Poster No:
601
Submission Type:
Abstract Submission
Authors:
Qiongyu Yan1, Teng Liang1, ziwei zhang1, Zeyu Shen1, wenchao zhou1, Shaojie Shi1, lin tian2, Chun Meng1
Institutions:
1School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, 2Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu
First Author:
Qiongyu Yan
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
Co-Author(s):
Teng Liang
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
ziwei zhang
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
Zeyu Shen
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
wenchao zhou
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
Shaojie Shi
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
lin tian
Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University
Wuxi, Jiangsu
Chun Meng
School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, Sichuan
Introduction:
Amygdala plays a key role in emotional function. Particularly basolateral amygdala (BLA), which can regulate nucleus accumbens by facilitating the release of dopamine (Floresco et al., 2001), is involved in mesolimbic dopaminergic pathway (Reynolds, 1983; Kröner et al., 2005). The lateral asymmetry of amygdala is susceptible for dysfunctions in schizophrenia (SZ) (Reynolds, 1983), such as decreased grey matter volume of left BLA and functional connectivity of right BLA (Zheng et al., 2019; Zhang et al., 2020). It remains unclear how the wiring pattern and underlying white matter microstructure of amygdala are altered and associated with dysfunctions in SZ, considering mesolimbic dopaminergic pathway involving cortex, BLA and striatum (Grèzes et al., 2014; Avecillas-Chasin et al., 2023).
Methods:
T1 weighted and Diffusion MRI (64 gradient directions with b=1000s/mm^2, plus 1 B0) were analyzed for 109 SZ and 105 matched healthy controls (HC), using FSL6.0 and MRtrix3.0. All patients were diagnosed by the DSM-IV, with symptom severity assessed by PANSS. The written informed consent was obtained from each subject and this study was approved by the local ethics committee.
The methods of this study were illustrated in Figure 1. In the bilateral brain, we segmented amygdala voxels into mixed- or dominant-wiring types (Levitt et al., 2020), based on probabilistic tractography from cortex and striatum respectively as well as apriori and connectivity-based segmentation of 7 subregions (Tziortzi et al., 2014). For example, one amygdala voxel, if ≥70% tractography streamlines coming from the same subregion, was labeled as a dominant-wiring voxel, otherwise it was labeled as a mixed-wiring voxel (Tziortzi et al., 2014). The group differences of mixed-wiring voxel number were tested using a general linear model while controlling for age, gender and bilateral amygdala voxel number. Then, we focused on the orbitofrontal-amygdala-striatal part of mesolimbic dopamine pathway (Figure 2a, involving amygdala's dominant-wiring voxels of orbitofrontal subregion), and applied the Fixel (Raffelt et al., 2017) and Tensor model to investigate the microstructure of amygdala and white matter streamlines. We tested group differences of the Fixel and Tensor metrics using a general linear model while controlling for age and gender. Further, we examined Pearson correlations between abnormalities and PANSS as well as illness duration while controlling for age and gender.

·methods description
Results:
As shown in Figure 2, SZ displayed reduced number of mixed-wiring voxels defined by amygdala-striatum connectivity in left hemisphere, but no significant mixed-wiring result was found for amygdala-cortex connectivity or right hemisphere. Left amygdala's mixed-wiring changes were associated with PANSS general symptom. Besides, reduced FA of right amygdala was found and related to PANSS negative symptom as well as illness duration in SZ based on Tensor model. Further, we observed significantly reduced fibre density (FD) and FDC (a combination of fibre density and area of fibre cross-section) of right striatum-amygdala based on Fixel model, which correlated with PANSS positive symptom in SZ. The attenuated mixed-wiring pattern may reflect decreased ability to integrate information, while the damaged Tensor- and Fixel-based microstructure characteristics could infer potential white matter degeneration and dysconnectivity, in schizophrenia.

·results
Conclusions:
Our results provide novel evidence about abnormal mixed-wiring pattern and microstructural changes in amygdala of SZ, which confirm amygdala-related lateralization. The hemisphere-specific changes in white matter of mesolimbic dopamine pathway and amygdala were selectively associated with schizophrenia symptoms and illness duration, which help better understand disrupted emotion and dopaminergic function of schizophrenia.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Segmentation and Parcellation
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Keywords:
Basal Ganglia
Data analysis
Dopamine
Hemispheric Specialization
Limbic Systems
Schizophrenia
Segmentation
Sub-Cortical
Tractography
White Matter
1|2Indicates the priority used for review
Provide references using author date format
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Floresco, S.B. et al. (2001) ‘Dopamine D 1 and NMDA Receptors Mediate Potentiation of Basolateral Amygdala-Evoked Firing of Nucleus Accumbens Neurons’, The Journal of Neuroscience, 21(16), pp. 6370–6376. Available at: https://doi.org/10.1523/JNEUROSCI.21-16-06370.2001.
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