Structural And Functional MRI Studies In Parkinson’s Disease

PART I. Mild cognitive impairment in Parkinson’s disease: A voxel-basedmorphometry studyBackgrounds and objective:Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a slow andprogressive degeneration of dopaminergic neurons in substantia nigra (SN) that leads toloss of dopamine (DA) terminals in the striatum. Among all the non-motor symptoms,cognitive impairment become focused. The Mild cognitive impairment (MCI) is oftenaccompanied by PD, even early in the disease, which is the risk factor of Parkinson’sdisease with dementia. The purpose of this study was to investigate the changes of greymatter in Parkinson’s disease (PD) patients with mild cognitive impairment (MCI) usingvoxel-based morphometry (VBM).Methods：Totally43PD patients were classified using cognitive testing as PD with normalcognition (single PD, n=21) and PD with MCI (PD-MCI, n=22). And20normalcontrols(NC) were enrolled. T1WI were derived using a3.0T MR scanner. The differencesgrey matter volumes were evaluated using VBM. In order to examine the gray matterdiference between each two groups, two-sample t-test was performed in SPM8, resultswere displayed using REST software with a threshold of P<0.05with multiple comparisoncorrected by FDR methods.Results：No significant differences were found between the three groups in gender, age, height,weight and education. Compared with NC, PD-MCI exhibited reduced grey matter volumein bilateral frontal cortex, bilateral cerebellum, the right occipital lobe, as well as in lefttemporal lobe, posterior cingulate and the hippocampus(P<0.05, FDR corrected). PDpatients without MCI showed limited grey matter atrophy in the left temporal and frontal cortex(P<0.05, FDR corrected). Compared to PD patients without MCI, areas of greymatter in the left middle temporal gyrus and parahippocampal reduced in PD-MCIpatients(P<0.001,uncorrected).Conclusion:PD with MCI is associated with structural neocortical changes in the brain, suggestingthat there may exist a gradient of neuropathology structures in PD. PART II. Localization of cerebral functional deficits in PD patients with mildcognitive impairment: A resting-state fMRI studyBackgrounds and objective:Grey matter changes was found in Parkinson’s disease with MCI in partⅠ. The aim ofthis study is to test the abnormality in Parkinson’s disease with MCI and explore whetherthere are any other dysfunctional brain regions using a resting-state functional magneticresonance imaging (fMRI).Methods：Totally43PD patients were classified using cognitive testing as PD with normalcognition (single PD, n=21) and PD with MCI (PD-MCI, n=22). And20normalcontrols(NC) were enrolled. All patients and NC were examined using resting-state fMRI,and fractional amplitude of low-frequency fluctuation (fALFF) approach method were usedto analyze fMRI data. The fMRI data were processed by SPM8soft and REST soft based onMATLAB2010a. In order to examine the fALFF diference between each two groups,two-sample t-test was performed in SPM8, results were displayed using REST softwarewith a threshold of P<0.01with multiple comparison corrected by AlphaSim methods.Results：No significant differences were found between each two groups in gender, age, height,weight and education. Two-sample t-test showed that, compared to the normal controls,patients with PD-MCI had significantly increased fALFF in multiple areas including leftmiddle temporal gyrus and inferior temporal gyrus, left inferior frontal gyrus, right medial frontal gyrus, right inferior temporal gyrus and parahippocampa gyrus as well as decreasedfALFF in several brain areas including right inferior occipital gyrus, right fusiform gyrusand right cingulate gyrus(P<0.01, AlphaSim corrected). And compared to the normalcontrols, PD patients without MCI showed increased fALFF in limited areas in the leftparahippocampa gyrus, right middle frontal gyrus and right cerebellum(P<0.01, AlphaSimcorrected). Compared to PD patients without MCI, PD-MCI patients showed increasedfALFF in the left superior frontal gyrus, left cingulate gyrus, right superior occipital gyrusand right inferior parietal lobule as well as decreased fALFF in cerebellum, right middleoccipital gyrus and left middle occipital gyrus(P<0.05,uncorrected).Conclusion:In conclusion, the present study observed the abnormal spontaneous activities inPD-MCI patients by analyzing resting-state fMRI data. Our findings suggest that theabnormal spontaneous activity of these brain regions may implicate the underlyingpathophysiology of cognitive dysfunction in PD patients. Future experimentations areexpected to combine different modalities to provide more information about the disorder. PART Ⅲ. A2-year longitudinal MR imaging voxel-based morphometry studyin patients with Parkinson’s diseaseBackgrounds and objective:Grey matter changes was found in Parkinson’s disease in cross-sectional studies. Theaim of this study is to investigate grey matter changes in Parkinson’s disease(PD) withoutdementia at baseline and2years later.Methods：17patients with PD without dementia were enrolled，who were studied at baseline and2year later again. Grey matter volume differences were evaluated using voxel basedmorphometry on the same cohort PD patients longitudinally. In order to examine the fALFFdiference, paired t-test was performed in REST, results were displayed using REST software with a threshold of P<0.01with multiple comparison corrected by FDR methods.Results：17patients with PD completed the MRI scans. Paired t-test showed that, at the2-yearfollow-up, GM volumes in the left middle frontal gyrus, left inferior parietal lobule andright cerebellum anterior lobe in patients had decreased significantly from baseline.Conclusion:In conclusion, these findings show that there is a significant loss of grey mattervolume in PD patients with disease progression, which may be the characteristic changes ofPD. Some progressive gray matter changes in patients may be related to motor functionaloutcome even without dementia. PART Ⅳ. Amplitude of low-frequency oscillations in in Parkinson’s disease: a2-year longitudinal resting state fMRI studyBackgrounds and objective:The aim of this study is to investigate dysfunctional changes in Parkinson’s disease(PD)at baseline and2years later using a resting-state functional magnetic resonance imaging(fMRI), and further investigate the relationship between the whole-brain voxel-basedspontaneous neuronal activity of patients with PD and clinical characteristics.Methods：17patients with PD underwent MRI at baseline and2years later using resting-statefMRI derived from the same3T MRI. And fractional amplitude of low-frequencyfluctuation (fALFF) approach was used to analyze fMRI data. Non-linear registration wasused to model within-subject change over the scanning interval and between PD, andstatistical parametric mapping was used to examine group differences and associations withclinical variables. Results were displayed using REST software with a threshold of P<0.01with multiple comparison corrected by AlphaSim methods.Correlative analysis wasperformed between fALFF values and clinical characteristics including the UPDRS motorscore and also the change in UPDRS motor score within the2years at the regions showing fALFF differences.Results：Compared with baseline, patients with PD2years later presented increased fALFFvalues in the right middle temporal gyrus and right middle occipital gyrus, as well asdecreased fALFF in the right cerebellum posterior lobe, right thalamus and striatum, leftsuperior parietal lobule, left inferior parietal lobule, left precentral gyrus and leftpostcentral gyrus (P<0.01alphasim corrected). Additionally fALFF values in the rightcerebellum were positively correlated with the UPDRS motor scores (r=0.51, P<0.05,uncorrected)， and also the change of fALFF values with the UPDRS motor score (r=0.61,P<0.05, uncorrected).Conclusion:The baseline and longitudinal changes of the fALFF values in our study suggest thebrain dysfunction may affect the regions related to cortico-striato-pallido-thalamic loopsand cerebello-thalamo-cortical loops with disease progression and the changed spontaneousneuronal activity of cerebellum may also play an important role in the disease progress ofPD patients.