title: Multidimensional frequency domain analysis of full-volume fMRI reveals significant effects of age, gender, and mental illness on the spatiotemporal organization of resting-state brain activity.
abstract: Clinical research employing functional magnetic resonance imaging (fMRI) is often conducted within the connectionist paradigm, focusing on patterns of connectivity between voxels, regions of interest (ROIs) or spatially distributed functional networks. Connectivity-based analyses are concerned with pairwise correlations of the temporal activation associated with restrictions of the whole-brain hemodynamic signal to locations of a priori interest. There is a more abstract question however that such spatially granular correlation-based approaches do not elucidate: Are the broad spatiotemporal organizing principles of brains in certain populations distinguishable from those of others? Global patterns (in space and time) of hemodynamic activation are rarely scrutinized for features that might characterize complex psychiatric conditions, aging effects or gender-among other variables of potential interest to researchers. We introduce a canonical, transparent technique for characterizing the role in overall brain activation of spatially scaled periodic patterns with given temporal recurrence rates. A core feature of our technique is the spatiotemporal spectral profile (STSP), a readily interpretable 2D reduction of the native four-dimensional brain × time frequency domain that is still "big enough" to capture important group differences in globally patterned brain activation. Its power to distinguish populations of interest is demonstrated on a large balanced multi-site resting fMRI dataset with nearly equal numbers of schizophrenia patients and healthy controls. Our analysis reveals striking differences in the spatiotemporal organization of brain activity that correlate with the presence of diagnosed schizophrenia, as well as with gender and age. To the best of our knowledge, this is the first demonstration that a 4D frequency domain analysis of full volume fMRI data exposes clinically or demographically relevant differences in resting-state brain function.
authors.affiliation: The Mind Research Network Albuquerque, NM, USA.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Miller
authors.affiliation: Department of Mathematics and Statistics, University of New Mexico Albuquerque, NM, USA.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Erhardt
authors.affiliation: The Mind Research Network Albuquerque, NM, USA ; Department of Electrical and Computer Engineering, University of New Mexico Albuquerque, NM, USA.
authors.forename: Oktay
authors.initials: O
authors.lastname: Agcaoglu
authors.affiliation: Bergen Center for Neuropsychiatric Research Bergen, Norway.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Allen
authors.affiliation: Geisinger Autism and Developmental Medicine Institute Lewisburg, PA, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Michael
authors.affiliation: Department of Psychology and Neuroscience, Georgia State University Atlanta, GA, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
authors.affiliation: Department of Psychiatry, University of New Mexico School of Medicine Albuquerque, NM, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Bustillo
authors.affiliation: Department of Psychiatry, University of California San Francisco School of Medicine San Francisco, CA, USA.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ford
authors.affiliation: Department of Psychiatry, University of California San Francisco School of Medicine San Francisco, CA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine Irvine, CA, USA.
authors.forename: Theo G M
authors.initials: TG
authors.lastname: Van Erp
authors.affiliation: Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine Irvine, CA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Potkin
authors.affiliation: Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine Irvine, CA, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Preda
authors.affiliation: Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Pearlson
authors.affiliation: The Mind Research Network Albuquerque, NM, USA ; Department of Psychiatry, University of New Mexico School of Medicine Albuquerque, NM, USA ; Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA ; Department of Electrical and Computer Engineering, University of New Mexico Albuquerque, NM, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
keywords: brain dynamics; fMRI; multidimensional Fourier transform; schizophrenia; spatiotemporal frequency domain