Abnormality In White Matter Functional Network Connectivity In Myotonic Dystrophy Type 1

Myotonic dystrophy type 1（DM1）is an inherited neuromuscular disease.In addition to myotonia and muscle atrophy,abnormalities of the central nervous system are also an important feature of the disease.Advances in brain imaging technology have provided researchers with the technical support to explore structural and functional brain abnormalities in DM1 disease,and they have found that the complex pathophysiological mechanisms behind the cognitive impairment in DM1 patients may be related to abnormalities in the integration of information across functional networks,rather than being caused solely by localized brain tissue damage.Large-scale functional brain networks allow for a comprehensive,unbiased assessment of changes in functional networks across the brain.Functional connectivity（FC）metrics can measure the synchronous changes between different brain networks.Currently,researchers have focused on structural and grey matter functional networks in DM1 patients and have not focused on functional signals in the white matter.However,some researchers have demonstrated that functional signals in white matter regions can be detected and have some physiological significance.The aim of this study was to investigate the changes in static FC（s FC）and dynamic FC（d FC）in the white matter functional networks of DM1 patients and to further validate the FC changes in the white matter networks as biomarkers using support vector machines（SVM）.In this study,we used resting-state functional magnetic resonance imaging（rs-f MRI）data from 16DM1 patients and 18 healthy controls（HCs）,and we constructed 13 white matter functional networks and further explored the variation in s FC and d FC among these networks.Similar to previous studies,all constructed white matter functional networks were mostly symmetrically distributed and functionally organized,and abnormal integration of functional connectivity was also found in the s FC and d FC.Compared to HCs,there was a widely distributed increase in s FC in DM1 patients.Within each layer of the white matter network,the increase in s FC was mainly located in the inferior longitudinal tract network,the prefrontal cortex network and the corpus callosum network.Between the layers of the white matter network,increased s FC in DM1 patients was mainly located in the superior radiocoronal network and the deep network.In addition,the d FC variance in DM1 patients differed in spatial distribution between the posterior central network and the deep network.The clustering results showed that the white matter network signal could be classified into 3 states.Compared to the control group,the DM1 patients showed a higher frequency of the positively connected state（state 1）and a lower frequency of the negatively connected state（state 2）,with the DM1 patients staying in state 2for a shorter period of time.This suggests that there is a temporal reorganization of white matter functional network activity in DM1 patients.SVM results show that both s FC features and d FC temporal parameter features can effectively distinguish DM1 from normal control subjects,but both types of indicators have their own advantages.d FC features are higher in sensitivity than s FC indicators,and s FC indicators are higher in specificity,accuracy and precision than d FC indicators.Thus,white matter network activity in DM1 patients is abnormal in terms of temporal synchrony as well as dynamics,suggesting that the pathological mechanisms of their dysfunction cannot be understood only in local terms,but are related to abnormal integration between functional networks.The findings of this paper provide new insights into understanding the pathophysiological mechanisms of DM1 patients.