A pairwise approach for fMRI group studies using the BrainSync Transform

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Due to the spontaneous nature of resting fMRI (rs-fMRI) signals, cross-subject comparison and group studies of rs-fMRI are challenging. Existing group comparison methods typically reduce the fMRI time series either to lower-dimensional connectivity features or use ICA to reduce dimensionality. We previously developed BrainSync, an orthogonal transformation that allows direct comparison of fMRI time-series across subjects.¹ This orthogonal transform performs a temporal alignment of time-series at homologous locations across subjects allowing a direct comparison of scans. In contrast with existing fMRI analysis methods, this transform does not involve dimensionality reduction and preserves the rich functional connectivity information in fMRI data. BrainSync Alignment (BSA) is an extension of this approach that jointly synchronizes fMRI data across time-series data for multiple subjects.²Point-wise distance measures, or Pearson correlations, can be computed between the reference and synchronized time-series as measures of inter-subject differences in functional connectivity at each location in the brain. In group studies, especially in the case of spectrum disorders, distances to a single atlas do not fully reflect the differences between subjects that may lie on a multi-dimensional spectrum. Here we describe an approach that measures the distances between pairs of subjects instead of to a single reference point.³ We present novel pairwise statistical methods for fMRI that can be used for regression and also for identifying group differences. We demonstrate the effectiveness of our method in two studies: (i) pairwise comparisons of fMRI data in subjects for performing regression to an ADHD index, and (ii) an F-test using pairwise statistical analysis to compare traumatic brain injury (TBI) subjects that develop post-traumatic epilepsy (PTE) to those that do not.