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Biomedical subjects

C A Kovera

Publications and source records attributed to C A Kovera.

8 recordsLinked to original sources

Neurobehavioral deficits in Persian Gulf veterans: evidence from a population-based study. Portland Environmental Hazards Research Center.

Reports of low-concentration nerve gas exposures during the Persian Gulf War have spurred concern about possible health consequences and refocused interest on the symptoms reported by many returning military veterans. The Portland Environmental Hazards Research Center is studying veterans from the Northwest USA who report persistent, unexplained "Persian Gulf" symptoms (cases) or who do not report those symptoms (controls). Of the first 101 veterans studied, cases differed substantially from controls on a broad range of psychological tests indicative of increased distress. A subgroup of cases was identified with objective deficits on neurobehavioral tests of memory, attention, and response speed.

Adult

Test-retest reliability of psychological and neurobehavioral tests self-administered by computer.

A series of 12 psychological and 7 neurobehavioral performance tests were administered twice to a nonclinical normative sample with 1 week between administrations. The tests were presented in a self-administered computerized format. One week test-retest reliabilities were comparable to conventional administration formats. The results suggest that individual test reliability is not affected when tests are administered as part of an extensive multi-measure battery. Computer administered test reliability coefficients also were compared to a Mixed Format (computer-conventional) administration with mixed format reliabilities generally similar to the reliabilities of published conventional tests but also generally lower than same format testing. Compared to psychological test reliability, neurobehavioral test reliability appeared more vulnerable to decreases with mixed format testing. These conclusions should not be generalized to all computer implemented tests as the qualities of the test implementation will affect the outcome.

Adult

Medication development of ibogaine as a pharmacotherapy for drug dependence.

The potential for deriving new psychotherapeutic medications from natural sources has led to renewal interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

Animals

Mechanisms underlying the effects of unsignaled delayed reinforcement on key pecking of pigeons under variable-interval schedules.

Three experiments were conducted to test an interpretation of the response-rate-reducing effects of unsignaled nonresetting delays to reinforcement in pigeons. According to this interpretation, rates of key pecking decrease under these conditions because key pecks alternate with hopper-observing behavior. In Experiment 1, 4 pigeons pecked a food key that raised the hopper provided that pecks on a different variable-interval-schedule key met the requirements of a variable-interval 60-s schedule. The stimuli associated with the availability of the hopper (i.e., houselight and keylight off, food key illuminated, feedback following food-key pecks) were gradually removed across phases while the dependent relation between hopper availability and variable-interval-schedule key pecks was maintained. Rates of pecking the variable-interval-schedule key decreased to low levels and rates of food-key pecks increased when variable-interval-schedule key pecks did not produce hopper-correlated stimuli. In Experiment 2, pigeons initially pecked a single key under a variable-interval 60-s schedule. Then the dependent relation between hopper presentation and key pecks was eliminated by arranging a variable-time 60-s schedule. When rates of pecking had decreased to low levels, conditions were changed so that pecks during the final 5 s of each interval changed the keylight color from green to amber. When pecking produced these hopper-correlated stimuli, pecking occurred at high rates, despite the absence of a peck-food dependency. When peck-produced changes in keylight color were uncorrelated with food, rates of pecking fell to low levels. In Experiment 3, details (obtained delays, interresponse-time distributions, eating times) of the transition from high to low response rates produced by the introduction of a 3-s unsignaled delay were tracked from session to session in 3 pigeons that had been initially trained to peck under a conventional variable-interval 60-s schedule. Decreases in response rates soon after the transition to delayed reinforcement were accompanied by decreases in eating times and alterations in interresponse-time distributions. As response rates decreased and became stable, eating times increased and their variability decreased. These findings support an interpretation of the effects of delayed reinforcement that emphasizes the importance of hopper-observing behavior.

Animals

Behavioral and neurochemical mechanisms of opioid-antidepressant interactions.

Twelve pigeons key-pecked under a multiple variable interval 15-s, 150-s schedule of food reinforcement. The effects of methadone were studied alone and in combination with chronic daily administration of either imipramine (IMI) or desipramine (DMI). Chronic IMI was also given following reductions in response rates by unsignaled delay-to-reinforcement (UDR). Acute administration of methadone produced dose-dependent reductions in response rates under both schedules of reinforcement. Chronic daily administration of IMI or DMI alone did not result in lasting changes in baseline responding. When administered in combination, chronic daily IMI significantly attenuated the rate-reducing effects of methadone, whereas neither a low nor a high dose of chronic daily DMI was effective. The same dose of chronic daily IMI failed to ameliorate response rate reductions under delayed reinforcement. The behavioral and neurochemical specificity of the antidepressant effect is discussed.

Animals

Human behavioral assessment in neurotoxicology: producing appropriate test performance with written and shaping instructions.

Neurotoxic effects are of such breadth and complexity that functional biomarkers (behavioral tests) that integrate many areas of the nervous system predominate in human neurotoxicology research. The increasing distribution of chemical and other manufacturing throughout the world, particularly in developing nations, suggests the acute need to develop biomarkers for chemical exposures and effects that can be employed internationally. A language-free method for training performance on behavioral tests is described, which holds promise for international research that circumvents the vagaries of translation. Four behavioral tests were administered to 74-114 adult US subjects. Procedures, collectively termed shaping, produced effective performance on three tests [Symbol Digit, Vigilant Attention Test (VAT), Digit Span Forward and Backward], and produced appropriate but unacceptably slow performance in initial testing on the Simple Reaction Time test. Effective performance on the Symbol-Digit test also was produced by shaping instruction, without assistance from examiners, in small groups of residents of Taipei (Taiwan) and US children between the ages of 5 and 16.

Adolescent

Computerized neurobehavioral testing: techniques for improving test instructions.

The development of new computer-administered neuropsychological tests has brought a renewed focus on the issue of written instructions. Designers and programmers often fail to take advantage of the display options and feedback potential available in modern computer systems to maximize the effectiveness of the instruction process. Guidelines from computer interface architecture and behavioral analysis are combined to present three principles for written instructions: precise language, attention focusing, and interactive instruction. A comparison of different instruction formats in the Symbol-Digit and Simple Reaction Time tests shows that the application of these principles can reduce training time without degrading performance.

Adult

Computer-administration of questionnaires: a health screening system (HSS) developed for veterans.

The introduction of microcomputers in psychological research has spawned a burgeoning number of tests of psychological or behavioral function, but few computerized systems for administering questionnaires have been developed. A Health Screening System (HSS) is described that combines the benefits of the paper-and-pencil format (e.g., convenient navigation within test questions) and the added benefits of computer-implementation (e.g., efficiency, automated scoring). The HSS features; a) appealing test appearance (e.g., text in large-size fonts, color backgrounds); b) clear wording of tests and instructions (identical wording as original tests except when clarity is served by changes); c) limiting need for Examiner-Subject interaction (e.g., continuously available on-line training, navigation within test questions, answer review capability, durable 9-button response unit); d) options (e.g., question skipping, spoken instructions, test questions, and answers on command); e) modification capabilities (e.g., color, text, test layout editing, control of test order, automated breaks, addition of tests to system); and f) extras (e.g., kernel of main instruction on each test screen, digitized video, audio message from Examiner in training, copyright notification on each screen, raw and summary data outputs in spreadsheet formal). Ten HSS tests were administered to 22 US military veterans, who took slightly longer to complete them than did 10 veterans who were administered the same tests in their original paper-and-pencil format. User reaction to the computerized HSS was positive.

Adult