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NASA's decision to resume manned deep space mission, first to the Moon and then Mars, necessitated a detailed assessment of the potential health effects that astronauts may experience on long-duration missions. Multiple studies suggest that there may be significant space radiation (SR)-induced impairment of neurocognitive processes, including advanced executive functions. However, given the multitude of SR-induced changes in the CNS, it is possible that completely different SR-induced sequelae will be induced in previously exposed individuals. Thus, current risk estimates are likely to be pertinent only for the early stages of a deep space mission, and even then only for astronauts that have no previous experience in space. In this study, rats that maintained high attentional set shifting (ATSET) performance after an initial exposure to 10 cGy of SR (either 250 MeV/n He or GCRsim), were exposed to an additional dose of 10 cGy GCRsim and their ATSET performance reassessed. The re-irradiated rats exhibited significant impairment of ATSET performance, however, the performance decrements differed in two important aspects from those typically observed after single exposures. First, the decrements were manifested when the rats were required to perform set shifting, specifically in the IDR and EDS stages of the ATSET test. Secondly, the main performance decrement was in a loss of processing speed, which in the IDR stage resulted in the re-irradiated rats taking 2-fold more time to solve the problem than did Sham rats. The functional consequence of this decrement was that compared to Sham rats, 20 % fewer SR-exposed rats solved the IDS and EDR problems within 20 s. These data suggests that prior SR exposure alters nature of ATSET impairments from that observed in radiation-naïve individuals. Risk estimates derived from studies that use radiation naïve rats may thus not fully reflect the incidence and nature of ATSET performance deficits that could occur over the entire duration of a mission to Mars, or in astronauts who return to deep space on multiple occasions. It would thus be germane to conduct in-flight monitoring for cognitive performance decrements observed in both radiation naïve and exposed rats during the mission, and ensure that the crew has sufficient overlapping skill sets to minimize the operational impact of these additional cognitive impairments., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

Light regulates both image- and various non-image forming responses in humans, including acute effects on attention and affect. To advance the understanding of light's immediate effects, this systematic review describes the acute effects of monochromatic/narrow bandwidth and polychromatic white light during daytime on distinct aspects of attention (alertness, sustained attention, working memory, attentional control and flexibility), and measures of affect (self-report measures, performance-based tests, psychophysiological measures) in healthy, adult human subjects. Original, peer-reviewed (quasi-) experimental studies published between 2000 and May 2024 were included according to predefined inclusion and exclusion criteria. Study quality was assessed, and results were synthesized across aspects of attention and affect and grouped according to light interventions; monochromatic/narrowband-width or polychromatic white light (regular white, bright white, and white with high correlated color temperature (CCT)). Results from included studies (n = 62) showed that alertness and working memory were most affected by light. Electroencephalographic markers of alertness improved the most with exposure to narrow bandwidth long-wavelength light, regular white, and white light with high CCT. Self-reported alertness and measures of working memory improved the most with bright white light. Results from studies testing the acute effects on sustained attention and attentional control and flexibility were inconclusive. Performance-based and psychophysiological measures of affect were only influenced by narrow bandwidth long-wavelength light. Polychromatic white light exerted mixed effects on self-reported affect. Studies were strongly heterogeneous in terms of light stimuli characteristics and reporting of light stimuli and control of variables influencing light's acute effects., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elisabeth Flo-Groeneboom reports financial support was provided by Research Council of Norway. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory., Patients and Methods: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability., Results: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study., Conclusion: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results., (Copyright © 2024. Published by Elsevier Masson SAS.)

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6-14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3-7 Hz, 300-800 ms), alpha (9-13 Hz, 400-900 ms), and beta responses (14-24 Hz, 400-900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued - validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

During the planned missions to Mars, astronauts will be faced with many potential health hazards including prolonged exposure to space radiation. Ground-based studies have shown that exposure to space radiation impairs the performance of male rats in cognitive flexibility tasks which involve processes that are essential to rapidly and efficiently adapting to different situations. However, there is presently a paucity of information on the effects of space radiation on cognitive flexibility in female rodents. This study has determined the impact that exposure to a low (10 cGy) dose of ions from the simplified 5-ion galactic cosmic ray simulation [https://www.bnl.gov/nsrl/userguide/SimGCRSim.php (07/2023)] (GCRSim) beam or 250 MeV/n 4He ions has on the ability of female Wistar rats to perform in constrained [attentional set shifting (ATSET)] and unconstrained cognitive flexibility (UCFlex) tasks. Female rats exposed to GCRSim exhibited multiple decrements in ATSET performance. Firstly, GCRSim exposure impaired performance in the compound discrimination (CD) stage of the ATSET task. While the ability of rats to identify the rewarded cue was not compromised, the time the rats required to do so significantly increased. Secondly, both 4He and GCRSim exposure reduced the ability of rats to reach criterion in the compound discrimination reversal (CDR) stage. Approximately 20% of the irradiated rats were unable to complete the CDR task; furthermore, the irradiated rats that did reach criterion took more attempts to do so than did the sham-treated animals. Radiation exposure also altered the magnitude and/or nature of practice effects. A comparison of performance metrics from the pre-screen and post-exposure ATSET task revealed that while the sham-treated rats completed the post-exposure CD stage of the ATSET task in 30% less time than for completion of the pre-screen ATSET task, the irradiated rats took 30-50% longer to do so. Similarly, while sham-treated rats completed the CDR stage in ∼10% fewer attempts in the post-exposure task compared to the pre-screen task, in contrast, the 4He- and GCRSim-exposed cohorts took more (∼2-fold) attempts to reach criterion in the post-exposure task than in the pre-screen task. In conclusion, this study demonstrates that female rats are susceptible to radiation-induced loss of performance in the constrained ATSET cognitive flexibility task. Moreover, exposure to radiation leads to multiple performance decrements, including loss of practice effects, an increase in anterograde interference and reduced ability or unwillingness to switch attention. Should similar effects occur in humans, astronauts may have a compromised ability to perform complex tasks., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Astronauts on the Artemis missions to the Moon and Mars will be exposed to unavoidable Galactic Cosmic Radiation (GCR). Studies using male rats suggest that GCR exposure impairs several processes required for cognitive flexibility performance, including attention and task switching. Currently no comparable studies have been conducted with female rats. Given that both males and females will travel into deep space, this study determined whether simulated GCR (GCRsim) exposure impairs task switching performance in female rats. Female Wistar rats exposed to 10 cGy GCRsim (n = 12) and shams (n = 14) were trained to perform a touchscreen-based switch task that mimics a switch task used to evaluate pilots' response times. In comparison to sham rats, three-fold more GCRsim-exposed rats failed to complete the stimulus response stage of training, a high cognitive loading task. In the switch task, 50% of the GCRsim-exposed rats failed to consistently transition between the repeated and switch blocks of stimuli, which they completed during lower cognitive loading training stages. The GCRsim-exposed rats that completed the switch task only performed at 65% of the accuracy of shams. Female rats exposed to GCRsim thus exhibit multiple decrements in the switch task under high, but not low, cognitive loading conditions. While the operational significance of this performance decrement is unknown, if GCRSim exposure was to induce similar effects in astronauts, our data suggests there may be a reduced ability to execute task switching under high cognitive loading situations., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Previous research revealed inconsistent effects of bright light or a short nap at noon on alertness and performance across different tasks. The current study aimed to explore whether the effects of bright light and a short nap at noon on task performance depended on the cognitive domain. Bright light (1,200 lx, 4,000 K at eye level), nap (near darkness) and control (200 lx, 4,000 K at eye level) conditions were performed from 1:00 to 1:40 PM on three non-consecutive days with a counterbalanced order across participants. After being assigned to one of three conditions, participants underwent two repeated test sessions, each including a psychomotor vigilance task, a go/no-go task, and a paced visual serial addition task, with an interval of more than 1 h, to assess the persistent effects of napping and bright light. Subjective sleepiness, vitality, self-control and mood were also measured. Results showed that accuracy on the go/no-go task and the paced visual serial addition task improved significantly throughout the entire experiment session after napping, whereas reaction speed on the paced visual serial addition task improved time-dependently in the bright light intervention, with a higher reaction speed in only the first test session. Nearly all subjective states benefited from napping but not from bright light. These findings suggested that the effects of bright light and an afternoon nap on task performance would depend on the cognitive domain. An afternoon nap may elicit more effective and persistent benefits on task performance and subjective states., (© 2020 European Sleep Research Society.)

