Background:In the midbrain of patients with Parkinson disease (PD), there is a selective loss of

The basal ganglia (BG) are impaired in Parkinson's disease (PD), but it remains unclear which nuclei are impaired during the performance of motor tasks in early-stage PD. Therefore, this study was conducted to determine which nuclei function abnormally, and whether cortical structures are also affected by early-stage PD. The study also determined if cerebellar hyperactivity is found early in the course of PD. Blood oxygenation level dependent activation was compared between 14 early-stage drug-naïve PD patients and 14 controls performing two precision grip force tasks using functional magnetic resonance imaging at 3 T. The grip tasks used in this study were chosen because both tasks are known to provide robust activation in BG nuclei, and the two tasks were similar except that the 2-s task required more switching between contraction and relaxation than the 4-s task. The 4-s task revealed that PD patients were hypoactive relative to controls only in putamen and external globus pallidus, and thalamus. In the 2-s task, PD patients were hypoactive throughout all BG nuclei, thalamus, M1, and supplementary motor area. There were no differences in cerebellar activation between groups during either task. Regions of interest analysis revealed that the hypoactivity observed in PD patients during the 2-s task became more pronounced over time as patients performed the task. This suggests that a motor task that requires switching can accentuate abnormal activity throughout all BG nuclei of early-stage, drug-naive PD, and that the abnormal activity becomes more pronounced with repeated task performance in these patients.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and antiparkinsonian medication (Meds) have proved to be effective therapies for treating bradykinesia in Parkinson's disease. However, it is not currently known how or to what extent STN stimulation alters the control signals to agonist and antagonist muscles to change movement speed. Our objective was to investigate movement speed along with the amplitude and temporal features of EMG activity to determine how and to what extent these parameters are changed by DBS and medication. Nine patients with Parkinson's disease were studied following neurosurgery that implanted high-frequency stimulating electrodes in the STN. The experiments for the patients were performed in each of four treatment conditions: (i) OFF treatment; (ii) STN DBS; (iii) Meds; and (iv) Meds plus STN DBS. Also, a group of age- and gender-matched control subjects were examined. Medication and DBS had similar effects in that both treatments increased movement speed, increased the amplitude of the first agonist burst, increased burst duration, reduced the number of agonist bursts, reduced cocontraction, increased the size of the antagonist EMG, and reduced the centroid time of the antagonist EMG. When DBS and medication were combined, only temporal measures of burst duration and the number of agonist bursts were different from the medication alone condition. There was a positive association between the level of bradykinesia OFF treatment and the level of bradykinesia following DBS and medication. The movement speed of neurologically normal control subjects' was over 40% higher during both flexion and extension movements when compared with the patients during Meds plus STN DBS. The changes in the muscle activation patterns provide a mechanism of action for the pharmacological and surgical interventions used to treat bradykinesia in Parkinson's disease. However, despite the success of medication and DBS at improving bradykinesia in patients with Parkinson's disease, patients' movement speed was not restored to normal due to limitations in the amplitude and temporal scaling of the agonist and antagonist bursting pattern. These findings suggest a link between basal ganglia function in scaling both the amplitude and temporal parameters of the input to the motor neuron pool.

Background Essential tremor (ET), characterized primarily by postural and kinetic tremor, is typically measured in the clinic with subjective tremor rating scales. These ratings are often used to adjust medications and assess efficacy in clinical trials. However, tremor ratings require the presence of a clinician and do not necessarily capture tremor fluctuations throughout the day during activities of daily living (ADL). Objective To evaluate the ability of motion sensors to discriminate tremor from voluntary posture and motion, classify tremor as postural or kinetic, and rate tremor severity during standardized tasks and non-standardized activities of daily living. Methods Ten subjects with ET wore motion sensors on the index finger and performed standardized motor tasks from the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) tremor rating scale (wTRS) and non-standardized ADL tasks. Four movement disorder specialists independently rated video segments of the standardized tasks but not the ADL tasks. Quantitative features were extracted from the motion sensors and used to develop mathematical models for predicting rating scores from kinematic data. Results The quantitative motion features were highly correlated with wTRS ratings for postural (r=0.90) and kinetic (r=0.80) tremors. Mathematical models produced tremor ratings that correlated strongly with clinician ratings of the wTRS tasks (mean r=0.80) and also produced ADL task ratings that correlated well with the most recent clinician wTRS ratings (mean r=0.72). Conclusions Recordings from motion sensors can be used to classify tremor as postural or kinetic and quantify tremor severity during both standardized and non-standardized activities.

To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify non-invasive measures of basal ganglia function that are sensitive to disease severity. This study examines the relation between blood oxygenation level dependent (BOLD) activation in every nucleus of the basal ganglia and symptom-specific disease severity in early stage, de novo PD. BOLD activation measured at 3 Tesla was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the basal ganglia nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified Parkinson's Disease Rating Scale (UPDRS) and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the basal ganglia and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the basal ganglia relates most consistently to bradykinesia. The findings demonstrate that functional magnetic resonance imaging has strong potential to serve as a non-invasive marker for the state of basal ganglia function in de novo PD.

Summary Diffusion tensor imaging could be useful in characterizing movement disorders because it non-invasively examines multiple brain regions simultaneously. We report a multi-target imaging approach focused on the basal ganglia and cerebellum in Parkinson’s disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, essential tremor, and healthy controls. Seventy-two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristics analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control vs. movement disorder (92% sensitivity, 88% specificity), control vs. parkinsonism (93% sensitivity, 91% specificity), Parkinson’s disease vs. atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson’s disease vs. multiple system atrophy (94% sensitivity, 100% specificity), Parkinson’s disease vs. progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy vs. progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson’s disease vs. essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinson’s disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects.

The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force.

Background The progressive resistance exercise (PRE) in Parkinson’s disease trial (PRET-PD) showed that PRE improved the motor signs of PD compared to a modified Fitness Counts (mFC) program. It is unclear how long-term exercise affects physical function in these individuals. Objective To examine the effects of long-term PRE and mFC on physical function outcome measures in individuals with PD. Methods A preplanned secondary analysis was conducted using data from the 38 patients with idiopathic PD who completed the PRET-PD trial. Participants were randomized into PRE or mFC groups and exercised 2 days/week up to 24 months. Blinded assessors obtained functional outcomes on and off medication at baseline, 6 and 24 months with the Modified Physical Performance Test (mPPT), five times sit to stand test (STS), Functional Reach Test (FRT), Timed Up and Go (TUG), Berg Balance Scale (BBS), 6 minute walk test (6MWT), and 50ft walking speed (walk speed). Results The groups did not differ on any physical function measure at 6 or 24 months (p’s > 0.1). Across time, all physical function measures improved from baseline to 24 months when tested on medication (p’s < .0001), except for 6MWT(p = .068). Off medication results were similar except that the 6MWT was now significant. Conclusions 24 months of supervised and structured exercise (either PRE or mFC) is effective at improving functional performance outcomes in individuals with moderate PD. Clinicians should strive to include structured and supervised exercise in the long-term plan of care for individuals with PD.