Alterations Of Brain Activity And Functional Connectivity In Different Motor Subtypes Of Parkinson's Disease Based On Resting-state Functional MRI

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Alterations of brain activity in different motor subtypes of Parkinson's disease based on regional homogeneity analysisObjective:To explore the changes of local brain activity in different motor subtypes of Parkinson's disease(PD)with resting-state functional magnetic resonance imaging(rs-fMRI).Materials and Methods:A total of 77 PD patients and 29 healthy controls undergoing rs-fMRI were included.PD patients were divided into two groups of tremor dominant(TD)(n=43)and postural instability gait difficulty(PIGD)(n=34)according to the Unified Parkinson's Disease Rating Scale(UPDRS)scores.Regional homogeneity(ReHo)method was used to investigate the modulations of neural activity in different motor subtypes of PD.Analysis of covariance(ANCOVA)and post-hoc t-test were performed to detect the differences of local brain activity among the three groups.Results:Compared to healthy controls,the TD group exhibited increased ReHo in the right superior and middle frontal gyrus,while decreased ReHo in the left temporal lobule,left putamen,left paracentral lobule,bilateral thalamus,bilateral cuneus,bilateral calcarine and left cerebellum.The PIGD group showed increased ReHo in the right superior frontal gyrus,right middle frontal gyrus and anterior cingulate gyrus(ACC),while decreased ReHo in the left putamen,left Pallidum,left temporal lobule,right occipital lobule,bilateral thalamus,bilateral middle cingulate gyrus,bilateral supplementary motor area(SMA).Compared with PIGD,the TD group showed increased ReHo in the left temporal lobule,left cerebellum,bilateral middle cingulate gyrus,whereas decreased ReHo in the left temporal lobule,left paracentral lobule,bilateral cuneus,right superior frontal gyrus,right ACC and right cerebellum crus.Additionally?ReHo in the right superior frontal gyrus was positively correlated with TD scores while ReHo in the left thalamus,left putamen,right putamen and right lingual gyrus negatively correlated with TD scores.ReHo in the right superior frontal gyrus and right ACC was positively correlated with PIGD scores while ReHo in the left thalamus,left putamen,inferior temporal gyrus,right putamen,right lingual gyrus and right inferior occipital gyrus negatively correlated with PIGD scores.Conclusions:The changes of brain activity in TD are caused by the interaction between cerebello-thalamo-cortical(CTC)circuit and striatal-thalamo-cortical(STC)loop while the changes in PIGD result largely from damaged STC loop and visual network cortex.This specific pattern of intrinsic activity in TD and PIGD may provide insights into neurophysiological mechanisms of PD with different motor subtypes.Part ? Alterations of brain functional connectivity in different motor subtypes of Parkinson's disease based on voxel-wise degree centrality analysisObjective:To study the changes of brain network node functional connectivity in different motor subtypes of Parkinson's disease(PD)with resting-state functional magnetic resonance imaging(rs-fMRI).Materials and Methods:A total of 77 PD patients and 29 healthy controls undergoing rs-fMRI were included.PD patients were divided into two groups of tremor dominant(TD)(n=43)and postural instability gait difficulty(PIGD)(n=34)according to the Unified Parkinson's Disease Rating Scale(UPDRS)scores.Degree centrality method was used to measure the strength of functional connectivity in different motor subtypes of PD.Analysis of covariance(ANCOVA)and post-hoc t-test were performed to detect the differences of local brain activity among the three groups.Results:Compared to healthy controls,significantly increased DC values of the TD group in the bilateral thalamus and caudate,while decreased DC values in the bilateral fusiform,bilateral hippocampus,bilateral parahippocampal gyrus,left orbital frontal gyrus,left superior frontal gyrus,left insula,left putamen,right inferior temporal gyrus,and right superior frontal gyrus.Significantly increased DC values of the PIGD group in the right superior/inferior parietal lobule,and left thalamus,while decreased DC values in the left precentral gyrus(Ml),left postcentral gyrus left paracentral lobule,left middle temporal gyrus,left middle occipital gyrus,left supramarginal gyrus,bilateral supplementary motor area(SMA),left posterior cingulate gyrus(PCC),and right middle cingulate gyrus(MCC).Compared with PIGD,the TD group showed increased DC values in the bilateral cuneus,left precuneus,bilateral calcarine,bilateral SMA,left precentral gyrus,and left paracentral lobule,whereas decreased DC values in the left orbital frontal gyrus,left middle frontal gyrus,and left superior frontal gyrus.DC value in the left putamen,left fusiform,left hippocampus,and left parahippocampal gyrus was negatively correlated with TD scores.DC value in the left SMA and left middle temporal gyrus negatively correlated with PIGD scores.Conclusions:Both of the two subtypes of PD exhibited decreased DC values in brain regions within the so-called default mode network(DMN).Especially,there is differential involvement of the brain network node functional connectivity in the two subtypes.The TD group demonstrated abnormality in basal ganglia(e.g.putamen)and thalamus,while the PIGD group showed abnormality in the motor-related regions like SMA,M1,as well as in the visual network.Voxel-wise degree centrality analysis of rs-fMRI provides a new method for exploring the underlying pathogenesis of PD patients with different subtypes.Part ? Alterations of brain activity and functional connectivity of freezing of gait in Parkinson's diseaseObjective:To investigate the patterns of brain activity and functional connectivity abnormalities in patients with Parkinson's disease with freezing of gait(PD FOG(+))compared with those without freezing(PD FOG(-))and healthy controls(HC).Materials and Methods:Resting state functional MRI(rs-fMRI)scan was obtained from 14 PD FOG(+),16 PD FOG(-)and 16HC.Between-group difference in based on regional homogeneity and pedunculopontine nucleus(PPN)functional connectivity(FC)were performed to assess brain activity abnormality and FC dysfunction.Results:Compared to healthy controls,PD FOG(+)showed decreased ReHo in the left inferior temporal gyrus,right lingual,bilateral fusiform,right occipital gyrus,right calcarine,and right cerebellum while increased ReHo in the right middle frontal gyrus,right superior frontal gyrus,right precentral gyrus,and right supplementary motor area(SMA).Compared to PD FOG(-),PD FOG(+)exhibited increased ReHo in the right precentral gyrus,right middle frontal gyrus,right inferior frontal gyrus,and right supplementary motor area(SMA),no decreased ReHo area was involved.Moreover,PD FOG(+)patients exhibited abnormal PPN FC,compared with HCs and with PD FOG(-),mainly in the corticopontine-cerebellar pathways(in the bilateral cerebellum and in the pons),as well as the visual temporal areas(in the right middle temporal gyrus and in the right inferior temporal gyrus).Conclusions:This study suggests that FOG in PD is associated with abnormalities in cerebellum,frontal lobe and visual network.And according to PPN FC network,the corticopontine-cerebellar pathways as well as visual temporal areas were affected.Combining brain activity and functional connectivity,our study should advance the understanding of neural mechanisms underlying FOG in PD.