Deborah Xiu-Ning Lin1, Shu-Wei Chu1, Ming-Chou Ho2, and Jun-Cheng Weng1,3
1Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, 2Department of Psychology, Chung Shan Medical University, Taichung, Taiwan, 3Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan
Synopsis
Betel
nut is the seed of the betel palm,
which grows in the tropical
or subtropical regions, especially in Taiwan, India, China and
parts of east Africa. It has been
confirmed that chewing
betel nuts can be addicted to it and is also carcinogenic to humans. Chewing
betel nuts lead to a greatly increased risk
of developing a range of serious diseases, including oral and esophagus cancers. In Taiwan, 88% of people who were
diagnosed to oral
cancer have the habit of chewing betel nuts, but very few researches studied on
how chewing betel nuts effects brian structure. Therefore, in this study we tried to find out the structural volume
and shape changes in the brain between betel nut chewers and healthy controls with voxel-based morphometry (VBM) and vertex-wise shape analyses. In
addition, the relationship between brain structural volume size and implicit
attitude or inhibitory control were also discussed.Purpose
Betel nut is the seed of the betel palm, which
grows in the tropical or subtropical
regions, especially in Taiwan, India, China and parts of east Africa.
It has been confirmed that chewing
betel nuts can be addicted to it and is also carcinogenic to humans [1, 2]. Chewing
betel nuts lead to a greatly increased risk of developing a range of serious diseases,
including oral and esophagus cancers [3]. In Taiwan,
88% of people who were diagnosed to oral cancer have the habit of chewing betel nuts, but very
few researches studied on how chewing betel nuts effects brian structure [4].
Therefore, in this study
we tried to find out the structural volume and shape changes in the brain
between betel nut chewers (BNC) and healthy controls (HC) with voxel-based
morphometry (VBM) and vertex-wise shape analyses. In addition, the relationship
between brain structural volume size and implicit attitude or inhibitory
control were also discussed.
Materials and Methods
We enrolled
11 BNCs and 13 HCs who all underwent magnetic
resonance imaging (MRI) examination on a
3T imaging system (Skyra, Siemens Medical System, Germany) with a 20 channel head neck coil. T1-weighted
images were obtained using the 3D MP-RAGE sequence, and the scan parameters
included TR/TE = 2500/22.27 ms; flip angle = 8°; voxel size = 1 x 1 x 1 mm3,
and 160 slices.
To investigate focal brain volume differences in both
gray matter and white matter between BNCs and HCs, voxel-based morphometry
(VBM) analysis of Statistical Parametric Mapping (SPM) was used. Vertex-wise
shape analysis of FMRIB Software Library (FSL) was also performed to enable 15
structures to be separated from brain and see the differences in shape between BNCs
and HCs of each structure. In addition, two psychometric testing, D score
(sensitivity index) and Stop-Signal Reaction Time (SSRT), were tested for 24 participants
to find the correlation between brain structural volume size and implicit
attitude or inhibitory control, respectively. The higher D score means the more
disgust participants feel about betel nuts, and the higher SSRT indicates worse
inhibitory control.
Results
In the VBM analysis, reduced gray matter volume of
anterior cingulum cortex (ACC) were found in the BNCs compared to HCs (Fig. 1a)
(p = 0.01). Decreased white matter volume of superior frontal gyrus (Fig. 1b),
and enlarged white matter volume of cingulate gyrus (Fig. 1c) were also
observed in the BNCs compared to HCs (p = 0.01). In the vertex-wise shape
analysis, altered shape was found in right accumbens (Fig. 2a), left amygdala (Fig.
2b), right caudate (Fig. 2c), and right hippocampus (Fig. 2d) between BNCs and
HCs.
In the correlation of D
score and gray matter volume, positive correlation was found in left inferior
frontal gyrus (pars triangularis) (Fig. 3a) and right anterior cingulum (Fig. 3b),
and negative correlation in superior frontal gyrus (Fig. 3c) (p = 0.006). In the
correlation of D score and white matter volume, positive correlation was found in
cuneus (Fig. 3d), and negative correlation in right supplementary motor area (rSMA)
(Fig. 3e) (p = 0.005). In the correlation of SSRT and gray matter volume, positive
correlation was found in right middle temporal gyrus (Fig. 3f), and negative
correlation in superior frontal gyrus (Fig. 3g) (p = 0.03). In the correlation
of SSRT and white matter volume, positive correlation was found in right superior
temporal (Fig. 3h), and negative correlation
in midbrain (Fig. 3i) (p = 0.04).
Discussion
The atrophy in gray matter of ACC of BNCs indicated that BNCs might have less error detection ability, attention,
and motivation. Previous study also found ACC decreased in BNC [4]. The
decreased white matter volume of superior frontal gyrus of BNCs might be
related to less self-awareness or less coordination with the action of the sensory system [5]. Larger white matter volume of cingulate gyrus of BNCs might
effect their emotion formation and processing, learning, and memory.
The positive correlation with D score indicated
those who like chewing betel nuts frequently had increased structural volumes
of left pars triangularis
inferior frontal, right anterior cingulum, and cuneus,
which were related to emotional disorder
and addiction. On the contrary, negative correlation with D
score indicated those who do not like or not usually chewing betel nuts had
decreased structural volumes of superior frontal gyrus and right supplementary
motor area, which were related to action of sensory system and coordinating temporal
sequences of actions.
The positive correlation
with SSRT indicated those who had worse
inhibitory control had increased structural volumes of right middle temporal and right superior
temporal gyrus. Temporal gyrus linked to the
perception of emotions in facial stimuli and the processing information ability of changeable face
characteristics. The negative correlation with SSRT indicated who had worse
inhibitory control had smaller structural volumes of superior frontal gyrus
and midbrain, which were related to motor system.
Conclusion
In
our study, the volume and shape
changes of brain structures in BNC included motor system,
cognitive system and emotion system, which
might reflect the underlying mechanism in BNC. The study validated the
application of VBM and vertex-wise shape analyses in the habitual betel nut’s
addictive brains. Together they provided better structural information of the
brain changes and might facilitate understanding of the underlying mechanism in
chewers.
Acknowledgements
This study was supported in part by the research program NSC103-2420-H-040-001-MY2,
which was sponsored by the Ministry of Science and Technology, Taipei, Taiwan.References
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