88

DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES, PHYSIOLOGY AND BIOMEDICAL ENGINEERING PROGRAM *

America Rivera, Ph. D., Program Administrator

Microelectronics Laboratory for Biomedical Sciences

Program Project Grant: 5 P01 GM 14267

Case Western Reserve University Cleveland, OH 44106

Wen H. Ko, Ph. D., Program Director

The aim of this program project is application of solid-state electronics to biomedical instrumentation. It comprises six projects grouped into two areas: "Technical Core" and "Biological and Clinical Systems."

The technical core provides the re­search and know-how for the production of the custom integrated circuits and transducers designed by the group. It also provides the research for the appro­priate packaging material of the final implantable telemetric devices which are assembled by the group.

The latter area includes two clinical instrumentation projects. The first of these (Intracranial Pressure Monitoring and Control System. R. J. Lorig. Ph.D .. Principal Investigator) involves develop­ment of a second-generation telemetric system for monitoring ICP and other parameters. The system will be evalu­ated first in animals and then in clinical situations.

Under the second project (Implant Functional Stimulation System. P. H. Peckham. Ph. D.. Principal Investigator). an implantable stimulator and control unit to restore partial function to para­lyzed limbs will be designed and clini­cally evaluated.

• Leo H. von Euler. M.D.. is the Acting Director. W. Sue Badman. Ph. D.. is the Chief, Biomedical Engineering and Instru­ment Development Section. NIGMS is lo­cated at Bethesda. Maryland 20205.

Control Systems for a Multi-Joint Prosthetic Arm

Regular Grant: 2 R01 GM 23499 University of Utah Salt Lake City, UT 84112

Stephen C. Jacobsen, Ph. D., Principal Investigator

This research is designed to generate the quantitative biomechanical informa­tion necessary to implement a small computer device controlling four move­ments of an artificial arm: raising the forearm. lowering the forearm. rotating the wrist and hand. and closing the fingers.

The goal of the project is to demon­strate the feasibility of activating the computer controller by neuromuscular electropotentials generated by contrac­tion of the amputee's remnant shoulder and stump musculature.

The control system will be refined through extensive evaluation not only in the laboratory but in the amputees' home. work. and recreational· environ­ments.

Polyethylene Behavior in Joint Replacements

Regular Grant: 1 R01 GM 28829 Massachusetts Institute of

Technology Cambridge, MA 02139

Robert M. Rose, Sc. D., Principal Investigator

The purposes of this research are to characterize and understand the in vivo behavior of ultra high molecular weight polyethylene (UHMWPEj-a material that is extensively used in total joint prostheses of the knee and hip-and to develop substantially improved versions of this material.

There is evidence of excessive wear of UHMWPE in some total hip prostheses and many total knee prostheses. even in the absence of ab­rasive acrylic debris. In isolated cases there has been fracture of the devices. Some designs have so exceeded the limits of UHMWPE that the behavior of

the prostheses after implantation has been catastrophic.

The occurrence of severe wear is associated with certain features of the structure of UHMWPE. including molec­ular weight distribution and fusion de­fects. Under this project. the investiga­tors propose to develop a series of UHMWPE specimens with superior properties; to make preliminary evalua­tions of wear resistance; and then. by total joint simulation, to test total joint components for relative fatigue resist­ance as a function of stress intensity. Nondestructive technologies will be de­veloped to monitor the structure of UHMWPE to ensure consistent pros­thesis performance.

Interfacial Behavior of Biomaterials

Regular Grant: 5 R01 GM 24858 University of Florida Gainesville, FL 32611

Larry L. Hench, Ph. D., Principal Investigator

The objective of this research is use of controlled surface reactive BioglassC

and Bioglass-coated implant devices to solve clinically relevant medical and den­tal problems.

In vitro tissue culture systems will be used to study the interactions of various cell types (osteoblasts. fibroblasts. epi­thelial cells. lymphocytes. and macro­phages) with Bioglass surfaces of vary­ing compositions and surface treatments. Through histochemical as­says. cultures will be monitored for cal­citonin. parathyroid hormone. and Vita­min 0 3 responses; collagen synthes.is; and hydroxylapatite formation. Cell Via­bility and morphology. growth rate. and saturation density will be determined for

each cell type. d Bioglass surface reactions produce

by cellular interactions will be measured by use of scanning electron microsCOPY with energy dispersive analysis and Au­ger electron microscopy. Rates of ~eac· tive inorganic thin film formation will ~ correlated with the cellular biology an

histochemical results.

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Bulletin of Prosthetics Research, BPR 10-35 (Vol. 18 No. 1j Spring 1981

Findings from the above studies will be used to establish a scientific basis for in vitro evaluation of toxicity and bond­ability of controlled surface reactive im­plant materials.

The Mechanics of Human Bone and Long Bones

Regular Grant: 1 R01 GM 28827 Stanford University Stanford. CA 94305

Robert L. Piziali. M.D.• Ph. D .• Principal Investigator

The goal of this project is develop­ment of a program that will establish analytical models and experimental data to provide accurate modeling of the elastic. plastic. and failure characteristics of the diaphysis of the human tibia and / or femur. The approach will be to use very general concepts in modeling and data reduction to formulate models. Simplifications will then be imposed, and the errors resulting from these sim­plifications will be evaluated.

A tensor quadratic failure theory will be developed for secondary osteonal bone. During strength tests, the elastic and plastic response of the bone will also be recorded. Large sections of sec­ondary osteonal bone will then be tested under combined loading to validate the analytical model and material character­ization.

The importance of circumferential la­mellar bone in whole bone response will be established along with its appropriate material characteristics. In addition, his­tological studies will be done to estab­lish the distribution of circumferential lamellar bone throughout cross sections along the length of bones. The aim is establishment of the simplest analytical and material model consistent with sig­nificant results.

The Dynamics of EMG-Force-Movement Relationships

Regular Grant: 5 R01 GM 26395 Rancho Los Amigos Hospital Downey. CA 90242

Jacquelin Perry. M.D.• Principal Investigator

Mathematical models of the relation­ships of electromyographic (EMG) sig­nals to muscle force in the presence of movement will be developed by both exp .

en mental and analytical methods. A

coordinated series of experimental stud­ies will be used to elucidate the major factors involved in the EMG / force re­lationship, in order to obtain necessary parameters and functional relationships for the mathematical model. The exper­imental results will be used in computer simulation with system identification methods to effect a synthesis of the mathematical model.

The resulting nonlinear differential equation model will be validated using experimental EMG measurement data. Extension of the human knee will be used as the test vehicle for both the experimental and mathematical portions of the study.

Definitive studies of EMG data collec­tion, processing, and quantification will underlie most other parts of the re­search. The aim of these studies will be to provide standardized methodology for quantitative electromyography while yielding the data needed for develop­ment of mathematical models. Other basic studies will be concerned with the comparison of electrodes, the effects of muscle fatigue, periarticular tissue re­sistance, and antagonistic muscle activ­ity.

Bone-Implant Interface Analysis

Regular Grant: 1 R01 GM 27868 Cleveland Clinic Foundation Cleveland. OH 44106

A. Seth Greenwald. D. Phil. (Oxon), Principal Investigator

Under this project, studies will be performed to assess the short-term (0, 1, 2, 3, and 4 weeks) stabilizing ability of low and high modulus microporous implant systems in weightbearing and non-weightbearing animal environ­ments.

Previous long-term studies of these materials in animals have demonstrated sufficient fixation capability; however, little work has been done to compare the stabilizing ability of these materials with that of acrylic bone cement. This evaluation will be accomplished by test­ing of a specially designed implant sys­tem in a canine model over a 25-week interval. (In vitro studies of bone cells in culture will also be employed to eluci­date initial cellular response to the mi­croporous material·s.)

