尽管有充足的证据表明大脑区域之间逐渐断开,但在肌萎缩侧索硬化症(ALS)中,维持步态的大脑网络的功能重组特征却很差。这项fMRI研究的主要目的是使用动态因果模型(DCM)评估ALS患者的步态图像特定网络,并辅以参数经验贝叶斯(PEB)框架。
17名下运动神经元占优势(LMNp)ALS患者,14名上运动神经元显性(UMNp)ALS患者和14名健康对照者参与了这项研究。每个受试者执行双重运动图像任务:正常和精确步态。使用运动意象问卷(MIQ-rs)和意象时间(IT)来评估每个参与者的步态意象。在神经生物学计算模型中,通过对正常/精确步态与连接强度之间的关系进行建模,研究了想象步态和姿势控制中涉及的回路。
行为结果显示,与健康对照(P校正<0.05)和LMNp(P校正<0.05)相比,UMNp患者的IT显着增加。在精确步态中,健康控制激活模型的电路参与想象的步态和姿势控制。在UMNp中,观察到从基底神经节(BG)到辅助运动区(SMA)以及从SMA到后顶叶皮层(PPC)的连通性(抑制)降低。与健康对照相反,DCM在UMNp和LMNpALS中均未检测到小脑-PPC连接。在精确步态中,与UMNp和健康对照相反,在LMNp组中观察到SMA和BG之间的双侧连通性(兴奋性)。
我们的发现证明了在特定患者表型中实施DCM和PEB以表征连接模式的实用性。我们的方法可以识别涉及姿势缺陷的特定回路,我们的发现表明了一种推定的兴奋性-抑制性失衡。更广泛地说,我们的数据证明了ALS中网络特异性断开现象是如何支持临床表现的.
The functional reorganization of brain networks sustaining gait is poorly characterized in amyotrophic lateral sclerosis (ALS) despite ample evidence of progressive disconnection between brain regions. The main objective of this fMRI
study is to assess gait imagery-specific networks in ALS patients using dynamic causal modeling (
DCM) complemented by parametric empirical Bayes (PEB) framework.
Seventeen lower motor neuron predominant (LMNp) ALS patients, fourteen upper motor neuron predominant (UMNp) ALS patients and fourteen healthy controls participated in this
study. Each subject performed a dual motor imagery task: normal and precision gait. The Movement Imagery Questionnaire (MIQ-rs) and imagery time (IT) were used to evaluate gait imagery in each participant. In a neurobiological computational model, the circuits involved in imagined gait and postural control were investigated by modelling the relationship between normal/precision gait and connection strengths.
Behavioral results showed significant increase in IT in UMNp patients compared to healthy controls (Pcorrected < 0.05) and LMNp (Pcorrected < 0.05). During precision gait, healthy controls activate the model\'s circuits involved in the imagined gait and postural control. In UMNp, decreased connectivity (inhibition) from basal ganglia (BG) to supplementary motor area (SMA) and from SMA to posterior parietal cortex (PPC) is observed. Contrary to healthy controls,
DCM detects no cerebellar-PPC connectivity in neither UMNp nor LMNp ALS. During precision gait, bilateral connectivity (excitability) between SMA and BG is observed in the LMNp group contrary to UMNp and healthy controls.
Our findings demonstrate the utility of implementing both
DCM and PEB to characterize connectivity patterns in specific patient phenotypes. Our approach enables the identification of specific circuits involved in postural deficits, and our findings suggest a putative excitatory-inhibitory imbalance. More broadly, our data demonstrate how clinical manifestations are underpinned by network-specific disconnection phenomena in ALS.