Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigeminovascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico-cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principal primary sensory areas or subcortical structures. In a large cohort of human migraine patients (N=40) and matched healthy controls (N=40), we used resting-state intrinsic functional connectivity to examine the cortical networks associated with the three main sensory perceptual modalities of vision, audition and somatosensation. Specifically, we sought to explore the complexity of the sensory networks as they converge and become functionally coupled in multimodal systems. We also compared self-reported retrospective migraine symptoms in the same patients, examining the prevalence of sensory symptoms across the different phases of the migraine cycle. Our results show widespread and persistent disturbances in the perceptions of multiple sensory modalities. Consistent with this observation, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). We speculate that corticocortical interactions are necessary for the integration of information within and across the sensory modalities, thus could play an important role in the initiation of migraine and/or the development of its associated symptoms.
Significance Statement: Migraine is a multifactorial disorder that is associated with abnormalities in sensory processing, including nociceptive and non-nociceptive processing. Here we examine the corticocortical circuitry in the migraine brain relating to the principle primary sensory areas (vision, audition and somatosensation). We also compare self-reported retrospective migraine symptoms in the same patients. Our results identified widespread and persistent disturbances in the perceptions of multiple sensory modalities. Furthermore, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). These findings provide new insights into the complex symptomatology of migraine, and highlight the need to consider network-level cortical processes in the pathophysiology of headache disorders.
Authors report no conflict of interest
National Institutes of Health (NIH) [RO1 NS073977 and K24 NS064050] funded this study.