Neuroinflammation After Stereotactic Radiosurgery-Induced Brain Tumor Disintegration Is Linked to Persistent Cognitive Decline in a Mouse Model of Metastatic Disease.

PURPOSE: Improved efficacy of anticancer therapy and a growing pool of survivors give rise to a question about their quality of life and return to premorbid status. Radiation is effective in brain metastasis eradication, although the optimal approach and long-term effects on brain function are largely unknown. We studied the effects of radiosurgery on brain function. METHODS AND MATERIALS: Adult C57BL/6J mice with or without brain metastases (rat 9L gliosarcoma) were treated with cone beam single-arc stereotactic radiosurgery (SRS; 40 Gy). Tumor growth was monitored using bioluminescence, whereas longitudinal magnetic resonance imaging, behavioral studies, and histologic analysis were performed to evaluate brain response to the treatment for up to 18 months. RESULTS: Stereotactic radiosurgery (SRS) resulted in 9L metastases eradication within 4 weeks with subsequent long-term survival of all treated animals, whereas all nontreated animals succumbed to the brain tumor. Behavioral impairment, as measured with a recognition memory test, was observed earlier in mice subjected to radiosurgery of tumors (6 weeks) in comparison to SRS of healthy brain tissue (10 weeks). Notably, the deficit resolved by 18 weeks only in mice not bearing a tumor, whereas tumor eradication was complicated by the persistent cognitive deficits. In addition, the results of magnetic resonance imaging were unremarkable in both groups, and histopathology revealed changes. SRS-induced tumor eradication triggered long-lasting and exacerbated neuroinflammatory response. No demyelination, neuronal loss, or hemorrhage was detected in any of the groups. CONCLUSIONS: Tumor disintegration by SRS leads to exacerbated neuroinflammation and persistent cognitive deficits; therefore, methods aiming at reducing inflammation after tumor eradication or other therapeutic methods should be sought.

Temporary inactivation of the medial prefrontal cortex impairs the formation, but not the retrieval of social odor recognition memory in rats.

The hippocampus, medial dorsal thalamus and the perirhinal and entorhinal cortices are essential for visual recognition memory whereas the neural substrates underlying olfactory recognition memories are less well characterized. In the present study we combined chemogenetic inactivation with a social odor recognition memory (SORM) task to test the hypothesis that the medial prefrontal cortex (mPFC) is involved in recognition memory. We demonstrate that temporary chemogenetic inactivation of the mPFC prior to an encoding session impairs social odor recognition memory, whereas silencing the mPFC just prior to the recognition session was without effect. Our data support the critical role of the mPFC in the formation rather than retrieval of social odor memory.

Short and Long-Term Changes in Social Odor Recognition and Plasma Cytokine Levels Following Oxygen (16O) Ion Radiation Exposure.

Future long-duration space missions will involve travel outside of the Earth's magnetosphere protection and will result in astronauts being exposed to high energy and charge (HZE) ions and protons. Exposure to this type of radiation can result in damage to the central nervous system and deficits in numerous cognitive domains that can jeopardize mission success. Social processing is a cognitive domain that is important for people living and working in groups, such as astronauts, but it has received little attention in terms of HZE ion exposure. In the current study, we assessed the effects of whole-body oxygen ion (16O; 1000 MeV/n) exposure (1 or 10 cGy) on social odor recognition memory in male Long-Evans rats at one and six months following exposure. Radiation exposure did not affect rats' preferences for a novel social odor experienced during Habituation at either time point. However, rats exposed to 10 cGy displayed short and long-term deficits in 24-h social recognition. In contrast, rats exposed to 1 cGy only displayed long-term deficits in 24-h social recognition. While an age-related decrease in Ki67+ staining (a marker of cell proliferation) was found in the subventricular zone, it was unaffected by radiation exposure. At one month following exposure, plasma KC/GRO (CXCL1) levels were elevated in the 1 cGy rats, but not in the 10 cGy rats, suggesting that peripheral levels of this cytokine could be associated with intact social recognition at earlier time points following radiation exposure. These results have important implications for long-duration missions and demonstrate that behaviors related to social processing could be negatively affected by HZE ion exposure.

Modeling Space Radiation Induced Bone Changes in Rat Femurs through Finite Element Analysis.

