title: Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia.
abstract: The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to subserve sustained attention and working memory. Taken together, these data suggest that the magnitude of resting-state BOLD oscillations shows promise as a biomarker of cognitive function in health and disease.
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.|San Francisco VA Medical Center, San Francisco, CA, USA.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Fryer
authors.affiliation: San Francisco VA Medical Center, San Francisco, CA, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Roach
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.|San Francisco VA Medical Center, San Francisco, CA, USA.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ford
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: Theo G M
authors.initials: TG
authors.lastname: van Erp
authors.affiliation: Department of Psychiatry, Duke University, Raleigh-Durham, NC, USA.
authors.forename: James
authors.initials: J
authors.lastname: Voyvodic
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: Adrian
authors.identifier: http://orcid.org/0000-0003-3373-2438
authors.initials: A
authors.lastname: Preda
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Aysenil
authors.initials: A
authors.lastname: Belger
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Bustillo
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Leary
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Mueller
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
authors.affiliation: Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: McEwen
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.|Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.|Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Department of Psychiatry, Duke University, Raleigh-Durham, NC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Diaz
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Glover
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Greve
authors.affiliation: Department of Psychiatry, Harvard University, Boston, MA, USA.|VA Boston Healthcare System, Brockton, MA, USA.
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Wible
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
authors.forename: Jatin
authors.initials: J
authors.lastname: Vaidya
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.|San Francisco VA Medical Center, San Francisco, CA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012146:Rest; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D010100:Oxygen