Purpose: The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients., Methods and Materials: In a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and magnetic resonance imaging/diffusion-weighted imaging at baseline (pre-radiation therapy) and 3-, 6-, and 12-months post-radiation therapy. CC (subregions, total) and IHWM tracts (left/right without CC, total) were autosegmented; tumor, tumor bed, and edema were censored. Biomarkers included volume changes (cm 3 ), mean diffusivity ([MD]; higher values indicate white matter injury), fractional anisotropy ([FA]; lower values indicate white matter injury). Reliable-change indices measured changes in attention (Weschler Adult Intelligence Scale [WAIS-IV] digits-forward; Delis-Kaplan Executive Function System Trail Making [D-KEFS-TM] visual-scanning), and processing speed (WAIS-IV coding; D-KEFS-TM number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between mean radiation dose and biomarkers (volume, MD, FA) and imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons., Results: Processing speed declined at 6 months following radiation therapy (number sequencing, letter sequencing; P < .04). Seizures and antiepileptic drug therapy were associated with lower visual-scanning attention reliable-change indices at 6 months (P = .039). Higher radiation dose correlated with smaller midanterior CC volume (P = .023); lower FA in posterior CC, anterior CC, and total CC (all P < .03); and higher MD in anterior CC (P = .012). Smaller midanterior CC and left IHWM volume correlated with worse processing speed (coding, letter-sequencing, number-sequencing; all P < .03). Higher FA in right, left, and total IHWM correlated with better coding scores (all P < .01). Lower FA in total IHWM (P = .009) was associated with worse visual-scanning attention scores. Higher FA in midposterior CC (P = .029) correlated with better digits-forward attention scores., Conclusions: The CC demonstrated radiation dose-dependent atrophy and WM injury. Microstructural injury within the CC and IHWM was associated with attention and processing speed decline after radiation therapy. These areas represent possible avoidance regions for preservation of attention and processing speed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To advance knowledge on the psychophysiological markers of "coordination cost" in team settings, we explored differences in meta-communication patterns (i.e., silence, speaking, listening, and overlap), perceived psychological states (i.e., core affect, attention, efficacy beliefs), heart rate variability (i.e., RMSSD), and brain rhythms (i.e., alpha, beta and theta absolute power) across three studies involving 48 male dyads (Mage = 21.30; SD = 2.03). Skilled participants cooperatively played three consecutive FIFA-17 (Xbox) games in a dyad against the computer, or competed against the computer in a solo condition and a dyad condition. We observed that playing in a team, in contrast to playing alone, was associated with higher alpha peak and global efficiency in the brain and, at the same time, led to an increase in focused attention as evidenced by participants' higher theta activity in the frontal lobe. Moreover, we observed that overtime participants' brain dynamics moved towards a state of "neural-efficiency", characterized by increased theta and beta activity in the frontal lobe, and high alpha activity across the whole brain. Our findings advance the literature by demonstrating that (1) the notion of coordination cost can be captured at the neural level in the initial stages of team development; (2) by decreasing the costs of switching between tasks, teamwork increases both individuals' attentional focus and global neural efficiency; and (3) communication dynamics become more proficient and individuals' brain patterns change towards neural efficiency over time, likely due to team learning and decreases in intra-team conflict.

Word-production theories argue that during language production, a concept activates multiple lexical candidates in left temporal cortex, and the intended word is selected from this set. Evidence for theories on spoken-word production comes, for example, from the picture-word interference task, where participants name pictures superimposed by congruent (e.g., picture: rabbit, distractor "rabbit"), categorically related (e.g., distractor "sheep"), or unrelated (e.g., distractor "fork") words. Typically, whereas congruent distractors facilitate naming, related distractors slow down picture naming relative to unrelated distractors, resulting in semantic interference. However, the neural correlates of semantic interference are debated. Previous neuroimaging studies have shown that the left mid-to-posterior STG (pSTG) is involved in the interference associated with semantically related distractors. To probe the functional relevance of this area, we targeted the left pSTG with focal repetitive transcranial magnetic stimulation (rTMS) while subjects performed a picture-word interference task. Unexpectedly, pSTG stimulation did not affect the semantic interference effect but selectively increased the congruency effect (i.e., faster naming with congruent distractors). The facilitatory TMS effect selectively occurred in the more difficult list with an overall lower name agreement. Our study adds new evidence to the causal role of the left pSTG in the interaction between picture and distractor representations or processing streams, only partly supporting previous neuroimaging studies. Moreover, the observed unexpected condition-specific facilitatory rTMS effect argues for an interaction of the task- or stimulus-induced brain state with the modulatory TMS effect. These issues should be systematically addressed in future rTMS studies on language production., Competing Interests: The authors have declared that no competing interests exist.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Creativity pervades many areas of everyday life and is considered highly relevant in several human living domains. Previous literature suggests that the posterior parietal cortex (PPC) is related to creativity. However, none of previous studies have compared the effect of transcranial random noise stimulation (tRNS) over bilateral PPC on both verbal and visual divergent thinking (DT) and Remote Associates Test (RAT) in the same experimental design. Forty healthy participants were randomly assigned to tRNS (100-500 Hz) over bilateral PPC or sham group, for 15 min and current was set at 1.5 mA. Participants' creativity skills were assessed before and after brain stimulation with the Unusual Uses and the Picture Completion subtests from the Torrance Test of Creative Thinking and the RAT. ANCOVA (baseline scores as covariate) results indicated that tRNS group had significantly higher scores at post-test in RAT and visual originality compared to sham group. Unusual Uses, on the other hand, was not significant. Improvement in RAT suggests the involvement of PPC during via insight solution which may reflect internally directed attention that helps the recombination of remotely associated information. The improvement in visual originality dimension from DT may be due to a higher internally directed attention while reducing externally oriented attention.

