Multi-region Local Field Potential Signatures and Brain Coherence Alternations in Response to Migraine Attacks

Abstract

Migraine is a recurrent primary headache disorder with moderate to severe disability. It has been ranked as the second leading cause of disability and the sixth most prevalent disease. However, the pathophysiology of migraine headaches remains not fully understood. Consequently, safe and effective therapies to alleviate migraine headaches are limited. Local field potential (LFP) recording, as a neurophysiological tool, has been widely utilized to investigate the combined neuronal activity. The purpose of this proposed study was to determine differential LFP signatures and brain coherence alternations from multiple brain regions associated with migraine-relevant pain networks, which enabled to remove barriers to understanding the migraine pathophysiology and facilitated the treatment study clinically. We conducted the migraine animal model which was induced by intraperitoneal (i.p.) injection of nitroglycerin (NTG), a well-established migraine model. As an initial part of this study, LFP signals were firstly recorded from anesthetized animals, followed by freely moving animals. Additionally, behavior measurements were implemented in freely moving animals. The hypothesis was that various brain areas, which are involved in different orders of neurons in the trigeminovascular system and pain processing, could show different response patterns/signatures with brain coherence changes to migraine attacks. In this study, LFPs from the anterior cingulate cortex (ACC), the posterior nucleus of the thalamus (Po), the trigeminal ganglion (TG), and the primary visual cortex (V1M) were simultaneously recorded. The rationale was that the trigeminal ganglion, thalamus, and visual cortex are involved in the pathophysiology of migraine attacks, and the ACC as one part of the limbic system is related to emotional processing. There were three specific aims. Aim 1: Determine LFP signatures containing ACC, Po, TG, and V1M when migraine occurs from anesthetized animals; Aim 2: Determine the multi-region LFP signatures in response to migraine attacks from freely moving animals and examine behavioral responses; Aim 3: Examine brain coherence alternations among paired brain sites.