Biomedical subjects

Richard A Normann

Publications and source records attributed to Richard A Normann.

15 recordsLinked to original sources

PubMed2007

Electrode independence in intraneural cochlear nerve stimulation.

OBJECTIVES/HYPOTHESIS: We have previously reported feline electrophysiological and anatomical studies focused on the development of an intraneural auditory neuroprosthesis. Because only the tips of the electrodes implanted in the cochlear nerve are the stimulating elements that abut the nerve axons, we hypothesize that intraneural stimulation will be highly focal in nature. In this article, we report the electrophysiological characterization of the selective activation of subpopulations of cochlear nerve fibers via electrodes implanted in feline cochlear nerve. STUDY DESIGN: We have used a forward-masking paradigm to estimate the extent of stimulation overlap produced by pairs of electrodes implanted into the cochlear nerve. METHODS: The technique uses sequential stimulation via masking and probe electrodes and monitoring of the electrically evoked auditory brain stem response as an index of cochlear nerve fiber recruitment. We investigated overlap in all possible electrode pair combinations. RESULTS AND CONCLUSION: Many electrode pairs manifest virtually no overlap in the subpopulations of fibers excited by perithreshold stimuli, whereas most had considerable overlap at higher stimulation levels. However, we also noted that our measured overlap was similar across electrodes possibly because of lack of specificity of the whole nerve electrically evoked auditory brain stem response as an assay for this parameter. These findings indicate that direct cochlear nerve stimulation via intraneural electrodes provides selective excitation of small subpopulations of cochlear nerve fibers, and suggest that cochlear nerve stimulation may selectively evoke narrow-band frequency percepts.

Animals↗

PubMed2006

Acute microelectrode array implantation into human neocortex: preliminary technique and histological considerations.

OBJECT: Researchers at The Center for Neural Interfaces at the University of Utah have designed and produced a silicon-based high-density microelectrode array that has been used successfully in mammalian models. The authors investigate the ability to transfer array insertion techniques to humans and examine the acute response of human cortical tissue to array implantation. METHODS: Six patients who were scheduled to undergo temporal lobectomy surgery were enrolled in an Institutional Review Board-approved protocol. Before the patients underwent lateral temporal cortical resection, one or two high-density microelectrode arrays were implanted in each individual by using a pneumatic insertion device. Cortical tissue was then excised and preserved in formalin. The specimens were sectioned and stained for histological examination. Pneumatic insertion of a microelectrode array into human cortex in the operating room was feasible. There were no clinical complications associated with implantation and no evidence of significant insertion-related hemorrhage. Tissue responses ranged from mild cortical deformity to small focal hemorrhages several millimeters below the electrode tines. Based on initial results, the insertion device was modified. A footplate that mechanically isolates a small area of cortex and a calibrated micromanipulator were added to improve the reproducibility of insertion. CONCLUSIONS: A high-density microelectrode array designed to function as a direct cortical interface device can be implanted into human cortical tissue without acute clinical complications. Further modifications to the insertion device and array design are ongoing and future work will assess the functional significance of the tissue reactions observed.

Electrodes, Implanted↗

PubMed2006

Electrophysiological mapping of cat primary auditory cortex with multielectrode arrays.

The present study employs simultaneous multielectrode recording techniques to study the feline primary auditory cortex (AI) to characterize its functional architecture. High electrode-count microelectrode arrays provide a high spatial and temporal view of AI, but at the potential cost of significant cortical insult. However, the number of electrodes that record single- and multiunit action potentials shown in this study suggest that the implantation of high electrode-count microelectrode arrays allows for reliable recordings from the cortex and that the neurons abutting the electrode tips appear to be spared from significant insult. Using these recordings, we have constructed a functional model of AI that best specifies the distribution of characteristic frequencies (CF's), and have reaffirmed that CF is logarithmically distributed across the cortical surface with a principal CF axis perpendicular to generally straight isofrequency contours. In four cats, we found that the average CF gradient was 0.53 +/- 0.08 octave per millimeter. This study demonstrates the use of high electrode count, microelectrode array recordings in characterizing the spatial distribution of acoustic information in the feline AI.

Acoustic Stimulation↗

PubMed2006

Discrete stimulus estimation from neural responses in the turtle retina.

In this paper, we investigate the decoding of flashed, full-field visual stimuli while recording from a population of retinal ganglion cells. We present a direct statistical method for determining the likelihood that a response was evoked by a particular stimulus, and use this method to estimate stimuli based on microelectrode array recordings in the turtle retina. This method uses the well-known time-varying Poisson model of neural firing, along with extensions to accommodate neural refractory periods. Unlike other approaches commonly used for Poisson processes, the specific formulation presented here is bin free and requires few user-specified parameters. Statistical dependency issues and the effects of stationarity on the estimation method are also discussed.

