Background and ObjectivesThe objective of this study was to propose a clustering approach to identify migraine subgroups and test the clinical usefulness of the approach by providing prognostic information for electroacupuncture treatment selection.MethodsParticipants with migraine without aura (MWoA) were asked to complete a daily headache diary, self-rating depression and anxiety, and quality-of-life questionnaires. Whole-brain functional connectivities (FCs) were assessed on resting-state functional MRI (fMRI). By integrating clinical measurements and fMRI data, partial least squares correlation and hierarchical clustering analysis were used to cluster participants with MWoA. Multivariate pattern analysis was applied to validate the proposed subgrouping strategy. Some participants had an 8-week electroacupuncture treatment, and the response rate was compared between different MWoA subgroups.ResultsIn study 1, a total of 97 participants (age of 28.2 & PLUSMN; 1.0 years, 70 female participants) with MWoA and 77 healthy controls (HCs) (age of 26.8 & PLUSMN; 0.1 years, 61 female participants) were enrolled (dataset 1), and 2 MWoA subgroups were defined. The participants in subgroup 1 had a significantly lower headache frequency (times/month of 4.4 & PLUSMN; 1.1) and significantly higher self-ratings of depression (depression score of 49.5 & PLUSMN; 2.3) when compared with participants in subgroup 2 (times/month of 7.0 & PLUSMN; 0.6 and depression score of 43.4 & PLUSMN; 1.2). The between-group differences of FCs were predominantly related to the amygdala, thalamus, hippocampus, and parahippocampal area. In study 2, 33 participants with MWoA (age of 30.9 & PLUSMN; 2.0 years, 28 female participants) and 23 HCs (age of 29.8 & PLUSMN; 1.1 years, 13 female participants) were enrolled as an independent dataset (dataset 2). The classification analysis validated the effectiveness of the 2-cluster solution of participants with MWoA in datasets 1 and 2. In study 3, 58 participants with MWoA were willing to receive electroacupuncture treatment and were assigned to different subgroups. Participants in different subgroups exhibited different response rates (p = 0.03, OR CI 0.086-0.93) to electroacupuncture treatment (18% and 44% for subgroups 1 and 2, respectively).DiscussionOur study proposed a novel clustering approach to define distinct MWoA subgroups, which could be useful for refining the diagnosis of participants with MWoA and guiding individualized strategies for pain prophylaxis and analgesia.