Research On The Thalamic Intrinsic Network In Patients With Wilson’s Disease And Its Correlation With The Syndrome Of Intermingled Phlegm And Stagnation

Objective: The objectives of this study were(1)to compare the intergroup differences in the volume of the thalamus between patients with Wilson’s disease(WD)and healthy controls;(2)to investigate the relationship between the volume of the thalamus and the neurological impairment in WD patients;(3)to explore the relationship between the volume of the thalamus and syndrome of intermingled phlegm and stagnate in WD patients;(4)to compare the topological properties of the thalamic intrinsic network between the WD patients and healthy controls;(5)to explore the relationship between syndrome of intermingled phlegm and stagnate and the thalamic intra-network;and(6)to investigate the relationship between the neurological function and the topological properties of the thalamic intrinsic network in WD patients.Methods: This study recruited 61 WD patients as the WD group and 33 healthy controls as the healthy control group.Classifying Wilson’s disease patients into neurological and non-neurological types based on Unified Wilson’s Disease Rating Scale-neurological subscale(UWDRS-N).According to the traditional Chinese medicine diagnosis and treatment plan for hepatolenticular degeneration,WD patients were classified as having WD patients with syndrome of intermingled phlegm and stagnate or WD patients without syndrome of intermingled phlegm and stagnate.The volumes of 2 5 bilateral thalamus nuclei were obtained using Freesurfer to compare thalamic volume between WD group and healthy control group,neurological and non-neurological WD patients,and WD patients with syndrome of intermingled phlegm and stagnate and WD patients without syndrome of intermingled phlegm and stagnate through linear regression models.The 25 bilateral thalami were used as nodes to compare the thalamic intrinsic network topology between the control and WD groups,neurological and non-neurological WD patients,and WD patients with syndrome of intermingled phlegm and stagnate and WD patients without syndrome of intermingled phlegm and stagnate using structural covariance network analysis.Result:(1)The volumes of bilateral Anteriorvental(AV),Ventral anterior(VA),Ventral anterior magnocellular(VAmc),Ventral lateral anterior(VLa),Ventral lateral posterior(VLp),Ventral posterolateral(VPL),Ventromedial(VM),Central median(Ce M),Central lateral(CL),Paracentral(Pc),Parafascicular(Pf),Paratenial(Pt),Reuniens-medial ventra(MV(Re)),Mediodorsal medial magnocellular(MDm),Lateral geniculate(LGN),Limitans-suprageniculate(L-Sg),Pulvinar anterior(Pu A),Pulvinar inferior(Pu M),Pulvinar medial(Pu I),and the right Mediodorsal lateral parvocellular(MDl)nuclei were all found to be smaller in volume in the WD group than in the healthy control group.(2)In the WD patients with syndrome of intermingled phlegm and stagnate,the volumes of the left AV and right Laterodorsal(LD),MV(Re),Pu I,VA were smaller than those in the WD patients without syndrome of intermingled phlegm and stagnate.(3)The volume of the right MDm in the neurological WD patients was smaller than that in the non-neurological WD patients.(4)Compared with the healthy control group,the global graph theory indicators of thalamic intrinsic network in the WD group showed a significant increase in the average local efficiency,modularity,normalized clustering coefficient,and small-world index,and a decrease in characteristic pathlength and average node betweenness centrality.(5)The thalamic intrinsic network in the neurological WD patients had a significantly increased modularity compared to the non-neurological WD patients.(6)The assortativity of the thalamic intrinsic network in the WD patients with syndrome of intermingled phlegm and stagnate was higher than that in the WD patients without syndrome of intermingled phlegm and stagnate.Conclusion: WD patients have widespread atrophy of the thalamic nuclei,involving the anterior,lateral,ventral,medial,pulvinar,and posterior subregions.Neurological WD patients exhibit right-side atrophy of the MDm,indicating its potential role in the development of neurological and psychiatric symptoms in WD patients.The relationship between the syndrome of intermingled phlegm and stagnation and the left AV and right LD,MV(Re),Pu I,and VA is closely related to WD patients.The abnormal network topology indicates that WD patients have undergone a reorganization of the thalamic intrinsic network.Neurological WD patients exhibit an increase in the modularity of the thalamic intrinsic network compared to non-neurological WD patients,while WD patients with the syndrome of intermingled phlegm and stagnation exhibit an increase in assortativety within the thalamic intrinsic network compared to WD patients without the syndrome.These results suggest a close relationship between neurological and psychiatric symptoms,as well as the syndrome of intermingled phlegm and stagnation,and the abnormal reorganization of the thalamic intrinsic network in WD patients.