Action Potentials↗

PubMed2005

Functional reorganization of primary visual cortex induced by electrical stimulation in the cat.

Compared to the high degree of plasticity observed in a juvenile, mature sensory cortices have long been held to be immutable but, recently, researchers have suggested some plasticity persists in the mature cortex. Cortical reorganization has particular saliency to the development of a cortically based, sensory neuroprosthesis, which will chronically evoke activity through electrical stimulation. We have examined the nature and extent of the reorganization induced by electrical stimulation. We found the receptive field size and synaptic efficacy can be increased, particularly for neurons near the stimulation site. As the changes are minimal, these results are not expected to impact neuroprosthetic applications.

Animals↗

PubMed2005

Statistical encoding model for a primary motor cortical brain-machine interface.

A number of studies of the motor system suggest that the majority of primary motor cortical neurons represent simple movement-related kinematic and dynamic quantities in their time-varying activity patterns. An example of such an encoding relationship is the cosine tuning of firing rate with respect to the direction of hand motion. We present a systematic development of statistical encoding models for movement-related motor neurons using multielectrode array recordings during a two-dimensional (2-D) continuous pursuit-tracking task. Our approach avoids massive averaging of responses by utilizing 2-D normalized occupancy plots, cascaded linear-nonlinear (LN) system models and a method for describing variability in discrete random systems. We found that the expected firing rate of most movement-related motor neurons is related to the kinematic values by a linear transformation, with a significant nonlinear distortion in about 1/3 of the neurons. The measured variability of the neural responses is markedly non-Poisson in many neurons and is well captured by a "normalized-Gaussian" statistical model that is defined and introduced here. The statistical model is seamlessly integrated into a nearly-optimal recursive method for decoding movement from neural responses based on a Sequential Monte Carlo filter.

Algorithms↗

PubMed2004

Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve.

We studied the consequences of long-term implantation of a penetrating microelectrode array in peripheral nerve over the time course of 4-6 mo. Electrode arrays without lead wires were implanted to test the ability of different containment systems to protect the array and nerve during contractions of surrounding muscles. Treadmill walking was monitored and the animals showed no functional deficits as a result of implantation. In a different set of experiments, electrodes with lead wires were implanted for up to 7 mo and the animals were tested at 2-4 week intervals at which time stimulation thresholds and recorded sensory activity were monitored for every electrode. It was shown that surgical technique highly affected the long-term stimulation results. Results between measurement sessions were compared, and in the best case, the stimulation properties stabilized in 80% of the electrodes over the course of the experiment (162 days). The recorded sensory signals, however, were not stable over time. A histological analysis performed on all implanted tissues indicated that the morphology and fiber density of the nerve around the electrodes were normal.

Action Potentials↗

PubMed2004

Interleaved, multisite electrical stimulation of cat sciatic nerve produces fatigue-resistant, ripple-free motor responses.

We studied the use of physiologically based, multisite, intrafascicular electrical stimulation of the sciatic nerve to achieve ripple-free contractions and sustained, fatigue-resistant forces over a physiological range of forces in cat gastrocnemius muscle. Electrode arrays containing 100, 0.5-1.5-mm-long penetrating microelectrodes were inserted into the sciatic nerves of cats, and forces generated by gastrocnemius muscles in response to stimulation of the nerves were monitored via a force transducer attached to the tendons. In single-electrode stimulation, responses evoked by low-frequency [15 pulses/second, (p/s)] stimulation exhibited greater fatigue resistance than did responses evoked by higher frequency stimulation (30 and 60 p/s), but showed far more ripple within each response. We compared interleaved 15 p/s stimulation of four electrodes (100 micros biphasic pulses, 750-ms pulse trains) that produced a net stimulation frequency of 60 p/s with multielectrode 60 p/s quasi-simultaneous stimulation protocols. Across a broad range of forces (10% to 80% of maximum), responses evoked by multielectrode 15 p/s interleaved stimulation exhibited substantially less fatigue than did responses evoked by 60 p/s quasi-simultaneous stimulation, and less ripple than responses evoked by single-electrode 15 p/s stimulation. The effectiveness of this physiologically based stimulation paradigm encourages its application in the field of motor neuroprosthetics.

Animals↗

PubMed2004

Spatiotemporal encoding of a bar's direction of motion by neural ensembles in cat primary visual cortex.

