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Neuroimage. 2017 Feb 1;146:959-970. doi: 10.1016/j.neuroimage.2016.10.020. Epub 2016 Oct 13.

Multisite reliability of MR-based functional connectivity.

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Yale University, Interdepartmental Neuroscience Program, New Haven, CT, USA. Electronic address:
Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT, USA.
Yale University, Interdepartmental Neuroscience Program, New Haven, CT, USA.
Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT, USA; Yale University, Department of Biomedical Engineering, New Haven, CT, USA.
University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA.
University of Calgary, Department of Psychiatry, Calgary, Alberta, Canada.
University of Calgary, Departments of Radiology, Clinical Neurosciences and Psychiatry, Calgary, Alberta, Canada.
University of California, San Diego, Department of Psychiatry, La Jolla, CA, USA.
Zucker Hillside Hospital, Department of Psychiatry Research, Glen Oaks, NY, USA.
University of California, San Francisco, Department of Psychiatry, San Francisco, CA, USA.
Yale University, Department of Psychiatry, New Haven, CT, USA.
University of North Carolina, Chapel Hill, Department of Psychiatry, Chapel Hill, NC, USA.
Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
University of California, Irvine, Department of Psychiatry and Human Behavior, Irvine, CA, USA.
Emory University, Department of Psychology, Atlanta, GA, USA.
Yale University, Departments of Psychology and Psychiatry, New Haven, CT, USA.


Recent years have witnessed an increasing number of multisite MRI functional connectivity (fcMRI) studies. While multisite studies provide an efficient way to accelerate data collection and increase sample sizes, especially for rare clinical populations, any effects of site or MRI scanner could ultimately limit power and weaken results. Little data exists on the stability of functional connectivity measurements across sites and sessions. In this study, we assess the influence of site and session on resting state functional connectivity measurements in a healthy cohort of traveling subjects (8 subjects scanned twice at each of 8 sites) scanned as part of the North American Prodrome Longitudinal Study (NAPLS). Reliability was investigated in three types of connectivity analyses: (1) seed-based connectivity with posterior cingulate cortex (PCC), right motor cortex (RMC), and left thalamus (LT) as seeds; (2) the intrinsic connectivity distribution (ICD), a voxel-wise connectivity measure; and (3) matrix connectivity, a whole-brain, atlas-based approach to assessing connectivity between nodes. Contributions to variability in connectivity due to subject, site, and day-of-scan were quantified and used to assess between-session (test-retest) reliability in accordance with Generalizability Theory. Overall, no major site, scanner manufacturer, or day-of-scan effects were found for the univariate connectivity analyses; instead, subject effects dominated relative to the other measured factors. However, summaries of voxel-wise connectivity were found to be sensitive to site and scanner manufacturer effects. For all connectivity measures, although subject variance was three times the site variance, the residual represented 60-80% of the variance, indicating that connectivity differed greatly from scan to scan independent of any of the measured factors (i.e., subject, site, and day-of-scan). Thus, for a single 5min scan, reliability across connectivity measures was poor (ICC=0.07-0.17), but increased with increasing scan duration (ICC=0.21-0.36 at 25min). The limited effects of site and scanner manufacturer support the use of multisite studies, such as NAPLS, as a viable means of collecting data on rare populations and increasing power in univariate functional connectivity studies. However, the results indicate that aggregation of fcMRI data across longer scan durations is necessary to increase the reliability of connectivity estimates at the single-subject level.

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