Ambulatory Monitoring of Activities and Motor Symptoms in Parkinson's Disease

Ambulatory monitoring of motor symptoms in Parkinson's disease (PD) can improve our therapeutic strategies, especially in patients with motor fluctuations. Previously published monitors usually assess only one or a few basic aspects of the cardinal motor symptoms in a laboratory setting. We developed a novel ambulatory monitoring system that provides a complete motor assessment by simultaneously analyzing current motor activity of the patient (e.g., sitting, walking, etc.) and the severity of many aspects related to tremor, bradykinesia, and hypokinesia. The monitor consists of a set of four inertial sensors. Validity of our monitor was established in seven healthy controls and six PD patients treated with deep brain stimulation (DBS) of the subthalamic nucleus. The patients were tested at three different levels of DBS treatment. Subjects were monitored while performing different tasks, including motor tests of the Unified PD Rating Scale (UPDRS). Output of the monitor was compared to simultaneously recorded videos. The monitor proved very accurate in discriminating between several motor activities. Monitor output correlated well with blinded UPDRS ratings during different DBS levels. The combined analysis of motor activity and symptom severity by our PD monitor brings true ambulatory monitoring of a wide variety of motor symptoms one step close

Ambulatory Monitoring of Activities and Motor Symptoms in Parkinson's Disease

Ambulatory monitoring of motor symptoms in Parkinson’s disease (PD) can improve our therapeutic strategies, especially in patients with motor fluctuations. Previously published monitors usually assess only one or a few basic aspects of the cardinal motor symptoms in a laboratory setting. We developed a novel ambulatory monitoring system that provides a complete motor assessment by simultaneously analyzing currentmotor activity of the patient (e.g., sitting, walking, etc.) and the severity of many aspects related to tremor, bradykinesia, and hypokinesia. The monitor consists of a set of four inertial sensors. Validity of our monitor was established in seven healthy controls and six PD patients treated with deep brain stimulation (DBS) of the subthalamic nucleus. The patients were tested at three different levels of DBS treatment. Subjects were monitored while performing different tasks, including motor tests of the Unified PD Rating Scale (UPDRS). Output of the monitor was compared to simultaneously recorded videos. The monitor proved very accurate in discriminating between several motor activities. Monitor output correlated well with blinded UPDRS ratings during different DBS levels. The combined analysis of motor activity and symptom severity by our PD monitor brings true ambulatory monitoring of a wide variety of motor symptoms one step closer

Motor cortex stimulation for Parkinson's disease: a modelling study

Chronic motor cortex stimulation (MCS) is currently being investigated as a treatment method for Parkinson's disease (PD). Unfortunately, the underlying mechanisms of this treatment are unclear and there are many uncertainties regarding the most effective stimulation parameters and electrode configuration. In this paper, we present a MCS model with a 3D representation of several axonal populations. The model predicts that the activation of either the basket cell or pyramidal tract (PT) type axons is involved in the clinical effect of MCS. We propose stimulation protocols selectively targeting one of these two axon types. To selectively target the basket cell axons, our simulations suggest using either cathodal or bipolar stimulation with the electrode strip placed perpendicular rather than parallel to the gyrus. Furthermore, selectivity can be increased by using multiple cathodes. PT type axons can be selectively targeted with anodal stimulation using electrodes with large contact sizes. Placing the electrode epidurally is advisable over subdural placement. These selective protocols, when practically implemented, can be used to further test which axon type should be activated for clinically effective MCS and can subsequently be applied to optimize treatment. In conclusion, this paper increases insight into the neuronal population involved in the clinical effect of MCS on PD and proposes strategies to improve this therapy

Subthalamic Neuronal Responses to Cortical Stimulation

Background:\ud Deep brain stimulation of the subthalamic nucleus alleviates motor symptoms in Parkinson’s disease patients. However, some patients suffer from cognitive and emotional changes. These side effects are most likely caused by current spread to the cognitive and limbic territories in the subthalamic nucleus. The aim of this study was to identify the motor part of the subthalamic nucleus to reduce stimulation-induced behavioral side effects, by using motor cortex stimulation.\ud \ud Methods:\ud We describe the results of subthalamic nucleus neuronal responses to stimulation of the hand area of the motor cortex and evaluate the safety of this novel technique.\ud \ud Results:\ud Responses differed between regions within the subthalamic nucleus. In the anterior and lateral electrode at dorsal levels of the subthalamic nucleus, an early excitation (~5–45 ms) and subsequent inhibition (45–105 ms) were seen. The lateral electrode also showed a late excitation (~125–160 ms). Focal seizures were observed following motor cortex stimulation.\ud \ud Conclusions:\ud To prevent seizures the current density should be lowered, so that motor cortex stimulationevoked responses can be safely used during deep brain stimulation surgery