Directionally selective neurons strongly fire when presented with a preferred direction of motion of a bar and only weakly respond otherwise. Intuition suggests these "specialist" neurons would be better suited to report this stimulus feature to higher visual centers than "generalist" neurons, neurons that broadly modulate their activity to the feature. However, as stimuli are encoded not by one cell but by large neural ensembles, we have studied the role of single-cell receptive field properties in stimulus representation. Using regression error statistics, we compared the performance of direction-of-motion estimators, using ensembles of neurons selectively responding to direction of motion and estimators using ensembles not specializing to direction. We found that direction-selective ensembles were no better at representing a bar's direction of motion than nonselective ensembles. Quite the opposite, the nonselective unit ensembles provided a better estimate of the direction (standard deviation of the error of 33 degrees) than the direction-selective ensembles (standard deviation of the error of 42 degrees). The nonselective neurons provided information through a latency code that is apparent only when a neuron's activity is considered in the context of the responses of neighboring neurons. These results suggest that models utilizing both generalist and specialist neurons may better reflect the encoding mechanisms that take place in sensory pathways.

Action Potentials↗

PubMed2003

Capabilities of a penetrating microelectrode array for recording single units in dorsal root ganglia of the cat.

The recording capability of a microelectrode array in the cat dorsal root ganglion (DRG) was studied in 11 acute experiments, 373 single, discriminable sensory units were recorded on 587 electrodes (0.64 units/electrode). Sensory action potentials as large as 1750 microV were obtained (mean=132 microV). These were comparable to literature reports of the best DRG extracellular recordings made with conventional electrodes. We were able simultaneously to activate and record over 50 discriminable, time-varying units from L6 and L7 DRGs during a cyclic ankle displacement. We also successfully recorded stable, phase dependent multiple sensory units with very little artifact or electromyographic (EMG) contamination during decerebrate walking. Thus, the array is capable of recording more effectively from more DRGs neurons than has been achieved by conventional recording techniques. The recording selectivity and stability of the array, coupled with the large number of neurons that can be recorded simultaneously, provide attractive features for better understanding sensorimotor control principles.

Action Potentials↗

PubMed2003

Robust, automatic spike sorting using mixtures of multivariate t-distributions.

A number of recent methods developed for automatic classification of multiunit neural activity rely on a Gaussian model of the variability of individual waveforms and the statistical methods of Gaussian mixture decomposition. Recent evidence has shown that the Gaussian model does not accurately capture the multivariate statistics of the waveform samples' distribution. We present further data demonstrating non-Gaussian statistics, and show that the multivariate t-distribution, a wide-tailed family of distributions, provides a significantly better fit to the true statistics. We introduce an adaptation of a new expectation-maximization based competitive mixture decomposition algorithm and show that it efficiently and reliably performs mixture decomposition of t-distributions. Our algorithm determines the number of units in multiunit neural recordings, even in the presence of significant noise contamination resulting from random threshold crossings and overlapping spikes.

Action Potentials↗

PubMed2003

Development of a novel eighth-nerve intraneural auditory neuroprosthesis.

OBJECTIVES/HYPOTHESIS: Cochlear nerve stimulation using a linear array of electrodes, the cochlear implant, has become an accepted treatment for profound deafness. Major limitations of this technology are high threshold of stimulation, poor performance in a noisy background, cross-talk between electrodes, unsatisfactory channel selectivity, and variable reconstruction of frequency space. A novel auditory neuroprosthesis is proposed that is expected to overcome these problems by implanting an array of three-dimensional microelectrodes, the Utah Electrode Array, directly into the cochlear nerve. STUDY DESIGN: We have conducted acute, extending for up to 12 hours and semichronic, extending for up to 52 hours, electrophysiological experiments, radiologic and histologic studies in 12 cats. METHODS: The electrically evoked auditory brainstem response was used as a means to characterize the threshold, dynamic range, and stability of cochlear nerve stimulation through the implanted Utah Electrode Array neuroprosthesis. Plain film, computed tomographic, and histological studies were conducted to determine the result of the implant. RESULTS: The electrically evoked auditory brainstem response thresholds were approximately one to two orders of magnitude lower than those evoked with conventional cochlear implants. We were able to close the cochleostomy, bring the cat into normal anatomical position, and obtain stable electrically evoked auditory brainstem responses for up to 52 hours. Plain film and computed tomographic studies indicated that the Utah Electrode Array neuroprosthesis was in the intended position in the nerve. Histological studies did not reveal hemorrhage or significant damage to the nerve. CONCLUSION: Because the presented stimulation paradigm appears to significantly mitigate some of the problems of conventional cochlear implants, it may offer a new therapeutic approach to profound deafness.

Animals↗

PubMed2003

Cochlear nerve stimulation with a 3-dimensional penetrating electrode array.

