Comparing Cyclicity Analysis With Pre-established Functional Connectivity Methods to Identify Individuals and Subject Groups Using Resting State fMRI.

Abstract

The resting state fMRI time series appears to have cyclic patterns, which indicates presence of cyclic interactions between different brain regions. Such interactions are not easily captured by pre-established resting state functional connectivity methods including zero-lag correlation, lagged correlation, and dynamic time warping distance. These methods formulate the functional interaction between different brain regions as similar temporal patterns within the time series. To use information related to temporal ordering, cyclicity analysis has been introduced to capture pairwise interactions between multiple time series. In this study, we compared the efficacy of cyclicity analysis with aforementioned similarity-based techniques in representing individual-level and group-level information. Additionally, we investigated how filtering and global signal regression interacted with these techniques. We obtained and analyzed fMRI data from patients with tinnitus and neurotypical controls at two different days, a week apart. For both patient and control groups, we found that the features generated by cyclicity and correlation (zero-lag and lagged) analyses were more reliable than the features generated by dynamic time warping distance in identifying individuals across visits. The reliability of all features, except those generated by dynamic time warping, improved as the global signal was regressed. Nevertheless, removing fluctuations >0.1 Hz deteriorated the reliability of all features. These observations underscore the importance of choosing appropriate preprocessing steps while evaluating different analytical methods in describing resting state functional interactivity. Further, using different machine learning techniques including support vector machines, discriminant analyses, and convolutional neural networks, our results revealed that the manifestation of the group-level information within all features was not sufficient enough to dissociate tinnitus patients from controls with high sensitivity and specificity. This necessitates further investigation regarding the representation of group-level information within different features to better identify tinnitus-related alternation in the functional organization of the brain. Our study adds to the growing body of research on developing diagnostic tools to identify neurological disorders, such as tinnitus, using resting state fMRI data.