Popular entomology and anthropomorphism in the nineteenth century: L.M. Budgen's episodes of insect life

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson's disease (PD) patients. However, in a substantial number of patients the beneficial effects of STN DBS are overshadowed by psychiatric side effects. We hypothesize that stimulation of the STN motor area will provide the optimal effect on the motor symptoms without inducing these side effects, and expect that motor cortex stimulation (MCS) evokes a spatially specific response within the STN, which identifies the STN motor area. We previously showed that MCS evokes responses in the unit activity specifically within certain areas of the STN. Unit activity is generally considered a measure of the output activity. To gain more insight into the neuronal input into the STN, we describe the results of cortically evoked subthalamic local field potentials (LFPs). We show that the cortically evoked LFPs follow a certain temporal and spatial pattern. The significant peaks of the evoked LFPs coincide with the timing of some of the inhibitions and excitations present in the unit responses. The spatial resolution of responses measured in the LFP to MCS is not high enough to identify the STN motor region. However, we believe that optimizing targeting techniques and the development of novel DBS electrodes will improve STN DBS therapy for PD patient

Spatial Localization of Sources in the Rat Subthalamic Motor Region Using an Inverse Current Source Density Method

Objective: In this study we introduce the use of the current source density (CSD) method as a way to visualize the spatial organization of evoked responses in the rat subthalamic nucleus (STN) at fixed time stamps resulting from motor cortex stimulation. This method offers opportunities to visualize neuronal input and study the relation between the synaptic input and the neural output of neural populations. Approach: Motor cortex evoked local field potentials and unit activity were measured in the subthalamic region, with a 3D measurement grid consisting of 320 measurement points and high spatial resolution. This allowed us to visualize the evoked synaptic input by estimating the current source density (CSD) from the measured local field potentials, using the inverse CSD method. At the same time, the neuronal output of the cells within the grid is assessed by calculating post stimulus time histograms. Main results: The CSD method resulted in clear and distinguishable sources and sinks of the neuronal input activity in the STN after motor cortex stimulation. We showed that the center of the synaptic input of the STN from the motor cortex is located dorsal to the input from globus pallidus. Significance: For the first time we have performed CSD analysis on motor cortex stimulation evoked LFP responses in the rat STN as a proof of principle. Our results suggest that the CSD method can be used to gain new insights into the spatial extent of synaptic pathways in brain structures

Advanced target identification in STN-DBS with beta power of combined local field potentials and spiking activity

Background:\ud In deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson’s Disease (PD), often microelectrode recordings (MER) are used for STN identification. However, for advanced target identification of the sensorimotor STN, it may be relevant to use local field potential (LFP) recordings. Then, it is important to assure that the measured oscillations are coming from the close proximity of the electrode.\ud New method:\ud Through multiple simultaneous recordings of LFP and neuronal spiking, we investigated the temporal relationship between local neuronal spiking and more global LFP. We analyzed the local oscillations in the LFP by calculating power only over specific frequencies that show a significant coherence between LFP and neuronal spiking. Using this ‘coherence method’, we investigated how well measurements in the sensorimotor STN could be discriminated from measurements elsewhere in the STN.\ud Results/comparison with existing methods:\ud The ‘sensorimotor power index’ (SMPI) of beta frequencies, representing the ability to discriminate sensorimotor STN measurements based on the beta power, was significantly larger using the ‘coherence method’ for LFP spectral analysis compared to other methods where either the complete LFP beta spectrum or only the prominent peaks in the LFP beta spectrum were used to calculate beta power.\ud Conclusions:\ud The results suggest that due to volume conduction of beta frequency oscillations, proper localization of the sensorimotor STN with only LFP recordings is difficult. However, combining recordings of LFP and neuronal spiking and calculating beta power over the coherent parts of the LFP spectrum can be beneficial in discriminating the sensorimotor STN