OBJECTIVE:Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of this study is to assess the performances of a new eight channel steering-DBS lead and compare this with a conventional cylindrical contact (CC) lead.APPROACH:The two leads were evaluated in a finite element electric field model combined with multicompartment neuron and axon models, representing the internal capsule (IC) fibers and subthalamic nucleus (STN) cells. We defined the optimal stimulation setting as the configuration that activated the highest percentage of STN cells, without activating any IC fibers. With this criterion, we compared monopolar stimulation using a single contact of the steering-DBS lead and CC lead, on three locations and four orientations of the lead. In addition, we performed a current steering test case by dividing the current over two contacts with the steering-DBS lead in its worst-case orientation.MAIN RESULTS:In most cases, the steering-DBS lead is able to stimulate a significantly higher percentage of STN cells compared to the CC lead using single contact stimulation or using a two contact current steering protocol when there is approximately a 1 mm displacement of the CC lead. The results also show that correct placement and orientation of the lead in the target remains an important aspect in achieving the optimal stimulation outcome.SIGNIFICANCE:Currently, clinical trials are set up in Europe with a similar design as the steering-DBS lead. Our results illustrate the importance of the orientation of the new steering-DBS lead in avoiding side effects induced by stimulation of IC fibers. Therefore, in clinical trials sufficient attention should be paid to implanting the steering DBS-lead in the most effective orientation.

This proof-of-principle study describes the methodology and explores and demonstrates the applicability of a system, existing of miniature inertial sensors on the hand and a separate force sensor, to objectively quantify hand motor symptoms in patients with Parkinson’s disease (PD) in a clinical setting (off- and on-medication condition). Four PD patients were measured in off- and on- dopaminergic medication condition. Finger tapping, rapid hand opening/closing, hand pro/supination, tremor during rest, mental task and kinetic task, and wrist rigidity movements were measured with the system (called the PowerGlove). To demonstrate applicability, various outcome parameters of measured hand motor symptoms of the patients in off- vs. on-medication condition are presented. The methodology described and results presented show applicability of the PowerGlove in a clinical research setting, to objectively quantify hand bradykinesia, tremor and rigidity in PD patients, using a single system. The PowerGlove measured a difference in off- vs. on-medication condition in all tasks in the presented patients with most of its outcome parameters. Further study into the validity and reliability of the outcome parameters is required in a larger cohort of patients, to arrive at an optimal set of parameters that can assist in clinical evaluation and decision-making.

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.

Objective. The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STNDBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of freedom in shaping the stimulating electric field. The objective of this study is to compare the performances of a new HD lead with a conventional cylindrical contact (CC) lead. Approach. A computational model, consisting of a finite element electric field model combined with multi-compartment neuron and axon models representing different neural populations in the subthalamic region, was used to evaluate the two leads. We compared ringmode and steering-mode stimulation with the HD lead to single contact stimulation with the CC lead. These stimulation modes were tested for the lead: (1) positioned in the centroid of the STN, (2) shifted 1 mm towards the internal capsule (IC), and (3) shifted 2 mm towards the IC. Under these conditions, we quantified the number of STN neurons that were activated without activating IC fibers, which are known to cause side-effects. Main results. The modeling results show that the HD lead is able to mimic the stimulation effect of the CC lead. Additionally, in steering-mode stimulation there was a significant increase of activated STN neurons compared to the CC mode. Significance. From the model simulations we conclude that the HD lead in steering-mode with optimized stimulation parameter selection can stimulate more STN cells. Next, the clinical impact of the increased number of activated STN cells should be tested and balanced across the increased complexity of identifying the optimized stimulation parameter settings for the HD lead.

Hand motor control is quite complex and measurement of hand kinematics is therefore of high interest in many fields. A new measurement system based on miniature inertial and magnetic sensors, the PowerGlove, has been developed. In the near future, the PowerGlove will be applied to study finger interdependency in healthy elderly and to objectively quantify hand motor symptoms in Parkinson's disease. To validate and test the feasibility of the PowerGlove for future application Validation experiments with an optoelectronic marker system and pilot experiments in young healthy subjects were performed, specifically focused on measurement of metacarpophalangeal joint flexion/extension (MCP), proximal interphalangeal joint flexion (PIP) and finger tapping. Mean root mean square (RMS) difference between the optoelectronic marker system and the PowerGlove was less than 5 degrees. The results from the pilot experiments showed the feasibility of the PowerGlove to quantify each finger and joint movement in different movement tasks that are of interest for application in aged subjects and Parkinson disease patients.

Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) is widely used in advanced stages of Parkinson's disease(PD) and has proven to be an effective treatment of the various motor symptoms. The therapy involves implanting a lead consisting of multiple electrodes in the STN through which continues high frequency electric pulses are delivered. The clinical outcome highly depends on the location of the electrodes within the STN. However, despite careful planning

Parkinson's disease (PD) is neurodegenerative movement disorder and a treatment method called deep brain stimulation (DBS) may considerably reduce the patient’s motor symptoms. The clinical procedure involves the implantation of a DBS lead, consisting of multiple electrode contacts, through which continuous high frequency (around 130 Hz) electric pulses are delivered in the brain. In this thesis, I presented the research which had the goal to improve current DBS technology, focusing on bringing the conventional DBS system a step closer to adaptive DBS, a personalized DBS therapy. The chapters in this thesis can be seen as individual building blocks for such an adaptive DBS system. After the general introduction, the first two chapters, two novel DBS lead designs are studied in a computational model. The model showed that both studied leads were able to exploit the novel distribution of the electrode contacts to shape and steer the stimulation field to activate more neurons in the chosen target compared to the conventional lead, and to counteract lead displacement. In the fourth chapter, an inverse current source density (CSD) method is applied on local field potentials (LFP) measured in a rat model. The pattern of CSD sources can act as a landmark within the STN to locate the potential stimulation target. The fifth and final chapter described the last building block of the DBS system. We introduced an inertial sensors and force sensor based measurement system, which can record hand kinematics and joint stiffness of PD patients. A system which can act as a feedback signal in an adaptive DBS system.