Multi-domain cognitive assessment of male mice shows space radiation is not harmful to high-level cognition and actually improves pattern separation.

Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56Fe and 28Si irradiation led to faster context discrimination in a non-touchscreen task and 56Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.

Meta-analysis of Cognitive Performance by Novel Object Recognition after Proton and Heavy Ion Exposures.

Experimental studies of cognitive detriments in mice and rats after proton and heavy ion exposures have been performed by several laboratories to investigate possible risks to astronauts exposed to cosmic rays in space travel and patients treated for brain cancers with proton and carbon beams in Hadron therapy. However, distinct radiation types and doses, cognitive tests and rodent models have been used by different laboratories, while few studies have considered detailed dose-response characterizations, including estimates of relative biological effectiveness (RBE). Here we report on the first quantitative meta-analysis of the dose response for proton and heavy ion rodent studies of the widely used novel object recognition (NOR) test, which estimates detriments in recognition or object memory. Our study reveals that linear or linear-quadratic dose-response models of relative risk (RR) do not provide accurate descriptions. However, good descriptions for doses up to 1 Gy are provided by exponentially increasing fluence or dose-response models observed with an LET dependence similar to a classical radiation quality response, which peaks near 100-120 keV/µm and declines at higher LET values. Exponential models provide accurate predictions of experimental results for NOR in mice after mixed-beam exposures of protons and 56Fe, and protons, 16O and 28Si. RBE estimates are limited by available X-ray or gamma-ray experiments to serve as a reference radiation. RBE estimates based on use of data from combined gamma-ray and high-energy protons of low-LET experiments suggest modest RBEs, with values <8 for most heavy ions, while higher values <20 are based on limited gamma-ray data. In addition, we consider a log-normal model for the variation of subject responses at defined dose levels. The log-normal model predicts a heavy ion dose threshold of approximately 0.01 Gy for NOR-related cognitive detriments.

Prenatal Sensory Stimulation Induces BDNF Gene Expression in the Brain and Potentiates the Development of Species-Specific Predisposition in Newborn Chicks.

We studied the effects of light and non-specific sound stimulation of domestic chick embryos on their filial preference as well as on the expression of two transcriptional factors c-Fos and Egr-1 and neurotrophin BDNF in the embryo brain. Prenatal light stimulation increased preference of the "natural" object, thus producing a priming effect. In the brain of E19 embryos, c-Fos and Egr-1 were expressed at a high basal level and neither light nor sound stimulation affected the number of cells expressing these factors. BDNF mRNA was also present in a number of brain areas of non-stimulated embryos, but light and sound stimulation enhanced the expression of BDNF mRNA in brain structures associated with filial imprinting. These findings suggest that BDNF is probably involved in the effects of prenatal priming on the development of species-specific behavior.

Effect of 1.8 GHz radiofrequency electromagnetic radiation on novel object associative recognition memory in mice.

Mounting evidence suggests that exposure to radiofrequency electromagnetic radiation (RF-EMR) can influence learning and memory in rodents. In this study, we examined the effects of single exposure to 1.8 GHz RF-EMR for 30 min on subsequent recognition memory in mice, using the novel object recognition task (NORT). RF-EMR exposure at an intensity of >2.2 W/kg specific absorption rate (SAR) power density induced a significant density-dependent increase in NORT index with no corresponding changes in spontaneous locomotor activity. RF-EMR exposure increased dendritic-spine density and length in hippocampal and prefrontal cortical neurons, as shown by Golgi staining. Whole-cell recordings in acute hippocampal and medial prefrontal cortical slices showed that RF-EMR exposure significantly altered the resting membrane potential and action potential frequency, and reduced the action potential half-width, threshold, and onset delay in pyramidal neurons. These results demonstrate that exposure to 1.8 GHz RF-EMR for 30 min can significantly increase recognition memory in mice, and can change dendritic-spine morphology and neuronal excitability in the hippocampus and prefrontal cortex. The SAR in this study (3.3 W/kg) was outside the range encountered in normal daily life, and its relevance as a potential therapeutic approach for disorders associated with recognition memory deficits remains to be clarified.

Effects of Proton and Combined Proton and (56)Fe Radiation on the Hippocampus.

