Similar Loss of Executive Function Performance after Exposure to Low (10 cGy) Doses of Single (4He) Ions and the Multi-Ion GCRSim Beam.

While astronauts are trained to deal with multiple issues that they are likely to encounter during a mission, it is likely that some problems will arise that astronauts have no direct experience in resolving. During International Space Station (ISS) missions, astronauts can rely on Mission Control to help resolve complex problems, however during the long-duration space missions planned to the Moon and Mars, astronauts will have to act more autonomously, thus the ability of astronauts to conduct executive function will be critical for problem solving during deep space missions. Several studies have shown that exposure to space radiation results in decreased executive function performance. However, to date these studies have used single ions, whereas there is a complex mixture of ion species and energies within the space-radiation spectrum that astronauts will be exposed to. Thus, there is some concern that the neurocognitive impairments reported from single ion studies will not be representative of the severity, frequency or nature of cognitive deficits that arise following exposure to more complex space-radiation spectra. The current study has determined the relative impact that isodoses of He ions or the simplified 6-ion-galactic cosmic ray simulation (GCRSim) beams had on the performance of male Wistar rats in executive function tasks, attentional set shifting (ATSET) task and unconstrained cognitive flexibility (UCFlex). Exposure to 10 cGy GCRSim induced performance deficits in the simple discrimination (SD) stage of the ATSET task, which appears to be universally impacted by all space-radiation ions studied to date. The magnitude of the SD performance decrements in the GCRSim-irradiated rats were comparable to those observed in He-irradiated rats. Importantly, space-radiation exposure does not appear to decrease the ability of rats to identify the key cues in the ATSET task, but increased the time/number of iterations required to successfully find the solution. Practice effect (PE) analysis (comparing prescreen to the postirradiation SD performance) revealed that while the sham-treated rats completed the second ATSET task in 30% less time than they did the prescreen ATSET test (despite the perceptual domain of the relevant (rewarded) cue being changed), the space-radiation-exposed rats took 50% longer to do so. The space-radiation-induced delay in problem solving was not confined to the ATSET task, but was also observed when rats were screened for UCFlex performance. Should similar changes occur in astronauts, these data raise the possibility that space-radiation exposure would reduce in-flight improvement in performance in repetitive tasks (PE) and may lead to a reduced ability to utilize transitive inference from "similar" problems to solve issues that have not been previously encountered.

Effects of Photobiomodulation on Changes in Cognitive Function and Regional Cerebral Blood Flow in Patients with Mild Cognitive Impairment: A Pilot Uncontrolled Trial.

BACKGROUND: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated. OBJECTIVE: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function. METHODS: Fourteen patients with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM. RESULTS: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function. CONCLUSION: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM.

A longitudinal, randomized experimental pilot study to investigate the effects of airborne ultrasound on human mental health, cognition, and brain structure.

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants' bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.Trial registration: The trial was registered at NIH www.clinicaltrials.gov , trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183 .

Microstructural Injury to Corpus Callosum and Intrahemispheric White Matter Tracts Correlate With Attention and Processing Speed Decline After Brain Radiation.

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 (cm3), 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.

Sleep fragmentation exacerbates executive function impairments induced by protracted low dose rate neutron exposure.

PURPOSE: Astronauts on the planned missions to Mars are expected to have to work more autonomously than on previous missions. Thus mission success may be influenced by the astronauts' ability to respond quickly to unexpected problems, processes that require several executive functions. The purpose of this study was to determine the impact that prolonged low dose and low dose rate exposure to neutrons had on two executive functions, and whether the severity and incidence of cognitive impairment was altered by sleep fragmentation. MATERIALS AND METHODS: In this study we assessed the impact that prolonged (six month) low dose rate neutron exposure had on the ability of male Wistar rats to perform in two executive function tasks (i.e. attentional set shifting (ATSET) - a constrained cognitive flexibility task and the UCFlex assay - an unconstrained cognitive flexibility task). In recognition of the fact that astronauts also have to contend with inadequate sleep quantity and quality for much of their time in space, we determined the impact that relatively mild sleep disruption had on the ability to perform in the ATSET test in sham and neutron-irradiated rats. RESULTS: Chronic low dose (18 cGy) and dose-rate (1 mGy/day) exposure of rats to mixed neutron and photon over the course of six months resulted in significant impairment of simple discrimination (SD) performance. Should similar effects occur in astronauts subjected to low dose rate exposure to Space Radiation, the impairment of SD performance would result in a decreased ability to identify and learn the 'rules' required to respond to a new task or situation. Analysis of the behavioral data by kernel density estimation revealed that 40% of rats had severe ATSET impairments. This value may be a best-case scenario because exposure to neutrons also adversely impacted performance in the UCFlex task. Furthermore, when the good performing rats were reevaluated after they had been subjected to sleep fragmentation, additional ATSET performance decrements were observed in the set shifting stages of the ATSET test, with only 7.4% of the neutron exposed rats able to successfully perform ATSET under normal and sleep fragmented conditions, as opposed to ∼55% of shams. CONCLUSION: Protracted low dose and low dose rate neutron exposures impairs executive functions in a high percentage of rats that were normally rested, however further detriments in performance become evident when the rats are subjected to sleep fragmentation.

