title: Template based rotation: a method for functional connectivity analysis with a priori templates.
abstract: Functional connectivity magnetic resonance imaging (fcMRI) is a powerful tool for understanding the network level organization of the brain in research settings and is increasingly being used to study large-scale neuronal network degeneration in clinical trial settings. Presently, a variety of techniques, including seed-based correlation analysis and group independent components analysis (with either dual regression or back projection) are commonly employed to compute functional connectivity metrics. In the present report, we introduce template based rotation,(1) a novel analytic approach optimized for use with a priori network parcellations, which may be particularly useful in clinical trial settings. Template based rotation was designed to leverage the stable spatial patterns of intrinsic connectivity derived from out-of-sample datasets by mapping data from novel sessions onto the previously defined a priori templates. We first demonstrate the feasibility of using previously defined a priori templates in connectivity analyses, and then compare the performance of template based rotation to seed based and dual regression methods by applying these analytic approaches to an fMRI dataset of normal young and elderly subjects. We observed that template based rotation and dual regression are approximately equivalent in detecting fcMRI differences between young and old subjects, demonstrating similar effect sizes for group differences and similar reliability metrics across 12 cortical networks. Both template based rotation and dual-regression demonstrated larger effect sizes and comparable reliabilities as compared to seed based correlation analysis, though all three methods yielded similar patterns of network differences. When performing inter-network and sub-network connectivity analyses, we observed that template based rotation offered greater flexibility, larger group differences, and more stable connectivity estimates as compared to dual regression and seed based analyses. This flexibility owes to the reduced spatial and temporal orthogonality constraints of template based rotation as compared to dual regression. These results suggest that template based rotation can provide a useful alternative to existing fcMRI analytic methods, particularly in clinical trial settings where predefined outcome measures and conserved network descriptions across groups are at a premium.
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA. Electronic address: aschultz@nmr.mgh.harvard.edu.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA.
authors.forename: Jasmeer P
authors.initials: JP
authors.lastname: Chhatwal
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA.
authors.forename: Willem
authors.initials: W
authors.lastname: Huijbers
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA; Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Trey
authors.initials: T
authors.lastname: Hedden
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA; Harvard University, Department of Psychology, Center for Brain Science, Cambridge, MA, 02138 USA.
authors.forename: Koene R A
authors.initials: KR
authors.lastname: van Dijk
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: McLaren
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, 02129 USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Ward
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wigman
authors.affiliation: Harvard Aging Brain Study, Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000033:anatomy & histology* / Q000502:physiology*; D012044:Regression Analysis; D015203:Reproducibility of Results; D055815:Young Adult