1229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T19:09:56Z","timestamp":1750792196000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rspb.2025.1229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":56,"journal-issue":{"issue":"2049","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1098\/rspb.2025.1229"],"URL":"https:\/\/doi.org\/10.1098\/rspb.2025.1229","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSPB.2025.1229\/v2\/decision1","asserted-by":"object"}]},"ISSN":["1471-2954"],"issn-type":[{"value":"1471-2954","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-28","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"20251229"}}