Functional Brain Connectivity Patterns of Headache-Mental Disorder Comorbidity in Patients With Migraine

To identify the functional brain connectivity patterns that were correlated with headache and mental conditions in migraineurs and then to elucidate their neurotransmitter basis and explore the potential clinical implications.

Eighty patients with migraine without aura (MwoA) and 94 healthy controls (HCs) were included. Firstly, we employed partial least-squares correlation (PLSC) to identify a set of resting-state functional connectivity (RSFC) that was co-related with headache symptoms and mental conditions in MwoA patients. Then, we investigated the specific neurotransmitter basis underlying headache-mental disorders-related RSFC patterns. Finally, we explored the potentials of these RSFC patterns in discriminating patients from HCs, interpreting patient symptoms, stratifying patients into subgroups, and predicting treatment outcomes.

The PLSC analysis revealed one robust latent component linking RSFC between the subcortical nuclei (in particular the thalamus and basal ganglia) and the occipital/temporal cortex to the headache-mental conditions in MwoA patients. These RSFC patterns were spatially correlated with the distribution of several neurotransmitters including 5HT1a, 5HT2a, and mGluR5 receptors. The third part of the analysis indicated that the RSFC patterns could discriminate MwoA patients from HCs with an accuracy of 0.793, differentiate patients into two subtypes, and to some extent predict the efficacy of acupuncture treatment.

This was the first "doubly" multivariate analysis identifying functional brain connectivity patterns underlying headache-mental disorder comorbidity in migraineurs. These findings reveal a neurobiological substrate for migraine-mental disorder comorbidity and highlight the potential of these connectivity patterns as biomarkers for diagnosis and treatment prediction.