Sleep Fragmentation Exacerbates Executive Function Impairments Induced by Low Doses of Si Ions.

Astronauts on deep space missions will be required to work autonomously and thus their ability to perform executive functions could be critical to mission success. Ground-based rodent experiments have shown that low (<25 cGy) doses of several space radiation (SR) ions impair various aspects of executive function. Translating ground-based rodent studies into tangible risk estimates for astronauts remains an enormous challenge, but should similar neurocognitive impairments occur in astronauts exposed to low-SR doses, a Numbers-Needed-to-Harm analysis (of the rodent data) predicts that approximately 30% of the astronauts could develop severe cognitive flexibility decrements. In addition to the health risks associated with SR exposure, astronauts have to contend with other stressors, of which inadequate sleep quantity and quality are considered to be major concerns. We have shown that a single session of fragmented sleep uncovered latent attentional set-shifting (ATSET) performance deficits in rats exposed to protracted neutron radiation that had no obvious defects in performance under rested wakefulness conditions. It is unclear if the exacerbating effect of sleep fragmentation (SF) only occurs in rats receiving protracted low-dose-rate-neutron radiation. In this study, we assessed whether SF also unmasks latent ATSET deficits in rats exposed to 5 cGy 600 MeV/n 28Si ions. Only sham and Si-irradiated rats that had good ATSET performance (passing every stage of the test on their first attempt) were selected for study. Sleep fragmentation selectively impaired performance in the more complex IDR, EDS and EDR stages of the ATSET test in the Si-irradiated rats. Set-shifting performance has rarely been affected by SR exposure in our studies conducted with rats tested under rested wakefulness conditions. The consistent SF-related unmasking of latent set-shifting deficits in both Si- and neutron-irradiated rats suggests that there is a unique interaction between sleep fragmentation and space radiation on the functionality of the brain regions that regulate performance in the IDR, EDS and EDR stages of ATSET. The uncovering of these latent SR-induced ATSET performance deficits in both Si- and neutron-irradiated rats suggests that the true impact of SR-induced cognitive impairment may not be fully evident in normally rested rats, and thus cognitive testing needs to be conducted under both rested wakefulness and sleep fragmentation conditions.

Multi-domain neurocognitive classification of primary brain tumor patients prior to radiotherapy on a prospective clinical trial.

INTRODUCTION: We investigated multi-domain baseline neurocognition of primary brain tumor patients prior to radiotherapy (RT), including clinical predictors of function and association between pre-RT and post-RT impairment on a prospective trial. METHODS: A multi-domain neuropsychological battery (memory, executive functioning, language, attention, processing) was performed on 37 patients, pre-RT and 3-(n = 21), 6-(n = 22) and 12-(n = 14) months post-RT. Impairment rate was the proportion of patients with standardized T-scores ≤ 1.5 standard deviations below normative means. Per-patient impairment across all domains was calculated using a global deficit score (GDS; higher value indicates more impairment). Associations between baseline GDS and clinical variables were tested. Global GDS impairment rate at each time point was the fraction of patients with GDS scores > 0.5. RESULTS: Statistically significant baseline neurocognitive impairments were identified on 4 memory (all p ≤ 0.03) and 2 out of 3 (p = 0.01, p = 0.027) executive functioning tests. Per-patient baseline GDS was significantly associated with tumor volume (p = 0.048), tumor type (p = 0.043), seizure history (p = 0.007), and use of anti-epileptics (p = 0.009). The percentage of patients with the same impairment status at 3-, 6-, and 12-months as at baseline were 88%, 85%, and 85% respectively. CONCLUSIONS: Memory and executive functioning impairment were the most common cognitive deficits prior to RT. Patients with larger tumors, more aggressive histology, and use of anti-epileptics had higher baseline GDS values. GDS is a promising tool to encompass multi-domain neurocognitive function, and baseline GDS can identify those at risk of cognitive impairment.

Corticostriatal stimulation compensates for medial frontal inactivation during interval timing.