Exposure to light, particularly blue-wavelength light, has been shown to acutely increase brain activation, alertness, and some elementary aspects of cognitive performance such as working memory and emotional anticipation. Whether blue light exposure can have effects on brain activation and performance during more complex cognitive control tasks up to 30 min after light cessation is unknown. In a sample of 32 healthy adults, we examined the effects of a 30 min exposure to either blue (n = 16) or amber control (n = 16) light on subsequent brain activation and performance during the Multi-Source Interference Task (MSIT) measured a half-hour after light exposure. Performance on the MSIT did not differ between the blue and amber conditions. However, brain activation within the task positive network (TPN) to the interference condition was significantly lower in the blue relative to the amber condition, while no group differences were observed for suppression of the default mode network (DMN). These findings suggest that, compared to control, a single exposure to blue light was associated with enhanced neural efficiency, as demonstrated by reduced TPN activation to achieve the same level of performance. Blue light may be an effective method for optimizing neurocognitive performance under some conditions., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Proton Beam Therapy (PBT) was developed to minimize the harmful results of radiation therapy as treatment for brain tumors. This study examined the neurocognitive outcomes of PBT in pediatric patients. A total of 8 patients, who received either PBT or photon radiotherapy (XRT), were evaluated with multiple cognitive functions, which include intelligence, memory, executive functions, and attention. Most of patients performed average-to-superior levels of neurocognitive functions (NCF), except that a deterioration of executive functions was revealed in two patients receiving XRT. This study might be the first one to show the maintenance of multidomain NCF after PBT.

Background: Pediatric patients with brain tumors who are treated with radiation therapy (RT) are at risk for neurocognitive and psychosocial late effects. Research to date has primarily examined these outcomes at a group level and in isolation. Advanced statistical techniques allow for person-centered analyses, as well as examination of relationships between domain-specific trajectories., Methods: Patients with brain tumors (craniopharyngioma, ependymoma, low-grade astrocytoma, high-grade astrocytoma) were enrolled on a phase II clinical trial of RT. Three hundred and fifty patients completed serial neurocognitive assessments as part of their treatment monitoring, including pre-RT baseline, 6 months post-RT, and then yearly for 5 years. This secondary analysis focused on outcomes of cognition (estimated IQ, parent-reported attention problems) and psychosocial effects (parent-reported socialization and social problems) post-RT., Results: Latent growth curve modeling indicated that estimated IQ and socialization were best served by quadratic models, while attention and social problems were best served by linear models. Growth mixture modeling indicated 3-class models were the best fit for IQ and socialization, and 2-class models for attention and social problems. Baseline IQ and socialization scores were associated, but there was no association over time. Young age at diagnosis and pre-RT treatments (surgery, chemotherapy) were associated with class membership., Conclusions: Person-centered statistical analyses provide rich information regarding the variability in neurocognitive and psychosocial functioning following RT for pediatric brain tumor. While many patients do well over time, a subset are exhibiting significant cognitive and/or psychosocial deficits. Class membership was associated with some medical factors (eg, pre-radiation surgery/chemotherapy, age at diagnosis, shunted hydrocephalus)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The frontal lobe hypothesis of age-related cognitive decline suggests that the deterioration of the prefrontal cortical regions that occurs with aging leads to executive function deficits. Photobiomodulation (PBM) is a newly developed, noninvasive technique for enhancing brain function, which has shown promising effects on cognitive function in both animals and humans. This randomized, sham-controlled study sought to examine the effects of PBM on the frontal brain function of older adults., Methods/designs: Thirty older adults without a neuropsychiatric history performed cognitive tests of frontal function (ie, the Eriksen flanker and category fluency tests) before and after a single 7.5-minute session of real or sham PBM. The PBM device consisted of three separate light-emitting diode cluster heads (633 and 870 nm), which were applied to both sides of the forehead and posterior midline, and delivered a total energy of 1349 J., Results: Significant group (experimental, control) × time (pre-PBM, post-PBM) interactions were found for the flanker and category fluency test scores. Specifically, only the older adults who received real PBM exhibited significant improvements in their action selection, inhibition ability, and mental flexibility after vs before PBM., Conclusions: Our findings support that PBM may enhance the frontal brain functions of older adults in a safe and cost-effective manner., (© 2018 John Wiley & Sons, Ltd.)

On future missions into deep space, astronauts will be required to work more autonomously than on previous missions, and thus their ability to perform executive functions could be critical to mission success. In this study, we determined the effect that ≤15 cGy of 600 MeV/n 56 Fe particles has on attentional set-shifting (ATSET) performance of ∼10 month-old (at the time of irradiation) male Wistar rats that had been prescreened for their ability to perform the task. Exposure to 1-15 cGy of 56 Fe particles leads to a significant impairment in compound discrimination (CD) performance. Should similar effects occur in astronauts, an impaired ability to execute CD would result in a decreased ability to identify and maintain focus on relevant aspects of the task being performed. The use of rats that had been prescreened for ATSET performance helped to establish that working memory of the rules for the food reward remained intact (for at least 100 days) even after 15 cGy irradiation with 600 MeV/n 56 Fe particles, but that 56 Fe radiation exposure affected associative cue learning/acquisition rather than an intrinsic inability to perform the CD tasks. Our data suggest that declarative memory, and the ability to transitively infer established rules, also remained intact in the irradiated rats. Thus, should similar effects occur in astronauts, 56 Fe-induced CD performance deficits may only be manifested in scenarios where astronauts are required to transitively apply their knowledge to solve problems that they have not previously encountered; nevertheless, potentially one-third of astronauts may not be able to perform event-critical tasks correctly. The implication of this data, from a probabilistic risk assessment perspective, is that cognitive performance studies that use naïve rodents, thus requiring task rule acquisition as well as task performance, are likely to overestimate the risk of 56 Fe-induced cognitive deficits.

Light is known to elicit non-image-forming responses, such as effects on alertness. This has been reported especially during light exposure at night. Nighttime results might not be translatable to the day. This article aims to provide an overview of (1) neural mechanisms regulating alertness, (2) ways of measuring and quantifying alertness, and (3) the current literature specifically regarding effects of different intensities of white light on various measures and correlates of alertness during the daytime. In general, the present literature provides inconclusive results on alerting effects of the intensity of white light during daytime, particularly for objective measures and correlates of alertness. However, the various research paradigms employed in earlier studies differed substantially, and most studies tested only a limited set of lighting conditions. Therefore, the alerting potential of exposure to more intense white light should be investigated in a systematic, dose-dependent manner with multiple correlates of alertness and within one experimental paradigm over the course of day.

To date, it is largely unknown which light settings define the optimum to steer alertness and cognitive control during regular daytime working hours. In the current article, we used a multimeasure approach combined with a relatively large sample size ( N = 60) and a large range of intensity levels (20-2000 lux at eye level) to investigate the dose-dependent relationship between light and correlates of alertness and executive control during regular working hours in the morning and afternoon. Each participant was exposed to a single-intensity light level for 1 h after a 30-min baseline phase (100 lux at the eye) in the morning and afternoon (on separate days) during their daily routine. Results revealed no clear dose-dependent relationships between 1-h daytime light exposure and correlates of alertness or executive control. Subjective correlates showed only very modest linear relationships with the log-transformed illuminance, and we found no significant effects of light intensity on the behavioral and physiological indicators. Overall, these results suggest that daytime exposure to more intense light, at least for 1 h of exposure, may not systematically benefit alertness or executive functioning. However, future research is required to investigate effects of longer exposure durations and potential moderations by prior light exposure, personal characteristics, and spectrum.