Early adequate implant stabilization,

allowing early mobility, would hold sig­nificant clinical promise.

90

DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH NATIONAL INSTITUTE OF NEUROLOGICAL AND COMMUNICATIVE DISORDERS AND STROKE BETHESDA, MARYLAND 20205

F. Terry Hambrecht M.D., Program Head

Neural Prosthesis Program-Devices that supplement, restore or extend neu­rological function are known as neural prostheses. Prototype prostheses have been designed for individuals with such disorders as involuntary movements, skeletal muscle paralysis. neurogenic bladder, deafness and blindness. During evaluation, fundamental problems have been identified, many of which are com­mon to several prostheses. The goal of the Neural Prosthesis Program is to encourage basic research and technol­ogy development to solve these prob­lems.

The Neural Prosthesis Program sup­ports research principally by contracts to universities, research organizations, and industry. Requests for proposals (RFP's) are advertised in the Commerce Business Daily and in supplements to the NIH Guide for Grants and Contracts. The latter can be obtained by filling out a Request for Inclusion on the Mailing List for the NIH Guide for Grants and Contracts (Form - NIH-2359-1) avail­able from the Computerized Distribution Support Unit. Building 31, Room B3BN 10, 9000 Rockville Pike, Be­thesda, Maryland 20205. Unsolicited re­search proposals are supported in the most part by grants. Grant application kits are available from the Division of Research Grants, National Institutes of Health, Bethesda, Maryland 20205.

There are presently 14 contractors in the program. They meet annually for exchange of technical information with other interested investigators at an an­nual Neural Prosthesis Workshop which is held in the fall at the NIH Campus in Bethesda. Invitations to the Workshop may be obtained by writing to the Pro­gram Head.

Summaries and workscopes of the individual research projects as well as a current bibliography of published papers describing results of work supported by the Neural Prosthesis Program follow this introduction.

Development of Transdermal Stimulators

Contract: N01-NS-5-2306 Stanford University Department of Electrical Engineering Stanford, California 94305

R.obert L. White, Ph. D., Principal Investigator

The design, development and fabri­cation of transdermal stimulation sys­tems for use in the evaluation of multi­channel auditory prostheses are being pursued. The specific workscope is as follows:

A. Design and develop 8-channel and 12-channel pulsatile implantable re­ceiver-stimulators for use with mono­polar electrodes, and fabricate at least 20 functional units of each design ac­cording to the following detailed speci­fications for each channel:

1. Monophasic capacitive coup­led, current source outputs.

2. Maximum charge output per phase-at least 100 nanocoulombs.

3. Pulse current output-:--O to 400 microamperes into 10,000 ohm load.

4. Pulse width-2 to 250 micro­seconds.

5. Pulse frequency-O to 2000 pps.

6. Timing requirements-the ca­pability of activating all channels simul­taneously should exist, and of activating any channel within 50 microseconds of activation of any other channel.

7. The implant should be hermet­ically packaged with appropriate feed­throughs, in a cylindrical shape with a maximum diameter of 25 mm and a maximum thickness (not including feedthroughs) of 10 mm.

B. Design an 8-channel pulsatile, im­plantable receiver-stimulator without common grounds between channels for use with bipolar electrodes, otherwise with the same detailed specifications as given in A. above.

C. Design an 8-channel analog-output implantable receiver-stimulator without common grounds between channels, ac­cording to the following detailed speci­

fications: 1. Capacitive coupled, current

source outputs. 2. Peak output current-500

microamperes per channel into a 10,000 ohm load.

3. Bandwidth per channel-O to 4 kHz.

D. Design, develop, and fabricate cus­tom or semi-custom designed integrated circuits as needed for use in thes,e stim­ulators.

E. Design. develop. and fabricate suit­able disconnect plugs for interfacing these stimulators with connecting leads to electrode arrays that will be supplied by the Project. Officer.

F. Design transmitters capable of driv­ing each of these receiver-stimulators over their rated ranges during in vitro tests. and fabricate at least two func­tional models for use with the 8-channel and the 12-channel monopolar pulsatile systems, respectively.

G. Perform suitable long-term in vitro testing in saline tanks, at or above 37°C, of representative samples of receiver­stimulators that are fabricated and her­metically packaged.

Development of Multichannel Electrodes for Auditory Prostheses

Contract: N01-NS-80-2337 University of California,

San Francisco Coleman Laboratory San Francisco Medical Center San Francisco, California 94122

Michael M. Merzenich, Ph. D., Principal Investigator

Contract: N01-NS-80-2336 Stanford University • Department of Electrical Engineenntl Stanford, California 94305

Robert L. White, Ph. D., Principal

Investigator . nina.

These two contractors are des1g _..I . multichanntP

developing and testing 1118 electrodes for auditory prostheses.

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Bulletin of Prosthetics Research. BPR 10-35 (Vol. 18 No.1) Spring 1981

specific workscope is as follows: A. Design-Compile sufficient infor­

mation from the literature and experi­ments as needed to determine:

1. The shape and mechanical characteristics of the electrode array.

2. The size. position. and number of electrode contacts.

3. The most promising materials for the array construction.

B. Fabrication-Develop techniques and processes as needed and construct prototype electrode arrays which appear promising based on the above deter­mined design information.

C. Testing-Evaluate the prototype arrays as follows:

1. Perform long-term in vivo test­ing of the integrity of the electrical and mechanical properties under anticipated in vivo levels of electrical stimulation.

2. Implant arrays into cadavers and animals for short terms to determine the actual position of the electrodes with respect to the neural tissue. to predict current pathways. and to determine me­chanical damage from implantation.

3. Lising appropriate electrophys­iological techniques in acute animals. evaluate and compare the degree of selectivity achieved by the prototype electrode arrays and possible neuro­physiological evidence of functional nerve damage due to short-term stimu­lation.

4. Evaluate histopathologically. a. the tissue surrounding

chronic. passive implants if new or un­usual materials or techniques are uti ­lized;

b. the tissue surrounding proto­type electrode arrays after chronic in vivo activation at anticipated stimulation levels.

Evaluation of Electrode Materials and Their Electrochemical Reactions

Contract: N01-NS-79-2315 EIC Laboratories 55 Chapel Street Newton. Massachusetts 02158

S.B. Brummer. Ph. D .• Principal Investigator

Contract: N01-NS-80-2316 Electrochemical Technology

Corporation 3935 Leary Way. N.W. Seattle. Washington 98107

Theodore R. Beck, Ph. D., Principal Investigator

These two contracts support studies of the electrochemical processes that occur at the electrode-electrolyte inter­face of stimulation electrodes and methods of reducing undesirable reac­tions. The specific workscope is as fol ­lows:

A. Determine the relationships be­tween current density. charge density. total charge transfer. the potential de­veloped vs. a standard reference elec­trode. and the chemical processes in the regions defined by these relationships for promising conductors in protein con­taining simulated and / or actual mam­malian extracellular fluid (such as cere­brospinal fluid) with stimulus parameters appropriate for neural prostheses.

1. Determine the maximum charge per pulse per square centimeter of electrode area (over an appropriate range of current densities) that can be passed before production of each of the reaction species that can enter solution:

a. Compare charge balanced. current density symmetrical. biphasic pulses with charge balanced but current density asymmetrical biphasic pulses.

b. Compare charge balanced.' biphasic pulses with zero to 5.0 msec delays between the two pulses in the biphasic pulse pair.

2. Study methods of improving the charge carrying capacity of these materials with respect to the charge density at which solution species are produced.

a. Determine the mechanism(s) of protection from dissolution afforded by adding protein to the solution.

b. Determine the extent to which the protein composition and levels

in normal mammalian CSF and other extracellular fluids can be expected to supply protection from dissolution.

c. Determine whether long­lasting methods of preventing solution species can be developed other than the application of insulating coatings (i.e .. other than capacitor electrodes).

