| Background and purposeParkinson’s disease(PD)is a common progressive neurodegenerative in the middle aged and elderly people.Diagnosis of PD is based on history and examination.PD is uncommon among individuals younger than 50 years old and increases in prevalence with age,peaking between ages 85 and 89 years.PD is more common in men.The most widely cited model to explain neuropathological progression of PD is the Braak hypothesis.This model suggests that PD starts(stages 1 and 2)in the medulla and the olfactory bulb.This early pathology is associated with symptoms occurring prior to the movement disorder onset,such as rapid eye movement sleep behavior disorder and decreased smell.In stages 3 and 4,pathology progresses to the substantia nigra pars compacta and other midbrain and basal forebrain structures.Pathology in these areas is associated with classic PD motor symptoms.PD is typically diagnosed at this stage.In advanced PD,the pathology progresses to the cerebral cortices with onset of cognitive impairment and hallucinations.In recent years,the number of PD patients worldwide has increased significantly compared with previous years.The disease progession is irreversible,the prognosis is poor,and the disability rate is high,so early clinical diagnosis is particularly important to delay disease progression.Diagnosis of PD is based on history and examination.Because of its occult onset,it is often difficult to diagnose.Up to now,the value of quantitative biomarkers for objective early diagnosis,evaluating disease progress and monitoring treatment effect is limited.In recent years,with the development of functional magnetic resonance imaging(fMRI),some studies on the changes of brain function in patients with early-stage PD provide a valuable basis for early diagnosis and prognosis.Degree centrality(DC),resting-state voxel-level whole-brain functional connectivity analysis,has provided a valuable way to explore the brain network mechanism underlying early-stage PD.In this study,DC combined with the seed-baesd functional connectivity(FC)analysis were used to study the changes of brain network in patients with early-stage PD.In addition,the relationship between DC value of some brain regions with statistical differences and cognitive function or disease severity was explored in patients with early-stage PD.Thus,we can have a deeper understanding of the pathogenesis of PD at the brain network level,and provide possible new biomarkers for the diagnosis and prognosis of PD.Materials and methods1.A total of 57 patients with early-stage PD(H-Y≤2.5)and 85 normal controls matched for age and sex were collected.All patients were assesed using the Unified Parkinson’s Disease Rating Scale(UPDRS),the Hoehn-Yahr stage(H-Y stage)and Montreal Cognitive Assessment(MoCA).All the subjects were scanned on a Prisma 3T MRI scanner with a 64-channel head/neck coil.The MRI examinations consisted of conventional MRI sequences and rs-fMRI sequence.2.The resting state fMRI sequence was preprocessed and the DC value was calculated by using DPARSFA software in Matlab platform.In addition,REST software was used to extract the DC values of the brain regions with statistical differences between the groups.The resting state fMRI sequence was preprocessed and each the brain region with statistical difference in DC value between the two groups was regarded as a seed point and analysed by seed-based resting state FC analysis by DPARSFA software.3.Statistical analysis was carried out on SPM 12,with sex and age as covariables,two-sample t-test was used to analyze the two groups of data,family-wise error(FWE)correction method was used to correct the results,and the brain regions with significant differences in DC value between the two groups were obtained,that is,the brain regions with significant changes in the number of functional connections between the two groups.Using the same statistical method,the brain regions with significant changes in FC between the two groups were obtained.In addition,the Spearman correlation analysis was carried out between the DC value with statistical difference in different brain regions and MoCA score and UPDRS score using SPSS 21.The test level a value was set to 0.05 during each statistical analysis.The difference was statistically significant when P<0.05.Results1.Compared with control group,early-stage PD group had higher DC values in the right cerebellar Crul(t=5.35,P=0.007),right inferior opercular-frontal and triangular-frontal gyrus(t=5.65,P=0.002),and lower DC values in the right precentral and postcentral gyrus(t=-6.50,P=0.001),left precentral and postcentral gyrus(t=-5.89,P=0.001),right paracentral lobule(t=-5.49,P=0.001),left paracentral lobule(t=-5.44,P=0.001),left middle and lateral cingulate gyrus and the left precuneus(t=-5.75,P=0.001).2.Seed-baesd functional connectivity analysis results:Taking the left precentral and postcentral gyrus as the seed,compared with the normal control group,the FC values of the bilateral calcarine cortex,bilateral precuneus,bilateral lingual gyrus,bilateral cuneus,bilateral supplementary motor area,bilateral middle and lateral cingulate gyrus,bilateral paracentral lobule,right precentral gyrus,right postcentral gyrus and the right inferior temporal gyrus decreased in PD group(P<0.05);Taking the right precentral and postcentral gyrus as the seed,compared with the normal control group,the FC values of the bilateral calcarine cortex,bilateral precuneus,bilateral cuneus,left superior occipital gyrus,left middle occipital gyrus,left lingual gyrus,left precentral gyrus and the left postcentral gyrus decreased in PD group(P<0.05);Using the left paracentral lobule as the seed,compared with the normal control group,the FC values of the bilateral calcarine cortex,bilateral precuneus,bilateral cuneus,left superior occipital gyrus,left middle occipital gyrus,right postcentral gyrus and the bilateral supplementary motor area decreased in PD group(P<0.05).Taking the right paracentral lobule as the seed,compared with the normal control group,the FC values of the calcarine cortex,bilateral precuneus,bilateral cuneus,left lingual gyrus,left superior occipital gyrus,left middle occipital gyrus,left angular gyrus,left precentral gyrus and the left postcentral gyrus decreased in PD group(P<0.05).The left middle and lateral cingulate gyrus and the left precuneus were used as the seed,compared with the normal control group,the FC values of the bilateral calcarine cortex,left cuneus,right precuneus,bilateral lingual gyrus,left superior occipital gyrus,left middle occipital gyrus,left fusiform gyrus,right paracentral lobule,right postcentral gyrus,left Rolandic opercular sulcus,left insular lobe,right middle and lateral cingulate gyrus decreased in PD group(P<0.05).Taking the right cerebellar Crul,the right inferior opercular-frontal and triangular-frontal gyrus as seed points,there was no significant difference in FC between the two groups(P>0.05).3.In early-stage PD group,there was a negative correlation between the DC value of the right precentral and postcentral gyrus,left precentral and postcentral gyrus and the left paracentral lobul and the MoCA score(r=-0.516,P=0.000;r=-0.429,P=0.002;r=-0.547,P=0.000),but there was no correlation between the DC value and the total score of UPDRS(P>0.05).Conclusions1.Using voxel-based whole brain functional connection analysis,it was found that the functional connections of patients with early-stage PD mainly changed in the precentral and postcentral gyrus,paracentral lobule,cingulate gyras,precuneus,cerebellar Crul,the inferior opercular-frontal and triangular-frontal gyrus,and the occipital lobe,which reflect abnormal functions in some brain networks such as sensorimotor network,default mode network,frontoparietal network,language network,visual network and so on.These changes suggest multifunctional impairment of the whole brain in the early-stage PD patients.2.There is a certain correlation between the DC value of some brain regions and MoCA score in patients with early-stage PD,mainly in the first sensorimotor area,indicating that there is a certain relationship between this area and cognitive function. |