title: Resting functional connectivity reveals residual functional activity in Alzheimer's disease.
abstract: BACKGROUND
  Functional magnetic resonance imaging (fMRI) has great potential for measuring mechanisms of functional changes in Alzheimer's disease (AD) and mild cognitive impairment, but task fMRI studies have produced conflicting results, partly due to failure to account for underlying morphological changes and to variations in patients' ability to perform the tasks. Resting fMRI has potential for assessing brain function independently from a task, but greater understanding of how networks of resting functional connectivity relate to the functioning of the brain is needed. We combined resting fMRI and task fMRI to examine the correspondence between these methods in individuals with cognitive impairment.
  
  
  METHODS
  Eighty elderly (25 control subjects, 25 mild cognitive impairment, 30 AD) underwent a combined multimodal magnetic resonance imaging protocol including task fMRI and resting fMRI. Task fMRI data were acquired during the execution of a memory paradigm designed to account for differences in task performance. Structural and physiological confounds were modeled for both fMRI modalities.
  
  
  RESULTS
  Successful recognition was associated with increased task fMRI activation in lateral prefrontal regions in AD relative to control subjects; this overlapped with increased resting fMRI functional connectivity in the same regions.
  
  
  CONCLUSIONS
  Our results show that task fMRI and resting fMRI are sensitive markers of residual ability over the known changes in brain morphology and cognition occurring in AD and suggest that resting fMRI has a potential to measure the effect of new treatments.
authors.affiliation: Oxford Project to Investigate Memory and Ageing, University of Oxford, United Kingdom. giovanna.zamboni@ndcn.ox.ac.uk
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zamboni
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Douaud
authors.forename: Erin
authors.initials: E
authors.lastname: Drazich
authors.forename: Ellen
authors.initials: E
authors.lastname: McCulloch
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
authors.forename: Jonathan C W
authors.initials: JC
authors.lastname: Brooks
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkinson
authors.forename: Clare E
authors.initials: CE
authors.lastname: Mackay
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology
keywords: AD; MCI; MRI; functional connectivity; functional magnetic resonance imaging (fMRI); resting fMRI; task fMRI