3. Study the effects of long-term pulsing (i.e .. greater than 2000 hours):

a. Determine the metal disso­lution rates as a function of stimulus levels.

b. Evaluate the electrode sur­face morphology before and after puls­ing.

4. Determine the maximum num­ber of charge balanced biphasic pulses that can be passed before solution spe­cies are produced when very high charge density (1000-10.000 microcoulombs per cm 2 per phase) pulses are utilized at a pulse frequency of 400 biphasic pulse­pairs per second.

a. Determine the maximum number of pulses before significant metal dissolution occurs.

b. Compare platinum iridium and tungsten.

B. Determine the factors contributing to stimulating electrode access resist­ance. (Access resistance is defined in this study as the initial voltage appearing across the electrodes divided by the initial pulse current).

1. Determine the access resis­tance of the conductors being evaluated during pulsing and attempt to correlate variations with changes in physical and chemical changes at the electrode-so­lution interface.

C. Develop the following techniques and be prepared to collaborate with other Neural Prosthesis Program inves­tigators in in vivo evaluation.

1. A method of measuring the real surface area of electrodes.

2. A method of determining re­gional solution oxygen tension that is suitable for chronic 'monitoring of local oxygen tension in brain cortical tissue beneath 1-mm diameter. cortical sur­face. platinum electrodes during electri ­cal stimulation of the tissue.

D. Develop percutaneous electrodes by coating high-tensile-strength mate­rials with conductors which have a high charge-carrying capacity. for use as in­tramuscular stimulating electrodes (e.g .. Reference: Caldwell. S.W.: A high

92 PROGRESS REPORTS: Neurological. Communicative, & Stroke

strength platinum percutaneous elec­trode for chronic use, EDC Report No, 7-70-30, Case Western Reserve Uni­versity, 1970),

1. Evaluate these electrodes as in

A.3. E. In collaboration with other contrac­

tors in the Neural Prosthesis Program and utilizing tissue and electrodes sup­plied by them:

1. Develop a method of determin­ing the quantity and distribution of plat­inum dissolution products in tissue sur­rounding pulsed platinum electrodes.

2. Develop a method of analyzing deposits on platinum electrodes after long-term in vivo pulsing,

Capacitor Stimulating Electrodes for Activation of Neural Tissue

Contract: N01-NS-78-2300 Giner, Inc. 14 Spring Street Waltham. Massachusetts 02154

Harry Lerner. Ph, D .• Principal Investigator

Contract: N01-NS-78-2392 EIC Laboratories. Inc. S5 Chapel Street Newton. Massachusetts 02158

S,B. Brummer. Ph. D., Principal Investigator

The principal goal of these two con­tracts is to develop capacitor stimulating electrodes suitable for intracortical im­plantation and activation of cortical neu­rons. The specific workscope is as fol­lows:

A. Investigate methods of increasing the charge storage per unit volume and reducing the pore resistance of capacitor electrodes compared with presently available electrodes. (Reference: Guy­ton. D.L., Hambrecht. FT. Theory and design of capacitor electrodes for chronic stimulation. Med. BioI. Engng. 12: 613-620. 1974).

B, Determine whether anodization with monophasic anodal pulses with pulse durations anticipated during use (i.e .. 0.05-1.0 msec) instead of direct current improves the usable charge stor­age capability of the electrodes.

C. Determine the safety margin be­tween the anodization potential and the peak pulse potential across the dielectric before significant oxidation-reduction re­

actions occur. D. Determine the effects of transient

cathodal potentials on the electrical characteristics of capacitor electrodes including:

1. Determination of the effects of bipolar. biphasic pulsing of pairs of ca­pacitor electrodes,

E. Fabricate and supply at least 20 samples to NIH of conically tipped. cy­lindrical capacitor electrodes suitable for intracortical stimulation with a maxi­mum diameter of 0.1 mm, with an ex­posed length of 0.2 mm, a total length of 1.5 mm and that can deliver .02 microcoulombs within 0.1 msec when immersed in a saline solution with a specific resistivity of 300 ohm-cm,

F. Characterize electrodes fabricated with respect to their electrical properties in normal saline including measurements of their capacitance, leakage resistance, and leakage current as a function of potential up to the designed operating potential.

G. It is suggested that materials eval­uated include tantalum-tantalum pen­toxide. but that emphasis be placed on other promising materials.

Development and Evaluation of Safe Methods of Intracortical and Peripheral Nerve Stimulation

Contract: N01-NS-80-2319 Huntington Institute of Applied

Research 734 Fairmount Avenue Pasadena. California 91105

William F. Agnew. Ph. D .• Principal Investigator

This project is developing neural stim­ulating electrodes and evaluating the effects of electrical stimulation on neural and surrounding tissue. The specific workscope is as follows:

A. Develop cortical penetrating elec­trodes suitable for chronic stimulation of cerebral neurons at various cortical depths,

B. Study the effects of acute and chronic stimulation through the elec­trodes in A. on surrounding neural, vas­cular, glial and other nearby tissues in­cluding extracellular fluid.

1. Examine the tissue with both light and electron microscopy.

2. Determine the relationships be­tween tissue damage, electrode depth,

and the stimulus variables of charge density, charge per phase, and current density (based on geometric. and if pos­sible, also on real exposed electrOde area) using charge balanced. current reg­ulated, chronic stimulation, (Chronic stimulation is defined in this study as a total stimulation period in excess of 30 hours).

3. Examine possible mechanisms of tissue damage including mechanical trauma and the effects of cortical stim­ulation on the surrounding extracellular fluid oxygen content, pH, potassium and calcium ion concentrations with stimu­lation levels at and below those known

. to cause histopathological damage, 4. If significant alterations of any

of the measured extracellular properties are noted during acute stimulation (stim­ulation periods less than 8 hours). inves­tigate methods of evaluating the altered property(s) in chronically stimulated an­imals and determining their re·lationship. if any, to tissue damage.

5. Determine the concentration and distribution of any corroded elec­trode prodljcts in the surrounding tissue,

6, As intracortical capacitor elec­trodes become available from other con­tractors in the Neural Prosthesis Pro­gram, evaluate representative samples with respect to B. 1 through B, 3,

7. Evaluate the effects of the fol­lowing on electrode access resistance: (Access resistance is defined in this study as the initial pulse voltage ap­pearing across the electrodes divided by the initial current).

a. Intermittent versus continu­

ous stimulation b. Cortical edema c. Electrode depth

C. Fabricate electrodes suitable for chronic stimulation of peripheral nerves such as the sacral nerve roots in dogs.

1. Use these electrodes to study histopathologically the effects on nerve tissue damage of the electrode constr~c­tion and the stimulus variables includJ09 charge density. charge per phase. and current density using charge balanced.

I . n regulated current chronic stimu atlo '.

2. Determine the cause(s) of flS­

sue damage at the upper limits of safe

stimulation. 0­3, Supply up to twenty (20) ~~

totype electrodes per year to the Pro! rei Officer for evaluation in functional neu....

I ProSfhe-prostheses by other Neura Program Contractors.

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Bulletin of Prosthetics Research. BPR 10-35 (Vol. 18 No.1) Spring 1981

Adhesion Studies

Contract: N01-NS-78-2394 City University St. John Street London, E.C.1., England

Keith W. Allen, Principal Investigator

The results of this work will be used to improve the adhesion of various ma­terials to substrates which are presently being used or are being considered for use in neural prosthetic implants. The specific workscope is as follows:

A. Evaluate potential adhesives and sealants for the following factors if such information is relevant to the intended uses. and if such information is not presently available.

