Showing papers by "Warren M. Grill published in 2009"

Implanted Neural Interfaces: Biochallenges and Engineered Solutions

Abstract: Neural interfaces are connections that enable two-way exchange of information with the nervous system. These connections can occur at multiple levels, including with peripheral nerves, with the spinal cord, or with the brain; in many instances, fundamental biophysical and biological challenges are shared across these levels. We review these challenges, including selectivity, stability, resolution versus invasiveness, implant-induced injury, and the host-interface response. Subsequently, we review the engineered solutions to these challenges, including electrode designs and geometry, stimulation waveforms, materials, and surface modifications. Finally, we consider emerging opportunities to improve neural interfaces, including cellular-level silicon to neuron connections, optical stimulation, and approaches to control inflammation. Overcoming the biophysical and biological challenges will enable effective high-density neural interfaces for stimulation and recording.

Impedance characteristics of deep brain stimulation electrodes in vitro and in vivo

Abstract: The objective of this study was to quantify the electrode-tissue interface impedance of electrodes used for deep brain stimulation (DBS). We measured the impedance of DBS electrodes using electrochemical impedance spectroscopy in vitro in a carbonate- and phosphate-buffered saline solution and in vivo following acute implantation in the brain. The components of the impedance, including the series resistance (R(s)), the Faradaic resistance (R(f)) and the double layer capacitance (C(dl)), were estimated using an equivalent electrical circuit. Both R(f) and C(dl) decreased as the sinusoidal frequency was increased, but the ratio of the capacitive charge transfer to the Faradaic charge transfer was relatively insensitive to the change of frequency. R(f) decreased and C(dl) increased as the current density was increased, and above a critical current density the interface impedance became nonlinear. Thus, the magnitude of the interface impedance was strongly dependent on the intensity (pulse amplitude and duration) of stimulation. The temporal dependence and spatial non-uniformity of R(f) and C(dl) suggested that a distributed network, with each element of the network having dynamics tailored to a specific stimulus waveform, is required to describe adequately the impedance of the DBS electrode-tissue interface. Voltage transients to biphasic square current pulses were measured and suggested that the electrode-tissue interface did not operate in a linear range at clinically relevant current amplitudes, and that the assumption of the DBS electrode being ideally polarizable was not valid under clinical stimulating conditions.

Conditional and continuous electrical stimulation increase cystometric capacity in persons with spinal cord injury.

Abstract: Aims Individuals with spinal cord injury (SCI) exhibit neurogenic detrusor overactivity (NDO) causing high intravesicle pressures and incontinence. The first aim was to measure changes in maximum cystometric capacity (MCC) evoked by electrical stimulation of the dorsal genital nerve (DGN) delivered either continuously or conditionally (only during bladder contractions) in persons with SCI. The second aim was to use the external anal sphincter electromyogram (EMGEAS) for real-time control of conditional stimulation. Methods Serial filling cystometries were performed in nine volunteers with complete or incomplete supra-sacral SCI. Conditional stimulation was delivered automatically when detrusor pressure increased to 8–12 cmH2O above baseline. MCCs were measured for each treatment (continuous, conditional, and no stimulation) and compared using post-ANOVA Tukey HSD paired comparisons. Additional treatments in two subjects used the EMGEAS for automatic control of conditional stimulation. Results Continuous and conditional stimulation increased MCC by 63 ± 73 ml (36 ± 24%) and 74 ± 71 ml (51 ± 37%), respectively (P < 0.05), compared to no stimulation. There was no significant difference between MCCs for conditional and continuous stimulation, but conditional stimulation significantly reduced stimulation time (174 ± 154 sec, or 27 ± 17% of total time) as compared to continuous stimulation (469 ± 269 sec, 100% of total time, P < 0.001). The EMGEAS algorithm provided reliable detection of bladder contractions (six of six contractions over four trials) and reduced stimulation time (21 ± 8% of total time). Conclusions Conditional stimulation generates increases in bladder capacity while substantially reducing stimulation time. Furthermore, EMGEAS was successfully used as a real-time feedback signal to control conditional electrical stimulation in a laboratory setting. Neurourol. Urodynam. 29:401–407, 2010. © 2009 Wiley-Liss, Inc.

