Abstract
BACKGROUND: The aberrance of gray matter morphology in migraineurs has been widely investigated. However, it remains largely unknown whether there are illness duration-related hierarchical changes in the gray matter structure. METHODS: A total of 86 migraine without aura (MwoA) patients and 73 healthy controls were included. The Voxel-Based Morphometry approach was utilized to compare the gray matter volume (GMV) differences between MwoA patients and healthy controls. The Structural Covariance Network analysis was conducted to quantify the cross-regional synchronous alterations of gray matter structure in MwoA patients. The Causal Structural Covariance Network analysis was performed to describe the progressive and hierarchical changes in the gray matter network of patients in the pathological progression of migraine. RESULTS: MwoA patients had duration-stage related GMV hypertrophy in the left parahippocampus, as well as synergistic GMV aberrance in the parahippocampus and the medial inferior temporal gyrus and cerebellum. Moreover, the GMV alteration of the parahippocampus, and the surrounding hippocampus, amygdala, and bilateral anterior cerebellum, preceded and causally influenced the morphological changes of lateral parietal-temporal-occipital gyrus, as well as the motor cortex and prefrontal gyrus with the increasing illness duration in MwoA patients. CONCLUSION: The current study indicated that gray matter structural alterations in the medial inferior temporal gyrus, especially the parahippocampus, is a critical pathological characteristic in MwoA patients, which drives the gray matter structure alteration of other regions. These findings provide further evidence for understanding the progressive gray matter morphological changes in migraine and may facilitate the development of neuromodulation therapies targeting this procession.