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Principal Investigator:
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Robert D. Hienz, Ph.D.
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Organization:
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The Johns Hopkins University School of Medicine
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Project Ended:
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2012
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Radiation exposure is one of most dangerous risks to humans during spaceflight. Before astronauts conduct long-duration missions beyond low-Earth orbit, it is necessary to understand the biological consequences of extended stays in the space radiation environment. Dr. Robert Hienz is leading a study to determine the effects of radiation on neurobehavioral functions, such as general motor function, memory, sustained attention and reaction time. The project, which uses an animal model, is also assessing any long-term damage that radiation may cause to the central nervous system.
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Principal Investigator:
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Robert D. Hienz, Ph.D.
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Organization:
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The Johns Hopkins University School of Medicine
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Project Ended:
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2012
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Original Aims - To assess the effects of space radiation across a range of cognitive/behavioral functions in rodents. Performance measures include assessments of general motor function and speed, fine motor control, inhibitory control (impulsivity), timing, short-term memory, spatial working memory, learning and selective attention, motivation, and basic sensory function. Groups of animals are separately trained on different tasks, exposed at Brookhaven National Laboratory to high-energy radiation at levels that astronauts would likely experience during lunar or planetary surface activities, and then immediately re-tested.
- To assess the long-term effects of radiation across a range of cognitive/behavioral functions via extended post-exposure testing for potential performance deficits.
- To assess both the acute and long-term effects of radiation on the neurochemical mechanisms underlying changes in cognitive/behavioral functions by examining the integrity of the neurotransmitter systems known to mediate those neurobehavioral functions found impaired.
Key Findings Results from the project thus far demonstrate the reliability and validity of the neurobehavioral procedures in detecting behavioral changes following radiation, that analogs of human psychomotor performance assessment procedures can be employed with rodents to automatically assess neurobehavioral function on a daily basis, and that such procedures can be used to effectively track changes in neurobehavioral function over extended intervals following radiation exposure. Specifically, the results have shown that head-only radiation produces discrete neurobehavioral changes by significantly decreasing discrimination accuracy and increasing false alarms in the reaction time procedure, with the latter result being indicative of a decrease in inhibitory control. These findings support the likely success of the rodent model for studying the risks of living in the space radiation environment due to changes in cognitive/neurobehavioral function.
During the current year studies continued to track daily performances on the rat psychomotor vigilance test (rPVT), which is an animal analog of the Psychomotor Vigilance Test (PVT) used to study sustained attention in humans. Following irradiation, performances on the rPVT were disrupted at all exposure levels studied (i.e., 25, 50, 100, and 200 cGy protons). Changes in motor function were manifested as consistent, significant increases (i.e., a slowing) in reaction times, indicative of a decrease in sustained attention. Other changes in sustained attention included decreases in accuracy, increases in performance lapses, and increases in impulsivity. New pilot studies of the effects of additional circadian disruptions on these rodent PVT performances have been conducted to determine the degree to which the observed radiation effects on neurobehavioral function may be compounded when disruptions in sleep/wake schedules occur (i.e., as under conditions of heavy workload and/or extended-duration exploration missions). Initial data indicates that disruptions in circadian rhythms has the potential to exacerbate ongoing radiation-induced neurobehavioral impairments, with radiation-exposed animals showing pronounced increases in sustained attention greater than those observed with radiation alone. Additionally, in a new study designed to measure impulsive choice behaviors in rodents, exposure to 200 cGy produced an increase in impulsivity compared to controls, indicating this may be an additional fruitful model for investigating biological consequences of radiation exposure as well as pharmacotherapy and other countermeasures aimed at preventing these radiation-induced brain and behavioral changes.
To summarize, the data obtained during the current year demonstrate that significant changes in sustained attention, impulsivity, and motor function can be shown to occur following proton exposures as low as 25 cGy for the exposure groups as a whole. Importantly, significant variations in responding to these proton doses occurred among animals within groups that indicate that these “average” effects of proton irradiation may not be indicative of all animals. In animals that respond significantly to proton irradiations, all exposure doses produced similar effects on accuracy, lapses, and reaction times. Finally, the changes in sustained attention were tracked over time for up to 1 year post-exposure and found to persist over this extended time period.
Impact of Findings
The present results demonstrate the sensitivity of tests such as the rPVT for assessing the effects of head-only space radiation on cognitive neurobehavioral function. Such deficits could significantly impact routine performances in operational environments during long-duration exploratory missions, and also negatively affect post-mission adjustment upon return to Earth. These findings support the likely continued success of the rodent model for studying the cognitive, neurobehavioral, and CNS risks associated with living in the space radiation environment while providing an innovative experimental platform for exploring the bases of individual vulnerability to radiation-induced impairments and evaluating potential prophylactics, countermeasures, and treatments.
Research Plan for the Coming Year
Animals are currently being trained in the rodent version of the PVT. Once training is completed, they will be transported and exposed in May 2011 at Brookhaven National Laboratory to iron ions over a dose range of 0 – 150 cGy, and then returned for extensive post-radiation testing. Studies of the effects of circadian disruptions as well as the effects of both stimulants and depressants, in combination with irradiations, will be completed. Additional data will be obtained via neuropathological imaging of the tissue with the translocator protein TSPO (Dr. Guilarte), as well as data on the integrity of the dopaminergic (DA) system using Western blot analyses (in collaboration with Dr. De Cicco-Skinner).
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Principal Investigator:
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Robert D. Hienz, Ph.D.
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Organization:
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The Johns Hopkins University School of Medicine
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Project Ended:
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2012
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Research conducted on the effects of ionizing radiation on cognitive/behavioral function provides the basis for extrapolating the effects of the space radiation environment on human cognitive function and performance. The Earth-based applications of this research extend to providing a means for generalizing these effects to numerous types of radiation exposures on earth (e.g., workplace, medical). Thus the outcomes of these studies are expected to have an important impact on safety and the quality of life in many Earth-based applied settings, and the society at large will further benefit from the resulting methodological advances that effectively provide quantitative risk assessments for radiation exposure on cognitive function. In addition, the development of a comprehensive and experimentally flexible animal model of neurobehavioral performance provides a useful tool for preclinical research and development in other domains such as sleep/chronobiology, neuropsychiatric disorders, aging, and cognitive enhancement.
Moreover, the human Psychomotor Vigilance Test (PVT) is a standardized and widely validated objective measure of neurobehavioral status not only employed by NASA, but also utilized in a variety of settings such as clinical neuropsychiatric assessment, military, shiftwork, and aviation. As such, the present rodent analog of the PVT provides a direct translational link to performance capacity on Earth. Once validated, the rPVT model developed here may be used as a basic and translational research tool to predict performance deficits induced by radiation or other CNS insults while providing an innovative experimental platform for exploring the bases of individual vulnerability to performance impairments and evaluating potential prophylactics, countermeasures, and treatments.
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