Non-regular electrical stimulation patterns for treating neurological disorders

Abstract: Systems and methods for stimulation of neurological tissue generate stimulation trains with temporal patterns of stimulation, in which the interval between electrical pulses (the inter-pulse intervals) changes or varies over time. Compared to conventional continuous, high rate pulse trains having regular (i.e., constant) inter-pulse intervals, the non-regular (i.e., not constant) pulse patterns or trains that embody features of the invention provide a lower average frequency.

Analysis of high-perimeter planar electrodes for efficient neural stimulation.

Abstract: Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to 2, 3 or 4 times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input-output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries.

Principles of Electric Field Generation for Stimulation of the Central Nervous System

Abstract: Publisher Summary This chapter focuses on the various principles of electric field generation for stimulation of the central nervous system (CNS). Electrical stimulation is used to study the form and function of the nervous system and is a technique to restore function following disease or injury. Applications of electrical stimulation for restoration of function include generation, inhibition, and modulation of brain activity. The electrical properties of the central nervous system are inhomogeneous, meaning that they vary at different positions within the tissue because the neuronal and glial elements have wide-ranging dimensions, varying orientations, and different packing densities. The electrical properties of the central nervous system are anisotropic, meaning that they vary along different directions through the tissue because of the nonrandom orientation of neural elements. In particular, the white matter has anisotropic conductivity as current can travel more easily in the direction parallel to the axons than in the direction transverse or perpendicular to the axons. The extracellular potentials are also dependent on the electrical properties of the tissue. The electrical conductivity of the tissue also varies with position within the CNS. The voltages generated in the central nervous system by applied currents can be calculated using quantitative approaches, and the results can be used to interpret the observed effects of stimulation and to design electrodes and stimuli appropriate for the intended application.

Deep brain stimulation that abolishes parkinsonian activity in basal ganglia improves thalamic relay fidelity in a computational circuit

Abstract: Deep brain stimulation (DBS) of the subthalamic nucleus reduces the severity of parkinsonian motor symptoms, but the therapeutic mechanisms are not understood. We hypothesize that clinically effective high frequency DBS suppresses disordered neuronal activity in the globus pallidus internus (GPi), a primary output structure of the basal ganglia. In a computational model of the basal ganglia thalamic circuit, periodic high frequency (>100Hz) stimulation of the subthalamic nucleus reduced the incidence of thalamic cell errors, from the high error rates seen in the parkinsonian case back to the low error rates seen in the normal-healthy case. In contrast, both low frequency (<70Hz) DBS and high frequency aperiodic DBS failed to alleviate thalamic errors. In high error rate conditions, disordered patterns of GPi activity lead to irregular synaptic inhibition of thalamus. In low error rate conditions, ordered patterns of GPi activity lead to regular synaptic inhibition of thalamus. Linear regression revealed that the variance of the GPi synaptic output accounted for 87-97% of the changes in thalamic error rate. In contrast, the average GPi synaptic output – a measure of total GPi activity – accounted for only 25-50% of the changes in thalamic error rate. Thus, while the firing rate of GPi cells may play some minor role, regularizing the pathological patterns of GPi activity is the mechanism by which DBS treats parkinsonian motor symptoms.

High efficiency electrodes for deep brain stimulation

Abstract: Deep brain stimulators are powered with primary cell batteries and require surgical replacement when they are depleted. We sought to decrease power consumption, and thereby increase device lifetime by increasing neuronal stimulating efficiency with novel electrode designs. Our hypothesis was that high-perimeter electrodes that increase the variation of current density on their surface would generate larger activating functions for surrounding neurons, hence increasing stimulation efficiency. We implemented finite element models of cylindrical DBS electrodes with conventional circular perimeters, with serpentine perimeters, and with segmented contacts. The high-perimeter electrodes significantly increased the variation of current density on the electrode surface. We randomly positioned a population of 100 model axons around the electrodes and quantified neural activation with 100 µs cathodic stimuli. Input-output curves of percentage axons activated as a function of stimulation intensity indicated that the novel electrode geometries decreased power consumption by up to ~20% for axons parallel to the electrode and up to ~35% for axons perpendicular to the electrode. Reduced power consumption achieved with these designs will reduce the costs and risks associated with surgeries to replace depleted stimulators.

