Attenuation of neural responses in subthalamic nucleus during internally guided voluntary movements in Parkinson's disease.

The proposed models of segregated functional loops describe the organization of motor control over externally triggered (ET) and internally guided (IG) movements. The dopamine deficiency in Parkinson's disease (PD) is considered to cause a disturbance in the functional loop regulating IG movements. At the same time, the neural mechanisms of movement performance and the role of basal ganglia in motor control remain unclear.The aim of this study was to compare neuronal responses in the subthalamic nucleus (STN) during ET and IG movements in PD. We found and analyzed 26 sensitive neurons in 12 PD patients who underwent surgery for implantation of electrodes for deep brain stimulation. We also analyzed the local field potentials (LFP) of the STN of six patients during the postoperative period. Patients were asked to perform voluntary movements (clenching and unclenching the fist) evoked by verbal command (ET) or self-initiated (IG). We showed heterogeneity of neuronal responses and did not find sensitive neurons associated with only one type of movement. Most cells were characterized by leading responses, indicating that the STN has an important role in movement initiation. At the same time, we found attenuation of motor responses during IG movement vs. stable responses during ET movements. LFP analysis also showed attenuation of beta desynchronization during multiple IG movements.We propose that stable neuronal response to ET movements is associated with the reboot of the motor program for each movement, while attenuation of responses to IG movement is associated with single motor program launching for multiple movements.

Oscillations of pause-burst neurons in the STN correlate with the severity of motor signs in Parkinson's disease.

BACKGROUND: Oscillatory activity in the subthalamic nucleus (STN) in Parkinson's disease (PD) is under extensive study. While rhythmic features of local field potentials are implicated in the manifestation of PD motor signs, less is known about single unit activity (SUA). SUA parameters inside the STN show significant heterogeneity, and various firing patterns may contribute unequally to PD pathophysiology. OBJECTIVES: We searched for correlations between SUA parameters and PD motor signs, taking neuronal activity patterns into account. METHODS: 829 spike trains for STN SUA were recorded during 25 DBS surgeries. We have isolated three firing patterns (tonic, irregular-burst and pause-burst) and, using mixed linear models, examined several spiking parameters and burst descriptors (for the last two patterns) for their correlation with UPDRS-III PD motor signs in the contralateral hemibody. RESULTS: The predominance of pause-burst as opposed to tonic activity was associated with a higher PD motor sign severity UPDRS-III. Spike synchronization in the alpha and beta range correlated positively with bradykinesia scores only for pause-burst neurons, while spike synchrony in the theta frequency (4-8 Hz) in these neurons showed an inverse correlation with bradykinesia scores. Other patterns showed no correlation with PD motor signs. CONCLUSIONS: Our work demonstrates the PD motor state is associated with distinct changes in firing patterns and oscillatory synchronization that can be associated with PD motor sign severity. Here, pause-burst patterns were identified as most informative, potentially reflecting a progressive shift from tonic to burst to rhythmic activity in the alpha and beta frequency bands in the parkinsonian state.

Hyperactivity of Basal Ganglia in Patients With Parkinson's Disease During Internally Guided Voluntary Movements.

The contribution of different brain areas to internally guided (IG) and externally triggered (ET) movements has been a topic of debate. It has been hypothesized that IG movements are performed mainly through the basal ganglia-thalamocortical loop while ET movements are through the cerebello-thalamocortical pathway. We hypothesized that basal ganglia activity would be modified in patients with Parkinson's disease during IG movement as compared with normal subjects. We used functional MRI (fMRI) to investigate the differences between IG and ET motor tasks. Twenty healthy participants and 20 Parkinson's disease patients (OFF-state) were asked to perform hand movements in response to sound stimuli (ET) and in advance of the stimuli (IG). We showed that ET movements evoked activation of a few large clusters in the contralateral motor areas: the sensorimotor and premotor cortex, supplementary motor area (SMA), insula, putamen, motor thalamus and ipsilateral cerebellum. IG movements additionally evoked activation of a large number of small clusters distributed in different brain areas including the parietal and frontal lobes. Comparison between the activity of Parkinson's disease patients and healthy volunteers showed few important differences. We observed that along with the activity of the posterior areas, an activation of the anterior areas of putamen was observed during IG movements. We also found hyperactivity of the ventral thalamus for both movements. These results showed that IG movements in PD patients were made with the involvement of both sensorimotor and associative basal ganglia-thalamocortical loops.