As the duration of manned missions outside of the Earth's protective shielding increase, astronauts are at risk for exposure to space radiation. Various organ systems may be damaged due to exposure. This study investigates the bone strength changes using finite element modeling of Long Evans rats (n=85) subjected to graded, head-only proton (0, 10, 25, and 100 cGy, 150 MeV/n) and 28silicon (0, 10, 25, and 50 cGy, 300 MeV/n) radiation. The strength of the femoral neck will be examined due its clinical relevance to hip fractures. It has been shown in previous studies that bone mineral density was not reduced at the site of fracture. These findings question whether measurements of bone mineral density may be used to assess risk of hip fracture. The mechanisms leading to the irregular relationship between bone density and strength are still uncertain within literature and investigated to greater extent in clinical applications. Finite element analysis within this study simulated physiological loading of the femoral neck. No significant changes in femoral neck strength were found across doses of proton or 28silicon head-only radiation. Future work includes performing mechanical testing of the bone samples. Moving from mouse to larger animal models may also provide the increased lifespan for assessing the long-term outcomes of radiation exposure.

Whole-Body Oxygen (16O) Ion-Exposure-Induced Impairments in Social Odor Recognition Memory in Rats are Dose and Time Dependent.

Future long-duration space missions will involve travel outside of the Earth's magnetosphere, which will result in increased radiation exposure for astronauts. Exposure could permanently damage multiple tissues, including the central nervous system (CNS), and result in deleterious effects on cognition and behavior during and beyond the mission. Here, we assessed the effects of whole-body oxygen ion (16O; 1,000 MeV/n) exposure (5 or 25 cGy) on social odor recognition memory in male Long-Evans rats at one and six months after exposure. At one month postirradiation, all rats displayed a preference for a novel 1 (N1) social odor experienced during the habituation phase. When assessed for recognition memory 24 h later, only sham-irradiated rats spent more time exploring a second novel social odor (novel 2, N2), whereas rats irradiated with 5 or 25 cGy 16O ions did not show a preference for the N2 odor compared to the N1 odor experienced 24 h earlier, thus displaying a memory deficit for recall of the social odor encountered 24 h prior. At six months postirradiation, rats exposed to 25 cGy showed persistent deficits in 24 h recognition memory, while the 5 cGy-exposed rats did not. Thus, 24 h recognition memory was apparently recovered at six months postirradiation for the low, but not the higher, dose of 16O ions. Both irradiated groups displayed similar numbers of Ki67+ cells, a marker of cell proliferation, in the subventricular zone. These results further demonstrate that space-relevant 16O ion exposure has deleterious effects on the CNS, which are related to both radiation dose and time after exposure.

A rodent model of the human psychomotor vigilance test: Performance comparisons.

BACKGROUND: The human Psychomotor Vigilance Test (PVT) is commonly utilized as an objective risk assessment tool to quantify fatigue and sustained attention in laboratory, clinical, and operational settings. NEW METHOD: Recent studies have employed a rodent version of the PVT (rPVT) to measure various aspects of attention (lapses in attention, reaction times) under varying experimental conditions. RESULTS: Data are presented here to evaluate the short- and long-term utility of the rPVT adapted for laboratory rats designed to track the same types of performance variables as the human PVT-i.e., motor speed, inhibitory control ("impulsivity"), and attention/inattention. Results indicate that the rPVT is readily learned by rats and requires less than two weeks of training to acquire the basic procedure. Additional data are also presented on the effects of radiation exposure on these performance measures that indicate the utility of the procedure for assessing changes in neurobehavioral function in rodents across their lifespans. COMPARISON WITH EXISTING METHOD(S): Once stable performances are obtained, rats evidence a high degree of similarity to human performance measures, and include similarities in terms of lapses and reaction times, in addition to percent correct and premature responding. Similar to humans, rats display both a vigilance decrement across time on task and a response-stimulus interval effect. CONCLUSIONS: The rPVT is a useful tool in the investigation of the effects of a wide range of variables on vigilance performance that compares favorably to the human PVT and for developing potential prophylactics, countermeasures, and treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice.

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT-termed the "rPVT"-that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human "time-on-task" effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

Deficits in Sustained Attention and Changes in Dopaminergic Protein Levels following Exposure to Proton Radiation Are Related to Basal Dopaminergic Function.

The current report assessed the effects of low-level proton irradiation in inbred adult male Fischer 344 and Lewis rats performing an analog of the human Psychomotor Vigilance Test (PVT), commonly utilized as an object risk assessment tool to quantify fatigue and sustained attention in laboratory, clinical, and operational settings. These strains were used to determine if genetic differences in dopaminergic function would impact radiation-induced deficits in sustained attention. Exposure to head-only proton irradiation (25 or 100 cGy) disrupted rPVT performance in a strain-specific manner, with 25 cGy-exposed Fischer 344 rats displaying the most severe deficits in sustained attention (i.e., decreased accuracy and increased premature responding); Lewis rats did not display behavioral deficits following radiation. Fischer 344 rats displayed greater tyrosine hydroxylase and dopamine transporter levels in the frontal cortex compared to the Lewis rats, even though radiation exposure increased both of these proteins in the Lewis rats only. Tyrosine hydroxylase was decreased in the parietal cortex of both rat strains following radiation exposure, regardless of proton dose. Strain-specific cytokine changes were also found in the frontal cortex, with the Lewis rats displaying increased levels of putative neurotrophic cytokines (e.g., CNTF). These data support the hypothesis that basal dopaminergic function impacts the severity of radiation-induced deficits in sustained attention.