Measurement of the current?distance relationship using a novel refractory interaction technique

Abstract: It is important to know the spatial extent of neural activation around the stimulating electrodes when using extracellular electrical stimulation for the determination of the structure and function of neural circuit connections or for the restoration of function. The current-distance relationship quantifies the relationship between the threshold current for excitation of a neuron, I(th), and the distance between the electrode and the neuron, r, with two parameters: the offset, I(0), and the current-distance constant, k, with a quadratic equation, I(th)(r) = I(0) + kr(2). We proposed a new method to determine the parameters of the current-distance relationship, and thereby estimate the spatial extent of activation, based on the refractory interaction technique. Refractory interaction is a method that exploits the interaction between the regions of activation produced by two electrodes, when the second stimulus is delivered while neurons activated by the first electrode are in their refractory period. Computer simulations of electrical stimulation of a population of nerve fibers were used to determine the accuracy of the method. The mean relative error in k was 19% and in I(0) was 17%, and the spatial extent of stimulation could be determined with an absolute error of 19 microm and a relative error less than 11%. Subsequently, the method was applied to measure the current-distance properties of peripheral motor nerve fibers and indicated that k = 27 microA mm(-2) and I(0) = 49 microA. This method provided robust estimates of the current-distance properties, and provides a means to determine the spatial extent of activation by extracellular stimulation.

Hindlimb Endpoint Forces Predict Movement Direction Evoked by Intraspinal Microstimulation in Cats

Abstract: We measured the forces produced at the cat's hindpaw by microstimulation of the lumbar spinal cord and the movements resulting from those forces. We also measured the forces and movements produced by co- and sequential activation of two intraspinal sites. Isometric force responses were measured at nine limb configurations with the paw attached to a force transducer. The active forces elicited at different limb configurations were summarized as patterns representing the sagittal plane component of the forces produced at the paw throughout the workspace. The force patterns divided into the same distinct types found with the femur fixed. The responses during simultaneous activation of two spinal sites always resembled the response for activation of one of the two sites, i.e., winner-take-all, and we did not observe vectorial summation of the forces produced by activation of each site individually as reported in chronic spinal animals. The movements produced by activation of each of the sites were consistent with the force orientations, and different movements could be created by varying the sequence of activation of individual sites. Our results highlight the absence of a vectorial summation phenomenon during intraspinal microstimulation in decerebrate animals, and the preservation during movement of the orientation of isometric forces.

Electrical stimulation for control of bladder function

Abstract: Electrical stimulation of sensory fibers in the pudendal nerve can generate either inhibition or activation of the bladder, and this is a promising approach to restoration of continence and micturition in neurological disease or injury. We review studies of pudendal afferent stimulation to excite the bladder and enhance bladder emptying in urinary retention or restore bladder emptying following spinal cord injury.

Intraurethral activation of excitatory bladder reflexes in persons with spinal cord injury

Abstract: Electrical activation of an excitatory reflex between sensory fibers in the pudendal nerve and the bladder has been demonstrated in cats and is a potential means of restoring micturition function in persons with spinal cord injury. We investigated the clinical feasibility of activating this reflex to restore bladder function in persons with spinal cord injury by using intraurethral electrical stimulation to activate pudendal sensory fibers innervating the urethra. Excitatory bladder responses (contractions) were evoked by trains of electrical pulses applied to either the proximal (29.7 ± 11.6 cmH 2 O) or distal (30.2 ± 11.6 cmH 2 O) segment of the urethra. The results indicate that an excitatory reflex between pudendal nerve afferents and the bladder exists in humans with spinal injury and may provide a substrate for restoring micturition function.

