Neural Circuit Dysfunctions in Migraine: A Stage-Specific Dynamic Perspective.

Abstract

ABSTRACT Migraine is increasingly recognized as a cyclical brain state disorder rather than an isolated vascular or nociceptive condition. Its clinical phases may reflect dynamic reorganization of interacting neural circuits involved in sensory processing, homeostasis, pain modulation, and cognition. This review aims to synthesize current evidence and propose a stage-specific neural circuit dynamic model of migraine, linking each clinical phase to distinct patterns of circuit dysfunction and recovery. A narrative review of studies published between January 2010 and December 2024 was conducted using PubMed, Web of Science, and Embase. Controlled vocabulary and free-text terms were combined, and the article selection process was documented numerically to improve transparency. Evidence from human neuroimaging, electrophysiology, preclinical circuit manipulation, and neuromodulation studies was qualitatively integrated according to migraine phase and circuit domain. The interictal phase is characterized by vulnerable homeostasis, with heightened cortical excitability, impaired sensory gating, and weakened descending inhibition. During the prodromal phase, hypothalamic involvement and altered limbic-reward signaling may contribute to attack-related network priming. The ictal phase involves trigeminovascular activation, thalamocortical amplification, and engagement of pain and sensory networks; in migraine with aura, cortical spreading depression may contribute to these processes. Attack resolution may involve endogenous reset mechanisms engaging brainstem and hypothalamic modulatory systems, whereas chronic migraine may reflect maladaptive circuit plasticity and more persistent network reconfiguration. A stage-specific circuit framework can integrate fragmented evidence on migraine pathophysiology and may support circuit-based biotyping, biomarker development, and targeted neuromodulatory or pharmacological interventions.