Broad-spectrum light applied during the night has been shown to affect alertness in a dose-dependent manner. The goal of this experiment was to investigate whether a similar relationship could be established for light exposure during daytime. Fifty healthy participants were subjected to a paradigm (0730-1730 h) in which they were intermittently exposed to 1.5 h of dim light (<10 lux) and 1 h of experimental light (24-2000 lux). The same intensity of experimental light was used throughout the day, resulting in groups of 10 subjects per intensity. Alertness was assessed with subjective and multiple objective measures. A significant effect of time of day was found in all parameters of alertness ( p < 0.05). Significant dose-response relationships between light intensity and alertness during the day could be determined in a few of the parameters of alertness at some times of the day; however, none survived correction for multiple testing. We conclude that artificial light applied during daytime at intensities up to 2000 lux does not elicit significant improvements in alertness in non-sleep-deprived subjects.

Various adverse symptoms resulting from exposure to very high-frequency sound (VHFS) and ultrasound (US) have previously been reported. This study aimed to establish whether these symptoms are experienced under controlled laboratory conditions and are specific to VHFS/US. To do this, participants were exposed to VHFS/US (at frequencies between 13.5 and 20 kHz and sound pressure levels between 82 and 92 dB) and to a 1 kHz reference stimulus, both at 25 dB above their hearing threshold. The VHFS/US and reference stimuli were presented 4 times, each time for 3 min, during which participants performed a sustained attention task, rated their symptom severity, and had their galvanic skin response (GSR) measured to assess their level of anxiety. Prior to exposure, participants were assigned either to a symptomatic or an asymptomatic group, based on their prior history of symptoms that they attributed to VHFS/US. In both groups, overall discomfort ratings were higher in the VHFS/US condition than the reference condition. In the symptomatic group only, difficulty concentrating and annoyance were also rated higher in the VHFS/US than the reference condition. No difference between the two stimulus conditions was seen in performance on the attention task or on average GSRs for either group.

Some people have reported symptoms such as nausea, dizziness, and headaches that they attribute to ultrasound (US) emitted by devices in public places. The primary aim of the present study was to investigate whether inaudible US can provoke adverse symptoms compared to a sham presentation, under double-blind conditions. A second aim was to investigate whether the expectation of US being present could provoke adverse symptoms (a nocebo response). The US stimulus was a 20 kHz tone presented continuously for 20 min set to at least 15 dB below the participants' detection threshold, giving a typical sound pressure level (SPL) of 84 dB. No evidence that US provoked symptoms was found, but there was evidence of small nocebo effects. A case study on an individual with high self-reported sensitivity to US gave similar results. The present study did not reproduce the severe symptoms reported previously by some members of the public; this may be due to the SPL or duration of the stimulus, or strength of the nocebo stimulus. These findings cannot be used to predict outcomes from exposures to sounds that are audible to the individual in question, or to sounds with higher SPLs, longer durations, or different frequency content.

Data from a growing number of experimental studies show that exposure to higher correlated color temperature (CCT) ambient light, containing more blue light, can positively impact alertness and cognitive performance in older children and adults. To date, few if any studies have examined whether light exposure influences cognitive task performance in preschool-age children, who are in the midst of rapid developmental changes in attention and executive function skills. In this study, healthy children aged 4.5-5.5 years (n = 20; 11 females) completed measures of sustained attention and task switching twice while being exposed to LED light set to either 3500K (a lower CCT) or 5000K (a higher CCT). A control group (n = 18; 10 females) completed the tasks twice under only the 3500K lighting condition. Although the lighting condition did not impact performance on the sustained attention task, exposure to the higher CCT light lead to greater improvement in preschool-age children's task switching performance (F(1,36) = 4.41, p = 0.04). Children in the control group showed a 6.5% increase in task switching accuracy between time points, whereas those in the experimental group improved by 15.2%. Our primary finding-that exposure to light at a higher correlated color temperature leads to greater improvement in task switching performance-indicates that the relationship between the spectral power distribution of light and executive function abilities is present early in cognitive development. These data have implications for designing learning environments and suggest that light may be an important contextual factor in the lives of young children in both the home and the classroom., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Exposure to light can have acute alerting and circadian phase-shifting effects. This study investigated the effects of evening exposure to blue-enriched polychromatic white (BEL) vs. polychromatic white light (WL) on sleep inertia dissipation the following morning in older adults., Methods: Ten healthy older adults (average age = 63.3 yrs; 6F) participated in a 13-day study comprising three baseline days, an initial circadian phase assessment, four days with 2-h evening light exposures, a post light exposure circadian phase assessment and three recovery days. Participants were randomized to either BEL or WL of the same irradiance for the four evening light exposures. On the next mornings at 2, 12, 22 and 32 min after each wake time, the participants completed a 90-s digit-symbol substitution test (DSST) to assess working memory, and objective alertness was assessed using a wake EEG recording. DSST and power density from the wake EEG recordings were compared between the two groups., Results: DSST performance improved with time awake (p < 0.0001) and across study days in both light exposure groups (p < 0.0001). There was no main effect of group, although we observed a significant day x group interaction (p = 0.0004), whereby participants exposed to BEL performed significantly better on the first two mornings after light exposures than participants in WL (post-hoc, p < 0.05). On those days, the BEL group showed higher EEG activity in some of the frequency bins in the sigma and beta range (p < 0.05) on the wake EEG., Conclusion: Exposure to blue-enriched white light in the evening significantly improved DSST performance the following morning when compared to polychromatic white light. This was associated with a higher level of objective alertness on the wake EEG, but not with changes in sleep or circadian timing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Astronauts on deep space missions will be required to work more autonomously than on previous missions, and thus their ability to perform executive functions could be critical to mission success. One of the most common measures of executive function in humans is the ability to perform attentional set shifting, which requires contributions from working memory, discrimination, reversal learning, attentional set shifting and attention. Rodent attentional set shifting assays require rats to form an association between the presence of the food reward and an associative cue, which is either the digging media or the scent that is placed in the bowl; by altering the combination of scent and digging media, progressively more complex cognitive processes can be tested. In this study, we have determined the effect that exposure to 5-20 cGy of 600 MeV/n 28 Si particles has on the ability of male retired breeder Wistar rats to perform attentional set shifting at three months postirradiation. All doses of Si resulted in a significant impairment in the ability of the rats to perform the first and most simple step of the ATSET assay, the simple discrimination (SD) task. If astronauts were to experience HZE-induced SD impairments, they would be unable to identify key factors to successfully resolve a situation. Performance in at least one other component of the ATSET test was impaired at all doses studied, however, these varied according to the dose. Compared with our previous studies using 1 GeV/n 56 Fe and 48 Ti particles, 600 MeV/n 28 Si ions impaired attentional set-shifting performance at lower doses than the heavier ions. However, when the effect of isofluences of the three HZE ions were compared, there were no significant differences in the severity of the impaired performance; there were, however, ion-specific decrements in the ability of rats to perform within the various stages of the test. This study further supports the notion that "mission-relevant" doses of HZE particles (<20 cGy) can impair certain aspects of attentional set-shifting performance in retired breeder rats, but there may be some ion-specific changes in the specific cognitive domains impaired.

