基于功能MRI研究主观认知下降患者初级嗅觉皮层的神经活动

The study of functional MRI on neuronal activity of primary olfactory cortex in patients with subjective cognitive decline

目的采用嗅觉刺激任务态功能磁共振(task-fMRI)探讨主观认知能力下降(SCD)患者与正常老年人的嗅觉脑区激活差异,探寻早期识别和评估SCD向阿尔茨海默病(AD)转化的客观影像标志物。方法2017年3月至2018年12月从社区招募20例SCD患者(SCD组)及20名匹配的正常老年人(NC组)。所有受试者均进行全套认知心理学量表测试、嗅觉行为学测试及嗅觉task-fMRI。分析两组被试之间的嗅觉行为学、认知心理学量表及task-fMRI脑激活之间的差异,进一步采用两组在任务态有差异的脑区为种子点做静息态功能连接分析,计算脑区激活与行为学的相关性。结果与正常被试比较,SCD患者的嗅觉行为学(嗅觉识别能力)显著下降(t=-3.042,P<0.01),嗅觉阈值差异没有统计学意义。在SCD自评量表(t=6.973,P<0.01)、费城词语学习的即刻(t=-4.623,P<0.01)和延迟(t=-2.746,P<0.01)测试中也出现显著下降,其余常规认知心理学量表均表现为正常。嗅觉任务态fMRI中,SCD患者双侧初级嗅觉皮层(POC)的激活显著下降,包括双侧内嗅皮层、梨状皮层、杏仁核、嗅前核以及海马头部。以POC为种子点,静息态功能连接显示SCD患者嗅觉系统与默认网络的功能连接显著减弱(AlphaSim校正,体素水平,P<0.01,簇水平,P<0.05)。偏相关分析发现,左侧POC的嗅觉激活与嗅觉阈值和蒙特利尔认知评估量表(MoCA)存在显著正相关(r=0.329,P=0.041;r=0.317,P=0.046)。以左侧POC为种子点,与右/左侧眶部额下回、左侧额中回及右侧顶下缘角回的功能连接值与即刻费城词语学习评分之间存在正相关(r=0.411,P=0.008;r=0.400,P=0.011;r=0.329,P=0.003;r=0.454,P=0.003);与右侧眶部额下回的功能连接值和连线测试B评分之间呈负相关(r=-0.317,P=0.047);与右侧顶下缘角回的功能连接值和语言流畅性测试评分之间呈负相关(r=-0.333,P=0.036)。以右侧POC为种子点,与左侧顶下缘角回的功能连接值和即刻费城词语学习评分之间呈正相关(r=0.315,P=0.048);与左侧枕中回的功能连接值和语言流畅性测试存在显著负相关(r=-0.403,P=0.01)。结论在常规认知心理学量表表玖为正常的SCD患者中,嗅觉功能已出现损伤,内嗅皮层等初级嗅觉皮层的活动改变可能是早期客观评价SCD神经环路损伤的生物标志物。

Objective Using olfactory task functional magnetic resonance imaging (fMRI) to investigate the difference in brain olfactory activation between patients with subjective cognitive decline and normal elderly subjects,and to explore the objective image markers for early identification and evaluation the progression from SCD to Alzheimer′s disease (AD).Methods Twenty patients with SCD (SCD group) and twenty matched normal elderly subjects (NC group) were recruited from the community from March 2017 to December 2018.A full neuropsychological scale tests battery,olfactory behavioral tests and olfactory task-fMRI were performed.The differences between olfactory behavior,neuropsychological scales,and task-fMRI brain activation between the two groups were tested.Further,brain regions,which had significantly different activations under task-fMRI,were used as seeds for resting state functional connectivity (FC) analysis.Finally,the correlations between brain activation and olfactory behavior along with clinical neuropsychological scale tests were examined.Results The results of this study showed SCD had a significant decrease in olfactory behavior (olfactory recognition ability) compared with NC (t=-3.042,P<0.01),and there was no statistically significant difference in olfactory threshold.Significant declines were also observed in the SCD self-rating scale (t=6.973,P<0.01),the immediate (t=-4.623,P<0.01) and delayed (t=-2.746,P<0.01) testing of Philadelphia word learning,while the remaining neuropsychological scales were normal.In the olfactory task-fMRI,activation of bilateral primary olfactory cortical regions was significantly reduced in SCD patients,including bilateral entorhinal cortex,amygdala,piriform cortex,anterior olfactory nucleus,and head of the hippocampus.The resting state functional connectivity with the primary olfactory cortex (POC) as the seed showed that the functional connectivity between the olfactory system and the default model network (DMN) of SCD patients was significantly weakened (AlphaSim correction with voxel level P<0.01 and cluster level P<0.05).The Beta value of the left POC was significantly positively correlated with the olfactory threshold and Montreal cognitive assessment (MoCA)(r=0.329,P=0.041;r=0.317,P=0.046).Partial correlation analysis indicated that there was a significantly positive correlation between the FC of the left POC with the right/left inferior frontal gyrus,the left frontal middle gyrus and the right inferior parietal,and the score of immediate Philadelphia word learning test(r=0.411,P=0.008;r=0.400,P=0.011;r=0.329,P=0.003;r=0.454,P=0.003).The FC between the left POC and the right inferior temporal gyrus was negatively correlated with the score of trail making test (TMT) B,and the FC between the left POC and the right inferior was negatively correlated with score of language fluency test (r=-0.317,P=0.047;r=-0.333,P=0.036).The FC between the right POC and the left inferior parietal was positively correlated with the score of immediate Philadelphia word learning (r=0.315,P=0.048),while the FC between right POC and left middle occipital gyrus was negatively corrected with Language Fluency Test (r=-0.403,P=0.01).Conclusion Olfactory function has been impaired in SCD patients with normal standard cognition and phychiatric rating scales,and the changes in the activation of the primary olfactory cortex,such as the entorhinal cortex,may be an early neural circuit damage biomarker for objective evaluation of SCD.