Biomedical subjects

R A Normann

Publications and source records attributed to R A Normann.

At least 37 records · Page 2Linked to original sources

PubMed1997

An advanced demultiplexing system for physiological stimulation.

A CMOS very large scale integration (VLSI) chip has been designed and built to implement a scheme developed for multiplexing/demultiplexing the signals required to operate an intracortical stimulating electrode array. Because the use of radio telemetry in a proposed system utilizing this chip may impose limits upon the rate of data transmission to the chip, the scheme described herein was used to reduce the amount of digital information which must be sent to control a large quantity (up to several hundred) of stimulating electrodes. By incorporating multiple current sources on chip, many channels may be stimulated simultaneously. By incorporating on-chip timers, control over pulse timing is assigned to the chip, reducing by up to fourfold the amount of control data which must be sent. By incorporating on-chip RAM, information associated with the desired stimulus amplitude and pulse timing can be stored on chip. In this manner, it is necessary to send control information to the chip only when the information changes, rather than at the stimulus repeat rate for each channel. This further reduces the data rate by a factor of five to ten times or more. The architecture described here, implemented as an eight-channel stimulator, is scalable to a 625-channel stimulator while keeping data transmission rates under 2 Mbps.

Analog-Digital Conversion↗

PubMed1996

Single unit recording capabilities of a 100 microelectrode array.

We have developed a three-dimensional silicon electrode array which provides 100 separate channels for neural recording in cortex. The device is manufactured using silicon micromachining techniques, and we have conducted acute recording experiments in cat striate cortex to evaluate the recording capabilities of the array. In a series of five acute experiments, 58.6% of the electrodes in the array were found to be capable of recording visually evoked responses. In the most recent acute study, the average signal-to-noise ratio for recordings obtained from 56 of the electrodes in the array was calculated to be 5.5:1. Using standard window discrimination techniques, an average of 3.4 separable spikes were identified for each of these electrodes. In order to compare the two-dimensional mapping capabilities of the array with those derived from other technologies, orientation preference and ocular dominance maps were generated for each of the evoked responses. Histological evaluation of the implant site indicates some localized tissue insult, but this is likely due to the perfusion procedure since high signal-to-noise ratio neural responses were recorded. The recording capabilities of the Utah Intracortical Electrode Array in combination with the large number of electrodes available for recording make the array a tool well suited for investigations into the parallel processing mechanisms in cortex.

Animals↗

PubMed1994

Optimizing recording capabilities of the Utah Intracortical Electrode Array.

The Utah Intracortical Electrode Array is a unique silicon-based monolithic structure designed for use as a multichannel interface to the central nervous system. In this paper, we describe a series of acute experiments designed to determine the neural recording capabilities of this electrode array and the dependence of the signal-to-noise ratio (SNR) of the recordings on the electrode surface area (length of metallized tip). We found that both separable unit and multiunit cluster responses could be recorded. Additionally, high SNR recordings could be achieved for some electrodes (with electrode tip lengths of 30-220 microns), while recordings with signals substantially greater than the noise could be made from most of the electrodes provided that the proper electrode surface area was used. The demonstrated recording capabilities of the Utah Intracortical Electrode Array and its unique three-dimensional structure should form the basis for innovative physiological investigations into the functional organization of the cortex as well as for long term neuroprosthesis development.

Algorithms↗

PubMed1993

Voltage- and time-dependent potassium conductances enhance the frequency response of horizontal cells in the turtle retina.

The contribution of voltage- and time-dependent potassium conductances to visual information processing in the distal turtle retina was studied in the isolated retina preparation. The effects of specific potassium channel blockers; tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the membrane potential and photoresponses of L-cones and L-type horizontal cells were monitored with intracellular microelectrodes. Both drugs produced a large depolarization of the L-type horizontal cells though the effect of 4-AP was more transient than that of TEA. While TEA produced response augmentation associated with negligible changes in the kinetics of the photoresponses, 4-AP induced profound changes in response kinetics which were seen as an overshoot of the resting potential at stimulus offset and a pronounced slowing down in the return of the membrane potential toward the prestimulus level. The effects of TEA on horizontal cells could be accounted for by the action of the drug on cone photoreceptors. The effects of 4-AP on the horizontal cells could not be attributed to an indirect action mediated by either the cone photoreceptors or by GABAergic and/or glycinergic neurons in the inner retina. These results suggest that voltage- and time-dependent potassium conductances act to speed up the recovery of the turtle horizontal cell membrane potential from the effects of bright light stimuli. Such a role was supported by the effects of potassium channel blockers on the frequency response curves of horizontal cells: the corner frequency was reduced on the average by 25%.