1. Adherence to typical substrates (e.g.. alumina ceramic. glass as used around feedthroughs. metal implant packages such as titanium. and metal conducting lead materials such as plat­inum. iridium. gold. tantalum. MP35. 304 stainless steel. and 316 stainless steel) in a saline environment and failure modes during destructive testing.

2. Methods of preparing and mod­ifying the substrate surface to improve adhesion.

3. Methods of modifying the ad­hesive to improve the adhesion.

4. Water absorption during im­mersion in saline over a period of at least 6 months.

5. Effect of sterilization. including autoclaving and ethylene oxide.

6. The chemical composition in­cluding any activators or catalysts re­quired.

7. Suggested specifications for medical grades if medical grades are not available.

. B. Materials to be evaluated should Include members of the silicone rubber f~~i1y of elastomers but need not be limited to this group.

Insulating Biomaterials

Co~tract: N01-NS-78-2393 ~mversi.ty of Missouri-Columbia

olumbla, Missouri 65211

Allen W H h . a n, Ph. D., Principal Investigator

This resea h' .fo . rc IS evaluating materials r Possible u ..for . se as electrical Insulators

Implanted neural prostheses. The

specific workscope is as follows: A. Evaluate potential encapsulants.

sealants and lead insulators for the fol­lowing factors (if such information is relevant to the intended uses. and if such information is not presently avail­able).

1. Biocompatibility and long-term stability as a passive implant in contact with meninges and cerebral cortex.

2. Water absorption and its effects on dimensional stability and adherence of the material to its substrate.

3. Permeability to water as a func­tion of thickness. .

4. Permeability to inorganic ions normally found in extracellular fluids

+ +(e.g.. Na . K , CI ) as a function of thickness.

5. Methods and conditions of ap­plying the material.

6. Adherence of the material to typical substrates (e.g., integrated circuit substrates, implant leads and electrodes. metal and metal ceramic packages) in a saline environment and methods of im­proving such adherence.

7. Fatigue resistance to repeated flexion. rotation and elongation in vitro.

8. Long-term flex life in vivo. 9. Protection from changes in

electrical characteristics afforded active semiconductor and passive interconnect test circuits by the materials as a func­tion of thickness and time.

10. Stability of electrical properties in a normal saline environment at 37 deg C as a function of time and as a function of in vitro flex life.

11. Effect of autoclaving and eth­ylene oxide sterilization on the above properties.

B. Evaluate combinations of materials applied in layers with respect to the factors detailed in A.

C. Materials to be evaluated shall include members of the Parylene@ (Union Carbide) and silicone rubber fam­ilies but should not be restricted to these.

D. Determine specifications for med­ical grades of the materials if medical grades are not available.

Functional Neuromuscular Stimulation

Contract: N01-NS-80-2330 Case Western Reserve University Laboratory of Applied Neural

Control Sears Tower, Room EB65 Cleveland, Ohio 44106

J. Thomas Mortimer, Ph. D.. Principal Investigator

This is a series of studies to determine the feasibility of regaining control of paralyzed muscles using the techniques of functional neuromuscular stimulation. The specific workscope is as follows:

A. The contractor shall develop and . evaluate upper-extremity orthotic sys­

tems which utilize electrical stimulation of paralyzed muscle. Specifically. the contractor shall investigate:

1. Methods of reducing demands on a subject's conscious awareness by using computer controlled stimulators including:

a. Algorithms for often-re­peated muscular activities.

b. Feedback from artificial ex­ternal sensors.

c. Adaptive control schemes. d. Voluntary interrupts for cor­

rection and override of stimulator output. 2. Methods of smoothing and li ­

nearizing muscle contractions and re­ducing muscle fatigue by:

a. The use of closed loop feed­back.

b. Conversion of muscle fiber contraction properties using chronic stimulation.

c. Electrode design and place­ment.

3. Proportional control of wrist. elbow and shoulder joints individually and in combination with each other and with finger grasp as appropriate for the available patient population.

4. Sources of potential propor­tional control signals.

B. The contractor shall evaluate and improve the reliability of intramuscular electrodes by:

1. Utilizing designs and materials that reduce breakage.

2. Utilizing designs that reduce migration.

3. In vivo testing in contracting muscles (this can include testing in non­paralyzed muscle.)

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PROGRESS REPORTS: Neurological. Communicative.·& Stroke

Transducer Development and Evaluation for Sensory Feedback in the Control of Paralyzed Extremities

Contract: N01-NS-80-2335 University of Utah Research

Institute 520 Wakara Way Salt Lake City. Utah 84108

A.A. Schoenberg. Ph. D .• Principal Investigator

Transducers suitable for use on or implanted in paralyzed hands without normal sensation are being developed and evaluated as part of a closed loop. functional neuromuscular stimulation control system for quadriplegic individ­uals. The specific workscope is as fol­lows:

A. Develop or adapt artificial sensor systems to detect:

1. Finger contact with objects. 2. Slippage of objects from grasp. 3. The pressure and force exerted

on a grasped object. 4. Fingertip position relative to a

fixed point on the hand. B. Consider methods of sensing fin­

gertip temperature. texture of grasped objects and the proximity of objects and estimate the potential value of these additional sensory signals.

C. Develop effective methods of cod­ing and presenting the information de­rived from the sensors to the remaining intact nervous system of a high-level (above C5) spinal-cord-injury subject (or a simulated subject) including:

1. Suitable interfaces and tempo­rary readouts for investigator evaluation of raw sensor outputs and coded out­puts.

2. Consideration in the design of possible future direct utilization of sen­sor output by microprocessor-based 3daptive control systems for control of the muscle stimulators.

D. Evaluate the sensors developed with a human or mechanical model silll ­ulating the functional-neuromuscular­stimulation-controlled paralyzed limb. or in quadriplegic patients if such a population is conveniently available.

1. Determine the important sensor properties such as threshold. dynamic range, signal-to-noise ratios, tempera­ture stability, and freedom from drift.

2. Determine possible causes of noise and ambiguous signals, and at­

tempt to eliminate or minimize these. 3. Determine the relative value of

each type of sensory system alone and in combination wth normal vision and as an aid in identifying. holding and manip­ulating objects of various sizes, weights, consistencies and textures.

4. Estimate the value of the sen­sor systems as part of a warning system for protecting against hand injury and as subconscious feedback signals in an adaptive control. microprocessor based. stimulation system.

Modification of Abnormal -Motor Control by Focal Electrical Stimulation

Contract: N01-NS-80-2338 University of Minnesota Department of Neurosurgery Minneapolis. Minnesota 55455

James R. Bloedel. M.D.• Ph. D.• Principal Investigator

Methods of reducing the incapacitat­ing aspects of certain motor control disorders accompanied by spasticity are being investigated. The specific work­scope is as follows:

A. Develop a relevant chronic animal model of a clinically defined movement disorder with a significant spastic com­ponent.

B. Select appropriate sites for selec­tive stimulation of known nervous sys­tem structures or pathways based on reasonable hypotheses and determine whether electrical stimulation modifies the motor control in the animal model. These experiments will include an eval­uation of the effects on:

1. Cutaneous and deep reflexes. 2. Passive movements. 3. Voluntary movements.

C. Study the effects of changes in stimulus variables with known exposed electrode surface areas at sites where modification of motor control is dem­onstrated. This should include an eval­uation of the effects of stimulus­

1. Frequency. 2. Charge density. 3. Current density. 4. Waveform.

D. Attempt to determine the mecha­nisms of any significant modifications of motor control.

E. Coordinate the experimental pro­gram with other collaborators of the Neural Prosthesis program.

Control of the Urinary Bladder

Contract: N01-NS-73-2307 University of California. San

Francisco. Department of Urology San Francisco. California 94143

Emil Tanagho. M.D.• Principal Investigator

The feasibility of developing prostheses for evacuating the neuro­genic bladder and for controlling urinary incontinence is being investigated. The specific workscope is as follows:

A. Conduct experiments on neuro­genic bladder evacuation to determine:

1. Optimal electrode size, elec­trode configuration. and stimulus para­meters for effective micturition while minimizing current spread and undesir­able side effects (e.g .. lower limb con­tractions. urethral sphincter contrac­tions. pain, autonomic dysreflexia).