Effects of X-ray radiation on complex visual discrimination learning and social recognition memory in rats.

The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal). One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min), while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation.

Individual differences in attentional deficits and dopaminergic protein levels following exposure to proton radiation.

To assess the possible neurobehavioral performance risks to astronauts from living in a space radiation environment during long-duration exploration missions, the effects of head-only proton irradiation (150 MeV/n) at low levels (25-50 cGy, approximating an astronaut's exposure during a 2-year planetary mission) were examined in adult male Long-Evans rats performing an analog of the human psychomotor vigilance test (PVT). The rodent version of PVT or rPVT tracks performance variables analogous to the human PVT, including selective attention/inattention, inhibitory control ("impulsivity") and psychomotor speed. Exposure to head-only proton radiation (25, 50, 100 or 200 cGy) disrupted rPVT performance (i.e., decreased accuracy, increased premature responding, elevated lapses in attention and slowed reaction times) over the 250 day testing period. However, the performance decrements only occurred in a subgroup of animals at each exposure level, that is, the severity of the rPVT performance deficit was unrelated to proton exposure level. Analysis of brain tissue from irradiated and control rats indicated that only rats with rPVT performance deficits displayed changes in the levels of the dopamine transporter and, to a lesser extent, the D2 receptor. Additional animals trained to perform a line discrimination task measuring basic and reversal learning showed no behavioral effects over the same exposure levels, suggesting a specificity of the proton exposure effects to attentional deficits and supporting the rPVT as a sensitive neurobehavioral assay.

SIV/macaque model of HIV infection in cocaine users: minimal effects of cocaine on behavior, virus replication, and CNS inflammation.

Studies of the effects of drugs of abuse on HIV immune status, disease progression, and neuroAIDS have produced conflicting data and have not definitively shown whether this combination promotes cognitive impairment or disease progression. Using a consistent SIV-macaque model, we investigated the effects of cocaine on behavior, virologic parameters, and CNS inflammation. Macaques received either vehicle or chronic administration of behaviorally active doses of cocaine (1.7 or 3.2 mg/kg/day). Chronic cocaine administration reduced CD8+ T cell counts during acute and late stage infection but had no effect on CD4+ T cell counts. Low-dose cocaine-treated animals had lower CSF vRNA levels late in infection, but cocaine did not alter plasma viral load or vRNA or protein in brain. There were no differences in CSF CCL-2 or interleukin (IL)-6 levels or severity of encephalitis in cocaine-treated as compared to vehicle-treated macaques. There were no differences in brain inflammation or neurodegeneration markers, as determined by interferon (IFN)-ß, MxA, CCL2, IL-6, TNFα, IFNγ, and indolamine 2,3-deoxygenase mRNA levels. APP levels also were not altered. The executive function of inhibitory control was not impaired in cocaine-treated or control animals following SIV infection. However, animals receiving 3.2 mg/kg/day cocaine performed more slowly in a bimanual motor test. Thus, chronic administration of cocaine produced only minor changes in behavior, encephalitis severity, CNS inflammation/neurodegeneration, and virus replication in SIV-infected pigtailed macaques, suggesting that cocaine would have only modest effects on the progression of neuroAIDS in HIV-infected individuals.

Neurobehavioral effects of head-only gamma-radiation exposure in rats.

The present report describes initial steps in the development of an animal model for assessing the effects of low levels of radiation encountered in the space environment on human cognitive function by examining the effects of radiation on a range of neurobehavioral functions in rodents that are similar to a number of basic human cognitive functions. The present report presents baseline data on the effects of gamma radiation on neurobehavioral functions in rodents (psychomotor speed, discrimination accuracy and inhibitory control) that are similar to those in humans. Two groups of eight Long-Evans rats were trained to perform a reaction-time task that required them to depress a lever for 1-3 s and to release the lever within 1.5 s of a release stimulus (correct trial) to receive a reward. Releasing the lever prior to the release stimulus (error) terminated the trial. One group was exposed to head-only gamma radiation (5 Gy at a dose rate of 1 Gy/min), while the second group was sham-irradiated using the same anesthesia protocol. The irradiated group showed significant deficits in both performance accuracy (percentage correct scores) and performance reliability (false alarm scores) from 1 to 4 months after irradiation, indicating clear performance impairments. The increase in false alarm scores is consistent with reduced inhibitory control and a shift toward increased anticipatory responses at the cost of decreased accuracy. The nonirradiated group showed no such changes over the same period.