The space radiation environment contains protons and (56)Fe, which could pose a significant hazard to space flight crews during and after missions. The space environment involves complex radiation exposures, thus, the effects of a dose of protons might be modulated by a dose of heavy-ion radiation. The brain, and particularly the hippocampus, may be susceptible to space radiation-induced changes. In this study, we first determined the dose-response effect of proton radiation (150 MeV) on hippocampus-dependent cognition 1 and 3 months after exposure. Based on those results, we subsequently exposed mice to protons alone (150 MeV, 0.1 Gy), (56)Fe alone (600 MeV/n, 0.5 Gy) or combined proton and (56)Fe radiations (protons first) with the two exposures separated by 24 h. At one month postirradiation, all animal groups showed novel object recognition. However, at three months postirradiation, mice exposed to either protons or combined proton and (56)Fe radiations showed impaired novel object recognition, which was not observed in mice irradiated with (56)Fe alone. The mechanisms in these impairments might involve inflammation. In mice irradiated with protons alone or (56)Fe alone three months earlier, there was a negative correlation between a measure of novel object recognition and the number of newly born activated microglia in the dentate gyrus. Next, cytokine and chemokine levels were assessed in the hippocampus. At one month after exposure the levels of IL-12 were higher in mice exposed to combined radiations compared with sham-irradiated mice, while the levels of IFN-γ were lower in mice exposed to (56)Fe radiation alone or combined radiations. In addition, IL-4 levels were lower in (56)Fe-irradiated mice compared with proton-irradiated mice and TNF-α levels were lower in proton-irradiated mice than in mice receiving combined radiations. At three months after exposure, macrophage-derived chemokine (MDC) and eotaxin levels were lower in mice receiving combined radiations. The levels of MDC and eotaxin correlated and the levels of MDC, but not eotaxin, correlated with the percentage of newly born activated microglia in the blades of the dentate gyrus. Finally, hippocampal IL-6 levels were higher in mice receiving combined radiations compared with mice receiving (56)Fe radiation alone. These data demonstrate the sensitivity of novel object recognition for detecting cognitive injury three months after exposure to proton radiation alone, and combined exposure to proton and (56)Fe radiations, and that newly-born activated microglia and inflammation might be involved in this injury.

Gender differences in facial expression recognition in survivors of pediatric brain tumors.

OBJECTIVE: To examine the relation between gender, history of cranial radiation therapy (CRT) and facial expression recognition (FER) skill in survivors of pediatric brain tumors. METHODS: Fifty-three survivors (27 females) completed a measure of FER and an intelligence test. RESULTS: There was a significant interaction between gender and CRT on ability to interpret low-intensity facial expressions, such that females who had not had CRT made fewer errors than either females who had CRT or males. CONCLUSION: A history of CRT has a notable effect on FER skill in females: girls who received CRT performed significantly more poorly than girls who did not.

10 Hz flicker improves recognition memory in older people.

BACKGROUND: 10 Hz electroencephalographic (EEG) alpha rhythms correlate with memory performance. Alpha and memory decline in older people. We wished to test if alpha-like EEG activity contributes to memory formation. Flicker can elicit alpha-like EEG activity. We tested if alpha-frequency flicker enhances memory in older people. Pariticpants aged 67-92 identified short words that followed 1 s of flicker at 9.0 Hz, 9.5 Hz, 10.0 Hz, 10.2 Hz, 10.5 Hz, 11.0 Hz, 11.5 Hz or 500 Hz. A few minutes later, we tested participants' recognition of the words (without flicker). RESULTS: Flicker frequencies close to 10 Hz (9.5-11.0 Hz) facilitated the identification of the test words in older participants. The same flicker frequencies increased recognition of the words more than other frequencies (9.0 Hz, 11.5 Hz and 500 Hz), irrespective of age. CONCLUSION: The frequency-specificity of flicker's effects in our participants paralleled the power spectrum of EEG alpha in the general population. This indicates that alpha-like EEG activity may subserve memory processes. Flicker may be able to help memory problems in older people.

Cognitive changes in short-term hypothyroidism assessed with event-related brain potentials.

Hypothyroidism is a common clinical problem during (131)Iodine-therapy of thyroid cancer. In the present investigation, possible cognitive dysfunction during hypothyroid state was assessed by means of neuropsychological tests and the recording of event-related brain potentials (ERPs). Fifteen patients undergoing therapy for thyroid cancer were examined twice: (1) substituted with thyroid hormones, (2) during hypothyroid state immediately prior to treatment. Standard neuropsychological tests were applied during both sessions and subjects showed a mild-to-moderate impairment in their hypothyroid state. In addition, ERPs were recorded from 19 scalp sites while subjects performed two visual search tasks. The serial task required the effortful one-by-one scanning of several items within a visual array, while the parallel task allowed processing of all stimulus items in parallel and automatically. ERPs showed a marked amplitude decrement and delay of the P3 component known to index the speed of stimulus evaluation and the amount of available processing resources. This effect was present only for the serial search task, while no changes were seen in the parallel search task. These data show that hypothyroidism during (131)Iodine-therapy is associated with clinically relevant cognitive dysfunctions, especially with effortful attention demanding tasks.