中国科学院行为科学重点实验室知识库

孤独症谱系障碍(autism spectrum disorder,ASD)是一种病因未明,患病率日益增高的神经发育障碍.目前大多数静息态功能磁共振成像(resting-state f MRI,R-f MRI)研究仅考察了ASD患者脑活动的静态特征,忽视了动态特征.近期研究发现,不同R-f MRI局部指标的动态性之间存在一致性.本研究基于ASD公开数据库,使用滑动时间窗方法系统计算了480名ASD患者和539名健康对照(typical control,TC)被试的主流R-f MRI局部指标的动态性及R-f MRI局部指标之间的一致性动态特征,并考察了这些指标与ASD行为指标之间的关系.我们发现ASD患者在外侧额叶呈现出动态性显著升高,该现象在低频振幅(amplitude of low-frequency fluctuations,ALFF)和度中心性(degree centrality,DC)的动态性中都有体现.我们也发现ALFF,DC和局部一致性(regional homogeneity,Re Ho)的动态性在视觉相关脑区,如梭状回、距状沟和舌回呈现下降.在进一步考察了这些指标之间的一致性动态特征后,发现ASD患者的一致性动态特征显著低于TC组被试,表现出显著下降的功能整合能力.我们的结果表明ASD患者存在着脑自发活动动态性及其整合的异常。

Autism spectrum disorder (ASD) is a neurodevelopmental disease with unknown etiology but high incidence. The objective biomarkers of ASD are urgently awaited to be developed using neuroimaging method including resting-state fMRI (R-fMRI). However, the majority of current R-fMRI studies only examined the static features of brain activity in ASD patients, but neglected the dynamic aspects especially for regional metrics. Furthermore, the concordance of the dynamic regional indices was reported imbedded in human intrinsic brain activity, while its abnormality in ASD is largely unknown.In order to shed light on the abnormity of ASD from dynamic perspective, we analyzed R-fMRI data of 480 ASD male patients and 539 healthy male controls (HC) gathered from ASD public database (ABIDE I/ABIDE II). We used sliding window method to calculate the dynamics of mainstream regional indices of R-fMRI (amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity (VMHC), degree centrality (DC) and the correlation with global signal (GSCorr)) and generated the SD statistic maps of these six dynamic regional indices. We performed z-standardization and smoothing on the SD statistic maps. After that, two-sample t-test between the SD statistic maps of ASD group and HC group was performed. We also calculated the concordance of dynamic regional indices for each time point, which is the Kendall’s coefficient of the ALFF, ReHo, DC, GSCorr and VMHC maps across voxels. Two-sample t-test between the SD and mean of concordance time series of ASD group and HC group was performed. We found a significant increase in the dynamics of ALFF and DC in the lateral

frontal cortices in ASD patients as compared to HCs. Dorsal lateral frontal cortex (dlPFC) is a critical brain area for cognitive control and execution network. The abnormal activities in dlPFC indicate the disruption of control execution system

and the impairment of relevant cognitive function. In the visual related brain areas, the dynamics of ALFF, DC and ReHo showed a decrease in fusiform gyrus, calcarine and lingual gyrus in ASD patients. Recent studies have indicated that the abnormal face processing in children with autism may be related with the impairment in social cognition of them. The deficits in face information processing of ASD patients may stem from the inflexible intrinsic brain activity in visual processing brain area (especially in fusiform gyrus). After further examining the concordance among these dynamic indices, the mean and SD of concordance of patients with ASD was found to be significantly lower than that of the HCs, demonstrating that the ASD patients’ inferior integration ability for different aspects of brain functions. These findings suggest that there exists abnormality in dynamics of spontaneous brain activity and its integration in ASD patients. Dynamic R-fMRI regional indices and the concordance of them could be efficient neuroimaging biomarkers for ASD.