Prefrontal dysfunction is a common feature of brain diseases such as schizophrenia and contributes to deficits in executive functions, including working memory, attention, flexibility, inhibitory control, and timing of behaviors. Currently, few interventions improve prefrontal function. Here, we tested whether stimulating the axons of prefrontal neurons in the striatum could compensate for deficits in temporal processing related to prefrontal dysfunction. We used an interval-timing task that requires working memory for temporal rules and attention to the passage of time. Our previous work showed that inactivation of the medial frontal cortex (MFC) impairs interval timing and attenuates ramping activity, a key form of temporal processing in the dorsomedial striatum (DMS). We found that 20-Hz optogenetic stimulation of MFC axon terminals increased curvature of time-response histograms and improved interval-timing behavior. Furthermore, optogenetic stimulation of terminals modulated time-related ramping of medium spiny neurons in the striatum. These data suggest that corticostriatal stimulation can compensate for deficits caused by MFC inactivation and they imply that frontostriatal projections are sufficient for controlling responses in time.

Identifying early diffusion imaging biomarkers of regional white matter injury as indicators of executive function decline following brain radiotherapy: A prospective clinical trial in primary brain tumor patients.

BACKGROUND AND PURPOSE: Executive function (EF) decline is common after brain radiation therapy (RT), yet the etiology is unclear. We analyzed the association between longitudinal changes in frontal lobe white matter microstructure and decline in EF following RT in brain tumor patients on a prospective clinical trial. MATERIALS AND METHODS: Diffusion tensor imaging was obtained on 22 patients with brain tumors prior to RT, as well as 3- and 6-months post-RT, in a prospective, observational trial. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated within the superficial white matter (SWM) of the anterior cingulate (AC) and dorsolateral prefrontal cortex. Measures of cognitive flexibility, verbal fluency, and verbal set-shifting were obtained pre- and post-RT. Reliable change indices were calculated to determine significant baseline to 6-month EF changes. RESULTS: Decreases in FA and increases in MD were observed in the caudal AC (CAC) at 3-months post-RT. CAC changes were characterized by increased RD bilaterally. From baseline to 6-months post-RT, decreased FA and increased MD and RD of the CAC was associated with decline in verbal set-shifting ability, whereas increased MD in the CAC was associated with a decline in cognitive flexibility. CONCLUSION: White matter underlying the AC may be particularly vulnerable to radiation effects. Early microstructural loss within AC SWM represents an important biomarker for EF decline, and dose reduction in this region may represent a possibility for cognitive preservation for patients receiving radiotherapy.

Long-term cognitive dysfunction after radiation therapy for primary brain tumors.

Background: The extent of radiation therapy (RT)-induced changes in cognitive function is unknown. RT with protons instead of photons spares the healthy brain tissue more and is believed to reduce the risk of cognitive dysfunction. There is modest knowledge on which parts of the brain we need to spare, to prevent cognitive dysfunction. To uncover which cognitive domains is most affected, we compared cognitive functioning in brain tumor patients treated with neurosurgery and RT with brain tumor patients treated with neurosurgery alone. Methods: A cross-sectional study assessing cognitive function in 110 patients with a primary brain tumor grades I-III or medulloblastoma (grade IV) treated at Aarhus University Hospital (AUH), Denmark between 2006 and 2016. Two cohorts were established: a cohort of 81 brain tumor patients who had received neurosurgery followed by RT (RT+), and a cohort of 29 brain tumor patients who had only received neurosurgery (RT-). The patients underwent questionnaires and neuropsychological assessment with standardized tests. Results: Mean age was 53.5 years with an average time since diagnosis of 7.3 years. Compared with normative data, lower average scores were observed for the entire group on domains concerning of verbal learning and memory (p < .001), attention and working memory (p < .001), processing speed (p < .001), and executive functioning (p < .001). Compared to RT- patients, RT + patients scored lower on domains concerning processing speed (p = .04) and executive function (p = .05) and had higher impairment frequency on verbal fluency (p = .02) with 16% of patients exceeding 1.5 SD below normative data. Conclusions: Our results indicate that treatment, including RT, for a primary brain tumor may have negative long-term impact on cognitive function, especially on processing speed and executive function.

Maintenance of multidomain neurocognitive functions in pediatric patients after proton beam therapy: A prospective case-series study.

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.

Photobiomodulation improves the frontal cognitive function of older adults.

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.

Exposure to ≤15 cGy of 600 MeV/n 56Fe Particles Impairs Rule Acquisition but not Long-Term Memory in the Attentional Set-Shifting Assay.