Study Objective: The purpose of this study was to investigate the acute effects of the electromagnetic waves (EMW) emitted by mobile phones on attention in emergency physicians., Methods: This single-center, prospective, randomized, double-blinded clinical study was performed among emergency physicians in a tertiary hospital. Thirty emergency physicians were enrolled in the study. Initial d2 test was applied in the evaluation of attention and concentration of all the physicians, who were randomly assigned into one of two groups. The control group members hold mobile phones in 'off' mode to their left ears for 15min. The members of the intervention group hold mobile phones in 'on' mode to their left ears for 15min, thus exposing them to 900-1800MHz EMW. The d2 test was re-applied to both groups after this procedure. Differences in attention and concentration levels between the groups were compared., Results: Difference between initial and final d2 test in total performance (TN-E, p=0.319), in total number of figures marked (TN, p=0.177), in test performance percentile (PR, p=0.619) and in attention fluctuation (FR, p=0.083) were similar between the groups. However, difference in the number of figures missed (E1 selective attention, p=0.025), difference between numbers of incorrectly marked figures (E2, p=0,018) and difference in focus levels (E, p=0.016) were significantly in favor of the intervention group., Conclusion: According to our study findings, the EMW emitted by mobile phones has no deleterious effect on the attention and concentration levels of emergency physicians, and even has a positive impact on selective attention levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Higher color temperature refers to a higher proportion of blue spectral components of light, that are known to be associated with higher alertness state in humans. Based on motivational intensity theory (Brehm & Self, 1989), here we predicted that this lighting-induced alertness state should inform about the readiness to perform and this way influence subjective task demand and thus mental effort. To test this, study participants spent 15min under one of four lighting color temperature conditions and then performed a cognitive task. As predicted, effort-related cardiac response, indexed by a shortened cardiac pre-ejection period, decreased with increasing color temperature of light, as indicated by a significant single planned linear contrast. These results demonstrate that spectral properties of light can influence mental effort mobilization., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Photobiomodulation using low-level laser therapy (LLLT) has been tested as a new technique to optimize recovery of patients with traumatic brain injury (TBI). The aim of this study is to evaluate inhibitory attentional control after 18 sessions of active LLLT and compare with the placebo group (sham LLLT). Our exploratory analysis will evaluate the efficacy of the active LLLT on verbal and visuospatial episodic memory, executive functions (working memory, verbal and visuospatial fluency, attentional processes), and anxiety and depressive symptoms compared to the sham group., Methods/design: A randomized double-blinded trial will be made in 36 patients with moderate and severe TBI. The active LLLT will use an optical device composed of LEDs emitting 632 nm of radiation at the site with full potency of 830 mW. The cranial region with an area of 400 cm 2 will be irradiated for 30 min, giving a total dose per session of 3.74 J/cm 2 . The sham LLLT group contains only an LED device with power < 1 mW, only serving to simulate the irradiation. Each patient will be irradiated three times per week for six weeks, totaling 18 sessions. Neuropsychological assessments will be held one week before the beginning of the sessions, after one week, and three months after the end of LLLT sessions. Memory domain, attention, executive functioning, and visual construction will be evaluated, in addition to symptoms of depression, anxiety, and social demographics., Discussion: LLLT has been demonstrated as a safe and effective technique in significantly improving the memory, attention, and mood performance in healthy and neurologic patients. We expect that our trial can complement previous finds, as an effective low-cost therapy to improve cognitive sequel after TBI., Trial Registration: ClinicalTrials.gov, NCT02393079 . Registered on 20 February 2015.

Artificial light endows a "round-the-clock", 24-h/7-d society. Chronic exposure to light at night contributes to health hazards for humans, including disorders of sleep. Yet the influence of inter-individual traits, such as sex-differences, on light sensitivity remains to be established. Here we investigated potential sex-differences to evening light exposure of 40 lx at 6500 K (blue-enriched) or at 2500 K (non-blue-enriched), and their impact on brightness perception, vigilant attention and sleep physiology. In contrast to women, men had higher brightness perception and faster reaction times in a sustained attention task during blue-enriched light than non-blue-enriched. After blue-enriched light exposure, men had significantly higher all-night frontal NREM sleep slow-wave activity (SWA: 2-4 Hz), than women, particularly during the beginning of the sleep episode. Furthermore, brightness perception during blue-enriched light significantly predicted men's improved sustained attention performance and increased frontal NREM SWA. Our data indicate that, in contrast to women, men show a stronger response to blue-enriched light in the late evening even at very low light levels (40lux), as indexed by increased vigilant attention and sleep EEG hallmarks. Collectively, the data indicate that sex differences in light sensitivity might play a key role for ensuring the success of individually-targeted light interventions.

The functionality of much of human lateral frontal cortex (LFC) has been characterized as "multiple demand" (MD) as these regions appear to support a broad range of cognitive tasks. In contrast to this domain-general account, recent evidence indicates that portions of LFC are consistently selective for sensory modality. Michalka et al. (2015) reported two bilateral regions that are biased for visual attention, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), interleaved with two bilateral regions that are biased for auditory attention, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). In the present study, we use fMRI to examine both the multiple-demand and sensory-bias hypotheses within caudal portions of human LFC (both men and women participated). Using visual and auditory 2-back tasks, we replicate the finding of two bilateral visual-biased and two bilateral auditory-biased LFC regions, corresponding to sPCS and iPCS and to tgPCS and cIFS, and demonstrate high within-subject reliability of these regions over time and across tasks. In addition, we assess MD responsiveness using BOLD signal recruitment and multi-task activation indices. In both, we find that the two visual-biased regions, sPCS and iPCS, exhibit stronger MD responsiveness than do the auditory-biased LFC regions, tgPCS and cIFS; however, neither reaches the degree of MD responsiveness exhibited by dorsal anterior cingulate/presupplemental motor area or by anterior insula. These results reconcile two competing views of LFC by demonstrating the coexistence of sensory specialization and MD functionality, especially in visual-biased LFC structures. SIGNIFICANCE STATEMENT Lateral frontal cortex (LFC) is known to play a number of critical roles in supporting human cognition; however, the functional organization of LFC remains controversial. The "multiple demand" (MD) hypothesis suggests that LFC regions provide domain-general support for cognition. Recent evidence challenges the MD view by demonstrating that a preference for sensory modality, vision or audition, defines four discrete LFC regions. Here, the sensory-biased LFC results are reproduced using a new task, and MD responsiveness of these regions is tested. The two visual-biased regions exhibit MD behavior, whereas the auditory-biased regions have no more than weak MD responses. These findings help to reconcile two competing views of LFC functional organization., (Copyright © 2017 the authors 0270-6474/17/378755-12$15.00/0.)

We tested the effect of different lights as a countermeasure against sleep-loss decrements in alertness, melatonin and cortisol profile, skin temperature and wrist motor activity in healthy young and older volunteers under extendend wakefulness. 26 young [mean (SE): 25.0 (0.6) y)] and 12 older participants [(mean (SE): 63.6 (1.3) y)] underwent 40-h of sustained wakefulness during 3 balanced crossover segments, once under dim light (DL: 8 lx), and once under either white light (WL: 250 lx, 2,800 K) or blue-enriched white light (BL: 250 lx, 9,000 K) exposure. Subjective sleepiness, melatonin and cortisol were assessed hourly. Skin temperature and wrist motor activity were continuously recorded. WL and BL induced an alerting response in both the older (p = 0.005) and the young participants (p = 0.021). The evening rise in melatonin was attentuated under both WL and BL only in the young. Cortisol levels were increased and activity levels decreased in the older compared to the young only under BL (p = 0.0003). Compared to the young, both proximal and distal skin temperatures were lower in older participants under all lighting conditions. Thus the color temperature of normal intensity lighting may have differential effects on circadian physiology in young and older individuals.

