title: Multisite reliability of MR-based functional connectivity.
abstract: 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.
authors.affiliation: Yale University, Interdepartmental Neuroscience Program, New Haven, CT, USA. Electronic address: stephanie.noble@yale.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noble
authors.affiliation: Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT, USA.
authors.forename: Dustin
authors.initials: D
authors.lastname: Scheinost
authors.affiliation: Yale University, Interdepartmental Neuroscience Program, New Haven, CT, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Finn
authors.affiliation: Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT, USA.
authors.forename: Xilin
authors.initials: X
authors.lastname: Shen
authors.affiliation: Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT, USA; Yale University, Department of Biomedical Engineering, New Haven, CT, USA.
authors.forename: Xenophon
authors.initials: X
authors.lastname: Papademetris
authors.affiliation: University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: McEwen
authors.affiliation: University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: University of Calgary, Department of Psychiatry, Calgary, Alberta, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.affiliation: University of Calgary, Departments of Radiology, Clinical Neurosciences and Psychiatry, Calgary, Alberta, Canada.
authors.forename: Bradley
authors.initials: B
authors.lastname: Goodyear
authors.affiliation: University of California, San Diego, Department of Psychiatry, La Jolla, CA, USA.
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Cadenhead
authors.affiliation: University of California, San Diego, Department of Psychiatry, La Jolla, CA, USA.
authors.forename: Heline
authors.initials: H
authors.lastname: Mirzakhanian
authors.affiliation: Zucker Hillside Hospital, Department of Psychiatry Research, Glen Oaks, NY, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Cornblatt
authors.affiliation: Zucker Hillside Hospital, Department of Psychiatry Research, Glen Oaks, NY, USA.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Olvet
authors.affiliation: University of California, San Francisco, Department of Psychiatry, San Francisco, CA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Yale University, Department of Psychiatry, New Haven, CT, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: McGlashan
authors.affiliation: Yale University, Department of Psychiatry, New Haven, CT, USA.
authors.forename: Diana O
authors.initials: DO
authors.lastname: Perkins
authors.affiliation: University of North Carolina, Chapel Hill, Department of Psychiatry, Chapel Hill, NC, USA.
authors.forename: Aysenil
authors.initials: A
authors.lastname: Belger
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Thermenos
authors.affiliation: University of California, San Diego, Department of Psychiatry, La Jolla, CA, USA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: University of California, Irvine, Department of Psychiatry and Human Behavior, Irvine, CA, USA.
authors.forename: Theo G M
authors.initials: TGM
authors.lastname: van Erp
authors.affiliation: Emory University, Department of Psychology, Atlanta, GA, USA.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Walker
authors.affiliation: Emory University, Department of Psychology, Atlanta, GA, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hamann
authors.affiliation: Yale University, Department of Psychiatry, New Haven, CT, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.affiliation: Yale University, Departments of Psychology and Psychiatry, New Haven, CT, USA.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.affiliation: Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D015337:Multicenter Studies as Topic; D009434:Neural Pathways / Q000502:physiology; D015203:Reproducibility of Results; D055815:Young Adult