Migraine is the most common type of primary headache in clinical practice. It is a common recurrent headache disorder. Migraine without aura is the most common type of migraine, accounting for approximately 80% of cases . It presents with recurrent episodes of pulsating headache on one or both sides of the frontotemporal region lasting 4–72 hours and may be accompanied by nausea, vomiting, photophobia, and vocal aversion. Migraine without aura (MwoA) has a high prevalence and high frequency of attacks, which affects the work, study, and life of patients .
The periaqueductal gray (PAG) is an important node of the descending pain modulatory system and the main hub for the upstream and downstream channels of nociceptive information. Tassorelli et al.  found that stimulation of the ventral lateral region of the PAG led to migraine-like symptoms. Raskin et al.  implanted stimulating electrodes into the periaqueductal gray matter of non-migraine patients, resulting in migraine-like attacks. It is hypothesized that PAG may be the source center of migraine pain perception.
With the development of neuroimaging techniques, different functional magnetic resonance imaging (fMRI) methods have been used to study the mechanisms of PAG in clinical migraine patients. Foci can be found on T2 structural images of PAG in most migraine patients . A study based on diffusion kurtosis imaging showed that the Mean kurtosis (MK) and mean diffusivity values of the PAG were significantly increased in the migraine patients compared with the controls. The MK values of the PAG were significantly positively correlated with both age and the untreated period in the patient group . Compared with healthy controls (HCs), migraine patients showed a significantly decreased resting-state functional connectivity (RSFC) between the PAG and prefrontal cortex, anterior cingulate, amygdala, and brain regions with a predominant role in pain modulation . MwoA patients also showed reduced RSFC between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC). The reduced RSFC between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, RSFC between the PAG and the rACC in MwoA patients significantly increased. The changes in RSFC among the PAG, rACC, and ventral striatum were significantly associated with headache intensity improvement .
However, the PAG, as an important node in the upstream and downstream of the nociceptive pathway, RSFC cannot detect the directional information of the PAG brain network . Effective connectivity (EC) reflects the direct causal effect of one brain region on another, which contributes to a detailed understanding of the neuropathological mechanisms of functional architecture. Granger causal analysis (GCA) provides a feasible approach to achieving this goal by identifying directional functional interactions from time-series data .
In the current study, we hypothesized that MwoA subjects would exhibit altered the resting state EC (RSEC) of the bilateral PAG regions in emotional, cognitive, and sensory-related brain areas. We utilized rsfMRI and voxel-wised GCA to investigate alterations in RSEC in MwoA patients, compared with HC.