Consistent, high-level ethanol consumption in pig-tailed macaques via a multiple-session, limited-intake, oral self-dosing procedure.

BACKGROUND: Alcohol abuse is a major public health burden that can lead to many adverse health effects such as impaired hepatic, gastrointestinal, central nervous system and immune system function. Preclinical animal models of alcohol abuse allow for experimental control over variables often difficult to control in human clinical studies (e.g., ethanol exposure before or during the study, history of other drug use, access to medical care, nutritional status, etc). Nonhuman primate models in particular provide increased genetic, anatomic and physiologic similarity to humans, relative to rodent models. A small percentage of macaques will spontaneously consume large quantities of ethanol; however, most nonhuman primate models of "voluntary" ethanol intake produce relatively low daily ethanol intake in the majority of monkeys. METHODS: To facilitate study of chronic exposure to high levels of ethanol intake, a macaque model has been developed that induces consistent, daily high-level ethanol consumption. This multiple-session procedure employed 4 drinking sessions per day, with sessions occurring once every 6 hours. RESULTS: The group average alcohol consumption was 4.6 g/kg/d (SEM 0.4), roughly twice the group average consumption of previous reports. Ethanol drinking sessions produced group mean blood ethanol levels of 95 mg/dl after 60 minutes, and fine motor control was impaired up to 90 minutes after a drinking session. CONCLUSION: This model of multiple-session, limited access, oral ethanol self-dosing produced consistent, high-level ethanol consumption with each session qualifying as a "binge" drinking session using the definition of "binge" provided by the NIAAA (>80 mg/dl/session). This model of ethanol drinking in macaques will be of great utility in the study of immunological, physiological and behavioral effects of ethanol in nonhuman primates.

Environmental cues, alcohol seeking, and consumption in baboons: effects of response requirement and duration of alcohol abstinence.

BACKGROUND: Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions. METHODS: Alcohol drinking was established in 4 baboons. A sequence of lights and tones was presented during daily 3-hour sessions. First, cues were presented alone and no programmed contingencies were in effect. Second, cues were paired with 3 linked components consisting of different behavioral contingencies leading to and concluding with access to alcohol for self-administration in the last component (i.e., a chained schedule of alcohol reinforcement). Third, the effects of withholding alcohol access (i.e., forced abstinence) and increasing the number of lever responses required per drink were evaluated. RESULTS: Cues paired with a chained schedule of alcohol reinforcement engendered behaviors that brought baboons into contact with alcohol-related cues and occasioned operant responding that facilitated access to alcohol (alcohol seeking) during components that preceded alcohol access. Increasing the response requirement for each drink decreased the number of drinks and volume of alcohol consumed, but did not alter alcohol seeking. On the first session after 14 days of alcohol abstinence, latency to complete the operant requirement that produced alcohol access was decreased while both alcohol self-administration and volume of alcohol consumed were increased. CONCLUSIONS: Alcohol self-administration and consumption were sensitive to increases in response requirement and duration of alcohol abstinence, while seeking was only enhanced by duration of alcohol abstinence. This animal model may be useful to further examine the interactions between environmental cues and behaviors associated with seeking and consumption of alcohol and to evaluate the efficacy of potential alcohol treatment drugs on these behaviors.

Effects of morphine on circadian rhythms of motor activity and body temperature in pig-tailed macaques.

Previous studies of the effects of opiates on motor activity and body temperature in nonhuman primates have been limited in scope and typically only conducted with restrained animals. The present study used radio-telemetry devices to continuously measure activity and temperature in unrestrained pig-tailed macaques for 24 h following morphine administration. Two dose-response functions (0.56 to 5.6 mg/kg, i.m.) were determined, one with morphine administered at 9 a.m. and one with morphine administrated at 3 p.m. Under both the 9 a.m. or 3 p.m. administration schedules, body temperature and activity were increased acutely. Activity was also reduced the following morning after morphine administered at either time. In other regards, morphine's effects on both temperature and activity differed between 9 a.m. and 3 p.m. injection, including periods of decreased activity immediately after the acute increases after 9 a.m. but not 3 p.m. administration. Surprisingly, motor activity also increased 9-12 h post-injection following morphine administered at 9 a.m., but not at 3 p.m. These results clearly show an interaction between timing of morphine administration and effects on temperature and activity. These results also underscore the fact that single injections of drugs may have multiple and delayed effects on circadian rhythms in macaques.

Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells.

Crewmember performance before, during, and after spaceflight.

The development of technologies for monitoring the welfare of crewmembers is a critical requirement for extended spaceflight. Behavior analytic methodologies provide a framework for studying the performance of individuals and groups, and brief computerized tests have been used successfully to examine the impairing effects of sleep, drug, and nutrition manipulations on human behavior. The purpose of the present study was to evaluate the feasibility and sensitivity of repeated performance testing during spaceflight. Four National Aeronautics and Space Administration crewmembers were trained to complete computerized questionnaires and performance tasks at repeated regular intervals before and after a 10-day shuttle mission and at times that interfered minimally with other mission activities during spaceflight. Two types of performance, Digit-Symbol Substitution trial completion rates and response times during the most complex Number Recognition trials, were altered slightly during spaceflight. All other dimensions of the performance tasks remained essentially unchanged over the course of the study. Verbal ratings of Fatigue increased slightly during spaceflight and decreased during the postflight test sessions. Arousal ratings increased during spaceflight and decreased postflight. No other consistent changes in rating-scale measures were observed over the course of the study. Crewmembers completed all mission requirements in an efficient manner with no indication of clinically significant behavioral impairment during the 10-day spaceflight. These results support the feasibility and utility of computerized task performances and questionnaire rating scales for repeated measurement of behavior during spaceflight.

Cocaine's effects on the perception of socially significant vocalizations in baboons.

The effects of cocaine on the ability of baboons to discriminate among their natural affiliative 'grunt' vocalizations were examined to determine whether cocaine would produce discrimination impairments similar to those observed previously with acoustically-similar human vowel sounds , or whether differences in cocaine's effects might occur associated with the social significance of the calls. The task employed digitized calls of actual vocalizations recorded in the wild . Baboons pressed a lever to produce a repeating 'standard' grunt, and released the lever only when one of four other 'target' grunts was selected to occur in place of the standard grunt. Cocaine (0.01-.56 mg/kg, i.m.) impaired call perception, and these impairments were more pronounced than those observed previously for acoustically-similar human vowel sounds. Cocaine also elevated reaction times as a function of dose. The results demonstrate that cocaine impairs perceptual discriminations of the natural grunt vocalizations of baboons, and suggest that cocaine may have more pronounced effects on the perception of biologically-relevant as opposed to non-relevant communication signals.

The discrimination of baboon grunt calls and human vowel sounds by baboons.

The ability of baboons to discriminate changes in the formant structures of a synthetic baboon grunt call and an acoustically similar human vowel (/epsilon/) was examined to determine how comparable baboons are to humans in discriminating small changes in vowel sounds, and whether or not any species-specific advantage in discriminability might exist when baboons discriminate their own vocalizations. Baboons were trained to press and hold down a lever to produce a pulsed train of a standard sound (e.g., /epsilon/ or a baboon grunt call), and to release the lever only when a variant of the sound occurred. Synthetic variants of each sound had the same first and third through fifth formants (F1 and F3-5), but varied in the location of the second formant (F2). Thresholds for F2 frequency changes were 55 and 67 Hz for the grunt and vowel stimuli, respectively, and were not statistically different from one another. Baboons discriminated changes in vowel formant structures comparable to those discriminated by humans. No distinct advantages in discrimination performances were observed when the baboons discriminated these synthetic grunt vocalizations.

Distributed interactive communication in simulated space-dwelling groups.

This report describes the development and preliminary application of an experimental test bed for modeling human behavior in the context of a computer generated environment to analyze the effects of variations in communication modalities, incentives and stressful conditions. In addition to detailing the methodological development of a simulated task environment that provides for electronic monitoring and recording of individual and group behavior, the initial substantive findings from an experimental analysis of distributed interactive communication in simulated space dwelling groups are described. Crews of three members each (male and female) participated in simulated "planetary missions" based upon a synthetic scenario task that required identification, collection, and analysis of geologic specimens with a range of grade values. The results of these preliminary studies showed clearly that cooperative and productive interactions were maintained between individually isolated and distributed individuals communicating and problem-solving effectively in a computer-generated "planetary" environment over extended time intervals without benefit of one another's physical presence. Studies on communication channel constraints confirmed the functional interchangeability between available modalities with the highest degree of interchangeability occurring between Audio and Text modes of communication. The effects of task-related incentives were determined by the conditions under which they were available with Positive Incentives effectively attenuating decrements in performance under stressful time pressure.