Sheng-Min Huang1, Kun-I Chao1, Kung-Chu Ho2, and Fu-Nien Wang1
1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, 2Division of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Synopsis
We investigated the DMN in ADHD rats of
different ages. A major difference of DMN between SHR and WKY rats was found in
caudate putamen area. As age increasing, the striatal activation presented in
the DMN of 6-week SHR started to decrease at 8-week and tend to fade out at
10-week. Since the volume difference of striatal region between SHR and WKY
rats has been reported, our result may suggest that the structural development is
followed by persisted functional network alteration. The correlation of
development of striatal volume and striatal resting state activity both suggest
that the timing is important. Purpose
Resting state functional MRI
(rs-fMRI) is an emerging neuroimaging method, examining the connectivity of brain
neural circuits. This technique has been used to study neurophysiological and
neuropsychiatric disorders, including attention deficit and hyperactivity
disorder (ADHD)
1. Several rs-fMRI literatures
showed the abnormalities of connectivity within default mode network (DMN), or
of the connectivity between DMNs and cognitive networks in human
2. Our previous study
3 has demonstrated distinct
differences between the DMNs of Spontaneously hypertensive rats (SHR, ADHD
rodent model
4) and Wistar Kyoto rats (WKY) in 6-week-old. Since the development of
ADHD symptoms is related to age
5, we set out to
investigate if the DMNs of rodent model would also be age-related. A seed-based
analysis was carried out to compare the DMNs of SHR and WKY rats among 6, 8 and
10 week of age.
Material & Method
SHR rats were used to model
ADHD according to Sagvolden’s work
4, and WKY were the control group. 6, 8 and 10
-week-old rats were scanned on 7T Bruker Clinscan with a surface coil for
signal receiving. Subject numbers of SHR/WKY were: 6 weeks (N=9 in each group),
8 weeks (N=4 in each group) and 10 weeks (N=4 in each group). Aneasthesia was
induced with around 1.5% isoflurane mixed with O2. Respiratory rates
of the free-breathing rat were monitored throughout whole scan period (around 65-75 times/min) and
body temperature was maintained by 37℃ water circulation. 525 consecutive volumes with 11 coronal slices were acquired
using gradient echo EPI with TE/TR=20ms/1000ms, FOV=30mm, matrix size=64x64 and
1mm slice thickness. All data were post-processed by tools below: Image
registration by Automated Image Registration (AIR), slice timing and smoothing
(1mm Gaussian kernel) by SPM8, temporal detrend and frequency filtering (0.002
- 0.1Hz) by REST toolkit. Seed-based and other analysis was performed on self-designed
Matlab scripts. To determine the DMN of a rat, the retrosplenial
cortex region at Bregma -4.8mm was chosen as the seed based on Paxinos
coordinates. Correlation coefficient
maps from all animals in each group were subject to one sample t test against 0
and a Bonferroni-corrected threshold was gated to generate final maps.
Results
As shown in Figure 1, the RSC-based DMN maps of SHR
and WKY rats in three different ages were overlaid on T2 anatomical images. For the 6-week-old group,
major difference between SHR and WKY rats were found with regard to caudate putamen and hippocampus area. As age
increasing, the striatal activation presented in the DMN of SHR started to
decrease at 8-week and tend to fade out at 10-week. Besides, cingulate cortex activity
in SHR also appears to be smaller at 10-week (red arrow). On the other hand, WKY
rats presented a relatively stable DMN among these ages. A distinct difference
can be found within hippocampal area in WKY groups. In particular, hippocampal activity
only presented in 6-week WKY rats.
Discussions
In
our rs-fMRI results, striatal activity presented at 6-week-old SHR rats and
then started to decrease at 8-week-old. The striatal activity then disappeared
from the DMN of SHR group. In literature, the volume difference of striatal
region between SHR and WKY rats has been reported in Hsu’s work
6. They found
that at 5 weeks of age there was a significant striatal volume difference
between SHRs and WKYs. The striatal volumes became stable and reach a plateau after
5-week in WKY group and after 6-week in SHR group. Interestingly, the alteration
of DMN observed in our rs-fMRI results was delayed comparing with the stable
development of striatal volume. This may suggest that the structural development is followed by persisted functional network alteration. The correlation of
development of striatal volume and striatal resting state activity suggest that
the timing may shed new light in ADHD research. Further investigations on the
correlation of DMN, structural volume, and behavior could be carried out.
Conclusion
A distinct
difference of DMN was found between the developmental brains of SHR and WKY rat
in this study, especially within the striatal region.
Acknowledgements
We wish to acknowledge the funding provided by the Ministry of Science
Technology (MOST, 104-2221-E-007-063) and the instrumentation support from
the Center for Advanced Molecular Imaging and Translation at Chang Gung
Memorial Hospital, Linkou. References
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