Yafei Wang1, Yu Sun1, Lingyi Xu1, Yue Zhang1, Jiaming Lu2, Bing Liu3, Bing Zhang2, and Suiren Wan1
1The Laboratory for Medical Electronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China, People's Republic of, 2Department of Radiology, The affiliated Drum Tower hospital of Nanjing University Medical School, Nanjing, China, People's Republic of, 3National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Science, Beijing, China, People's Republic of
Synopsis
The
functional
connectivity between hippocampus subfields and perirhnial cortices
(PRC)/parahippocampal
cortices (PHC) among normal cognition controls (NC), mild
cognitive impairment (MCI) and Alzheimer’s disease (AD) was investigated in
this study. The result shows the significant differences of functional
connectivity in 3 pairs of ROIs among NC, AD and MCI. It may reveal that the
difference of functional connectivity can be the marker to diagnosis AD and
MCI.Purpose
To
study Alzheimer’s disease (AD) and mild cognitive impairment (MCI), the medial
temporal lobes (MTL), identified as the components of neuronal system for
declarative memory [1], have received considerable interest. perirhinal
cortices (PRC) and parahippocampal cortices (PHC) are both part of MTL. However,
the possible functional connections between PRC or PHC and hippocampus
subfields in patients with MCI and AD were unknown. Therefore, this study aimed
to explore the different functional connectivity among PHC/PRC and hippocampus
subfields in NC, MCI and AD patients with resting-state blood oxygen
level–dependent (BOLD) sequence. Based on the research by Laura A.
Libby et all[2],we divided the hippocampus into three subfields as
head, body and tail.
Methods
Subjects:
a total of 90 subjects, including 32 AD patients, 31 MCI patients and 27 NC, were recruited
from the Department of Neurology of the Affiliated Drum Tower Hospital of
Nanjing University Medical School in this study. The characteristics of patients
are presented in Table1.
Sequence:
each subject underwent a 3DT1W scan and a resting-state BOLD scan,
respectively, with a 3 Tesla MR scanner (Achieva 3.0T TX dual-source parallel
RF excitation and transmission technology, Philips Medical Systems, The
Netherlands). The parameters of the 3DT1W and BOLD scan are shown in table 2.
Data Processing:
The
pre-processing was taken on the Brainnetome fMRI Toolkit (BRAT 1.0), which is
designed by the Brainnetome Center, Institute of Automation, Chinese Academy of
Science. All patients passed the quality control of head motion which is 3mm
and 3 degree. The right and left PHC masks were taken from AAL(Anatomical
Automatic Labeling) Template and the right and left PRC masks were taken from
Bordmann Template. Therefore, the region of interest (ROI) included PHC(L/R),
PRC(L/R), hippocampus head(L/R), hippocampus body(L/R) and hippocampus
tail(L/R). Function connectivity among ROIs was processed on the BRAT 1.0
software with the pre-processed data.
Statistical Analysis: Statistics analyses including One-way analysis of
variance (ANOVA) and multiple comparison correction (MC) with a p value of < 0.05. ANOVA was taken on SPSS (V 21.0)
and multiple comparison correction was applied with Matlab code based on FDR
principle. Finally, Gaussian
mixture model was used to cluster the MCI
data.
Results
As
shown in table 3, the functional connectivity in
three
pairs of ROIs
has statistical significant differences among NC, MCI and
AD. The three pairs of ROIs are right PRC connected with right hippocampus
tail, left PRC connected with right hippocampus tail, and right PHC connected with
right hippocampus head. Figure 1 and table 3 show that in AD group
more functional connection decrease between PRC and right hippocampus tail
sub-region occurs compared with MCI. In contract, the functional connection between right
PHC and the right hippocampus head sub-region significantly increases in MCI (p=0.003)
and decreases in AD (p=0.03) compared with NC.
Discussion
The result reveals that the decrease of
functional connectivity between PRC and right hippocampus tail affects the cognitive
ability. Compared with NC, there is a significant increase of functional connectivity
between right PHC and the right hippocampus head sub-region in MCI subjects. It
appears that, in the course of MCI there may be hyper-activation in some
functional connections, possibly representing inefficient compensatory
mechanism for memory encoding activity.
MCI is a heterogeneous clinical entity
with multiple sources of heterogeneity. According to the result of
functional connections between PRC / PHC and the three hippocampus subfields, we
clustered MCI subjects in this research into two types, shown in figure 2,
using Gaussian mixture model (GGM). This result suggests that the
different functional connection patterns in MCI patients can be the basis and another
criterion of MCI classification.
The limitation is that MCI subjects in
this
research were not divided into different subtypes with clinical manifestation, therefore
it’s hard to find the difference of functional connectivity in MCI subtypes as
well as the relationship between subtypes and the classification result we achieved.
In the next step, we will continue our research on comparing the functional
connectivity in different MCI subtypes and follow the progress of clinical
changes in MCI subjects by follow-up visit. It’s promising that our research
can help the classification of AD, MCI and NC, as well as benefiting the early
diagnosis of AD.
Conclusion
Our result indicates significant
differences of functional connectivity between right PRC and right
hippocampus tail, between left PRC and right hippocampus tail, and between right
PHC and right hippocampus head among AD, MCI and NC subjects.
The result may reveal some neuronal alterations with the disease evolvement, and
make further efforts on classification of AD, MCI and NC.
Acknowledgements
The author would like to thank Prof. Suiren
Wan and Dr. Yu Sun for their technical suggestions in data processing, Prof.
Bing Liu and Dr. Bing Zhang for their guidance of research directions, Lingyi
Xu, Yue Zhang and Jiaming Lu for their help in research and abstract writing.References
[1] Squire, L.R. and S. Zola-Morgan, The medial temporal lobe memory system.
Science, 1991. 253(5026): p.
1380-1386.
[2] Laura A. Libby., et al., Differential
Connectivity of Perirhinal and Parahippocampal Cortices within Human Hippocampal
Subregions Revealed by HighResolution Functional Imaging. The Journal of
Neuroscience,2012.32(19):p.6550-6560.