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Trigeminal nociceptive somatotopy across brainstem and cortex and their functional interactions.

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Title: Trigeminal nociceptive somatotopy across brainstem and cortex and their functional interactions.
Authors: Scutelnic A; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Neurology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland., Peng KP; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kokian K; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., May A; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. a.may@uke.uni-hamburg.de., Mehnert J; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Source: The journal of headache and pain [J Headache Pain] 2026 Aug 31; Vol. 27 (1). Date of Electronic Publication: 2026 Aug 31.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: BioMed Central Country of Publication: England NLM ID: 100940562 Publication Model: Electronic Cited Medium: Internet ISSN: 1129-2377 (Electronic) Linking ISSN: 11292369 NLM ISO Abbreviation: J Headache Pain Subsets: MEDLINE
Imprint Name(s): Publication: [2018]- : [London, United Kingdom] : BioMed Central
Original Publication: Milano : Springer Verlag Italia, c2000-c2017.
MeSH Terms: Brain Stem*/physiology , Brain Stem*/diagnostic imaging , Trigeminal Nerve*/physiology , Trigeminal Nerve*/diagnostic imaging , Cerebral Cortex*/physiology , Cerebral Cortex*/diagnostic imaging , Nociception*/physiology, Neural Pathways/physiology ; Neural Pathways/diagnostic imaging ; Somatosensory Cortex/physiology ; Somatosensory Cortex/diagnostic imaging ; Humans ; Female ; Adult ; Magnetic Resonance Imaging ; Male ; Electric Stimulation ; Brain Mapping
Abstract: Background: The trigeminal nerve innervates the face and the meninges via its three branches, with central relay neurons located in the brainstem's spinal trigeminal nucleus. We have shown a somatotopic organization on human brainstem level and aimed, using an independent new sample, to characterize the functional somatotopy with a focus on within-brainstem and brainstem-cortical connectivity.
Methods: Electrical stimulation was applied to the three branches of the trigeminal nerve at two intensities (high and low) to examine the somatotopic organization in healthy participants during fMRI. Neuroimaging was preregistered (NCT06534880) and covered the upper spinal cord, brainstem, thalamus, insula, primary somatosensory cortex (S1), S2/parietal operculum, and cingulate cortex. Activation patterns following stimulation of each trigeminal branch were analyzed. Branch-specific functional connectivity was estimated within the brainstem as well as between brainstem and cortical targets.
Results: In a cohort of 30 healthy participants (mean age 32.1 ± 8.8 years, 18 female (60%)), spatially distinct brainstem representations of the trigeminal branches were identified, replicating previous reports. Activation at the cortical level was largely bilateral and symmetric, except in the primary somatosensory cortex and the insula, where it was predominantly contralateral. Within the brainstem, functional connectivity was strongest between the left and right subnuclei at the same level and was independent of the stimulated branch (all F(2,116) ≤ 5.67, threshold F = 8.00, α = 0.05/90). Brainstem-cortex connectivity showed a robust rostrocaudal gradient that was modulated by the stimulated branch across insular, somatosensory, and opercular regions (significant in 37/48 ROIs, F-Range 2.46-5.19, PFWE<0.05).
Conclusion: We replicated somatotopic representation of the three trigeminal branches in the brainstem and revealed distinct bilateral activation and branch-specific functional connectivity across multiple levels of the afferent neuraxis.
(© 2026. The Author(s).)
