Cerebellar Structural And Functional Abnormalities In Patients With Bipolar Disorder:A Multimodality MRI Study

Part ?: Microstructural abnormalities of cerebellum and its related neural circuits in non-medicated bipolar disorder: a diffusion kurtosis and perfusion imaging studyObjective: The purpose of this study was to investigate the cerebellar microstructural and blood perfusion abnormalities in non-medicated bipolar disorder by using diffusional kurtosis imaging and three dimensional arterial spin labeling technique.Methods: Patients with BD?n = 27?and healthy controls?n = 27?underwent diffusional kurtosis imaging?DKI?and three dimensional arterial spin labeling?3D ASL?.The DKI parameters including mean kurtosis?MK?,axial kurtosis?Ka?,radial kurtosis?Kr?,fractional anisotropy?FA?,mean diffusivity?MD?,axial diffusivity?Da?and radial diffusivity?Dr?and 3D ASL parameters?i.e.cerebral blood flow?was measured by using regions-of-interest?ROIs?analysis in the superior cerebellar peduncles?SCP?,middle cerebellar peduncles?MCP?,dentate nuclei?DN?,tonsil,vermis of cerebellum,thalamus and red nucleus by using the Functool software in the GE Advantage Workstation 4.5.The comparison of the parameters between the two groups using the independent sample t test,A P-value of less than 0.05 was considered statistically significant,and Pearson's correlation coefficients were used to correlate the clinical variables?HAMD-24,YMRS,number of episodes,age of illness onset,total duration?for the patients to their measured DKI and 3D ASL parameters.Results: ?: The group differences of DKI parameters: When compared with the HC group,in the right SCP,BD-? showed significantly decreased MK?P=0.029??Kr?P=0.047?and FA?P=0.003?and increased Dr?P=0.003?;In the DN,BD-? showed significantly decreased MK?P=0.010?in the left and decreased Kr?left: P=0.017,right: P=0.030?in the left and right;In the tonsil,BD-? showed significantly decreased Kr?P=0.018?in the left;In the vermis,BD-? showed significantly decreased MK?P=0.015?and Kr?P=0.004?;In the thalamus,BD-? showed significantly decreased MK?P=0.031?in the left and increased Ka?P=0.040?in the right;In the red nucleus,BD-? showed significantly decreased MK?P=0.047?in the right.?: The group differences of 3D ASL parameters?CBF?: When compared with the HC group,BD-? showed significantly decreased CBF in the right and left DN?left: P=0.007,right: P=0.020?and right red nucleus?P=0.033?.?: There were no significant correlations between the DKI and 3D ASL parameters in these ROIs and the clinical variables in the patients with BD-?.Conclusions: ?: DKI parameters abnormalities in the cerebellum,red nucleus and thalamus was exist in the patients with BD-?,suggested that the water diffusion limitation was decreased,the tissue complexity was reduced,indicating the Microstructural integrity was impared.?: The present study found the DKI parameters abnormalities in the the cerebellum,red nucleus and thalamus which are key nodes in the prefrontal-thalamic-cerebellar circuitry may play a important role in the neurobiological process in patient with BD-?.Part?: Cerebellar abnormalities of aquaporins and its related indexes in non-medicated bipolar disorder: a enhance diffusion weighted imaging studyObjective: The purpose of this study was to reveal the cerebellar characteristics of the water diffusion in bipolar disorder by using tri-component model of enhance diffusion weighted imaging?e DWI?,and investigate the role of aquaporins?AQPs?in the pathogenesis of bipolar disorder.Methods: Patients with BD?n = 36?and age,sex matched HC?n = 37?underwent e DWI and the routine MR scan.The e DWI parameters including pure water diffusion?D?,pseudo-diffusion?D*?,ultra-high apparent diffusion coefficient(ADC_uh)and the fraction of pseudo-diffusion?f?was measured by using regions-of-interest?ROIs?analysis in the superior cerebellar peduncles?SCP?,middle cerebellar peduncles?MCP?,dentate nuclei?DN?,tonsil,vermis of cerebellum,thalamus and red nucleus by using the Functool software in the GE Advantage Workstation 4.5.The comparison of the parameters between the two groups using the independent sample t test,A P-value of less than 0.05 was considered statistically significant,and Pearson's correlation coefficients were used to correlate the clinical variables for the patients to their measured e