Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, USA.
Brain. 2020 Apr 1;143(4):1249-1260. doi: 10.1093/brain/awaa058.
There is both clinical and neuroanatomical variability at the single-subject level in Alzheimer's disease, complicating our understanding of brain-behaviour relationships and making it challenging to develop neuroimaging biomarkers to track disease severity, progression, and response to treatment. Prior work has shown that both group-level atrophy in clinical dementia syndromes and complex neurological symptoms in patients with focal brain lesions localize to brain networks. Here, we use a new technique termed 'atrophy network mapping' to test the hypothesis that single-subject atrophy maps in patients with a clinical diagnosis of Alzheimer's disease will also localize to syndrome-specific and symptom-specific brain networks. First, we defined single-subject atrophy maps by comparing cortical thickness in each Alzheimer's disease patient versus a group of age-matched, cognitively normal subjects across two independent datasets (total Alzheimer's disease patients = 330). No more than 42% of Alzheimer's disease patients had atrophy at any given location across these datasets. Next, we determined the network of brain regions functionally connected to each Alzheimer's disease patient's location of atrophy using seed-based functional connectivity in a large (n = 1000) normative connectome. Despite the heterogeneity of atrophied regions at the single-subject level, we found that 100% of patients with a clinical diagnosis of Alzheimer's disease had atrophy functionally connected to the same brain regions in the mesial temporal lobe, precuneus cortex, and angular gyrus. Results were specific versus control subjects and replicated across two independent datasets. Finally, we used atrophy network mapping to define symptom-specific networks for impaired memory and delusions, finding that our results matched symptom networks derived from patients with focal brain lesions. Our study supports atrophy network mapping as a method to localize clinical, cognitive, and neuropsychiatric symptoms to brain networks, providing insight into brain-behaviour relationships in patients with dementia.
在阿尔茨海默病患者中，个体水平的临床和神经解剖学存在变异性，这使得我们对大脑-行为关系的理解变得复杂，也使得开发神经影像学生物标志物来跟踪疾病的严重程度、进展和对治疗的反应变得具有挑战性。先前的工作表明，在临床痴呆综合征的群体水平萎缩和局灶性脑损伤患者的复杂神经症状中，都定位于大脑网络。在这里，我们使用一种称为“萎缩网络映射”的新技术来检验这样一个假设，即患有临床诊断的阿尔茨海默病患者的个体萎缩图谱也将定位于综合征特异性和症状特异性的大脑网络。首先，我们通过将每个阿尔茨海默病患者的皮质厚度与两个独立数据集（总共 330 名阿尔茨海默病患者）中的一组年龄匹配的认知正常受试者进行比较，定义了个体萎缩图谱。在这些数据集中，没有超过 42%的阿尔茨海默病患者在任何特定位置有萎缩。接下来，我们使用基于种子的功能连接，在一个大型（n=1000）规范连接组中，确定与每个阿尔茨海默病患者萎缩位置功能连接的大脑区域网络。尽管在个体水平上萎缩区域存在异质性，但我们发现，100%的临床诊断为阿尔茨海默病的患者的萎缩与内侧颞叶、后扣带回皮层和角回的相同大脑区域具有功能连接。结果与对照组具有特异性，并在两个独立的数据集之间得到了复制。最后，我们使用萎缩网络映射来定义与记忆障碍和妄想相关的症状特异性网络，发现我们的结果与源自局灶性脑损伤患者的症状网络相匹配。我们的研究支持萎缩网络映射作为将临床、认知和神经精神症状定位到大脑网络的方法，为痴呆患者的大脑-行为关系提供了深入的了解。