Introduction: Night-shift works are basically accompanied by reduced cognitive performance, sleepiness, and higher possibility for human error and related incidents. It is therefore crucial to improve individuals' performance and alertness in sensitive places like industries' control room with the ultimate goal of increasing efficiency and reducing the number of possible incidents. Previous research has indicated that blue light is a critical cue for entraining circadian rhythm. As a result, the present study was an attempt to investigate whether blue-enriched white light illumination was a practical strategy to decrease sleepiness and improve cognitive performance during night shifts., Martial and Methods: The study, which adopted a before-after interventional design, was conducted among 30 control room staff members of petrochemical industry. After baseline assessments under existing lighting conditions, every participant was exposed to two new lighting conditions (namely, 17,000K and 6500K blue-enriched white light), each lasting for a week. Assessments were conducted again at the end of these treatments. In order to measure the subjective sleepiness, Karolinska Sleepiness Scale (KSS) was utilized. Subjects also performed the Conners' Continuous Performance Test II (CPT-II) and 1-back test in order to gauge their cognitive performance, and melatonin assessment was carried out using salivary and Eliza technique. The data was analyzed using two-way repeated measure ANOVA., Results: The results indicated that, compared to normal lighting conditions, participants' sleepiness and melatonin rhythm significantly declined when they were exposed to blue-enriched white light. Furthermore, the experimental condition had a significant effect on the reduction of working memory errors. It also decreased omission errors and the reaction time during the sustained attention task., Conclusions: Thus, using blue-enriched white light may be a proper ergonomic strategy for improving performance and alertness, especially during night, in sensitive environments like control rooms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Exposures to melanopsin-stimulating (melanopic) component-rich blue light enhance arousal level. We examined their effects in office workers. Eight healthy university office workers were exposed to blue and orange lights for 30 min during lunch break on different days. We compared the effects of light color on autonomic arousal level assessed by heart rate variability (HRV) and behavioral alertness by psychomotor vigilance tests (PVT). Heart rate was higher and high-frequency (HF, 0.150.45 Hz) power of HRV was lower during exposure to the blue light than to orange light. No significant difference with light color was observed, however, in any HRV indices during PVT or in PVT performance after light exposure., Short Conclusion: Exposure to blue light during lunch break, compared with that to orange light, enhances autonomic arousal during exposure, but has no sustained effect on autonomic arousal or behavioral alertness after exposure.

Background and Purpose: This study examines attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy (PBRT)., Material and Methods: We examined 39 survivors (age 6-19years) who were 3.61years post-PBRT on average. Craniospinal (CSI; n=21) and focal (n=18) subgroups were analyzed. Attention, processing speed, and executive functioning scores were compared to population norms, and clinical/demographic risk factors were examined., Results: As a group, survivors treated with focal PBRT exhibited attention, processing speed, and executive functioning that did not differ from population norms (all p>0.05). Performance in the CSI group across attention scales was normative (all p>0.05), but areas of relative weakness were identified on one executive functioning subtest and several processing speed subtests (all p<0.01)., Conclusions: Survivors treated with PBRT may exhibit relative resilience in cognitive domains traditionally associated with radiation late effects. Attention, processing speed, and executive functioning remained intact and within normal limits for survivors treated with focal PBRT. Among survivors treated with CSI, a score pattern emerged that was suggestive of difficulties in underlying component skills (i.e., processing speed) rather than true executive dysfunction. No evidence of profound cognitive impairment was found in either group., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To examine the psychosocial outcomes and impact of attention problems in survivors of pediatric brain tumor., Study Design: The survivors' cognitive functioning was measured using the Wechsler Intelligence Scale for Children. The Child Behavior Checklist-Attention Problems scale was used to screen for attention problems, and participants were classified as having attention problems (n=15) or normal attention (n=36). Psychosocial functioning was examined with the Korean Personality Rating scale for Children (K-PRC) at precraniospinal radiation and at 2-year follow-up., Results: The attention problem group showed significantly higher depression and externalizing symptoms (delinquency, hyperactivity) and more significant impairment in family relationships than did the normal attention group at baseline. At follow-up, the attention problem group demonstrated significantly more delinquency and impaired family and social relationships. With the K-PRC scores, except for the somatization, social relationship subscale, there were significant differences between groups, but not in terms of treatment by time interaction or within time. At follow-up, multiple linear regressions showed that age at diagnosis significantly predicted K-PRC somatization (B=-1.7, P=0.004) and social relationships (B=-1.7, P=0.004), baseline full-scale intelligence quotient predicted K-PRC depression (B=-0.4, P=0.032) and somatization (B=-0.3, P=0.015), and attention problems at baseline predicted K-PRC depression (B=-15.2, P=0.036) and social relationships (B=-11.6, P=0.016)., Conclusion: Pediatric brain tumor survivors, in particular, patients with attention problems, had worse psychosocial functioning at baseline and follow-up. Attention problems at baseline need to be carefully evaluated in assessing psychosocial functioning of pediatric brain tumor survivors.

Objective: Environmental (little outdoor light; low indoor lighting) and age-related physiological factors (reduced light transmission through the ocular lens, reduced mobility) contribute to a light-deprived environment for older people living in care homes., Methods: This study investigates the effect of increasing indoor light levels with blue-enriched white lighting on objective (rest-activity rhythms, performance) and self-reported (mood, sleep, alertness) measures in older people. Eighty residents (69 female), aged 86 ± 8 yrs (mean ± SD), participated (MMSE 19 ± 6). Overhead fluorescent lighting was installed in communal rooms (n=20) of seven care homes. Four weeks of blue-enriched white lighting (17000 K ≅ 900 lux) were compared with four weeks of control white lighting (4000 K ≅ 200 lux), separated by three weeks wash-out. Participants completed validated mood and sleep questionnaires, psychomotor vigilance task (PVT) and wore activity and light monitors (AWL). Rest-activity rhythms were assessed by cosinor, non-parametric circadian rhythm (NPCRA) and actigraphic sleep analysis. Blue-enriched (17000 K) light increased wake time and activity during sleep decreasing actual sleep time, sleep percentage and sleep efficiency (p < 0.05) (actigraphic sleep). Compared to 4000 K lighting, blue-enriched 17000 K lighting significantly (p < 0.05) advanced the timing of participants' rest-activity rhythm (cosinor), increased daytime and night-time activity (NPCRA), reduced subjective anxiety (HADA) and sleep quality (PSQI). There was no difference between the two light conditions in daytime alertness and performance (PVT)., Conclusion: Blue-enriched lighting produced some positive (increased daytime activity, reduced anxiety) and negative (increased night-time activity, reduced sleep efficiency and quality) effects in older people., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The use of electronic devices with light-emitting screens has increased exponentially in the last decade. As a result, humans are almost continuously exposed to unintentional artificial light. We explored the independent and combined effects of two aspects of screen illumination, light wavelength, and intensity, on sleep, its biological regulation, and related functional outcomes. The 2 × 2 repeated-measure design included two independent variables: screen light intensity (low ([LI] versus high [HI]) and wavelength (short [SWL] versus long [LWL]). Nineteen participants (11F, 8M; mean age 24.3 [±2.8] years) underwent four light conditions, LI/SWL, HI/SWL, LI/LWL, and HI/LWL, in counterbalanced order. Each light exposure lasted for two hours (21:00-23:00), following which participants underwent an overnight polysomnography. On each experimental night, oral temperature and urine samples (for melatonin analysis) were collected at multiple time points. Each morning, participants filled out questionnaires and conducted a computerized attention task. Irrespective of light intensity, SWL illumination significantly disrupted sleep continuity and architecture and led to greater self-reported daytime sleepiness. SWL light also altered biological rhythms, subduing the normal nocturnal decline in body temperature and dampening nocturnal melatonin secretion. Light intensity seemed to independently affect sleep as well, but to a lesser degree. Both light intensity and wavelength negatively affected morning attention. In sum, light wavelength seems to have a greater influence than light intensity on sleep and a wide-range of biological and behavioral functions. Given the widespread use of electronic devices today, our findings suggest that screen light exposure at evening may have detrimental effects on human health and performance.

