Abnormal glutamatergic and serotonergic connectivity in visual snow syndrome and migraine with aura

Neuropharmacological changes in visual snow syndrome (VSS) are poorly understood. We aimed to use receptor target maps combined with resting fMRI data to identify which neurotransmitters might modulate brain circuits involved in VSS.We used Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) to estimate and compare the molecular-enriched functional networks related to four neurotransmitter systems of patients with VSS (n = 24), healthy controls (HC, n = 24) and migraine patients (MIG, n = 25, n = 15 with aura-MwA). For REACT we employed receptor density templates for the transporters of noradrenaline, dopamine and serotonin, GABA-A and NMDA receptors, 5HT1B and 5HT2A receptors, and estimated the subject-specific voxel-wise maps of functional connectivity (FC). We then performed voxel-wise comparisons of these maps between HC, MIG and VSS.VSS patients had reduced FC in glutamatergic networks localised in the ACC compared to HC and MIG, and reduced FC in serotoninergic networks localised in the insula, temporal pole and orbitofrontal cortex compared to controls, similar to MwA. VSS patients also showed reduced FC in 5HT2A -enriched networks, largely localised in occipito-temporo-parietal association cortices. As revealed by subgroup analyses, these changes were independent of, and analogous to, those found in MwA.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. This article is protected by copyright. All rights reserved.