Genetic Algorithm Reveals Energy-Efficient Waveforms for Neural Stimulation

Abstract: Energy consumption is an important consideration for battery-powered implantable stimulators. We used a genetic algorithm (GA) that mimics biological evolution to determine the energy-optimal waveform shape for neural stimulation. The GA was coupled to NEURON using a model of extracellular stimulation of a mammalian myelinated axon. Stimulation waveforms represented the organisms of a population, and each waveform's shape was encoded into genes. The fitness of each waveform was based on its energy efficiency and ability to elicit an action potential. After each generation of the GA, waveforms mated to produce offspring waveforms, and a new population was formed consisting of the offspring and the fittest waveforms of the previous generation. Over the course of the GA, waveforms became increasingly energy-efficient and converged upon a highly energy-efficient shape. The resulting waveforms resembled truncated normal curves or sinusoids and were 3–74% more energy-efficient than several waveform shapes commonly used in neural stimulation. If implemented in implantable neural stimulators, the GA optimized waveforms could prolong battery life, thereby reducing the costs and risks of battery-replacement surgery.

Effect of Electrode Geometry on Deep Brain Stimulation: Monopolar Point Source vs. Medtronic 3389 Lead

Abstract: Deep brain stimulation (DBS) has emerged as an effective treatment for a variety of neurological and movement disorders; however, the fundamental mechanisms by which DBS works are not well understood. Computational models of DBS can be used to gain insights into these fundamental mechanisms and typically require two steps: computation of the electrical potentials generated by DBS and, subsequently, determination of the effects of the extracellular potentials on neurons. The objective of this study was to assess the validity of utilizing the point source approximation versus realistic finite element models (FEMs) in calculating the potentials generated by monopolar DBS. The distributions of extracellular potentials generated in a homogenous isotropic volume conductor were calculated using either the point source approximation or a realistic finite element model of the DBS lead. These extracellular potentials were then coupled to populations of simulated axons, and input-output curves of the number of stimulated axons as a function of stimulation intensity were calculated for different stimulus polarities, pulse durations, and axon orientations (parallel or perpendicular to the electrode). The differences in input-output curves calculated with the point source and FEM were small; FEM-predicted thresholds were on average 4.83% lower than point source predicted thresholds across all the conditions tested. The distance from and location relative to the electrode was the primary factor determining the error between point source and FEM geometries, and larger differences in predicted thresholds were evident in axons located immediately adjacent to the realistic electrode. Thus, under the conditions tested, the point source was a valid approximation for predicting population excitation in response to monopolar DBS. The results of this study reveal new insights that may aid in future computational modeling studies of DBS.

Computer-based Finite Element Modeling of Insulated Tuohy Needles Used in Regional Anesthesia

Abstract: Background: Differences in needle design may impact nerve localization. This study evaluates the electrical properties of two insulated Tuohy needles using computational finite element modeling. Methods: Three-dimensional geometric computer-based models were created representing two 18-gauge, insulated Tuohy needles: (1) with an exposed metal tip and (2) with an insulated tip. The models were projected in simulated human tissue. Using finite element methodology, distributions of current-density were calculated. Voltages in the modeled medium were calculated, and activation patterns of a model nerve fiber around the tip of each needle were estimated using the activating function. Results: Maximum current density on the exposed-tip needle occurred along the edge of the distal tip; the distal edge was 1.7 times larger than the side edges and 3.5 times larger than the proximal edge. Conversely, maximum current density occurred along the proximal edge of the insulated-tip Tuohy opening; the proximal edge was 1.9 times larger than the side edges of the opening and 3.5 times larger than the distal edge of the open- ing. Voltages generated by the exposed-tip needle were larger and had a wider spatial distribution than that of the insulated-tip needle, which restricted to the area immediately adjacent to the opening. Different changes in threshold were predicted to excite a nerve fiber as the needles were rotated or advanced toward the modeled nerve. Conclusions: The needles displayed different asymmetric distributions of current density and positional effects on threshold. If this analysis is validated clinically, it may prove useful in testing stimulating needles before clinical application.