The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale.The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores.Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA.The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment., Competing Interests: The authors have no conflicts of interest to disclose.

To understand neurocognitive effects of proton radiation therapy (PRT) in patients with low-grade glioma, we evaluated 20 patients who received this therapy prospectively and over 5 years with a comprehensive neuropsychological battery. 20 patients were evaluated at baseline and at yearly intervals for up to 5 years with a battery of neuropsychological measures that assessed intellectual, attention, executive, visuospatial and memory functions as well as mood and functional status. We evaluated change in cognitive functioning over time. We analyzed the relationship between cognitive performance and tumor location and also examined whether patients' performance differed from that reported in a study of normative practice effects. Overall, patients exhibited stability in cognitive functioning. Tumor location played a role in performance; those with tumors in the left hemisphere versus in the right hemisphere were more impaired at baseline on verbal measures (p < .05). However, we found greater improvement in verbal memory over time in patients with left than with right hemisphere tumors (p < .05). Results of our study, the first to investigate, in depth, neurocognitive effects of PRT in adults with low-grade gliomas, are promising. We hypothesize that the conformal advantage of PRT may contribute to preservation of cognitive functioning, although larger sample sizes and a longer period of study are required. Our study also highlights the need to consider normative practice effects when studying neurocognitive functioning in response to treatment over time, and the need to utilize comprehensive neuropsychological batteries given our findings that differentiate patients with left and right hemisphere tumors.

Astronauts on deep space missions will be required to work more autonomously than on previous missions, and thus their ability to perform executive functions could be critical to mission success. In this study we have determined the impact that exposure to 10, 15 and 20 cGy of 1 GeV/n (48)Ti particles has on the long-term (three-months post exposure) ability of male retired breeder Wistar rats to perform attentional set shifting. The ability of the rats to conduct compound discrimination reversal (CDR) was significantly impaired at all doses studied, with compound discrimination (CD) being impaired at 10 and 15 cGy. Impaired CD performance would result in a decreased ability to identify and focus on relevant aspects of a task being conducted, while the functional consequence of an impaired CDR performance would be a reduction in the individual's ability to recognize when that factor changes from a positive to a negative factor for the successful completion of a task. In contrast to our previous study with 1 GeV/n (56)Fe particles, there were no significant impairments in the ability of the (48)Ti-irradiated rats to conduct simple discrimination. This study further supports the notion that "mission-relevant" doses of HZE particles (<20 cGy) can impair certain aspects of attentional set-shifting performance in retired breeder rats, but there may be some ion-specific changes in the specific cognitive domains impaired.

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.

The gap effect refers to a reduction in saccadic reaction time (SRT) to an eccentric target, when the fixation point is removed before the target onset. Though it is known that the gap effect peaks when the fixation point is offset about 200 ms before the onset of the eccentric target, it is unknown how this effect is modulated by stimulus variations. In this paper, we propose and investigate a model of saccadic reaction time as a function of the fixation point brightness gain. The brightness gain is defined as the ratio of the final and initial intensities of the stimulus. We have conducted a typical gap effect experiment with 15 participants, where the brightness of the fixation point was manipulated under four conditions and two gap intervals, at the same time and 200 ms before the onset of the eccentric target. The conditions included removing the fixation point (offset), leaving it with constant brightness (overlap), reducing, and increasing its brightness (lower and higher brightness conditions). Experimental data showed a significant gap effect in the offset and lower brightness conditions when compared to the overlap condition. On the other hand, the SRT was significantly longer for the higher brightness condition than the SRT for the overlap condition. Linear regression analysis using ten values of brightness gain shows that our model fits the data well for the 0- and 200-ms gap, with a coefficient of determination of .89 and .94, respectively.

Purpose: This study aimed at examining the effects of 2 weeks of dawn simulation on attentional performance in adolescents., Methods: On the whole, 56 adolescents (24 females and 32 males) took part to the study, with a mean age of 17.68 ± 0.97 years (age ranging between 15 and 20 years). Each adolescent was requested to participate for 5 consecutive weeks and the research design included the baseline and two counterbalanced conditions, dawn simulator and control (no dawn simulator). Attentional performance of adolescents was measured through the attention network test (ANT) that allowed assessing the efficiency of three separable attentional networks, namely alerting, orienting and executive. Overall, participants performed the ANT three times (i.e., one time for each condition), while sleep quality, sleep duration and sleep timing were concurrently monitored by means of actigraphy and were treated as potential confounders., Results: The only improvement of the attentional performance attributable to the use of dawn simulator was observed for the efficiency of alerting network (45.97 ± 32.76 ms) that significantly increased in comparison to the baseline (31.57 ± 26.97 ms) (p < 0.05). On the contrary, the sleep quality, sleep quantity and sleep timing did not significantly change., Conclusion: These results show for the first time that, controlling for sleep quality, sleep duration and sleep timing, the use of dawn simulator across 2 weeks is able to determine an alerting effect in adolescents.

Objectives: To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared., Methods: This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105., Results: Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p < 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p < 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis., Conclusions: The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials., (Copyright © 2014 John Wiley & Sons, Ltd.)

