TY - JOUR
T1 - Abnormal Glutamatergic and Serotonergic Connectivity in Visual Snow Syndrome and Migraine with Aura
AU - Puledda, Francesca
AU - Dipasquale, Ottavia
AU - Gooddy, Benjamin J M
AU - Karsan, Nazia
AU - Bose, Ray
AU - Mehta, Mitul A
AU - Williams, Steven C R
AU - Goadsby, Peter J
N1 - Funding Information:
The authors thank all the patients who took part in the study. This study represents independent research part funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The study was supported in part by the Visual Snow Initiative and by crowdfunding from the self‐help group for visual snow Eye On Vision Foundation. O.D., M.A.M., S.C.R.W. and P.J.G. are supported by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.
Publisher Copyright:
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2023/11
Y1 - 2023/11
N2 - OBJECTIVE: Neuropharmacological changes in visual snow syndrome (VSS) are poorly understood. We aimed to use receptor target maps combined with resting functional magnetic resonance imaging (fMRI) data to identify which neurotransmitters might modulate brain circuits involved in VSS.METHODS: We used Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) to estimate and compare the molecular-enriched functional networks related to 5 neurotransmitter systems of patients with VSS (n = 24), healthy controls (HCs; n = 24), and migraine patients ([MIG], n = 25, 15 of whom had migraine with aura [MwA]). For REACT we used receptor density templates for the transporters of noradrenaline, dopamine, and serotonin, GABA-A and NMDA receptors, as well as 5HT
1B and 5HT
2A receptors, and estimated the subject-specific voxel-wise maps of functional connectivity (FC). We then performed voxel-wise comparisons of these maps among HCs, MIG, and VSS.
RESULTS: Patients with VSS had reduced FC in glutamatergic networks localized in the anterior cingulate cortex (ACC) compared to HCs and patients with migraine, and reduced FC in serotoninergic networks localized in the insula, temporal pole, and orbitofrontal cortex compared to controls, similar to patients with migraine with aura. Patients with VSS also showed reduced FC in 5HT
2A -enriched networks, largely localized in occipito-temporo-parietal association cortices. As revealed by subgroup analyses, these changes were independent of, and analogous to, those found in patients with migraine with aura.
INTERPRETATION: Our results show that glutamate and serotonin are involved in brain connectivity alterations in areas of the visual, salience, and limbic systems in VSS. Importantly, altered serotonergic connectivity is independent of migraine in VSS, and simultaneously comparable to that of migraine with aura, highlighting a shared biology between the disorders. ANN NEUROL 2023;94:873-884.
AB - OBJECTIVE: Neuropharmacological changes in visual snow syndrome (VSS) are poorly understood. We aimed to use receptor target maps combined with resting functional magnetic resonance imaging (fMRI) data to identify which neurotransmitters might modulate brain circuits involved in VSS.METHODS: We used Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) to estimate and compare the molecular-enriched functional networks related to 5 neurotransmitter systems of patients with VSS (n = 24), healthy controls (HCs; n = 24), and migraine patients ([MIG], n = 25, 15 of whom had migraine with aura [MwA]). For REACT we used receptor density templates for the transporters of noradrenaline, dopamine, and serotonin, GABA-A and NMDA receptors, as well as 5HT
1B and 5HT
2A receptors, and estimated the subject-specific voxel-wise maps of functional connectivity (FC). We then performed voxel-wise comparisons of these maps among HCs, MIG, and VSS.
RESULTS: Patients with VSS had reduced FC in glutamatergic networks localized in the anterior cingulate cortex (ACC) compared to HCs and patients with migraine, and reduced FC in serotoninergic networks localized in the insula, temporal pole, and orbitofrontal cortex compared to controls, similar to patients with migraine with aura. Patients with VSS also showed reduced FC in 5HT
2A -enriched networks, largely localized in occipito-temporo-parietal association cortices. As revealed by subgroup analyses, these changes were independent of, and analogous to, those found in patients with migraine with aura.
INTERPRETATION: Our results show that glutamate and serotonin are involved in brain connectivity alterations in areas of the visual, salience, and limbic systems in VSS. Importantly, altered serotonergic connectivity is independent of migraine in VSS, and simultaneously comparable to that of migraine with aura, highlighting a shared biology between the disorders. ANN NEUROL 2023;94:873-884.
KW - Humans
KW - Migraine with Aura/diagnostic imaging
KW - Serotonin
KW - Magnetic Resonance Imaging/methods
KW - Brain/diagnostic imaging
UR - http://www.scopus.com/inward/record.url?scp=85167345856&partnerID=8YFLogxK
U2 - 10.1002/ana.26745
DO - 10.1002/ana.26745
M3 - Article
C2 - 37466404
SN - 0364-5134
VL - 94
SP - 873
EP - 884
JO - Annals of Neurology
JF - Annals of Neurology
IS - 5
ER -