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 56Fe 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 56Fe 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 56Fe particles, but that 56Fe 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, 56Fe-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 56Fe-induced cognitive deficits.

Light correlated color temperature and task switching performance in preschool-age children: Preliminary insights.

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.

Bright light exposure before bedtime impairs response inhibition the following morning: a non-randomized crossover study.

INTRODUCTION: Bright light exposure in the late evening can affect cognitive function the following morning either by changing the biological clock and/or disturbing sleep, but the evidence for this effect is scarce, and the underlying mechanism remains unknown. In this study, we first aimed to evaluate the effect of bright light exposure before bedtime on frontal lobe activity the following morning using near-infrared spectroscopy (NIRS) during a Go/NoGo task. Second, we aimed to evaluate the effects of bright light exposure before bedtime on polysomnographic measures and on a frontal lobe function test the following morning. METHODS: Twenty healthy, young males (mean age, 25.5 years) were recruited between September 2013 and August 2014. They were first exposed to control light (150 lux) before bedtime (from 20:00 h to 24:00 h) for 2 days and then to bright light (1,000 lux) before bedtime for an additional 5 days. We performed polysomnography (PSG) on the final night of each light exposure period (on nights 2 and night 7) and performed NIRS, which measures the concentrations of oxygenated and deoxygenated hemoglobin (OxyHb and DeoxyHb, respectively), coupled with a Go/NoGo task the following morning (between 09:30 h and 11:30 h). The participants also completed frontal lobe function tests the following morning. RESULTS: NIRS showed decreased hemodynamic activity (lower OxyHb and a tendency toward higher DeoxyHb concentration) in the right frontal lobe during the NoGo block after 1000-lux light exposure compared with that during the NoGo block after 150-lux light exposure. The commission error rate (ER) during the Go/NoGo task was higher after 1000-lux light exposure than that during the Go/NoGo task after 150-lux light exposure (1.24 ± 1.09 vs. 0.6 ± 0.69, P = 0.002), suggesting a reduced inhibitory response. CONCLUSION: This study shows that exposure to bright light before bedtime for 5 days impairs right frontal lobe activation and response inhibition the following morning.

Photobiomodulation using low-level laser therapy (LLLT) for patients with chronic traumatic brain injury: a randomized controlled trial study protocol.

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 cm2 will be irradiated for 30 min, giving a total dose per session of 3.74 J/cm2. 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.

Cognitive function following head CT in childhood: a randomized controlled follow-up trial.

Background The question has been raised whether low dose radiation toward the brain in childhood can affect cognitive functions. Purpose To examine if a head computed tomography (CT) examination in childhood affect later cognitive functions. Material and Methods A total of 147 participants (67 girls/women, 80 boys/men) from a previous randomized controlled trial on management strategies after mild head injury (head CT examination or in-hospital observation) were followed up. Participants were aged 6-16 years (mean age = 11.2 ± 2.8) at first inclusion and 11-24 years (mean age = 17.8 ± 2.9) at follow-up. Computerized neuropsychological measures used for the assessment were motor speed and coordination, reaction time, selective attention, visuospatial ability, verbal and non-verbal short-term and long-term memory, and executive function tests from the neurocognitive test battery EuroCog and the Wechsler Memory Scale III. Results were analyzed with Student's t-tests and multivariate analyses adjusting for sex, age at time of injury/exposure, and age at assessment were performed with Factorial ANOVAs. Results The exposed and unexposed groups did not differ in any of the neuropsychological measures and results did not change when sex, age at time of injury/exposure, and age at assessment were included in the analyses. Conclusion A head CT examination at the age of 6-16 years does not seem to affect later cognitive functions.

Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy.

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.

Exposure to Mission-Relevant Doses of 1 GeV/n (48)Ti Particles Impairs Attentional Set-Shifting Performance in Retired Breeder Rats.

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.

Executive Dysfunction 25 Years after Treatment with Cranial Radiotherapy for Pediatric Lymphoid Malignancies.

The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found deficits in working memory capacity, inhibition, cognitive flexibility, executive visuomotor control, attentional fluctuations, and sustained attention. Older age was associated with poorer performance on executive visuomotor control and inhibition. On executive visuomotor control, 50% of female survivors performed more than 1.5 SD below average, versus 15.4% of male survivors. The combination of visuospatial working memory problems and decreasing executive visuomotor control could result in difficulty with learning new motor skills at older ages, like walking with a cane. Deterioration of executive control and inhibition may result in decreased behavioral and emotional regulation in aging survivors. Especially the deficiency in executive visuomotor control in female survivors should be considered for (prophylactic) intervention.