title: Reproducibility and Temporal Structure in Weekly Resting-State fMRI over a Period of 3.5 Years.
abstract: Resting-state functional MRI (rs-fMRI) permits study of the brain's functional networks without requiring participants to perform tasks. Robust changes in such resting state networks (RSNs) have been observed in neurologic disorders, and rs-fMRI outcome measures are candidate biomarkers for monitoring clinical trials, including trials of extended therapeutic interventions for rehabilitation of patients with chronic conditions. In this study, we aim to present a unique longitudinal dataset reporting on a healthy adult subject scanned weekly over 3.5 years and identify rs-fMRI outcome measures appropriate for clinical trials. Accordingly, we assessed the reproducibility, and characterized the temporal structure of, rs-fMRI outcome measures derived using independent component analysis (ICA). Data was compared to a 21-person dataset acquired on the same scanner in order to confirm that the values of the single-subject RSN measures were within the expected range as assessed from the multi-participant dataset. Fourteen RSNs were identified, and the inter-session reproducibility of outcome measures-network spatial map, temporal signal fluctuation magnitude, and between-network connectivity (BNC)-was high, with executive RSNs showing the highest reproducibility. Analysis of the weekly outcome measures also showed that many rs-fMRI outcome measures had a significant linear trend, annual periodicity, and persistence. Such temporal structure was most prominent in spatial map similarity, and least prominent in BNC. High reproducibility supports the candidacy of rs-fMRI outcome measures as biomarkers, but the presence of significant temporal structure needs to be taken into account when such outcome measures are considered as biomarkers for rehabilitation-style therapeutic interventions in chronic conditions.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States of America; International Center for Spinal Cord Injury, Kennedy Krieger Institute, Baltimore, MD, United States of America.
authors.forename: Ann S
authors.initials: AS
authors.lastname: Choe
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States of America.
authors.forename: Craig K
authors.initials: CK
authors.lastname: Jones
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States of America.
authors.forename: Suresh E
authors.initials: SE
authors.lastname: Joel
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Muschelli
authors.affiliation: International Center for Spinal Cord Injury, Kennedy Krieger Institute, Baltimore, MD, United States of America; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Visar
authors.initials: V
authors.lastname: Belegu
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Caffo
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lindquist
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States of America.
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pekar
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; D008875:Middle Aged; D015203:Reproducibility of Results; D012146:Rest / Q000502:physiology*; D055815:Young Adult