Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
Children's Hospital Los Angeles, Los Angeles, CA, USA; University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Neuroimage Clin. 2019;22:101692. doi: 10.1016/j.nicl.2019.101692. Epub 2019 Jan 29.
Neurofibromatosis type 1 (NF1) is a common single gene disorder resulting in multi-organ involvement. In addition to physical manifestations such as characteristic pigmentary changes, nerve sheath tumors, and skeletal abnormalities, NF1 is also associated with increased rates of learning disabilities, attention deficit hyperactivity disorder, and autism spectrum disorder. While there are established NF1-related structural brain anomalies, including brain overgrowth and white matter disruptions, little is known regarding patterns of functional connectivity in NF1. Here, we sought to investigate functional network connectivity (FNC) in a well-characterized sample of NF1 participants (n = 30) vs. age- and sex-matched healthy controls (n = 30). We conducted a comprehensive investigation of both static as well as dynamic FNC and meta-state analysis, a novel approach to examine higher-dimensional temporal dynamism of whole-brain connectivity. We found that static FNC of the cognitive control domain is altered in NF1 participants. Specifically, connectivity between anterior cognitive control areas and the cerebellum is decreased, whereas connectivity within the cognitive control domain is increased in NF1 participants relative to healthy controls. These alterations are independent of IQ. Dynamic FNC analysis revealed that NF1 participants spent more time in a state characterized by whole-brain hypoconnectivity relative to healthy controls. However, connectivity strength of dynamic states did not differ between NF1 participants and healthy controls. NF1 participants exhibited also reduced higher-dimensional dynamism of whole-brain connectivity, suggesting that temporal fluctuations of FNC are reduced. Given that similar findings have been observed in individuals with schizophrenia, higher occurrence of hypoconnected dynamic states and reduced temporal dynamism may be more general indicators of global brain dysfunction and not specific to either disorder.
神经纤维瘤病 1 型（NF1）是一种常见的单基因疾病，可导致多器官受累。除了特征性色素改变、神经鞘瘤和骨骼异常等身体表现外，NF1 还与学习障碍、注意力缺陷多动障碍和自闭症谱系障碍的发生率增加有关。虽然已经确定了与 NF1 相关的结构性大脑异常，包括脑过度生长和白质破坏，但对于 NF1 中的功能连接模式知之甚少。在这里，我们试图在经过充分特征描述的 NF1 参与者样本（n=30）与年龄和性别匹配的健康对照组（n=30）中研究功能网络连接（FNC）。我们对静态和动态 FNC 以及元状态分析进行了全面研究，这是一种检查全脑连接更高维度时间动态性的新方法。我们发现 NF1 参与者的认知控制域的静态 FNC 发生了改变。具体来说，与健康对照组相比，NF1 参与者的认知控制域中，前认知控制区域与小脑之间的连接减少，而认知控制域内的连接增加。这些改变与智商无关。动态 FNC 分析显示，与健康对照组相比，NF1 参与者在全脑低连接性状态下花费的时间更多。然而，NF1 参与者和健康对照组之间的动态状态的连接强度没有差异。NF1 参与者还表现出全脑连接的更高维度动态性降低，这表明 FNC 的时间波动减少。鉴于在精神分裂症患者中也观察到了类似的发现，低连接动态状态和降低的时间动态性的更高发生率可能是全局脑功能障碍的更普遍指标，而不是特定于任何一种疾病。