4-Aminopyridine↗

PubMed1992

A method for pneumatically inserting an array of penetrating electrodes into cortical tissue.

The goal of this research was to find a practical means by which an array of 100 needle-shaped electrodes could be implanted into the cerebral cortex with minimal brain tissue trauma. It was found that insertion of these structures into cortical tissues could only be performed using high insertion speeds. A pneumatically actuated impact insertion system has been developed that is capable of inserting an electrode array into feline brain tissue at speeds from about 1 to 11 m/s. We found that a minimum array insertion speed of 8.3 m/s was necessary for a complete, safe insertion of all 100 electrodes in the array to a depth of 1.5 mm into feline cortex. The performance of the impact insertion system is discussed in terms of a simplified representation of cortical tissue.

Animals↗

PubMed1992

A glass/silicon composite intracortical electrode array.

A new manufacturing technique has been developed for creating silicon-based, penetrating electrode arrays intended for implantation into cerebral cortex. The arrays consist of a 4.2 mm x 4.2 mm glass/silicon composite base, from which project 100 silicon needle-type electrodes in a 10 x 10 array. Each needle is approximately 1,500 microns long, 80 microns in diameter at the base, and tapers to a sharp point at the metalized tip. The technique used to manufacture these arrays differs from our previous method in that a glass dielectric, rather than a p-n-p junction, provides electrical isolation between the individual electrodes in the array. The new electrode arrays exhibit superior electrical properties to those described previously. We have measured interelectrode impedances of at least 10(13) omega, and interelectrode capacitances of approximately 50 fF for the new arrays. In this paper, we describe the manufacturing techniques used to create the arrays, focusing on the dielectric isolation technique, and discuss the electrical and mechanical characteristics of these arrays.

Electric Conductivity↗

PubMed1992

Simulation of a phosphene-based visual field: visual acuity in a pixelized vision system.

A visual prosthesis for the blind using electrical stimulation of the visual cortex will require the development of an array of electrodes. Passage of current through these electrodes is expected to create a visual image made up of a matrix of discrete phosphenes. The quality of the visual sense thus provided will be a function of many parameters, particularly the number of electrodes and their spacing. We are conducting a series of psychophysical experiments with a portable "phosphene" simulator to obtain estimates of suitable values for electrode number and spacing. The simulator consists of a small video camera and monitor worn by a normally sighted human subject. To simulate a discrete phosphene field, the monitor is masked by an opaque perforated film. The visual angle subtended by images from the masked monitor is 1.7 degrees or less, depending on the mask, and falls within the fovea of the subject. In the study presented here, we measured visual acuity as a function of the number of pixels and their spacing in the mask. Visual acuity was inversely proportional to pixel density, and trained subjects could achieve about 20/26 visual acuity with a 1024 pixel image. We conclude that 625 electrodes implanted in a 1 cm by 1 cm area near the foveal representation of the visual cortex should produce a phosphene image with a visual acuity of approximately 20/30. Such an acuity could provide useful restoration of functional vision for the profoundly blind.

Blindness↗

PubMed1992

Mobility performance with a pixelized vision system.

A visual prosthesis, based on electrical stimulation of the visual cortex, has been suggested as a means for partially restoring functional vision in the blind. The prosthesis would create a pixelized visual sense consisting of punctate spots of light (phosphenes). The present study investigated the feasibility of achieving visually-guided mobility with such a visual sense. Psychophysical experiments were conducted on normally sighted human subjects, who were required to walk through a maze which included a series of obstacles, while their visual input was restricted to information from a pixelized vision simulator. Walking speed and number of body contacts with obstacles and walls were measured as a function of pixel number, pixel spacing, object minification, and field of view. The results indicate that a 25 x 25 array of pixels distributed within the foveal visual area could provide useful visually guided mobility in environments not requiring a high degree of pattern recognition.

