| The brain has a variety of cognitive functions and is the most complex organ of the human body.It controls human feeling,movement,memory,emotions and so on.During this process,multiple neurotransmitters in the brain need to be involved in the coordination of brain function.As one of the most important neurotransmitters in the brain,dopamine has an important impact on human cognitive behavior and can also cause a variety of mental disorders,such as schizophrenia.Studies have shown that the Catechol-O-methyltransferase(COMT)Val158Met polymorphism has important regulatory effects on dopamine.COMT genotype influences not only the structure and function of the brain,but also the onset of mental illness and cognitive impairment in psychotic patients.Therefore,this study used imaging genetic analysis to investigate the modification of COMT Val158 Met polymorphism on brain structure,spontaneous brain activity phenotype and its impact on memory performance in 186 healthy Chinese Han young people using multimodal magnetic resonance imaging data.We would like to reveal the neural mechanisms of how COMT genotype may affect brain and memory performance through this study.First,based on high-resolution structural magnetic resonance imaging data,we explored the effect of COMT genotype on the gray matter volume and volume of hippocampus and hippocampal subfields,which is the core area of memory function in the brain.We also investigated whether there is a significant correlation between volume and episodic as well as working memory performance.The voxel-based morphometry(VBM)was used to calculate the gray matter volume of the brain,and we then used Freesurfer toolkit to perform hippocampal subfields segmentation based on the template.All the participants were divided into MM / MV(Met / Met and Met / Val)group and the VV(Val / Val)group based on COMT Val158 Met polymorphism.We then tried to investigate whether the brain structure was significantly different between the COMT groups.We found that there was no significant difference in the volume of gray matter between the COMT groups,but the volume of the right hippocampal CA1 region in the MM / MV group was significantly smaller than that in the VV group,and the volume of the right hippocampal CA1 region played a significant role as a mediated factor in the regulation of COMT genotype on episodic memory performance.This demonstrates the modification of COMT genotype and dopamine on hippocampal subregional volume and its impact on episodic memory performance.Next,we further focused on the large-scale spontaneous activity of the brain to explore the interactions between various regions of the brain and their relationship to memory performance.We used independent component analysis with the resting-state functional magnetic resonance imaging data to identify the resting-state brain networks of the brain.The default mode network,executive control network,and frontal-parietal network that are closely related to brain cognitive function were involved in a twofactor analysis of variance to explore the relationship between functional connectivity inside the network and COMT genotype as well as memory performance.Our result showed that the functional connectivity of left superior parietal lobule in the left frontalparietal network of MM / MV group is significantly greater than that in VV group.Moreover,the functional connectivity of left superior parietal lobule is also a mediator of the relationship between COMT genotype and episodic memory performance.This suggests that COMT genotype and dopamine also have significant influence on functional connectivity within the large-scale functional network of the brain and has a significant impact on episodic memory performance.Finally,considering that changes in functional connectivity only include information about interactions between brain regions,but cannot explain the changing of regional spontaneous activity in human brain,we further explored the effect of COMT genotype on regional brain spontaneous activity by calculating the parameters of regional resting-state spontaneous brain activity.Our study found that the COMT genotype has a significant regulatory effect on the fractional amplitude of low frequency fluctuations(f ALFF)of the left inferior parietal lobe,while the MM / MV group is significantly lower than that in the VV group.At the same time,the f ALFF of left inferior parietal lobule was significantly related to episodic memory in MM / MV group,and f ALFF of left inferior parietal lobule played a significant mediating role in the regulation of episodic memory by COMT genotype.Our study shows that the intrinsic brain activity of the posterior parietal cortex is significantly regulated by COMT Val158 Met polymorphism and the dopamine neurotransmitter,and is closely related to episodic memory performance.Using imaging genetic analysis,our research focused on COMT Val158 Met polymorphisms that are closely related to dopamine neurotransmitter.Starting from brain structure to function,from global to local,we explored COMT genotype ? brain structure or function ? memory performance pathway,which reflects the influence of dopamine on brain structure and function.This helps us understand the neural mechanism behind cognitive impairment in patients with dopamine-related psychotic disorders in a better way,and paves the way for more precise clinical diagnosis and treatment in the future. |
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