Objective: To characterize the brain functional changes of amyotrophic lateral sclerosis (ALS) patients with various levels of cognitive impairment as measured by resting-state functional MRI (RS-fMRI). Methods: From September 2013 to March 2017, a total of 55 patients diagnosed with ALS in Peking Union Medical College Hospital and 20 healthy controls (HCs) were included in this study, and all participants underwent neuropsychological assessments and diffusion tensor imaging scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n=27), those with cognitive impairment (ALS-Ci, n=17) and ALS-FTD (n=11). Comparisons of fractional amplitude of low frequency fluctuation (fALFF) value and regional homogeneity (ReHo) value were conducted among the 4 subgroups. Results: The fALFF showed significant differences in bilateral frontal lobe, left temporal lobe and cingulate gyrus, (P<0.001, uncorrected) and the ReHo showed significant differences in left frontal lobe, right temporal lobe and left cingulate gyrus (P<0.001, FDR corrected). The differences mainly stemmed from that patients with ALS-FTD showed decreased fALFF and ReHo in these areas when compared to the other three groups, especially in relation to HCs, mainly locating in left prefrontal lobe and anterior cingulate cortex. The whole-brain comparisons of fALFF and ReHo between ALS-Ci, ALS-Cn and HCs revealed no significant difference (P<0.001, uncorrected). Conclusion: Hypoactivities are detected in extramotor areas in patients with ALS-FTD. RS-fMRI is helpful in investigating the pathophysiologic mechanism of cognitive impairment in ALS.
目的： 比较不同认知水平的肌萎缩侧索硬化(ALS)患者的静息态功能磁共振(RS－fMRI)数据，探索其脑功能改变。 方法： 2013年9月至2017年3月于北京协和医院神经科门诊及病房诊断的55例ALS患者及20名健康对照者(HC)被纳入研究，所有受试者均进行成套的神经心理学测验及RS－fMRI扫描。按照其认知功能，ALS患者被进一步分为三个亚组：27例无认知功能障碍的ALS(ALS－Cn)、17例ALS伴认知损害(ALS－Ci)及11例ALS合并额颞叶痴呆(ALS－FTD)。应用分数低频振幅(fALFF)法和局部一致性(ReHo)法，比较不同亚组间的静息激活差异。 结果： 四组受试者的fALFF值在双侧额上回、额中回、左侧颞中回、左侧扣带回存在差异(P<0.001，未校正)，ReHo值在左侧额上回、额下回、右侧颞中回、左侧扣带回存在差异(P<0.05，FDR校正)，对灰质体积进行校正后上述差异减小。差异来源主要为ALS－FTD较其他三组受试者在上述区域存在fALFF值及ReHo减低，且与健康对照的差异最为显著，主要位于左侧前额叶及前扣带回。ALS－Ci与ALS－Cn，ALS－Ci与健康对照，ALS－Cn与健康对照相比较，在设定阈值下(P<0.001，未校正)未发现全脑RS－fMRI数据存在显著差异。 结论： ALS－FTD患者存在运动区外的激活减低，RS－fMRI有助于探索ALS认知功能障碍发生发展的病理生理机制。.
Keywords: Amyotrophic lateral sclerosis; Cognition disorders; Dementia; Frontotemporal lobar degeneration; Magnetic resonance imaging.