Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep Brain Stimulation Lead.

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.

Quantification of Hand Motor Symptoms in Parkinson's Disease: A Proof-of-Principle Study Using Inertial and Force Sensors.

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.

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.

A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region.

OBJECTIVE: The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) 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 ring-mode 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.