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eNeuro. 2017 Jan 17;3(6). pii: ENEURO.0163-16.2016. doi: 10.1523/ENEURO.0163-16.2016. eCollection 2016 Nov-Dec.

Cortico-Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine.

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Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School , Boston, Massachusetts 02115.
Department of Neurology & Neurological Sciences, Stanford University , Palo Alto, California 94305.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129.
Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital , Boston, Massachusetts 02115.
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts 02115.


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 trigemino-vascular 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 principle primary sensory areas or subcortical structures. In a large cohort of human migraine patients (N = 40) and matched healthy control subjects (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 cortico-cortical interactions are necessary for the integration of information within and across the sensory modalities and, thus, could play an important role in the initiation of migraine and/or the development of its associated symptoms.


connectivity; cortico–cortical; headache; migraine; pain; sensory

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