Yannan Cheng1, Chao Jin2, Xianjun Li2, Congcong Liu2, Miaomiao Wang2, Huifang Zhao2, Xiaoyu Wang2, Yuli Zhang2, Fan Wu2, Mengxuan Li2, Cong Tian2, Peiyao Chen2, Xiaocheng Wei3, Jianxin Guo2, and Jian Yang2
1Department of Radiology, the First Affiliated Hospital, Xi’an Jiaotong University, Xi'an, China, Xi'an, China, 2the First Affiliated Hospital, Xi’an Jiaotong University, Xi'an, China, Xi'an, China, 3MR Research China, GE Healthcare, Bei Jing, People's Republic of China, Xi'an, China
Synopsis
Seizures
are the most common disease in children and some types like epilepsy usually cause
many serious co-morbidities such as cognitive dysfunction. We detailed the alterations
of brain white matter network in children with seizure and cognitive
dysfunction by comparing the difference of network properties and connectivity
strength between the patient and control groups. Here, we found that children
with seizure and cognitive dysfunction show a suboptimal brain organization
with reduced information integration ability, and abnormalities in multiple intrinsic
functional connectivity may be the structural basis for cognitive impairment in
patients with seizures.
Purpose
Seizures
are the most common disease in children and some types like epilepsy usually cause
many serious co-morbidities1,2. Among these, cognitive dysfunction is
the most common and troublesome2. Studies have shown that cognitive
functions benefit from the efficient communication between different brain
regions in a large-scale network3. And functional and structural
studies both have found that distinct seizures with cognitive impairment
manifests as abnormal brain network connectivity and network topology changes
in adult4-6. While less is known regarding alterations of brain white
matter structural network in children with seizure and cognitive disfunction, which
was evaluated in this study.Materials and Methods
The Institutional Review Broad of the first author’s affiliation
approved this study and written informed consent were obtained from parents of
the children. Subjects Forty-eight children with seizure and no abnormality on MRI participated
in the study. Cognitive ability was assessed by the Chinese Wechsler Young
Children scale of Intelligence (C-WYCSI) for children aged 4 to 6 years and
Chinese Wechsler Intelligence Scale for Children (C-WISC) aged 6 to 18 years. Then,
all subjects were divided into control (seizure with normal cognitive function)
(n=34) and patients (seizure with cognitive dysfunction) (n=14) according to full
scale intelligence quotient (FSIQ). Cognitive dysfunction was defined as FSIQ
<85 scores. MR Protocols All subjects were examined by using a 3.0T scanner (Signa HDxt, General
Electric Medical System, Milwaukee, WI, USA) with an 8-channel head coil. Data
acquisition included three-dimensional fast spoiled gradient-echo T1-weighted
sequence (TR/TE, 10.2ms/4.6ms; NEX, 1; isotropic 1×1×1mm3; FOV,
24cm) and transverse fast
spin-echo T2-weighted sequence (TR/TE, 4200ms/113ms; NEX of 1.5; matrix,
320×320; thickness, 4mm; FOV, 24cm),
followed by a DTI (30 directions; b value, 600s/mm2; TR/TE,
11000ms/67.4ms; NEX, 1; thickness, 2.5mm; FOV, 24cm; matrix, 172×172). Data and statistical analysis DTI and T1 data were
processed through standard pipeline in PANDA software. The brain connectivity
matrix was constructed based on fiber number, using AAL atlas as a reference. A
network-based statistic (NBS) was used to identify the difference in connectivity
strength between the two groups. Network properties were computed by Gretna
software using graph theory, including (1) global network properties:
small-worldness (σ), global efficiency
and shortest path length; (2) nodal network properties: efficiency and shortest
path length. SPSS 18.0 (SPSS, Chicago, IL, USA) was used to find the difference
in network properties between two groups. p<0.05
was considered as statistically significant difference.Results
Forty-eight children were included in this study. Significant differences
presented in FSIQ scores between the two groups, while no differences were
observed in age at MRI scan, sex, age of onset and duration of seizures (Table 1).
All children demonstrated small-world
property of the white matter networks (σ>1). Both global and nodal results
showed that increased shortest path length and reduced efficiency in patients group compared with control
group. Furthermore, we also found these regions mainly consisted of (1) bilateral
default mode network: superior frontal gyrus (medial), anterior cingulate
gyrus, middle cingulate gyrus, posterior cingulate gyrus and precuneus; (2) left
frontoparietal network (superior frontal gyrus, middle frontal gyrus, inferior frontal
gyrus triangular and rolandic operculum); (3) visual network:
bilateral fusiform, left middle temporal gyrus and lingual gyrus, right
inferior occipital gyrus and heschl’s gyrus (Figure 1).
From
the results of NBS analysis, forty-three connections demonstrated reduced
connectivity (P<0.001, corrected) in patients group relative to control
group. Consistent with the previous findings, these connections also mainly
distributed in bilateral default mode network, left frontoparietal network, and
right visual network (Figure 2). None of the connections showed
increased connectivity in patient group.Discussion
All
children's structural brain white matter network showed a small world topology,
which was consistent with previous studies7. Then, we also found
that increased shortest
path length and reduced
global efficiency in patients group relative to control group. Previous studies
have found that the above parameters usually represent the ability to integrate
information in the whole brain, indicating that altered organization of brain
white matter networks may impact the ability to effectively integrate
information from different brain regions in children with seizure and cognitive
dysfunction7. In addition, children with seizure and cognitive
dysfunction showed reduced nodal efficiency and increased path length affecting
many regions. And according to Yeo’ study8, we found that the affecting
area primarily located in the bilateral default mode network, followed by the
left frontoparietal network and the right visual network. Last, we discovered
that forty-three connections demonstrated reduced connectivity in patient
group. Consistent with the above results, these connections also mainly
distributed in above functional network. Based on these findings, we can induce
that children with seizure and cognitive dysfunction may present as impairment
in language, visual function and some psychiatric disorders 8.Conclusion
Children
with seizure and cognitive dysfunction show a suboptimal brain organization
with reduced information integration ability, and abnormalities in multiple intrinsic
functional connectivity may be the structural basis for cognitive impairment in
patients with seizures.Acknowledgements
This study was supported by the National Natural Science Foundation of China (81901516, 81971581, 81901823, 81771810 and 51706178), Shaanxi Provincial Innovation Team (2019TD-018), National Key Research and Development Program of China (2016YFC0100300), the 2011 New Century Excellent Talent Support Plan of the Ministry of Education, China (NCET-11-0438), the Project Funded by China Postdoctoral Science Foundation (No. 2019M653659), and the Natural Science Basic Research Plan in Shaanxi Province of China (No.2019JQ-198).References
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