2. Causes and methods of pre­venting outflow obstruction during elec­trical stimulation.

3. Histopathological effects of long-term electrical stimulation on the stimulated tissue.

4. Information on neurophysiolog­ical control mechanisms involved in mic­turition.

5. Relative effectiveness of sacral root stimulation for voiding compared with direct cord stimulation and direct bladder wall stimulation.

6. Develop and evaluate elec­trodes specifically designed for use in humans.

7. Evaluate the effectiveness of sacral root stimulation in human sub­jects.

B. Conduct experiments on urinary incontinence to determine:

1. Optimal electrode size, elec­trode configuration and stimulus para­meters for safe and effective control of

incontinence. 2. Methods of reducing sphincter

fatigue during chronic stimulation. 3. Histopathological effects of

chronic electrical stimulation on the

stimulated tissue. 4. Information on neurophys;ol~-

.' d' ma,n­ical control mechanism Involve In

taining continence. eleC­5 Develop and evaluate

. 58 .n trodes specifically designed for u

humans. 55 6. Evaluate the effectivene

01

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Bulletin of Prosthetics Research, BPR 10-35 (Vol. 18 No.1) Spring 1981

the electrodes developed in (5) for treat­

ing urinary incontinence in humans.

publications List

(The following listing shows publica­

tions resulting from Neural Prosthesis

Program Support as of January 1981;

the list does not include articles in press

at that time. The list does not include

abstracts. and it does not include articles

written by these authors wth NIH grant

support in these areas.)

(Dr. Hambrecht believes that all re­

prints should be relatively easy to ob­

tain.)

FUNDAMENTAL STUDIES

Guyton. D. L.. Hambrecht. F. T.: Capacitor electrode stimulates nerve or muscle with­out oxidation-reduction reactions. Science 181:74-76.1973.

Guyton. D. L.. Hambrecht. F, T,: Theory and design of capacitor electrodes for chronic stimulation. Med. Biolog. Eng, 7:613­619.1974.

Brummer. S, B.. Turner. M. J,: Electrical stimulation of the nervous system: The principle of safe charge injection with noble metal electrodes. Bioelectrochem. & Bioenergetics 2: 13-25. 1975.

Pudenz. R. H.. Bullara. L. A. Tallalla. A.: Electrical stimulation of the brain: I. Elec­trodes and electrode arrays. Surg. Neurol. 4:37-42. 1975.

Pudenz. R. H .. Bullara. L. A. Dru. D,. Talalla. A: Electrical stimulation of the brain: II. Effects on the blood-brain barrier. Surg. Neurol. 4:265-270. 1975.

Pudenz. R. H.. Bullara. L. A. Jacques. S.. Hambrecht. F. T.: Electrical stimulation of the brain: III. The neural damage model. Surg. Neurol. 4:389-400. 1975.

Agnew. W. F.. Yuen. T. G. H.. Pudenz. R. H,. Bullara. L. A: Electrical stimulation of the brain: IV, Ultrastructural studies. Surg. Neurol. 4:438-448. 1975.

Hench. L. L.. Etheridge. E. C.: Biomaterials­the interfacial problem. In: Advances in Biomedical Engineering (J. H. U. Brown. J. F. Dickson. eds.) Academic. New York. 1975. pp 36-139.

Johnson. P. F.. Hench. L. L.: An in vitro model for evaluating neural stimulating electrodes. J. Biomed. Mater. Res. 10:907-928. 1976.

Bernstein. J. J.: Neural Prostheses: Mate­rials. Physiology al)d Histopathology of Electrical Stimulation of the Nervous Sys­tem. Karger. Basel. 1976.

Brummer. S. B.. Turner. M. J.: Electro­chemical considerations for safe electrical stimulation of the nervous system with platinum electrodes. IEEE Trans, Biomed. Eng. 24:59-63.1977.

Brummer. S. B.. Turner. M. J.: Electrical stimulation with Pt electrodes: I-A method for determination of "real" elec­trode areas, IEEE Trans. Biomed. Eng. 24:436-439. 1977.

Brummer. S. B.. Turner. M, J.: Electrical stimulation with Pt electrodes: II-Esti ­mation of maximum surface redox (theo­retical non-gassing) limits. IEEE Trans. Biomed. Eng. 24:440-443. 1977.

Agnew. W. F.. Yuen. 1. G. H.. Pudenz. R. H .. Bullara. L. A.: Neuropathological effects of intercranial platinum salt injections. J. Neuropath. Exp. Neurol. 36:533-545. 1977.

Loeb. G. E.. Walker. A E,. Uematsu. S.. Konigsmark. B. W.: Histological reaction to various conductive and dielectric films chronically implanted in the subdural space. J. Biomed. Mater. Res. 11: 195­210.1977.

Bernstein. J. J .. Johnson. P. F.. Hench. L. L.. Hunter. G,. Dawson. W. W.: Cortical histopathology following stimulation with metallic and carbon electrodes, Brain Be­hav. Evol. 14:126-157. 1977.

Bartlett. J. R.. Doty, R. W.. Lee. B. B.. Negrao. N.. Overman. W. H. Jr.: Delete­rious effects of prolonged electrical exci­tation of striate cortex in macaques. Brain Behav. Evol. 14:46-66. 1977.

Johnson. P. F.. Hench. L. L.: An in vitro analysis of metal electrodes for use in the neural environment, Brain Behav. Evol. 14:23-45.1977,

Johnson. P. F.. Bernstein. J. J .. Hunter. G.. Dawson. W. W .. Hench. L. L.: An in-vitro and in-vivo analysis of anodized tantalum capacitive electrodes: Corrosion response. physiology and histology, J. Biomater. Res. 11 :637-656. 1977.

Pudenz. R. H.. Agnew. W. F.. Bullara. L. A: Effects of electrical stimulation of the brain: Light- and electron-microscopy studies. Brain Behav. Evol. 14: 103-125. 1977.

McHardy. J .. Geller. D .. Brummer. S. B.: An approach to corrosion control during elec­trical stimulation. Ann. Biomed. Eng. 5:144-149.1977,

Brummer. S. B.. McHardy. J., Turner, M. J.: Electrical stimulation with Pt electrodes: Trace analysis for dissolved platinum and other dissolved electrochemical products. Brain Behav, Evol. 14: 10-22, 1977.

Harrison, J. M., Dawson. W. W.: The visual cortex during chronic stimulation. Brain Behav. Evol. 14:87-102.1977.

Pudenz, R. H.. Agnew. W. F.. Yuen. T. G. H.. Bullara. L. A.: Electrical stimulation of brain: Light and electron microscopy stud­ies, In: Functional Electrical Stimulation: Applications in Neural Prostheses (F. T. Hambrecht. J. B. Reswick, eds,) Marcel Dekker. New York, 1977. pp 437-458.

Bernstein, J. J., Hench, L. L., Johnson. P. F.. Dawson, W. W., Hunter. G.: Electrical stimulation of the cortex with tantalum pentoxide capacitive electrodes, In: Func­tional Electrical Stimulation: Applications in Neural Prostheses (F. 1. Hambrecht. J. B. Reswick, eds.) Marcel Dekker. New Yo~, 1977. pp. 465-477.

