Frontotemporal Dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioral variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls (HCs) at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA, and 30 non-fluent variant PPA (nfvPPA) cases, and 110 HCs from Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus HCs. Next, the network of brain regions functionally connected to each FTD patient’s location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 HCs in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 HCs in Dataset 2) and symptom-specific networks [combined dataset 1 and 2, apathy without depression Vs non-apathy without depression (80:26), disinhibition Vs non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region, and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.

中文翻译：

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额颞叶痴呆临床亚型及主要症状的萎缩网络图谱

额颞叶痴呆（FTD）是一种高度异质性、冷漠和去抑制的疾病，存在于 FTD 的所有亚型中，给家庭/社会带来了巨大的负担。由于个体临床和神经解剖学的变异性，传统的神经影像分析在阐明网络定位方面存在局限性。该研究旨在识别与不同 FTD 临床亚型相关的萎缩网络图，并确定冷漠和去抑制网络的具体定位。宣武医院的 80 名 FTD 患者[45 名行为变异型 FTD (bvFTD) 和 35 名语义变异型进行性原发性失语症 (svPPA)] 和 58 名健康对照 (HC) 被纳入数据集 1；数据集 2 包括 112 名 FTD 患者，包括 50 名 bvFTD、32 svPPA 和 30 名非流畅变异 PPA (nfvPPA) 病例，以及来自额颞叶变性神经影像计划 (FTLDNI) 数据集的 110 名 HC。最初，定义了单受试者萎缩图通过比较每位 FTD 患者与 HC 的皮质厚度。接下来，使用大型（n = 1000）规范连接组中基于种子的功能连接来确定与每个 FTD 患者萎缩位置功能连接的大脑区域网络。最后，我们使用萎缩网络映射来定义临床亚型特异性网络（数据集 1 中的 45 bvFTD、35 svPPA 和 58 HC；数据集 2 中的 50 bvFTD、32 svPPA、30 nfvPPA 和 110 HC）和症状特异性网络 [组合数据集1和2，无抑郁的冷漠与无抑郁的非冷漠(80:26)，去抑制与非去抑制(88:68)]。我们将结果与来自局灶性脑损伤患者的匹配症状网络或联合分析进行比较。通过对两个数据集的分析，我们确定了 FTD 患者萎缩模式的异质性。然而，这些萎缩模式与共同的大脑网络有关。FTD 中受萎缩影响的主要区域包括额叶和颞叶，特别是前颞叶。bvFTD 连接额叶和颞叶皮质区域，svPPA 主要影响前颞叶区域，nfvPPA 针对额下回和中央前皮质区域。冷漠特异性网络位于眶额皮质和腹侧纹状体，而去抑制特异性网络位于双侧眶额回和右颞叶。冷漠和去抑制萎缩网络分别类似于已知的动机和犯罪病变网络。发现冷漠/去抑制评分与萎缩图和网络峰值之间的功能连接之间存在显着相关性。这项研究定位了 FTD 临床亚型和主要症状的常见网络，指导未来的 FTD 神经调节干预。