Shephard Elizabeth, McEwen Fiona S, Earnest Thomas, Friedrich Nina, Mörtl Isabelle, Liang Holan, Woodhouse Emma, Tye Charlotte, Bolton Patrick F
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, UK; Department of Psychiatry, University of São Paulo, Brazil.
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, UK; Department of Psychology, Queen Mary University of London, UK.
Cortex. 2022 Jan;146:50-65. doi: 10.1016/j.cortex.2021.10.007. Epub 2021 Nov 4.
Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations on the TSC1/TSC2 genes, which result in alterations in molecular signalling pathways involved in neurogenesis and hamartomas in the brain and other organs. TSC carries a high risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), although the reasons for this are unclear. One proposal is that TSC-related alterations in molecular signalling during neurogenesis lead to atypical development of neural networks, which are involved in the occurrence of ASD and ADHD in TSC. We investigated this proposal in young people with TSC who have been studied longitudinally since their diagnosis in childhood. Electroencephalography (EEG) was used to examine oscillatory connectivity in functional neural networks and local and global network organisation during three tasks (resting-state, attentional and inhibitory control Go/Nogo task, upright and inverted face processing task) in participants with TSC (n = 48) compared to an age- and sex-matched group of typically developing Controls (n = 20). Compared to Controls, the TSC group showed hypoconnected neural networks in the alpha frequency during the resting-state and in the theta and alpha frequencies during the Go/Nogo task (P ≤ .008), as well as reduced local network organisation in the theta and alpha frequencies during the Go/Nogo task (F = 3.95, P = .010). There were no significant group differences in network metrics during the face processing task. Increased connectivity in the hypoconnected alpha-range resting-state network was associated with greater ASD and inattentive ADHD symptoms (rho≥.40, P ≤ .036). Reduced local network organisation in the theta-range during the Go/Nogo task was significantly associated with higher hyperactive/impulsive ADHD symptoms (rho = -.43, P = .041). These findings suggest that TSC is associated with widespread hypoconnectivity in neural networks and support the proposal that altered network function may be involved in the co-occurrence of ASD and ADHD in TSC.
结节性硬化症（TSC）是一种由TSC1/TSC2基因突变引起的遗传性疾病，这些突变导致参与神经发生以及大脑和其他器官错构瘤形成的分子信号通路发生改变。TSC与自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）的发生风险较高相关，尽管其原因尚不清楚。一种观点认为，神经发生过程中与TSC相关的分子信号改变会导致神经网络的非典型发育，而这与TSC患者中ASD和ADHD的发生有关。我们对自童年时期诊断以来就一直进行纵向研究的TSC青年患者进行了此项研究。与年龄和性别匹配的典型发育对照组（n = 20）相比，使用脑电图（EEG）检查了TSC患者（n = 48）在三项任务（静息状态、注意力和抑制控制的Go/Nogo任务、正立和倒立面部处理任务）期间功能性神经网络中的振荡连接性以及局部和全局网络组织。与对照组相比，TSC组在静息状态下的α频率以及Go/Nogo任务期间的θ和α频率显示神经网络连接减少（P≤0.008），并且在Go/Nogo任务期间θ和α频率的局部网络组织也减少（F = 3.95，P = 0.010）。在面部处理任务期间，两组在网络指标上没有显著差异。静息状态下连接减少的α频段网络中连接性增加与更严重的ASD和注意力不集中的ADHD症状相关（rho≥0.40，P≤0.036）。Go/Nogo任务期间θ频段局部网络组织减少与更高的多动/冲动ADHD症状显著相关（rho = -0.43，P = 0.041）。这些发现表明，TSC与神经网络中广泛的连接减少有关，并支持这样一种观点，即网络功能改变可能与TSC患者中ASD和ADHD的共病有关。