Blindness↗

PubMed1992

A three-dimensional architecture for a parallel processing photosensing array.

A three-dimensional architecture for a photosensing array has been developed. This silicon based architecture consists of a 10 x 10 array of photosensors with 80 microns diameter, through chip interconnects to the back side of a 500 microns thick silicon wafer. Each photosensor consists of a 300 x 300 microns pn-junction photodiode. The following processes were used to create this photosensing architecture: 1) thermomigration of aluminum pads through an n-type silicon wafer; 2) creation of pn-junction photosensors on one side of the wafer; and 3) creation of aluminum pad ohmic contacts to the thermomigrated, through chip interconnects and the substrate on the back side of the wafer. The electrical and optical characteristics of the three-dimensional architecture indicates that it should be well suited as a photosensing framework around which a "silicon retina" could be built.

Artificial Organs↗

PubMed1992

Reading speed with a pixelized vision system.

A visual prosthesis based on electrical stimulation of the visual cortex with an array of penetrating electrodes is expected to produce pixelized visual images consisting of punctate spots of light (phosphenes). We measured reading speed in subjects viewing text with optically simulated phosphene fields in order to obtain estimates of the following design parameters for such an electrode array: pixel number, pixel spacing, and visual-field size. Comparisons were made between scanning the text with eye movements and scanning the text with head movements. The results indicate that a 25 x 25 array of pixels representing four letters of text projected on a foveal visual field of 1.7 degrees is sufficient to provide reading rates near 170 words/min with scrolled text and near 100 words/min with fixed text.

Humans↗

PubMed1991

Synaptic inputs to physiologically defined turtle retinal ganglion cells.

Two physiologically distinct, HRP-marked turtle retinal ganglion cells were examined for their morphology, GABAergic, glycinergic, and bipolar cell synaptic inputs, using electron-microscopic autoradiography and postembedding immunocytochemistry. One cell was a color-opponent, transient ON/OFF ganglion cell. Its center response to red was a sustained hyperpolarization, and its center response to green was a depolarization with increased spiking at onset. The HRP-injected cell most resembled G6, from previous Golgi-impregnation studies (Kolb, 1982; Kolb et al., 1988). It was a narrow-field bistratified cell, whose two broad dendritic strata peaked at approximately levels L20-25 (sublamina a) and L60 (sublamina b) of the inner plexiform layer. Bipolar cell synapses onto G6 were found evenly distributed between its distal and proximal dendritic strata, spanning L20-75. These inputs probably originated from several different bipolar cells, reflecting the complexity of the center response. GABAergic inputs were found onto both the distal and proximal strata, from near L20-L85. Only a few glycinergic inputs, confined to dendrites at L50-70, were observed. A second ganglion cell type that we physiologically characterized and HRP-injected had sustained ON-center, sustained OFF-surround responses. Two examples were studied; both were bistratified in sublamina b, near L60-70 and L85-100, with branches up to near L40. They resembled G10, from previous Golgi-impregnation studies (Kolb, 1982; Kolb et al., 1988). One cell was partially reconstructed to look at the distributions of GABAergic and glycinergic amacrine cell, and bipolar cell inputs. Although synapses from bipolar cells were equally divided between the two major dendritic strata of G10, the inputs to the distal stratum were close to the soma, and the inputs to the more proximal stratum were on the peripheral dendrites. This arrangement may reflect input from two distinct types of ON-bipolar cell. GABAergic and glycinergic inputs to G10 costratified to both strata and to the distal branches; but where glycinergic inputs were found distributed throughout the arbor, GABAergic inputs appeared to be confined to peripheral dendrites. We hypothesize on the neural elements involved and the circuitry that may underlie the physiologically recorded receptive fields of these two very different ganglion cell types in the turtle retina.

Animals↗

PubMed1991

A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array.

