title: Functional integration of parietal lobe activity in early Alzheimer disease.
abstract: OBJECTIVE
  Parietal lobe dysfunction is an important characteristic of early Alzheimer disease (AD). Functional studies have shown conflicting parietal activation patterns indicative of either compensatory or dysfunctional mechanisms. This study aimed at examining activation differences in early AD using a visuospatial task. We focused on functional characteristics of the parietal lobe and examined compensation or disconnection mechanisms by combining a fMRI task with effective connectivity measures from Granger causality mapping (GCM).
  
  
  METHODS
  Eighteen male patients with amnestic mild cognitive impairment (aMCI) and 18 male cognitively healthy older individuals were given a mental rotation task with different rotation angles.
  
  
  RESULTS
  There were no behavioral group differences on the fMRI task. Separate measurements at each angle revealed widespread activation group differences. More temporal and parietal activation in the higher angle condition was observed in patients with aMCI. The parametric modulation, which identifies regions associated with increasing angle, confirmed these results. The GCM showed increased connectivity within the parietal lobe and between parietal and temporal regions in patients with aMCI. Decreased connectivity was found between the inferior parietal lobule and posterior cingulate gyrus. Connectivity patterns correlated with memory performance scores in patients with aMCI.
  
  
  CONCLUSIONS
  Our results demonstrate increased effective temporoparietal connectivity in patients with aMCI, while maintaining intact behavioral performance. This might be a compensational mechanism to counteract a parietal-posterior cingulate gyrus disconnection. These findings highlight the importance of connectivity changes in the pathophysiology of AD. In addition, effective connectivity may be a promising method for evaluating interventions aimed at the promotion of compensatory mechanisms.
authors.affiliation: School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands. h.jacobs@maastrichtuniversity.nl
authors.forename: H I L
authors.initials: HI
authors.lastname: Jacobs
authors.forename: M P J
authors.initials: MP
authors.lastname: Van Boxtel
authors.forename: A
authors.initials: A
authors.lastname: Heinecke
authors.forename: E H B M
authors.initials: EH
authors.lastname: Gronenschild
authors.forename: W H
authors.initials: WH
authors.lastname: Backes
authors.forename: I H G B
authors.initials: IH
authors.lastname: Ramakers
authors.forename: J
authors.initials: J
authors.lastname: Jolles
authors.forename: F R J
authors.initials: FR
authors.lastname: Verhey
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D001931:Brain Mapping; D015984:Causality; D060825:Cognitive Dysfunction / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007092:Imagination / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000503:physiopathology*; D011930:Reaction Time / Q000502:physiology; D012959:Socioeconomic Factors; D013702:Temporal Lobe / Q000503:physiopathology