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Characterizing functional connectivity gradients for the hippocampus-amygdala complex in healthy and psychiatric cohorts.

Overview

Authors: Xiang-Shen Liu1, Janna N Vrijsen2,3, Linlin Yan1, Koen V Haak1,4, Rose M Collard5, Philip F P van Eijndhoven2, Christian F Beckmann1, Guillén Fernández1, Indira Tendolkar2,6, Nils Kohn1
  1. Department of Medical Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
  2. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
  3. Depression Expertise Center, Pro Persona Mental Health Care, Nijmegen, The Netherlands
  4. Department of Cognitive Science and Artificial Intelligence, Tilburg University, Tilburg, The Netherlands
  5. Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands
  6. Department of Psychiatry and Psychotherapy, Medical Faculty, LVR-University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Institutions: Radboud University Nijmegen (Netherlands); Radboud University Medical Center (Netherlands); Donders Institute for Brain, Cognition and Behaviour (Netherlands); Pro Persona (Netherlands); Tilburg University (Netherlands); Donders Centre for Cognitive Neuroimaging (Netherlands); Essen University Hospital (Germany); University of Duisburg-Essen (Germany)
Journal: Brain structure & function, volume 231, issue 5, article 80
Dates: received 29 December 2025; accepted 16 May 2026; published online 3 June 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1007/s00429-026-03134-4 · PMID 42234210 · PMCID PMC13233971 · OpenAlex W4413943141
Open access: hybrid, a free copy (OpenAlex)
Preprint: doi:10.21203/rs.3.rs-7032613/v1
Status: code on request
Categories: fMRI (modality), PET / SPECT (modality), human (organism)
Methods: Statistics, Smoothing, state filtering, decompositions, Connectivity, fMRI & imaging
Keywords: Hippocampus–amygdala complex, Functional connectivity, Connectopic mapping, Serotonin, Dopamine, Psychopathology
MeSH: Amygdala*, Hippocampus*, Mental Disorders*, Adult, Brain Mapping, Cohort Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Positron-Emission Tomography, Tomography, Emission-Computed, Single-Photon, Young Adult (* major topic)
Topic: Functional Brain Connectivity Studies (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: Ph.D. fellowship from the Chinese Scholarship Council
Citations: cited by 1 paper (Europe PMC); 83 references in the paper

Abstract

The hippocampus and amygdala play essential roles in human cognition and emotion, through their extensive connectivity with other brain regions and close interaction between them. Uncovering the functional organization of the hippocampus–amygdala complex and its relationship with neurotransmitter distribution can enhance our understanding of their biological functionality, and provide a basis for further exploration of the clinical relevance. An emerging functional connectivity analysis method termed connectopic mapping, may offer a novel approach to characterize this functional organization. In this study, we applied connectopic mapping to the hippocampus-amygdala complex, testing its utility with resting-state functional magnetic resonance imaging (fMRI) scans of two independent datasets: one comprising healthy individuals (N = 410) and another comprising a psychiatric cohort (N = 367). The spatial organization of derived gradient maps was compared to 18 positron emission tomography (PET) or single photon emission computed tomography (SPECT) scan templates for different neurotransmitter systems. Individual gradient–neurotransmitter similarity indices were correlated with mental health outcomes. Our analyses identified six distinct gradient maps in both datasets. The third-order gradients showed stable similarity with 5-HT1A receptor maps across various resting-state scans. Similarities were also observed between gradient maps and the distribution patterns of neurotransmitters within the dopaminergic system. Individual gradient-to-5-HT1A similarity was positively correlated with depressive severity and anxiety sensitivity, highlighting the psychopathological relevance. These findings demonstrate that across the psychiatric continuum, connectopic mapping is a powerful tool for exploring the relationship between functional connectivity organization and neurotransmitter distribution, showing potential as a comprehensive transdiagnostic biomarker.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00429-026-03134-4.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability

The processed data and codes are archived in the institutional repository of the Donders Institute for Brain, Cognition and Behavior, and available upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: — → Springer Science+Business Media

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 6 keywords, 15 MeSH terms, 1 funder, 80 references.

Cite

This paper

Liu, X.-S., Vrijsen, J. N., Yan, L., Haak, K. V., Collard, R. M., van Eijndhoven, P. F. P., Beckmann, C. F., Fernández, G., Tendolkar, I., & Kohn, N. (2026). Characterizing functional connectivity gradients for the hippocampus-amygdala complex in healthy and psychiatric cohorts. Brain structure & function, 231(5), 80. https://doi.org/10.1007/s00429-026-03134-4

BibTeX

@article{liu2026characterizing,
author = {Liu, Xiang-Shen and Vrijsen, Janna N and Yan, Linlin and Haak, Koen V and Collard, Rose M and van Eijndhoven, Philip F P and Beckmann, Christian F and Fernández, Guillén and Tendolkar, Indira and Kohn, Nils},
title = {{Characterizing functional connectivity gradients for the hippocampus-amygdala complex in healthy and psychiatric cohorts}},
journal = {Brain structure \& function},
year = {2026},
month = jun,
volume = {231},
number = {5},
pages = {80},
publisher = {Springer Science+Business Media},
issn = {1863-2653},
doi = {10.1007/s00429-026-03134-4},
url = {https://doi.org/10.1007/s00429-026-03134-4},
pmid = {42234210},
pmcid = {PMC13233971}
}

RIS

TY - JOUR
AU - Liu, Xiang-Shen
AU - Vrijsen, Janna N
AU - Yan, Linlin
AU - Haak, Koen V
AU - Collard, Rose M
AU - van Eijndhoven, Philip F P
AU - Beckmann, Christian F
AU - Fernández, Guillén
AU - Tendolkar, Indira
AU - Kohn, Nils
TI - Characterizing functional connectivity gradients for the hippocampus-amygdala complex in healthy and psychiatric cohorts
T2 - Brain structure & function
J2 - Brain Struct Funct
PY - 2026
DA - 2026/06/03
VL - 231
IS - 5
SP - 80
SN - 1863-2653
PB - Springer Science+Business Media
DO - 10.1007/s00429-026-03134-4
UR - https://doi.org/10.1007/s00429-026-03134-4
LA - en
ER -

CSL-JSON

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