DWI parameters.Results: ?: The group differences of e DWI parameters: When compared with the HC group,in the right SCP,BD group showed significantly increased D in the left and right SCP?left:P=0.004,right: P=0.001?and MCP?left: P=0.010,right: P=0.033?;Also showed increased D?left: P=0.001,right: P=0.000?,ADC_uh?P=0.041?and f?P=0.049?in the left and right DN.In the tonsil,BD group showed significantly increased D in the left?P=0.024?and increased ADC_uh?left: P=0.045,right: P=0.048?and f?left: P=0.008,right: P=0.014?.In the vermis,BD showed significantly increased D?P=0.010?and f?P=0.007?.In the thalamus,BD showed significantly increased D?left: P=0.001,right: P=0.001?and ADC_uh?left: P=0.004,right: P=0.003?.In the red nucleus,BD group showed significantly increased D?left: P=0.001,right: P=0.000?and ADC_uh?left: P=0.007,right: P=0.003?.?: There were no significant correlations between the e DWI parameters in these ROIs and the clinical variables in the patients with BD.Conclusions:?: increased ADC_uh was existed in the cerebellar dentate nucleus,cerebellar tonsil,thalamus and red nucleus in patients with BD-?,illustrating that the active transport of water molecules were increased,suggesting that updating of the AQP4 expression,Impaired water homeostasis due to the upregulation of AQP4 could be involved in the pathophysiological process of BD.?: The present study found that the D values of all the ROIs including the cerebellar,thalamus and red nucleus were increased,indicating that the ristriction of the transmembrane movement of water molecules was decreased,suggesting the imparement of the microstructure barrier in histology,which support the Part I of this doctoral thesis,and further verified the important role of the prefrontal-thalamic-cerebellar circuitry in the pathogenesis of BD.Part ?: Disruptive changes of cerebellar functional connectivity with the default mode network in bipolar disorder:a resting-state fMRI studyObjectives: The purpose of this study was to investigate the the potential contribution of the cerebellum to the abnormal functional connectivity of the cerebral network-especially the DMN in non-medicated bipolar disorder.Methods: Thirty patients with bipolar II disorder during a depressive episode as well as 37 age and sex matched healthy controls underwent resting-state functional magnetic resonance imaging.Seed-based correlation analysis was performed by using seeds from the left Crus I,right Crus I and Lobule IX,which have previously been identified as being involved in the DMN.The time series of each seed region were calculated by averaging the fMRI time series over all voxels within the sphere.For each subject,correlation maps were created by calculating the Pearson's correlation coefficients between the time series of the seed regions and that of each voxel in the brain.These correlation maps were converted to z-value maps using Fisher's r-to-z transformation,to improve the normality of the correlation coefficients.Group analyses were performed for the correlation maps of each seed region.Once significant group differences were observed in any brain regions,we further computed Pearson's correlation coefficients between these time series correlation coefficient and the clinical variables.Results: For each group,each seed ROI exhibited distributed FCs with the DMN using one-sample t-tests.Two sample t test revealed that,compared with the healthy controls,the patients showed significantly reduced cerebellar functional connectivity between the left Crus I and the right inferior parietal lobule,as well as between the right Crus I and the ipsilateral inferior temporal gyrus/ contralateral Crus I.There was no significant difference in functional connectivity between the cerebellum Lobule and IX and the voxel of the whole brain.No significantly increased FC was found in the whole brain.No significant correlations were found between the significant brain regions and the clinical variables.Conclusions: The functional connectivity between cerebellar-DMN was decreased in patients with BD-?,suggesting that the disruptive changes of the cerebellar-DMN may plays a important role in the pathophysiology of BD-? pathogenesis.The present study further confirmed the key role of the cerebellum in the pathogenesis of BD by using the seed-based functional connectivity analysis...