Yong Zhang1, Naying He2, Hua-Wei Lin2, Ajit Shankaranarayanan3, Zhenyu Zhou1, and Fu-Hua Yan2
1MR Research China, GE Healthcare, Beijing, China, People's Republic of, 2Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, People's Republic of, 3GE Healthcare, Menlo Park, CA, United States
Synopsis
This preliminary study investigated
functional connectivity changes in Alzheimer’s Disease (AD) and amnestic
mild cognitive impairment (MCI) using degree centrality (DC), a novel
resting-state fMRI parameter to provide voxel-wise whole brain functional
connectivity measurement. Twelve AD patients, twelve MCI patients and fifteen
healthy controls were recruited for comparison. As compared to normal controls,
AD patients showed the deceased DC in the posterior cingulate cortex while MCI
patients showed decreased DC in bilateral cuneus (visual processing) but
increased DC in bilateral hippocampus (memory) and right angular gyrus
(language). The different patterns of FC
changes might provide insight into disease evolvement.Purpose
Progressive cognitive
decline in neurodegenerative disorders such as Alzheimer’s disease (AD) and amnestic
mild cognitive impairment (MCI) may be caused by altered functional
connectivity (FC) between various brain regions.
1 The previous resting-state
fMRI studies often used local parameters, for example, Amplitude of Low
Frequency Fluctuation (ALFF) and Regional homogeneity (ReHo) to investigate local
spontaneous brain activities, which might be incapable to reflect whole brain
FC changes.
2 Degree centrality (DC), a novel resting-state fMRI
parameter has been developed to calculate the number of functional connectivity
of each voxel with all the other voxels in the brain to avoid subjectivity associated
with manual seed region definition from traditional FC methods.
3 In
this preliminary study, we used DC to perform a voxel-wise whole brain FC
analysis for AD and MCI patients as compared to normal controls.
Methods
The study was approved by the local ethical committee and
written informed consent was obtained from all the participants. Twelve AD patients
(aged 72.6±10.1 years, five females) and twelve MCI
patients (aged 76.3±12.7 years, six females) were
recruited according to the criteria of NINCDS-ADRDA, PADCS and Mini-Mental
State Examination (MMSE) scores. The MMSE scores were 15.4±5.84 for
AD patients and 25.3±2.63 for MCI patients respectively. Fifteen
age- and gender-matched NC subjects (aged 72.4±9.39 years, seven females) were selected for group comparison. All subjects
were right-handed. Thirty-five axial slices covering the whole brain were
acquired using a 3.0-T HDXT scanner (GE Healthcare, Milwaukee, WI) with an 8-channel
phase array head coil (TR/TE 2000/30 ms, flip angle 90°, matrix 64 × 64, FOV 24
cm, thickness/gap 4/0 mm, total 210 volumes). Data preprocessing included slice
timing and realignment for temporal and spatial adjustment using SPM8, followed
by spatial normalization to warp all the images into the same stereotactic
space for group comparison. An in-house software REST was used for DC analysis (
http://www.restfmri.net).
All the time series were de-trended and band-pass filtered (0.01-0.08Hz). DC
was calculated as the weighted sum of correlation coefficients between each
pair of voxels and standardized by the global mean within the whole brain. The
statistical analysis was one-way ANOVA to make comparison among AD, MCI and control
groups. The AlphaSim program implemented in AFNI was used for multiple
comparison correction (corrected p<0.05).
Results
As
compared to the AD group, the control group showed increased DC in the left orbitofrontal
cortex and posterior cingulate cortex but decreased DC in the bilateral
cerebellum and vermis (Fig. 1). For comparison between the MCI and control
groups, the control group showed increased DC in bilateral cuneus and right
middle occipital gyrus but decreased DC in left caudate nucleus, bilateral hippocampus and right angular gyrus (Fig.
2).
Discussion and Conclusion
In this preliminary study, we found deceased DC in the posterior
cingulate cortex for AD patients, which was consistent with previous studies. The
posterior cingulate cortex served as an important hub in default mode network,
suggesting substantial FC changes in AD patients. MCI patients showed decreased
DC in bilateral cuneus (visual processing) but increased DC in bilateral
hippocampus (memory) and right angular gyrus (language). The different patterns of FC changes might
provide interesting insight into the mechanism of disease evolvement.
Acknowledgements
No acknowledgement found.References
1. Liu Y, Wang K, Yu C, et al. Regional homogeneity,
functional connectivity and imaging markers of Alzheimer's disease: a review of
resting-state fMRI studies. Neuropsychologia. 2008;46(6):1648-1656.
2. Zang Y, Jiang T, Lu Y, et al. Regional homogeneity
approach to fMRI data analysis. NeuroImage. 2004;22(1):394– 400.
3. Buckner R, Sepulcre J, Talukdar T et al. Cortical hubs
revealed by intrinsic functional connectivity: mapping, assessment of
stability, and relation to Alzheimer's disease. J Neurosci 2009;29(6):1860-1873.