A method has been developed for the manufacture of a "three-dimensional" electrode array geometry for chronic intracortical stimulation. This silicon based array consists of a 4.2 x 4.2 x 0.12 mm thick monocrystalline substrate, from which project 100 conductive, silicon needles sharpened to facilitate cortical penetration. Each needle is electrically isolated from the other needles, and is about 0.09 mm thick at its base and 1.5 mm long. The sharpened end of each needle is coated with platinum to facilitate charge transfer into neural tissue. The following manufacturing processes were used to create this array. 1) Thermomigration of 100 aluminum pads through an n-type silicon block. This creates trails of highly conductive p+ silicon isolated from each other by opposing pn junctions. 2) A combination of mechanical and chemical micromachining which creates individual penetrating needles of the p+ silicon trails. 3) Metal deposition to create active electrode areas and electrical contact pads. 4) Array encapsulation with polyimide. The geometrical, mechanical, and electrical properties of these arrays should make them well suited as interfaces to cortical tissue.

Animals↗

PubMed1990

The effects of GABA and related drugs on horizontal cells in the isolated turtle retina.

The role of GABA in the outer plexiform layer of the turtle retina has been examined by intracellular recordings from L- and C-type horizontal cells in the isolated retina preparation. GABA (1-5 mM) slightly depolarized the L-type horizontal cells, reduced the amplitude of their photoresponses, and slowed down the rate of hyperpolarization during the ON component of the photoresponse. These effects could not be replicated by either muscimol or baclofen. When synaptic transmission from the photoreceptors had been blocked by either kynurenic acid or cobalt ions, GABA depolarized L-type horizontal cells and augmented the remaining photoresponses. Neither muscimol nor baclofen exerted any effect on L-type horizontal cells under these conditions. Nipecotic acid, a competitive inhibitor of the GABA-uptake system, induced effects on turtle L-type horizontal cells which were similar to those exerted by GABA. Thus, the complex GABA effect on turtle L-type horizontal cells seems to represent the summation of at least two actions; an indirect one mediated by the red cones via GABAa-type receptors and a direct one which probably reflects the activation of an electrogenic GABA-uptake system. GABA (1-5 mM) induced a transient depolarization in C-type horizontal cells but eliminated color opponency in only three cells out of seven studied. This observation is inconsistent with the notion that the only neural mechanism responsible for the chromatic properties of C-type horizontal cells in the turtle retina is a GABAergic negative feedback from the L-type horizontal cells onto the green ones.

Animals↗

PubMed1990

Effects of calcium ions on L-type horizontal cells in the isolated turtle retina.

A technique by which the retina can be isolated from the turtle eye is described. Scanning electron microscopy revealed morphological variability between preparations and also between regions of the same one. Large areas were often totally free of any pigment epithelial cells, yet contained a high proportion of photoreceptors with complete outer segments. However, adjacent regions may contain photoreceptors without outer segments or with fragmented ones. The physiological properties of the horizontal cells also demonstrated large variability between different preparations. In all cases, lowering calcium concentration from 2 mM to 0.1-0.5 mM depolarized the horizontal cells and augmented the amplitude of the maximum photoresponses. However, these effects were accompanied by changes in the photoresponse kinetics and by a reduction in the horizontal cell sensitivity to light. Moreover, prolonged exposure to low calcium induced permanent damage to the retina as was indicated by the reduction in the response amplitude after superfusion with 2 mM calcium solution had been resumed. The toxic effects of low calcium were most apparent when superfusion with 0.1-1.0 microM calcium concentration was performed. These solutions induced complex time-dependent effects on the resting potential of horizontal cells and on the amplitude and kinetics of the photoresponses. We conclude from these observations that the normal concentration of extracellular calcium in the turtle retina is in the 2 mM range.

Animals↗

PubMed1990

Background and bleaching adaptation in luminosity type horizontal cells in the isolated turtle retina.