Cognitive performance and alertness are two determinants for work efficiency, varying throughout the day and depending on bright light. We conducted a prospective crossover study evaluating the impacts of exposure to an intense, early morning illumination on sustained attention, alertness, mood, and serum melatonin levels in 33 healthy individuals. Compared with a dim illumination, the intense illumination negatively impacted performance requiring sustained attention; however, it positively impacted subjective alertness and mood and had no impact on serum melatonin levels. These results suggest that brief exposure to bright light in the morning hours can improve subjective measures of mood and alertness, but can also have detrimental effects on mental performance as a result of visual distraction. Therefore, it is important that adequate lighting should correspond to both non-visual and visual demands., (Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Cynomolgus monkeys are widely used as models of diseases and in pre-clinical studies to assess the impact of new pharmacotherapies on brain function and behaviour. However, the time course of electroencephalographic delta activity during sleep, which represents the main marker of sleep intensity associated with recovery during sleep, has never been described in this non-human primate. In this study, telemetry implants were used to record one spontaneous 24-h sleep-wake cycle in four freely-moving Cynomolgus monkeys, and to quantify the time course of electroencephalographic activity during sleep using spectral analysis. Animals presented a diurnal activity pattern interrupted by short naps. During the dark period, most of the time was spent in sleep with non-rapid eye movement sleep/rapid eye movement sleep alternations and sleep consolidation profiles intermediate between rodents and humans. Deep non-rapid eye movement sleep showed a typical predominance at the beginning of the night with decreased propensity in the course of the night, which was accompanied by a progressive increase in rapid eye movement sleep duration. Spectral profiles showed characteristic changes between vigilance states as reported in other mammalian species. Importantly, delta activity also followed the expected time course of variation, showing a build-up with wakefulness duration and dissipation across the night. Thus, Cynomolgus monkeys present typical characteristics of sleep architecture and spectral structure as those observed in other mammalian species including humans, validating the use of telemetry in this non-human primate model for translational sleep studies., (© 2014 European Sleep Research Society.)

Previous ground-based experiments have shown that cranial irradiation with mission relevant (20 cGy) doses of 1 GeV/nucleon (56)Fe particles leads to a significant impairment in Attentional Set Shifting (ATSET) performance, a measure of executive function, in juvenile Wistar rats. However, the use of head only radiation exposure and the biological age of the rats used in that study may not be pertinent to determine the likelihood that ATSET will be impaired in Astronauts on deep space flights. In this study we have determined the impact that whole-body exposure to 10, 15 and 20 cGy of 1 GeV/nucleon (56)Fe particles had on the ability (at three months post exposure) of socially mature (retired breeder) Wistar rats to conduct the attentional set-shifting paradigm. The current study has established that whole-body exposures to 15 and 20 (but not 10) cGy of 1 GeV/nucleon (56)Fe particles results in the impairment of ATSET in both juvenile and socially mature rats. However, the exact nature of the impaired ATSET performance varied depending upon the age of the rats, whether whole-body versus cranial irradiation was used and the dose of 1 GeV/u (56)Fe received. Exposure of juvenile rats to 20 cGy of 1 GeV/nucleon (56)Fe particles led to a decreased ability to perform intra-dimensional shifting (IDS) irrespective of whether the rats received head only or whole-body exposures. Juvenile rats that received whole-body exposure also had a reduced ability to habituate to the assay and to complete intra-dimensional shifting reversal (IDR), whereas juvenile rats that received head only exposure had a reduced ability to complete compound discrimination reversal (CDR). Socially mature rats that received whole-body exposures to 10 cGy of 1 GeV/nucleon (56)Fe particles exhibited no obvious decline in set-shifting performance; however those exposed to 15 and 20 cGy had a reduced ability to perform simple discrimination (SD) and compound discrimination (CD). Exposure to 20 cGy of 1 GeV/nucleon (56)Fe particles also led to a decreased performance in IDR and to ∼25% of rats failing to habituate to the task. Most of these rats started to dig for the food reward but rapidly (within 15 s) gave up digging, suggesting that they had developed appropriate procedural memories about food retrieval, but had an inability to maintain attention on the task. Our preliminary data suggests that whole-body exposure to 20 cGy of 1 GeV/nucleon (56)Fe particles reduced the cholinergic (but not the GABAergic) readily releasable pool (RRP) in nerve terminals of the basal forebrain from socially-mature rats. This perturbation of the cholinergic RRP could directly lead to the loss of CDR and IDR performance, and indirectly [through the metabolic changes in the medial prefrontal cortex (mPFC)] to the loss of SD and CD performance. These findings provide the first evidence that attentional set-shifting performance in socially mature rats is impaired after whole-body exposure to mission relevant doses (15 and 20 cGy) of 1 GeV/nucleon (56)Fe particles, and importantly that a dose reduction down to 10 cGy prevents that impairment. The ability to conduct Discrimination tasks (SD and CD) and reversal learning (CDR) is reduced after exposure to 15 and 20 cGy of 1 GeV/nucleon (56)Fe particles, but at 20 cGy there is an additional decrement, ∼ 25% of rats are unable to maintain attention to task. These behavioral decrements are associated with a reduction in the cholinergic RRP within basal forebrain, which has been shown to play a major role in regulating the activity of the PFC.

Purpose: The standard of care for pediatric patients with ependymoma involves postoperative radiation therapy. Prior research suggests that conformal radiation therapy (CRT) is associated with relative sparing of cognitive and academic functioning, but little is known about the effect of CRT on emotional and behavioral functioning., Methods and Materials: A total of 113 patients with pediatric ependymoma underwent CRT using photons as part of their enrollment on an institutional trial. Patients completed annual evaluations of neurocognitive functioning during the first 5 years after CRT. Emotional and behavioral functioning was assessed via the Child Behavior Checklist., Results: Before CRT, emotional and behavioral functioning were commensurate with those of the normative population and within normal limits. After 5 years, means remained within normal limits but were significantly below the normative mean. Linear mixed models revealed a significant increase in attention problems over time. These problems were associated with age at diagnosis/CRT, tumor location, and extent of resection. A higher-than-expected incidence of school problems was present at all assessment points after baseline., Conclusions: The use of photon CRT for ependymoma is associated with relatively stable emotional and behavioral functioning during the first 5 years after treatment. The exception is an increase in attention problems. Results suggest that intervening earlier in the survivorship period-during the first year posttreatment-may be beneficial., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Study Objectives: Permanent night-shift workers may develop shift-work disorder (SWD). In the current study, we evaluated neurophysiological and behavioral indices of distractibility across times prior to the night shift (T1), during night hours (T2), and after acute sleep deprivation (T3) in permanent hospital night workers with and without SWD., Methods: Ten asymptomatic night workers (NW) and 18 NW with SWD participated in a 25-h sleep deprivation study. Circadian phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective sleepiness was evaluated using the Multiple Sleep Latency Test (MSLT). Electrophysiological distractibility was evaluated by brain event-related potentials (ERP), whereas behavioral distractibility was evaluated by performance on a visual task in an auditory-visual distraction paradigm., Statistical Analyses: Comparisons of ERP results were performed by repeated-measures analysis of variance, and t-tests were used where appropriate. A Mann-Whitney U test was used for comparison of variables (MLST, Stanford Sleepiness Scale, and DLMO) that deviated from normal., Results: First, in the SWD group, the reorienting negativity ERP amplitude was significantly attenuated compared to that in the NW group. Second, the SWD group had shorter MSLT during night shift hours (4.8 ± 4.9 min) compared to that in NW (7.8 ± 3.7 min; U = 47; z = -2.1; P < 0.03). Third, NW with SWD had a DLMO at 20:27 ± 5.0 h, whereas healthy NW had a DLMO at 05:00 ± 3.4 h (U = 43.5; z = -2.22, P < 0.03). Finally, acute sleep deprivation impaired behavioral performance and the P3a ERP in both groups., Conclusions: Our results demonstrate specific deficits in neurophysiological activity in the attentional domain among the shift-work disorder group relative to night workers.