Neurodegenerative dementias have a profound impact on higher-order cognitive and behavioural functions. Investigating macroscale functional networks through cortical gradients provides valuable insights into the neurodegenerative dementia process and overall brain function. This approach allows for the exploration of unimodal-multimodal differentiation and the intricate interplay between functional brain networks. We applied cortical gradients mapping to resting-state functional MRI data of patients with frontotemporal dementia (FTD) (behavioural-bvFTD, non-fluent and semantic) and healthy controls. In healthy controls, the principal gradient maximally distinguished sensorimotor from default-mode network (DMN) and the secondary gradient visual from salience network (SN). In all FTD variants, the principal gradient’s unimodal-multimodal differentiation was disrupted. The secondary gradient, however, showed widespread disruptions impacting the interactions among all networks specifically in bvFTD, while semantic and non-fluent variants exhibited more focal alterations in limbic and sensorimotor networks. Additionally, the visual network showed responsive and/or compensatory changes in all patients. Importantly, these disruptions extended beyond atrophy distribution and related to symptomatology in patients with bvFTD. In conclusion, optimal brain function requires networks to operate in a segregated yet collaborative manner. In FTD, our findings indicate a collapse and loss of differentiation between networks not solely explained by atrophy. These specific cortical gradients’ fingerprints could serve as a functional signature for identifying early changes in neurodegenerative diseases or potential compensatory processes.

神经退行性痴呆症对高阶认知和行为功能有深远影响。通过皮质梯度研究宏观功能网络为神经退行性痴呆过程和整体大脑功能提供了有价值的见解。这种方法允许探索单峰-多模态分化和功能脑网络之间错综复杂的相互作用。我们将皮质梯度映射应用于额颞叶痴呆 （FTD） （behavioural-bvFTD，非流利和语义）患者和健康对照者的静息态功能性 MRI 数据。在健康对照中，主梯度最大限度地区分了感觉运动与默认模式网络 （DMN） 以及次级梯度视觉与显著性网络 （SN）。在所有 FTD 变体中，主梯度的单峰-多峰分化被破坏。然而，次级梯度显示广泛的中断影响了所有网络之间的交互，特别是在 bvFTD 中，而语义和非流畅变体在边缘和感觉运动网络中表现出更多的局灶性改变。此外，视觉网络显示所有患者的反应性和/或代偿性变化。重要的是，这些干扰超出了萎缩分布，并与 bvFTD 患者的症状有关。总之，最佳大脑功能需要网络以隔离但协作的方式运行。在 FTD 中，我们的研究结果表明网络之间的分化崩溃和丧失，而不仅仅是由萎缩来解释。这些特定皮质梯度的指纹可以作为识别神经退行性疾病的早期变化或潜在代偿过程的功能特征。