Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function

Directional Local Field Potentials in the Subthalamic Nucleus During Deep Brain Implantation of Parkinson’s Disease Patients

Segmented deep brain stimulation leads feature directional electrodes that allow for a finer spatial control of electrical stimulation compared to traditional ring-shaped electrodes. These segmented leads have demonstrated enlarged therapeutic windows and have thus the potential to improve the treatment of Parkinson's disease patients. Moreover, they provide a unique opportunity to record directional local field potentials. Here, we investigated whether directional local field potentials can help identify the best stimulation direction to assist device programming. Four Parkinson's disease patients underwent routine implantation of the subthalamic nucleus. Firstly, local field potentials were recorded in three directions for two conditions: In one condition, the patient was at rest; in the other condition, the patient's arm was moved. Secondly, current thresholds for therapeutic and side effects were identified intraoperatively for directional stimulation. Therapeutic windows were calculated from these two thresholds. Thirdly, the spectral power of the total beta band (13-35 Hz) and its sub-bands low, high, and peak beta were analyzed post hoc. Fourthly, the spectral power was used by different algorithms to predict the ranking of directions. The spectral power profiles were patient-specific, and spectral peaks were found both in the low beta band (13-20 Hz) and in the high beta band (20.5-35 Hz). The direction with the highest spectral power in the total beta band was most indicative of the 1st best direction when defined by therapeutic window. Based on the total beta band, the resting condition and the moving condition were similarly predictive about the direction ranking and classified 83.3% of directions correctly. However, different algorithms were needed to predict the ranking defined by therapeutic window or therapeutic current threshold. Directional local field potentials may help predict the best stimulation direction. Further studies with larger sample sizes are needed to better distinguish the informative value of different conditions and the beta sub-bands. Keywords: Parkinson’s disease; deep brain stimulation; local field potentials; segmented leads; subthalamic nucleus

Analysis of patient-specific stimulation with segmented leads in the subthalamic nucleus

Objective Segmented deep brain stimulation leads in the subthalamic nucleus have shown to increase therapeutic window using directional stimulation. However, it is not fully understood how these segmented leads with reduced electrode size modify the volume of tissue activated (VTA) and how this in turn relates with clinically observed therapeutic and side effect cur- rents. Here, we investigated the differences between directional and omnidirectional stimu- lation and associated VTAs with patient-specific therapeutic and side effect currents for the two stimulation modes. Approach Nine patients with Parkinson’s disease underwent DBS implantation in the subthalamic nucleus. Therapeutic and side effect currents were identified intraoperatively with a seg- mented lead using directional and omnidirectional stimulation (these current thresholds were assessed in a blinded fashion). The electric field around the lead was simulated with a finite-element model for a range of stimulation currents for both stimulation modes. VTAs were estimated from the electric field by numerical differentiation and thresholding. Then for each patient, the VTAs for given therapeutic and side effect currents were projected onto the patient-specific subthalamic nucleus and lead position. Results Stimulation with segmented leads with reduced electrode size was associated with a signifi- cant reduction of VTA and a significant increase of radial distance in the best direction of stimulation. While beneficial effects were associated with activation volumes confined within the anatomical boundaries of the subthalamic nucleus at therapeutic currents, side effects were associated with activation volumes spreading beyond the nucleus’ boundaries. Significance The clinical benefits of segmented leads are likely to be obtained by a VTA confined within the subthalamic nucleus and a larger radial distance in the best stimulation direction, while steering the VTA away from unwanted fiber tracts outside the nucleus. Applying the same concepts at a larger scale and in chronically implanted patients may help to predict the best stimulation area

Controlled Release Drug Coatings on Flexible Neural Probes

We present the development, characterization and in vivo validation of a novel drug eluting coating that has been applied to flexible neural probes. The coating consists of drug eluting nanoparticles loaded with an anti-inflammatory drug embedded in a biodegradable polymer. The drug eluting coating is applied to flexible polymer neural probes with platinum electrodes. The drug eluting device is implanted in one hemisphere of a rat, while a control device is implanted in the opposite hemisphere. Impedance measurements are performed to determine the effect of the drug eluting coating on the tissue reaction surrounding the probe and the electrical characteristics of the devices. Probes that are coated with drug eluting coatings show better long term impedance characteristics over control probes. These coatings can be used to increase the reliability and long term success of neural prostheses

Demonstration of cortical recording using novel flexible polymer neural probes

We present the fabrication, characterization, use in cortical recording and histological results of a flexible implantable neural probe. The microfabricated device is implemented in polyimide and platinum providing mechanical flexibility, high quality electrical characteristics and excellent biocompatibility. Two layers of platinum electrodes are used which greatly reduces the size of the neural probes thereby limiting the insertion damage. The quality of the individual recording sites was characterized using impedance spectroscopy. In recording experiments, acute in vivo measurements were performed in the mouse cortex. Local field potential, single- and multi-neuron activities were simultaneously recorded. We demonstrate using immunohistochemistry techniques a study of the inflammation at the neural probe implantation site. We show that the major advantage of using polymer probes over silicon probes is the reduced damage due to insertion and probe-brain compliance mismatch