Brummer. S. B.. McHardy. J.: Current prob­lems in electrode development. In: Func­tional Electrical Stimulation: Applications in Neural Prostheses (F. T. Hambrecht, J. B. Reswick, eds.) Marcel Dekker, New York, 1977, pp 499-514.

Pudenz, R. H.. Agnew, W. F., Yuen. 1. G. H., Bullara, L. A, Jacques, S.. Shelden. C. H.: Adverse effects of electrical energy ap­plied to the nervous system. Appl. Neu­rophysiol. 40: 72-87, 1977/78.

Stensaas. S. S.. Stensaas, L. J.: Histopath­ological evaluation of materials implanted in the cerebral cortex. Acta neuropath. (Berl.) 41: 145-155. 1978.

Hambrecht. F. T.: Comments on "Stereotaxic implantation of electrodes in the human brain: A method for long-term study and treatment." IEEE Trans. Biomed. Eng. 25:107.1978.

Agnew. W. F.. Yuen. T. G. H.. Bullara, L, A .. Jacques, D.. Pudenz, R. H.: Intracellular calcium deposition in brain following elec­trical stimulation, Neurol. Res. 1: 187­202, 1979,

Bullara, L. A, Agnew. W. F., Yuen. 1. G. H.. Jacques, S.. Pudenz, R. H.: Evaluation of electrode array material for neural prostheses. Neurosurg. 5: 681-686. 1979.

van den Honert, C.. Mortimer. J. T.: Gener­ation of unidirectionally propagated action potentials in a peripheral nerve by brief stimuli. Science 206: 1311-1312, 1979.

van den Honert. C.. Mortimer, J. T.: The response of the myelinated nerve fiber to short duration biphasic stimulating cur­rents, Ann. Biomed. Eng. 7:117-125, 1979.

McHardy. J., Robblee, L. S., Marston, J. M .. Brummer, S. B.: Electrical stimulation with Pt electrodes, IV. Factors influencing Pt dissolution in inorganic saline. Bio­materials 1: 129-134, 1980.

Robblee. L. S.. McHardy. J" Marston, J. M., Brummer. S. B.: Electrical stimulation with Pt electrodes. V. The effect of protein on Pt dissolution. Biomaterials 1: 135-139. 1980.

NEURAL PROSTHESES, GENERAL REVIEWS

Hambrecht. F. T.. Frank. K.: The future pos­sibilities for neural control. Adv. Electron. Electron Physics 38:55-81. 1975.

Frank, K., Hambrecht. F. T.: Neural prostheses. Brain Behav. Evol. 14:7-9. 1977.

Hambrecht. F. T.. Reswick, J. B. (eds.): Func­tional Electrical Stimulation: Applications in Neural Prostheses. Marcel Dekker, New York. 1977.

Frank, K.. Hambrecht, F, T.: Present status of neural prostheses: Visual, auditory, and motor. Clin. Neurosurg, 24:337-346, 1977,

Hambrecht, F. T.: Functional electrical stim­ulation: An overview of the present and speculations on the future. Electroenceph. Clin. Neurophysiol .. Suppl. 34:369-372, 1978.

Hambrecht, F. T.: Neural prostheses. Ann, Rev. Biophys. Bioeng. 8: 165-223. 1979.

CEREBRAL CORTICAL PROSTHESES

Chapanis. N. P., Uematsu. S.. Konigsmark, B.. Walker. A E.: Central phosphenes in

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PROGRESS REPORTS: Neurological. Communicative. & Stroke

man: A report of three cases. Neuropsy­chologia 11: 1-19. 1973.

Dobelle. W. H.. Stensaas. S. S.. Mladejovsky. M. G.. Smith. J. B.: A prosthesis for the deaf based on cortical stimulation. Ann. Otol. Rhinol. Laryngol. 82:445-463. 1973.

Hambrecht. F. T.: The current status of visual prostheses. Amer. J. Ophthal. 7: 161-163. 1973.

Hambrecht. F. T.: Visual prostheses: Theo­retical objectives. In: Neural Organization and its Relevance to Prosthetics. Stratton Intercon.. New York. 1973. pp 281-291.

Talalla. A. Bullara. L.. Pudenz. R.: Electrical stimulation of the human visual cortex: Preliminary report. Can. J. Neurol. Scis. 1:236-238. 1974.

Dobelle. W. H.. Mladejovsky. M. G.: Phos­phenes produced by electrical stimulation of human occipital cortex. and their appli­cation to the development of a prosthesis for the blind. J. Physiol. (Lond.) 243:553­576. 1974.

Dobelle. W. H.. Mladejovsky. M. G.. Girvin. J. P.: Artificial vision for the blind: Elec­trical stimulation of visual cortex offers hope for a functional prosthesis. Science 183:440-444. 1974.

Uematsu. S.. Chapanis. N.. Gucer. G.. Kon­igsmark. B.. Walker. A E.: Electrical stim­ulation of the cerebral visual system in man. Confin. Neurol. 36:113-124. 1974.

Pollen. D. A: Some perceptual effects of electrical stimulation of the visual cortex in man. In: The Nervous System. The Clinical Neurosciences. Vol. 2. (D. B. Tower. ed.) Raven Press. New York. 1976. pp 519-528.

Bartlett. J. R.. Doty. R. W.. Lee. B. B.. Sakakura. H.: Influence of saccadic eye movements on geniculostriate excitability in normal monkeys. Exp. Brain Res. 25:487-509. 1976.

Sakakura. H.. Doty. R. W.: EEG of striate cortex in blind monkeys: Effects of eye movements and sleep. Arch. Ital. BioI. 114:23-48. 1976.

Pollen. D. A: Responses of single neurons to electrical stimulation of the surface of the visual cortex. Brain. Behav. & Evol. 14:67-86.1977.

Pollen. D. A. Andrews. B. W .. Levy. J. C.: Electrical stimulation of the visual cortex in man and cat. In: Functional Electrical Stimulation: Applications in Neural Prostheses (F. 1. Hambrecht. J. B. Re­swick. eds.) Marcel Dekker. New York. 1977. pp 277-287.

BLADDER PROSTHESES

Jonas. U.. Jones. L. W .. Tanagho. E. A: La section medullaire experimentale chez I'animal etude des soins postoperatoires. (Experimental section of sacral marrow in animals: Study on postoperative care.) J. Urol. Nephrol. (Paris) 80:290. 1974.

Jonas. U.. Tanagho. E. A: Stimulation elect­rique de la moelle sacree pour obtenir la miction chez Ie chien. (Electrical stimula­tion of sacral marrow in dogs to initiate urination.) J. Urol. Nephrol. (Paris)

80:290-293. 1974. Jonas. U.. Jones. L. W .. Tanagho. E. A:

Etude comparative de la stimulation de la moelle sacree et de la stimulation du detrusor chez Ie chien. (Comparative study of sacral medullary stimulation and stim­ulation of detrusor in the dog.) J. Urol. Nephrol. (Paris) 80:293-295. 1974.

Jonas. U.. Tanagho. E. A: Studies on vesi­courethral reflexes: I. Urethral sphincteric responses to detrusor stretch. Invest. Urol. 12:357-373.1975.

Jonas. U.. Heine. J. P.. Tanagho. E. A: Studies on the feasibility of urinary bladder evacuation by direct spinal cord stimula­tion: I. Parameters of most effective stim­ulation. Invest. Urol. 13: 142-150. 1975.

Jonas. U.. Tanagho. E.A: Studies on the feasibility of urinary bladder evacuation direct spinal cord stimulation: II. Post­stimulus voiding: A way to overcome outflow resistance. Invest. Urol. 13: 151 ~

153. 1975. Jonas. U.. Jones. L. W .. Tanagho. E. A:

Spinal cord stimulation versus detrusor stimulation: A comparative study in six "acute" dogs. Invest. Urol. 13: 171-174. 1975.