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
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Entry Date(s): Date Created: 20260901 Date Completed: 20260901 Latest Revision: 20260909
Update Code: 20260910
PubMed Central ID: PMC13528110
DOI: 10.1186/s10194-026-02476-y
PMID: 42675463
Database: MEDLINE
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  Data: Trigeminal nociceptive somatotopy across brainstem and cortex and their functional interactions.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Scutelnic+A%22&quot;&gt;Scutelnic A&lt;/searchLink&gt;; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Neurology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Peng+KP%22&quot;&gt;Peng KP&lt;/searchLink&gt;; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Kokian+K%22&quot;&gt;Kokian K&lt;/searchLink&gt;; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22May+A%22&quot;&gt;May A&lt;/searchLink&gt;; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. a.may@uke.uni-hamburg.de.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Mehnert+J%22&quot;&gt;Mehnert J&lt;/searchLink&gt;; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: The trigeminal nerve innervates the face and the meninges via its three branches, with central relay neurons located in the brainstem&#39;s spinal trigeminal nucleus. We have shown a somatotopic organization on human brainstem level and aimed, using an independent new sample, to characterize the functional somatotopy with a focus on within-brainstem and brainstem-cortical connectivity.&lt;br /&gt;Methods: Electrical stimulation was applied to the three branches of the trigeminal nerve at two intensities (high and low) to examine the somatotopic organization in healthy participants during fMRI. Neuroimaging was preregistered (NCT06534880) and covered the upper spinal cord, brainstem, thalamus, insula, primary somatosensory cortex (S1), S2/parietal operculum, and cingulate cortex. Activation patterns following stimulation of each trigeminal branch were analyzed. Branch-specific functional connectivity was estimated within the brainstem as well as between brainstem and cortical targets.&lt;br /&gt;Results: In a cohort of 30 healthy participants (mean age 32.1 &#177; 8.8 years, 18 female (60%)), spatially distinct brainstem representations of the trigeminal branches were identified, replicating previous reports. Activation at the cortical level was largely bilateral and symmetric, except in the primary somatosensory cortex and the insula, where it was predominantly contralateral. Within the brainstem, functional connectivity was strongest between the left and right subnuclei at the same level and was independent of the stimulated branch (all F(2,116) ≤ 5.67, threshold F = 8.00, α = 0.05/90). Brainstem-cortex connectivity showed a robust rostrocaudal gradient that was modulated by the stimulated branch across insular, somatosensory, and opercular regions (significant in 37/48 ROIs, F-Range 2.46-5.19, P&lt;subscript&gt;FWE&lt;/subscript&gt;&amp;lt;0.05).&lt;br /&gt;Conclusion: We replicated somatotopic representation of the three trigeminal branches in the brainstem and revealed distinct bilateral activation and branch-specific functional connectivity across multiple levels of the afferent neuraxis.&lt;br /&gt; (&#169; 2026. The Author(s).)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declarations. Competing interests: The authors declare no competing interests.
– Name: Ref
  Label: References
  Group: RefInfo
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  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260901 &lt;i&gt;Date Completed: &lt;/i&gt;20260901 &lt;i&gt;Latest Revision: &lt;/i&gt;20260909
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  Data: 10.1186/s10194-026-02476-y
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  Data: 42675463
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42675463
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    Identifiers:
      – Type: doi
        Value: 10.1186/s10194-026-02476-y
    Languages:
      – Code: eng
        Text: English
    Subjects:
      – SubjectFull: Neural Pathways physiology
        Type: general
      – SubjectFull: Neural Pathways diagnostic imaging
        Type: general
      – SubjectFull: Somatosensory Cortex physiology
        Type: general
      – SubjectFull: Somatosensory Cortex diagnostic imaging
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Adult
        Type: general
      – SubjectFull: Magnetic Resonance Imaging
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Electric Stimulation
        Type: general
      – SubjectFull: Brain Mapping
        Type: general
      – SubjectFull: Brain Stem physiology
        Type: general
      – SubjectFull: Brain Stem diagnostic imaging
        Type: general
      – SubjectFull: Trigeminal Nerve physiology
        Type: general
      – SubjectFull: Trigeminal Nerve diagnostic imaging
        Type: general
      – SubjectFull: Cerebral Cortex physiology
        Type: general
      – SubjectFull: Cerebral Cortex diagnostic imaging
        Type: general
      – SubjectFull: Nociception physiology
        Type: general
    Titles:
      – TitleFull: Trigeminal nociceptive somatotopy across brainstem and cortex and their functional interactions.
        Type: main
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      – PersonEntity:
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            NameFull: Scutelnic A
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            NameFull: Peng KP
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            NameFull: Kokian K
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            NameFull: May A
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            NameFull: Mehnert J
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          Dates:
            – D: 31
              M: 08
              Text: 2026 Aug 31
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1129-2377
          Numbering:
            – Type: volume
              Value: 27
            – Type: issue
              Value: 1
          Titles:
            – TitleFull: The journal of headache and pain
              Type: main
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