title: [Structural and functional neuronal connectivity in Alzheimer's disease: a combined DTI and fMRI study].
abstract: BACKGROUND
  Cognitive performance depends on intact cortical connectivity. Important for memory processing in the human brain is the connection between posterior cingulate cortex and hippocampus, directly as well as indirectly via the parahippocampal gyrus. These brain areas are involved early in Alzheimer's disease (AD). At the same time, they belong to the default mode network (DMN), a functional network showing high functional connectivity under resting state conditions. In AD, this connectivity in specifically compromised, offering the possibility to investigate the structural basis of functional brain connectivity.
  
  
  METHODS
  We studied 18 patients with mild to moderate AD, 16 patients with mild cognitive impairment (MCI) and 20 healthy control subjects using diffusion tensor imaging (DTI) and resting state fMRI at 3.0 Tesla. We determined the effect of structural integrity in the posterior cingulate as assessed by DTI on the functional connectivity between posterior cingulate, hippocampus and parahippocampus during resting state in these three groups.
  
  
  RESULTS
  Structural integrity was reduced in posterior cingulate fibre tracts in patients with AD in the left hemisphere; however, this effect was partly accounted for by age differences. All three groups showed high functional connectivity between posterior cingulate cortex and hippocampus, via both the direct and the indirect pathways. Determination of effective connectivity yielded a negative fractional anisotropy (FA)-moderated correlation on the direct pathway in AD and MCI for both hemispheres, and in healthy controls for the right hemisphere. The indirect pathway showed a negative FA-moderated correlation in AD for the right hemisphere and in MCI for both hemispheres. Healthy controls showed a positive correlation on the indirect pathway for the left hemisphere.
  
  
  CONCLUSIONS
  Our data suggest that under healthy conditions, effective connectivity in the DMN between posterior cingulate cortex and hippocampus is mainly maintained by the indirect pathway via the parahippocampal gyrus. Patients with AD and patients with MCI show changes in this connectivity with a partial allocation to the direct pathway, most likely reflecting early parahippocampal lesions. The combination of DTI and fMRI broadens our understanding of human brain connectivity and its pathological changes with AD.
authors.affiliation: Alzheimer Gedächtniszentrum, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität München, München, Deutschland.
authors.forename: J
authors.initials: J
authors.lastname: Soldner
authors.forename: T
authors.initials: T
authors.lastname: Meindl
authors.forename: W
authors.initials: W
authors.lastname: Koch
authors.forename: A L W
authors.initials: AL
authors.lastname: Bokde
authors.forename: M F
authors.initials: MF
authors.lastname: Reiser
authors.forename: H-J
authors.initials: HJ
authors.lastname: Möller
authors.forename: K
authors.initials: K
authors.lastname: Bürger
authors.forename: H
authors.initials: H
authors.lastname: Hampel
authors.forename: S J
authors.initials: SJ
authors.lastname: Teipel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology* / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D059906:Neuroimaging / Q000379:methods*; D013382:Subtraction Technique