Jonas. U.. Tanagho. E. A: Studies on vesi­courethral reflexes: II. Urethral sphincteric responses to spinal cord stimulation. In­vest. Urol. 13:278-285.1975.

Jones. L. W .. Jonas. U.. Tanagho. E. A .. Heine. J. P.: Urodynamic evaluation of a chronically implanted bladder pacemaker. Invest. Urol. 13:375-379. 1975.

Jonas. U.• Jones. L. W .. Tanagho. E. A: Controlled electrical bladder evacuation via stimulation of the sacral micturition center or direct detrusor stimulation. Urol. Int. 31:108-110.1976.

Dreyer. D. A .. Nashold. B. S.. Somjen. G.. Grimes. J. H.: Improved voiding in re­sponse to electrical stimulation of the spinal cord of paraplegic dogs. Invest. Urol. 14:54-56. 1976.

Heine. J. P.. Schmidt. R. A .. Tanagho. E. A: Intraspinal sacral root stimulation for con­trolled micturition. Invest. Urol. 15:78-82. 1977.

Schmidt. R. R.. Witherow. R.. Tanagho. E. A: Recording urethral pressure profile: Comparison of methods and clinical im­plications. Urol. 10:390-397. 1977.

Bruschini. H.. Schmidt. R. A .. Tanagho. E. A: Effect of urethral stretch on urethral pres­sure profile. Invest. Urol. 15:107-111. 1977.

Tanagho. E. A: Induced micturition via in­traspinal sacral root stimulation: Clinical implications. In: Functional Electrical Stimulation: Applications in Neural Prostheses. (F. T. Hambrecht. J. B. Re­swick. eds.) Marcel Dekker; New York. 1977. pp 157-172.

Tanagho. E. A: Bladder pacemaker-Fact or fiction? Contemp.Surg. 13:61.65.66.68­70. 1978.

Schmidt. R. A. Bruschini H.. Tanagho. E. A.: Feasibility of inducing micturition through chronic stimulation of the sacral roots. Urol. 12:471-477. 1978.

Kotokas. N. S.. Schmidt. R. A. Tanagho. E. A: Axonal transport of horseradish per­

oxidase: A new method for tracing nerv­ous control of the bladder. Urol. Int. 33:427-434. 1978.

Kokotas. N. S.. Schmidt. R. A. Tanagho. E. A: Motor innervation of the urinary tract studied by retrograde axonal transport of protein. Invest. Urol. 16: 179-185. 1978.

Schmidt. R. A. Bruschini. H.. Van Gool. J.. Tanagho. E. A: Micturition and the male genitourinary response to sacral root stim­ulation. Invest. Urol. 17:125-129.1979.

Schmidt. R. A. Bruschini. H.. Tanagho. E. A.: Sacral root stimulation in controlled mic­turition: Peripheral somatic neurotomy and stimulated voiding. Invest. Ural. 17:130-134.1979.

Schmidt. R. A. Tanagho. E. A: Feasibility of controlled micturition through electric stimulation. Urol. Int. 34: 199-230.

CEREBELLAR STIMULATION

Bantli .. H.. Bloedel. J. R.: Monosynaptic ac­tivation of a direct reticulo-spinal pathway by the dentate nucleus. Pfli.igers Arch. 357:237-242. 1975.

Tolbert. D. L.. Bantli. H.. Bloedel. J. R.: Anatomical and physiological evidence for a cerebellar nucleo-cortical projection in the cat. Neuroscience. 1:205-217. 1976.

Bantli. H.. Bloedel. J. R.. Tolbert. D. J.: Activation of neurons in the cerebellar nuclei and ascending reticular formation by stimulation of. the cerebellar surface. J. Neurosurg. 45: 539-554. 1976.

Bantli. H.. Bloedel. J. R.: Characteristics of the output from the dentate nucleus to spinal neurons via pathways which do not involve the primary sensorimotor cortex. Exp. Brain Res. 25: 199-220. 1976.

Tolbert. D. L.. Bantli. H.. Bloedel. J. R.: The intracerebellar nucleocortical projection. Exp. Brain Res. 30:425-434. 1977.

Brown. W. J .. Babb. T. L.. Soper. H. V.. Ueb. J. P.. Ottino. C. A .. Crandall. P. H.: Tissue reactions to long-term electrical stimula­tion of the cerebellum in monkeys. J. Neurosurg. 47:366-379.1977.

Babb. T. L.. Soper. H. V.. Lieb. J. P.. Brown. W. J .. Ottino. C. A .. Crandall. P. H.: Elec­trophysiological studies of long-term ele~­trical stimulation of the cerebellum In monkeys. J. Neurosurg. 47:353-365. 1977.

Crow. T. J .. Finch. D. M .. Babb. T. L.: Ab­sence of cerebellar influence on hipPO­campal neurons in the cat. Exp. Neurol. 57:486-505. 1977.

Bantli. H.. Bloedel. J. R.: Spinal input to the lateral cerebellum mediated by infraten­torial structures. Neurosc. 2:555-568. 1977.

Tolbert. D. L. Bantli. H.. Bloedel. J. R.: M I . I b h' f cerebellar efferent u tiP e ranc mg 0 . R s. projections m cats. Exp. Brain e 31 :305-316. 1978. L'eb

Soper. H. V.. Strain. G. M .. Babb.T. \ In~ J. P.. Crandall. P. H.: ChroniC a u~~p. temporal lobe seizures In monkeys. Neurol. 62:99-121. 1978. G

I· H BI d I J R Anderson. .•Bant I. .• oe e. ... ff ts of McRoberts. R.. Sandberg. E.: E eC the stimulating the cerebellar surface 0

n

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activity in penicillin foci. J. Neurosurg. 48:69-84, 1978.

Van Buren, J. M .. Wood, J. H., Oakley, J., Hambrecht, F. T.: Preliminary evaluation of cerebellar stimulation by double-blind stimulation and biological criteria in the treatment of epilepsy. J. Neurosurg. 48:407-416, 1978.

Bloedel, J. R.. Bantli, H.: A spinal action of the dentate nucleus mediated by descend­ing systems originating in the brain stem. Brain Res. 153: 602-607, 1978.

Finch, D. M., Feld, R. E.. Babb, T. L.: Effects of mesencephalic and pontine electrical stimulation on hippocampal neuronal ac­tivity in drug-free cat. Exp. Neurol. 61:318-336,1978.

Tolbert, D. L., Bantli, H., Bloedel, J. R.: Organizational features of the cat and monkey cerebellar nucleocortical projec­tion. J. Compo Neur. 182:39-56, 1978.

Strain, G. M .. Babb, 1. L., Soper, H. V.. Perryman, K. M., Lieb, J. P.. Crandall, P. H.: Effects of chronic cerebellar stimula­tion on chronic limbic seizures in monkeys. Epilepsia 20:651-664, 1979.

Babb, T. L., Perryman, K. N.. Lieb, J. P.. Finch, D. M .. Crandall, P. H.: Procaine­induced seizures in epileptic monkeys with bilateral hippocampal foci. EEG & Clin. Neurophysiol. 47:725-737,1979.

Tolbert, D. J .. Bantli, H.: An HRP and auto­radiographic study of cerebellar corticon­uclear-nucleocortical reciprocity in the monkey. Exp. Brain Res. 36: 563-571, 1979.

Tolbert, D. J., Bantli, H.: Uptake and trans­port of H3-GABA (gamma-aminobutyric acid) injected into the cat dentate nucleus. Exp. Neurol. 70: 525-538, 1980.

