An Functional MRI Study Of Sensation And Sensorimotor Integration Deficits In Early Parkinson's Disease

Introduction:It is long known that sensory and sensory-motor integrations are deficient in patients with Parkinson's diseases(PD).These deficits are found in early,as well as in moderate and advanced patients,and appear to pertain to a high level linkage between perception and action.A body of studies have identified the accuracy of movements depends to a large extent on the availability of proprioceptive information.Current knowledge attributes movement disorders of Parkinson's disease to a dysfunction of the basal ganglia-motor cortex circuits,abnormalities in the peripheral afferent inputs or in their central processing may interfere with motor program execution,and its pathophysiological mechanisms have been proposed:disruptions in cortico-striatal circuits or a deficiency in frontal dopamine.Sensorimotor integration,that is,the processing to use sensory information properly for assisting motor program execution. Patients with the most common movement disorders --- Parkinson's disease --- rely strongly on external sensory information for their motor ability(movement initiation and execution).For example,motor execution of PD patients depends largely on a deficiency in the internal cueing mechanisms used to release successive stages of a movement sequence providing external,visual or auditory,cues,appreciably improves specific features of parkinsonian bradykinesia.Hence,defective sensorimotor integration may have an important role in PD patients' symptoms.Moreover,some researchers have mentioned a cortico-subcortico-cortical loop about sensorimotor integration that includes the basal ganglia as well as the premotor and supplementary motor areas,and it has been demonstrated that PD patients- especially in the early stages of the disease--- show a severely depressed frontal responsiveness to sensory stimuli as tested via SEPs(sensory evoked potential).By now,some positron emission tomography(PET) and functional magnetic resonance imaging(fMRI) has been extensively used on PD research.These investigations have focused on task-related or resting state brain activity,and found some pathophysilogical and functional changes in PD.For example,the supplementary motor area(SMA) is commonly found hypoactivated,and some other cortical motor regions,like the cerebellum,premotor area(PMA),and parietal cortex are hyperactivated in patients with PD compared to normal controls during performing motor tasks.Also,there is ample evidence that direct and indirect to explain the cognitive and behavioral deficits of PD.As is frequently reported in the literature,patients with PD cognitive and behavioral impairments may be attributed to dysfunction of multiple systems associated with the disease process in Parkinson's disease that are not necessarily related to motor symptoms.A fundamental question in motor research relates to how motor planning operations and sensory feed-back are implemented in the human brain.Prior studies have shown that there were several sensory systems separate processing of motor planning,for example:haptics, vision,and auditory.In order to prepare and accomplish an action punctually,the information from these systems must somehow be integrated.For PD patients,some deficiency could happen in the sensory-movement integrating process,and the anatomical foci maybe located in prefrontal lobe.Thus,to investigate which regions involved in integration of sensory and movement, whether activity model in these regions are difference between PD and normal controls, we employed a multitask functional magnetic resonance imaging(fMRI) to represent these.Methods and subjects:Twenty-one right-handed patients with at Hoehn and Yahr stage 1 and 2 of Parkinson's disease(11 female,10 male;age range,43-81 years,mean age 60.43±9.65). Patients were studied only after their medication had been withdrown for at least 15h. They were assessed with the UPDRS(Unified Parkinson's Disease Rating Scale),the Hoehn and Yahr disability scale and MMSE(Mini-Mental Stated Examination) while off their medications.Twenty-two neurologically normal subjects(11 female,11 male;age range,42-75 years,mean age 59.23±11.12) participated in this study as control,were right-handed and gender matched with patients.The experimental design was block design,which included passive tactile stimulations,right-hand motor tasks,and sensory-movement integrating tasks.Imaging collecting included a high-resolution T1-weighted three-dimensional volume acquisition for anatomical localization and an acquisitions of echoplanar T2*-weighted images with blood oxygenation level-dependent(BOLD) contrast.fMRI data analysis was performed with SPM2 software.Both first- and second-level analyses were performed.In the first-level,data were modelled using a general linear model design.These contrast data were used in the second level for random effects analysis.For the within group analysis,a one-sample t-test model was used to identify the brain activity for each tasks(P <0.001,without correction for multiple comparisons),and spatial extent threshold was cluster size greater than 20 voxels.For intergroup comparisions,a two-sample t-test model(P <0.01,uncorrected) was used to explore the difference between patients and normal controls under each tasks.Locations of activated areas for different conditions were displayed by superimposing them on the Montreal Neurological Institute(MM) template.All coordinates reported were in Talairach space converted from MNI space. Results:As predicted,the results revealed decreased activated in the PD group compared with age-matched controls in somatosensory cortical areas bilaterally,left premotor cortex,thalamus,and the right cerebellum when they performing above three tasks(P < 0.01).Surprisingly and interestingly,significant decreases in activation were observed in the extrastriate visual cortex in the PD group during performing these three tasks, especially during movement task(P < 0.01).In contrast,increasing activities were observed in bilateral frontal lobe in the PD group compared with the aged-matched control group(P < 0.01).Conclusions:There are different neural networks engaged in sensory,movement and sensory-movement integration between PD group and normal controls.The extrastriate visual cortex maybe are multisensory processing regions and play an important role in sensory,movement and sensorimotor integration,nevertheless,in early stage PD, nigrostriatal dopamine depletion and intracortical dopamine deficiency may leads to the decreased activation in extrastriate visual cortex,and to fulfill these integrate processing, the compensation in bilateral prefrontal lobe will be happen.By now,whether the activation in the extrastriate visual cortex in sensorimotor integration is changed in patients with PD has never been reported.Our study is the first time to demonstrate above findings.