HYPOTHESIS: An array of penetrating microelectrodes can be implanted into the cochlear nerve to produce stable evoked responses with important electrophysiologic advantages over conventional electrode technology. BACKGROUND: A totally implantable cochlear implant system would benefit from new electrode technology that lowers the current required for stimulation. Modern cochlear implant arrays placed in the scala tympani have an appreciable distance between the electrodes and the cochlear nerve, the site of intended stimulation. This distance can create the problem of cross-talk, limiting the number of electrodes that can represent discrete frequencies over a given length as well as significantly increasing stimulation thresholds and producing nonfocal stimulation of the fibers in the nerve. An electrode in direct contact with neurons in the cochlear nerve could reduce these problems. The Utah Electrode Array is a novel, three-dimensional, penetrating electrode array intended for direct neural stimulation with the potential ability to implant up to 200 electrodes directly into the cochlear nerve. METHODS: Arrays containing 6 to 19 electrodes were implanted acutely into six separate cat cochlear nerves for analysis. Thresholds and input/output functions were measured with electrically induced auditory brainstem responses. RESULTS: Current injections in 38 of 70 implanted electrodes produced stable brainstem responses after implantation. The median threshold was 15 microA. CONCLUSIONS: An array of penetrating electrodes can be implanted into the cochlear nerve and used to evoke brainstem responses. The responses are of low threshold and are stable. Arrays of electrodes, inserted into auditory nerve, could form the neural interfaces for the next generation of auditory prostheses.

Animals↗

PubMed2002

A technique for implantation of a 3-dimensional penetrating electrode array in the modiolar nerve of cats and humans.

BACKGROUND: We believe that direct intraneural stimulation of the modiolar nerve using an array of electrodes will have lower thresholds, offer greater frequency selectivity and more stimulation sites, and have a greater frequency representation than conventional cochlear implants. OBJECTIVES: To describe a potential auditory prosthesis based on electrical stimulation of the modiolar cochlear nerve and to report the development of a surgical approach in human and animal models. DESIGN: Cadaveric human and animal studies conducted in temporal bones indicated that an array of penetrating microelectrodes could be implanted in the modiolar nerve. Cat studies using anesthesia were performed to develop the surgical procedure in an animal model. Nerve viability was assessed by measurement of electrically evoked auditory brainstem responses at different stages of the surgery. SUBJECTS: Two fresh cadaveric human temporal bones, 3 cat cadavers, 1 pig cadaver, and 6 anesthetized cats were used in the experiments. RESULTS: We were able to implant arrays containing 20 microelectrodes in the human modiolar nerve after exposure by a modified extended facial recess approach. In animals, the modiolar nerve was accessed by the transbulla and the middle fossa approach. The cat was chosen as the appropriate animal model, and the transbulla approach was selected. The round window was exposed by ventral access to the bulla and after cochleostomy; drilling the modiolar bone exposed the modiolar nerve. The mean +/- SD diameter of the exposed nerve in cats was 1.64 +/- 0.07 mm (n = 9), and the mean +/- SD exposed length was 2.50 +/- 0.11 mm (n = 9); this is adequate to accommodate 20 microelectrodes. The electrically evoked auditory brainstem responses indicated nerve survival during and after the surgery. CONCLUSIONS: The surgical technique allows implantation of up to 20 microelectrodes in the cat and human modiolar nerve. The nerve survives the surgical procedure. This work enables studies in the electrophysiological properties and consequences of long-term implantation.

Animals↗

PubMedDate not supplied

Selective motor unit recruitment via intrafascicular multielectrode stimulation.

Recruitment of force via independent asynchronous firing of large numbers of motor units produces the grace and endurance of physiological motion. We have investigated the possibility of reproducing this physiological recruitment strategy by determining the selectivity of access to large numbers of independent motor units through intrafascicular multielectrode stimulation (IFMS) of the peripheral nerve. A Utah Slanted Electrode Array containing 100, 0.5-1.5 mm-long penetrating electrodes was inserted into the sciatic nerve of a cat, and forces generated by the 3 heads of triceps surea in response to electrical stimulation of the nerve were monitored via force transducers attached to their tendons. We found a mean of 17.4 +/- 4.9 (mean +/- SEM) electrodes selectively excited maximal forces in medial gastrocnemius before exciting another muscle. Among electrodes demonstrating selectivity at threshold, a mean of 7.3 +/- 2.7 electrodes were shown to recruit independent populations of motor units innervating medial gastrocnemius (overlap < 20%). Corresponding numbers of electrodes were reported for lateral gastrocnemius and soleus, as well. We used these stimulation data to emulate physiological recruitment strategies, and found that independent motor unit pool recruitment approximates physiological activation more closely than does intensity-based recruitment or frequency-based recruitment.

Animals↗