Ebner, T. J .. Bantli, H., Bloedel, J. R.: Effects of cerebellar stimulation on unitary activity within a chronic epileptic focus in a pri­mate. EEG & Clin. Neurophysiol. 49: 585­599, 1980.

Finch, D. M .. Babb, T. L.: Neurophysiology of the caudally directed hippocampal ef­ferent system in the rat: Projections to the subicular complex. Brain Res. 197: 11-26, 1980.

Tolbert. D. L., Bantli, H.. Hames, E. G., Ebner, T. J., McMullen, T. A, Bloedel, J. R.: A . demonstration of the dentato-reticulos­pinal projection in the cat. Neuroscience 5:1479-1488,1980.

Finch, D. M., Babb, T. L.: Inhibition in subi­cular and entorhinal principal neurons in response to electrical stimulation of the fornix and hippocampus. Brain Res. 196:89-98, 1980.

Ebner, T. J .. Vitek, J. L., Schwartz, A B., Bloedel, J. R.: Effects of cerebellar stim­ulation on abnormal proprioceptive re­flexes in spastic primates. Exp. Neurol. 70: 721-725, 1980.

AUDITORY PROSTHESES

Gheewala, T. R.. Melen, R. G.. White, R. L.: A CMOS implantable multielectrode au­ditory stimulator for the deaf. IEEE J. Solid-State Circs. 10:472-479, 1975.

Merzenich, M. M., White, M. W.: Cochlear

implant: The interface problem. In: Func­tional Electrical Stimulation: Applications in Neural Prostheses (F. T. Hambrecht, J. B. Reswick, eds.) Marcel Dekker, New York, 1977, pp 321-340.

White, R. L.: Electronics and electrodes for sensory prostheses. In: Functional Elec­trical Stimulation: Applications in Neural Prostheses (F. T. Hambrecht. J. B. Re­swick, eds.) Marcel Dekker, New York, 1977, pp 485-498.

Mercer, H. D., White, R. L.: Photolithographic fabrication and physiological performance of microelectrode arrays for neural stim­ulation. IEEE Trans. Biomed. Eng. 25:494-500, 1978.

White, R. L.: Multielectrode arrays. Proc. NSF Wrkshp. Opportunities for Science, Engng. & Technol., Airlie House, Va. 149­154, 1978.

Merzenich, M. M., White, M. W., Vivion, M. C.. Leake-Jones, P. A, Walsh, S. M.: Some considerations of multichannel elec­trical stimulation of the auditory nerve in the profoundly deaf; interfacing electrode arrays with the auditory nerve array. Acta Otolaryngol. 87: 196-203, 1979.

Merzenich, M. M. Cochlear i~plants; state of development and application. In: Pro­ceedings from Conference on Interrela­tions of the Communicative Senses. (L. D. Harmon, Ed.) National Science Founda­tion, Asilomar, Calif., 1979, pp 325-337.

Hambrecht, F. T.: Current status of multi ­channel cochlear prostheses. Ann. Otol. Rhinol. Laryngol. 88: 729-733, 1979.

White, R. L.. May, G. A, Duval, F.. Mathews, R. G.. Walker, M. G., Soma, M .. Shamma, S.: Integrated circuit technology and the realization of an implantable auditory prosthesis. In: Advanced Technobiology, Proc. of a NATO Advanced Study Inst., Paris. (B. Rybak, Ed.) Sijthoff & Noordhoff Internatl. Pubs.. Alphen aan den Rijn, Netherlands, 1979, pp 405-418.

May, G. A, Shamma, S. A., White, R. L.: A tantalum-on-sapphire microelectrode ar­ray. IEEE Trans. Electron Devices 26: 1932-1939, 1979.

Soma, M.: Design and fabrication of an implantable multichannel neural stimula­tor. Technical Report No. G908-1. Stan­ford Electronics Laboratories, Stanford, June, 1980.

Merzenich, M. M .. White, M.: Coding consid­erations in design of cochlear prostheses. Ann. Otol. Rhinol. Laryngol. 89: 84-87, 1980.

Leake-Jones, P. A, O'Reilly, B. F.. Vivion, M. C.: Neomycin ototoxicity: Ultrastructural surface pathology of the organ of Corti. Scan. Electron Microsc. #3:427-434, 1980.

Walsh, S. M., Merzenich, M. M .. Schindler, R. A, Leake-Jones, P. A: Some practical considerations in development of multi ­channel scala tympani prostheses. Au­diology 19: 164-175, 1980.

Soma, M., May, G. A, Duval, F., White, R. L.: Integrated circuits fabrication for an implantable multichannel neural stimula­tor. Proc. of the Custom Integrated Cir­cuits Conference, 1980, pp 28-30.

White, R. L., Duval, F., May, G. A, Mathews,

R. G.. Walker, M. G.: Technical consider­ations in the realization of a cochlear prosthesis. In: Advances in Prosthetic Devices for the Deaf: A Technical Work­shop. (D. L. McPherson, Ed.) Natl. Tech. Inst. for the Deaf, Rochester, 1980, pp 324-329.

Merzenich, M., Vivion, M., Leake-Jones, P., White, M.: Progress in development of implantable multielectrode scala tympani arrays for a cochlear implant prosthesis. In: Advances in Prosthetic Devices for the Deaf: A Technical Workshop. (D. L. McPherson, Ed.) Natl. Tech. Inst. for the Deaf, Rochester, 1980, pp 262-270.

MOTOR PROSTHESES, FUNCTIONAL NEUROMUSCULAR STIMULATION

Mortimer, J. T., Peckham, P. H.: Intramus­cular electrical stimulation. In: Neural Or­ganization and its Relevance to Prosthet­ics (W. S. Fields, ed.) Symposia Specialists, 1973, pp 131-146.

Peckham, P. H.. Mortimer, J. T., Marsolais, E. B.: Upper and lower motor neuron lesions in the upper extremity muscles of tetraplegics. Paraplegia 14: 115-121, 1976.

Peckham, P. H., Mortimer, J. T., Marsolais, E. B.: Alteration in the force and fatiga­bility of skeletal muscle in quadriplegic humans following exercise induced by chronic electrical stimulation. Clin. Or­thoped. & ReI. Res. 114:326-334, 1976.

Peckham, P. H., Mortimer, J. T.: Restoration of hand function in the quadriplegic through electrical stimulation. In: Func­tional Electrical Stimulation: Applications in Neural Prostheses (F. T. Hambrecht. J. B. Reswick, eds.) Marcel Dekker, New York, 1977, pp 83-95.

Thomas, J. S., Schmidt, E. M .. Hambrecht. F. T.: Facility of motor unit control during tasks defined directly in terms of unit behaviors. Exp. Neurol. 59:384-395, 1978.

Crago, P. E., Mortimer, J. T.. Peckham, P. H.: Closed-loop control of force during elec­trical stimulation of muscle. IEEE Trans. Biomed. Eng. 27:306-312,1980.

Crago, P. E.. Peckham, P. H.. Thrope, G. B.: Modulation of muscle force by recruitment during intramuscular stimulation. IEEE Trans. Biomed. Eng. 27:679-684, 1980.

DIAGNOSTIC ULTRASOUND

Kak, A C., Fry, F. J.: Acoustic impedance profiling: An analytical and physical model study. Paper 7.1 in Chapter 7, Impedance profile techniques. Proceedings of Semi­nar on Ultrasonic Tissue Characterization. National Bureau of Standards, Gaithers­burg, Md.. 1976, pp 231-251.

Barnes, R. W .. Toole, J. F.. McKinney, W. M.: An ultrasound digital moving target indicator system for diagnostic use. IEEE Trans. Sonics Ultrason. 24:350-354, 1977.

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INTRACRANIAL PRESSURE MONITORING

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