Whole‐brain functional gradients reveal cortical and subcortical alterations in patients with episodic migraine

Abstract

Migraine is a type of headache with multiple neurological symptoms. Prior neuroimaging studies in patients with migraine based on functional magnetic resonance imaging have found regional as well as network‐level alterations in brain function. Here, we expand on prior studies by establishing whole‐brain functional connectivity patterns in patients with migraine using dimensionality reduction techniques. We studied functional brain connectivity in 50 patients with episodic migraine and sex‐ and age‐matched healthy controls. Using dimensionality reduction techniques that project high‐dimensional functional connectivity onto low‐dimensional representations (i.e., eigenvectors), we found significant between‐group differences in the eigenvectors between patients with migraine and healthy controls, particularly in the sensory/motor and limbic cortices. Furthermore, we assessed between‐group differences in subcortical connectivity with subcortical weighted manifolds defined by subcortico‐cortical connectivity multiplied by cortical eigenvectors and revealed significant alterations in the amygdala. Finally, leveraging supervised machine learning, we moderately predicted headache frequency using cortical and subcortical functional connectivity features, again indicating that sensory and limbic regions play a particularly important role in predicting migraine frequency. Our study confirmed that migraine is a hierarchical disease of the brain that shows alterations along the sensory‐limbic axis, and therefore, the functional connectivity in these areas could be a useful marker to investigate migraine symptomatology.

Patients with episodic migraine without aura have an increased rate of delayed discounting

“…Our results are consistent with previous reports suggesting that reduced VMPFC and striatal activity are correlated with higher delay discounting in substance detection and gambling addiction (Luijten et al, 2017). The weaker functional connectivities between the striatum and VMPFC have been observed in migraine groups (Lee et al, 2023;Schneider & Koenigs, 2017). Hence, we propose that the reduced strength of functional connectivity in the striatum and VMPFC in patients with migraines may lead to a reduction in individuals' expectation of longterm value, which in turn leads to an increase in delayed discounting.…”

“…. The vSTR activity response to positive and negative feedback as well as the functional connectivity intensity with other brain regions can predict an individual's impulsive choice (Knorr et al, 2020;Lee et al, 2023). The vSTR helps regulate the activity and behavioral effects of dopaminergic and serotonin neurons by receiving and filtering excitatory inputs specific to multiple brain regions (Christoffel et al, 2021).…”

Functional gradients reveal cortical hierarchy changes in multiple sclerosis

“…This discrepancy has been previously observed and attributed to different factors, including preprocessing strategies (Hong et al, 2020;Knodt et al, 2023), age range of the studied population (Bethlehem et al, 2020;Hu et al, 2022), and sample size (Zang et al, 2023), whereas it should be independent from parcellation resolution (Vos de Wael et al, 2020). In this study, participants were relatively young, thus suggesting that age should not significantly affect FGs; on the other hand, the sample size was not as small as in other works reporting the canonical FGs (Lee et al, 2023;Zhang et al, 2022). Therefore, it is reasonable to hypothesize an influence of the rs-fMRI data preprocessing strategy behind the inverted FGs.…”

“…FGs have been widely used for investigating brain hierarchical organization in various pathological populations, including migraine (Lee et al, 2023 ), Alzheimer's disease (Borne et al, 2023 ; Hu et al, 2022 ), epilepsy (Lucas et al, 2023 ; Meng et al, 2021 ), as well as in healthy individuals (Bethlehem et al, 2020 ; Cross et al, 2021 ; Katsumi et al, 2023 ; Kong et al, 2023 ; Shen et al, 2023 ; Vos de Wael et al, 2018 ; Yang et al, 2020 ). However, to date, gradients have never been studied in an MS population.…”

Different vulnerability of fast and slow cortical oscillations to suppressive effect of spreading depolarization: state-dependent features potentially relevant to pathogenesis of migraine aura

“…The amygdala, playing an important role in pain processing, attracts growing attention due to its potential role in migraine pathogenesis [ 23 – 26 ]. SDs involving subcortical structures (basal ganglia, thalamus, amygdala) are referred as a plausible mechanism for some aura symptoms in migraine with aura patients [ 3 , 6 , 14 , 27 ].…”