An FMRI-based Study Of Effective Connectivity In Amyotrophic Lateral Sclerosis

In recent years,using fMRI technology,we can explore neural activity of brain and more deeply understand our brain.This technology has laid a foundation for revealing the information of interval brain effective connectivity.And dynamic causal model provides an effective and direct method to estimate brain effective connectivity.Based on brain effective connectivity,researchers explore the neural correlates of brain cognitive activities and brain network in a new way,and have made a breakthrough to study pathophysiology of various neuropsychiatric disorders.Amyotrophic lateral sclerosis(ALS)is a fatally neurodegenerative disorder characterized by rapidly progressive paralysis.Many studies have reported abnormal regions in sensorimotor network(SMN)with ALS have been related their pathogenesis,but the causal influence in this network is still unclear.It has long been deemed as a disorder of the motor system,but the clinical manifestations are not confined to motor symptoms.In ALS,both functional and structural studies have revealed significant abnormalities in the default mode network(DMN),suggesting that dysfunctional DMN may be a common feature of ALS and might contribute to non-motor symptoms of this disease.The contents of this dissertation are as follows:1.Using spectral dynamic causal modeling(spectral DCM),we evaluated the causal influences of SMN in ALS patients with matched healthy controls.The SMN components were collected by an independent component analysis(ICA),and contrasted the two groups to find the abnormalities in SMN of ALS: the right supplementary motor area(SMA),the left primary somatosensory cortex(S1),and the left primary motor cortex(M1).Using spectral DCM to these region,we found,in ALS,lost circuit between the right SMA and the left M1,and missing connectivity from the right SMA to the left S1.Our results may explain the effects of the missing of motor neurons on motor function in ALS,and also illustrate a neurobiological model that reveals the functional impairment of the SMN in ALS.2.Applying spectral DCM,our study aimed to implement an effective connectivity analysis on the DMN among ALS patients with matched healthy controls.Firstly,we employed ICA to extract the DMN components: medial prefrontal cortex(mPFC),precuneus/posterior cingulate cortices(Pcu/PCC),bilateral inferior parietal lobules(IPL).Then,we evaluated effective connectivity among these regions in the DMN of ALS and healthy controls.Finally,we compared the effective connectivity between the two groups,and estimated the correlation between the clinical status and the effective connectivity in the DMN of ALS.Our findings illustrate causal relationship in the DMN may provide a brain mechanism to represent reduced local inhibitory interneuronal function and compensation for structural damage of the brain.Thus,the DMN may be of potential clinical value as markers of ALS,and abnormal causal relationship of DMN may provide novel insights in the neural mechanism of ALS based on non-motor symptoms.Therefore,this dissertation investigated the effective connectivity analysis on the SMN and DMN in ALS to explore the interactive mechanism of brain.And our studies may provide deeper and more comprehensive insights in the pathophysiology of ALS.