1. The effects of background illumination and bleached photopigment on luminosity type horizontal cells were studied in the isolated turtle retina. 2. Background illumination, which produced less than 60% bleaching, hyperpolarized and desensitized the horizontal cells to a degree which depended upon the background intensity. The desensitization of horizontal cells by these backgrounds is described by a Weber-Fechner type relationship. This desensitization primarily reflects the activation of a 'gain reduction' mechanism and cannot be accounted for by 'response compression'. 3. Following the termination of these backgrounds, horizontal cell sensitivity partially recovered but did not return to the pre-background, dark-adapted level. This desensitization was attributed to the presence of bleached photoproducts which were produced by the background exposure. 4. Application of very bright backgrounds caused the horizontal cells to initially hyperpolarize, and then to gradually depolarize towards the dark-adapted level along an exponential time course which appeared to reflect the decreased quantal catching associated with very high levels of photopigment bleaching. 5. From the time constant of the exponential decay of horizontal cell potential during the bright background illumination, the photosensitivity to bleaching of the cone photopigment was determined to be 4.5 x 10(7) effective quanta (633 nm) microns-2. 6. After termination of bright backgrounds which bleached more than 99% of the cone photopigment, the horizontal cell sensitivity increased linearly with time and after 25 min reached a level which was about 15% of the pre-background sensitivity. 7. Bleached photopigment reduces light sensitivity via at least two different mechanisms. For moderate degrees of bleaching (less than 95%), the presence of bleached photoproducts plays the major role in sensitivity control, producing a desensitization which is logarithmically related to the fraction of bleached pigment. During extensive bleaching (greater than 99%), the contribution of reduced quantal catching to sensitivity control becomes apparent and produces an additional loss in sensitivity which is linearly related to the fraction of unbleached pigment present.

Adaptation, Ocular↗

PubMed1990

A 100 electrode intracortical array: structural variability.

A technique has been developed for fabricating three dimensional "hair brush" electrode arrays from monocrystalline silicon blocks. Arrays consist of a square pattern of 100 penetrating electrodes, with 400 microns interelectrode spacing. Each electrode is 1.5mm in length and tapers from about 100 microns at its base to a sharp point at the tip. The tips of each electrode are coated with platinum and the entire structure, with the exception of the tips, is insulated with polyimide. Electrical connection to selected electrodes is made by wire bonding polyimide insulated 25 microns diameter gold lead wires to bonding pads on the rear surface of the array. As the geometrical characteristics of the electrodes in such an aray will influence their electrical properties (such as impedance, capacitance, spreading resistance in an electrolyte, etc.) it is desirable that such an array have minimal variability in geometry from electrode to electrode. A study was performed to determine the geometrical variability resulting from our micromachining techniques. Measurements of the diameter of each of the 100 electrodes were made at various planes above the silicon substrate of the array. For the array that was measured, the standard deviation of the diameters was approximately 9% of the mean diameter near the tip, 8% near the middle, and 6% near the base. We describe fabrication techniques which should further reduce these variabilities.

Animals↗

PubMed1989

A continuous cardiac output computer based on thermodilution principles.

A totally self-contained instrument for the measurement of cardiac output is described. The microcomputer controlled instrument is based upon the principles of thermodilution and is capable of making cardiac output determinations on a minute by minute basis. A bolus of heat is delivered to the blood via a resistive heating element wound on the surface of a conventional thermodilution catheter, and the resulting transient pulmonary artery blood temperature increases is monitored with the thermistor located near the tip of the catheter. The performance of the instrument was tested in a mock circulatory loop and in dogs for periods of up to 13 hours. The accuracy and reproducibility of flow determinations made with the system compare favorably with those made with a conventional cardiac output monitor. This study demonstrates the feasibility of a stand-alone cardiac output computer that can provide virtually continuous measurements of blood flow without the intervention of a technician.

Animals↗

PubMed1989

Central venous blood temperature fluctuations and thermodilution signal processing in dogs.

Pulmonary artery blood temperature fluctuations are a principle source of variability of thermodilution cardiac output measurements. Two signal processing strategies were investigated to decrease this variability; a subtractive noise cancellation algorithm, developed from a heat balance model of heat transport through the right heart, and a band pass integration technique. Blood temperature fluctuations were recorded from the inferior and superior vena cavae and the pulmonary artery in four dogs. The recorded temperature signals were processed off line to investigate the performance of the signal processing strategies. The findings indicate that the accuracy of the heat transport model, while dependent on the accuracy of the sensing of caval blood temperature, is sufficient for cancellation of a significant fraction of the pulmonary artery thermal noise power if the amplitude of the fluctuations is large. The use of the subtractive cancellation algorithm improved the standard deviation of thermodilution curve area determinations by a factor of five, relative to area estimates made without noise cancellation. Band pass integration produced a more modest improvement in area estimate reproducibility. These results demonstrate that it is possible to reduce, but not eliminate, the variability of thermodilution cardiac output measurements with the described processing strategies.

Animals↗