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Classification approaches have been increasingly applied to differentiate patients and normal controls using resting-state functional magnetic resonance imaging data (RS-fMRI). Although most previous classification studies have reported promising accuracy within individual datasets, achieving high levels of accuracy with multiple datasets remains challenging for two main reasons: high dimensionality, and high variability across subjects. We used two independent RS-fMRI datasets ( n  = 31, 46, respectively) both with eyes closed (EC) and eyes open (EO) conditions. For each dataset, we first reduced the number of features to a small number of brain regions with paired  t -tests, using the amplitude of low frequency fluctuation (ALFF) as a metric. Second, we employed a new method for feature extraction, named the PAIR method, examining EC and EO as paired conditions rather than independent conditions. Specifically, for each dataset, we obtained EC minus EO (EC—EO) maps of ALFF from half of subjects ( n  = 15 for dataset-1,  n  = 23 for dataset-2) and obtained EO—EC maps from the other half ( n  = 16 for dataset-1,  n  = 23 for dataset-2). A support vector machine (SVM) method was used for classification of EC RS-fMRI mapping and EO mapping. The mean classification accuracy of the PAIR method was 91.40% for dataset-1, and 92.75% for dataset-2 in the conventional frequency band of 0.01–0.08 Hz. For cross-dataset validation, we applied the classifier from dataset-1 directly to dataset-2, and vice versa. The mean accuracy of cross-dataset validation was 94.93% for dataset-1 to dataset-2 and 90.32% for dataset-2 to dataset-1 in the 0.01–0.08 Hz range. For the UNPAIR method, classification accuracy was substantially lower (mean 69.89% for dataset-1 and 82.97% for dataset-2), and was much lower for cross-dataset validation (64.69% for dataset-1 to dataset-2 and 64.98% for dataset-2 to dataset-1) in the 0.01–0.08 Hz range. In conclusion, for within-group design studies (e.g., paired conditions or follow-up studies), we recommend the PAIR method for feature extraction. In addition, dimensionality reduction with strong prior knowledge of specific brain regions should also be considered for feature selection in neuroimaging studies.

PAIR Comparison between Two Within-Group Conditions of Resting-State fMRI Improves Classification Accuracy