{"title":"位置小脑功能网络活动的病理和神经化学相关性","authors":"","doi":"10.1016/j.biopsycho.2024.108847","DOIUrl":null,"url":null,"abstract":"<div><p>The locus coeruleus (LC) produces the neuromodulators norepinephrine and dopamine, and projects widely to subcortical and cortical brain regions. The LC has been a focus of neuroimaging biomarker development for the early detection of Alzheimer’s disease (AD) since it was identified as one of the earliest brain regions to develop tau pathology. Our recent research established the use of positron emission tomography (PET) to measure LC catecholamine synthesis capacity in cognitively unimpaired older adults. We extend this work by investigating the possible influence of pathology and LC neurochemical function on LC network activity using functional magnetic resonance imaging (fMRI). In separate sessions, participants underwent PET imaging to measure LC catecholamine synthesis capacity ([18F]Fluoro-m-tyrosine), tau pathology ([18F]Flortaucipir), and amyloid-β pathology ([11C]Pittsburgh compound B), and fMRI imaging to measure LC functional network activity at rest. Consistent with a growing body of research in aging and preclinical AD, we find that higher functional network activity is associated with higher tau burden in individuals at risk of developing AD (amyloid-β positive). Critically, relationships between higher LC network activity and higher pathology (amyloid-β and tau) were moderated by LC catecholamine synthesis capacity. High levels of LC catecholamine synthesis capacity reduced relationships between higher network activity and pathology. Broadly, these findings support the view that individual differences in functional network activity are shaped by interactions between pathology and neuromodulator function, and point to catecholamine systems as potential therapeutic targets.</p></div>","PeriodicalId":55372,"journal":{"name":"Biological Psychology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pathological and neurochemical correlates of locus coeruleus functional network activity\",\"authors\":\"\",\"doi\":\"10.1016/j.biopsycho.2024.108847\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The locus coeruleus (LC) produces the neuromodulators norepinephrine and dopamine, and projects widely to subcortical and cortical brain regions. The LC has been a focus of neuroimaging biomarker development for the early detection of Alzheimer’s disease (AD) since it was identified as one of the earliest brain regions to develop tau pathology. Our recent research established the use of positron emission tomography (PET) to measure LC catecholamine synthesis capacity in cognitively unimpaired older adults. We extend this work by investigating the possible influence of pathology and LC neurochemical function on LC network activity using functional magnetic resonance imaging (fMRI). In separate sessions, participants underwent PET imaging to measure LC catecholamine synthesis capacity ([18F]Fluoro-m-tyrosine), tau pathology ([18F]Flortaucipir), and amyloid-β pathology ([11C]Pittsburgh compound B), and fMRI imaging to measure LC functional network activity at rest. Consistent with a growing body of research in aging and preclinical AD, we find that higher functional network activity is associated with higher tau burden in individuals at risk of developing AD (amyloid-β positive). Critically, relationships between higher LC network activity and higher pathology (amyloid-β and tau) were moderated by LC catecholamine synthesis capacity. High levels of LC catecholamine synthesis capacity reduced relationships between higher network activity and pathology. Broadly, these findings support the view that individual differences in functional network activity are shaped by interactions between pathology and neuromodulator function, and point to catecholamine systems as potential therapeutic targets.</p></div>\",\"PeriodicalId\":55372,\"journal\":{\"name\":\"Biological Psychology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-07-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Psychology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0301051124001066\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Psychology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0301051124001066","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
脑室小叶(LC)产生神经调节物质去甲肾上腺素和多巴胺,并广泛投射到皮层下和皮层脑区。自从被确定为最早出现 tau 病理学的脑区之一以来,LC 一直是用于早期检测阿尔茨海默病(AD)的神经影像生物标记物开发的重点。我们最近的研究确立了使用正电子发射断层扫描(PET)来测量认知功能未受损的老年人的半叶儿茶酚胺合成能力。我们利用功能性磁共振成像(fMRI)研究了病理学和LC神经化学功能对LC网络活动可能产生的影响,从而扩展了这项工作。在不同的疗程中,参与者分别接受了 PET 成像检查以测量 LC 儿茶酚胺合成能力([18F]氟-m-酪氨酸)、tau 病理学([18F]Flortaucipir)和淀粉样蛋白-β病理学([11C]匹兹堡化合物 B),并接受了 fMRI 成像检查以测量 LC 在静息状态下的功能网络活动。与越来越多的老龄化和临床前注意力缺失症研究结果一致,我们发现,在注意力缺失症高风险人群(淀粉样蛋白-β阳性)中,较高的功能网络活性与较高的tau负荷相关。重要的是,较高的低密度脂蛋白血症网络活性与较高的病理(淀粉样蛋白-β和tau)之间的关系受到低密度脂蛋白血症儿茶酚胺合成能力的调节。高水平的 LC 儿茶酚胺合成能力降低了较高的网络活性与病理学之间的关系。总的来说,这些研究结果支持这样一种观点,即功能性网络活动的个体差异是由病理学和神经调节器功能之间的相互作用形成的,并指出儿茶酚胺系统是潜在的治疗靶点。
Pathological and neurochemical correlates of locus coeruleus functional network activity
The locus coeruleus (LC) produces the neuromodulators norepinephrine and dopamine, and projects widely to subcortical and cortical brain regions. The LC has been a focus of neuroimaging biomarker development for the early detection of Alzheimer’s disease (AD) since it was identified as one of the earliest brain regions to develop tau pathology. Our recent research established the use of positron emission tomography (PET) to measure LC catecholamine synthesis capacity in cognitively unimpaired older adults. We extend this work by investigating the possible influence of pathology and LC neurochemical function on LC network activity using functional magnetic resonance imaging (fMRI). In separate sessions, participants underwent PET imaging to measure LC catecholamine synthesis capacity ([18F]Fluoro-m-tyrosine), tau pathology ([18F]Flortaucipir), and amyloid-β pathology ([11C]Pittsburgh compound B), and fMRI imaging to measure LC functional network activity at rest. Consistent with a growing body of research in aging and preclinical AD, we find that higher functional network activity is associated with higher tau burden in individuals at risk of developing AD (amyloid-β positive). Critically, relationships between higher LC network activity and higher pathology (amyloid-β and tau) were moderated by LC catecholamine synthesis capacity. High levels of LC catecholamine synthesis capacity reduced relationships between higher network activity and pathology. Broadly, these findings support the view that individual differences in functional network activity are shaped by interactions between pathology and neuromodulator function, and point to catecholamine systems as potential therapeutic targets.
期刊介绍:
Biological Psychology publishes original scientific papers on the biological aspects of psychological states and processes. Biological aspects include electrophysiology and biochemical assessments during psychological experiments as well as biologically induced changes in psychological function. Psychological investigations based on biological theories are also of interest. All aspects of psychological functioning, including psychopathology, are germane.
The Journal concentrates on work with human subjects, but may consider work with animal subjects if conceptually related to issues in human biological psychology.