BACKGROUND: Exposure to moderate levels of simulated hypoxia has subtle cognitive effects relative to ground level, in healthy individuals. However, there are few data on the cognitive consequences of the combination of hypoxia and partial sleep deprivation, which is a classic military or civilian operational context. In this study, we tested the hypothesis that exposure to moderate hypoxia while sleep-restricted impairs several domains of cognition, and we also assessed physiological parameters and salivary concentrations of cortisol and alpha-amylase.
METHODS: Seventeen healthy males completed two sessions of cognitive tests (sustained attention using the PVT psychomotor vigilance task and executive functions using the Go-NoGo inhibition task and N-Back working memory task) after 30 minutes (T+30\') and 4 hours (T+240\') of exposure in a normobaric hypoxic tent (FIO2 = 13.6%, ≃ 3,500 m) (HY). This was completed after one night of sleep restriction (3 a.m. to 6 a.m. bedtime, SRHY) and one night of habitual sleep (10 p.m. to 6 a.m. bedtime, HSHY) (with cross-over randomization). The two nights sleep architecture and physiological parameters (oxygen saturation (SpO2) and heart rate (HR) during T+30\' and T+240\'sessions were analyzed. Salivary cortisol and alpha-amylase (sAA) concentrations were analyzed before hypoxia, after the T+30\' and T+240\' cognitive sessions, and after leaving the hypoxic tent.
RESULTS: Sustained attention (RT and number of lapses in the PVT) and executive functions (Go-NoGo and 1-Back and 2-Back parameters, as inhibition and working memory signatures) were impaired in the SRHY condition compared to HSHY. SpO2 and HR were higher after 4 hours compared with 30 minutes of hypoxia in the HSHY condition, while only HR was statistically higher in the SRHY condition. In SRHY, salivary AA concentration was lower and cortisol was higher than in HSHY. A significant increase in sAA concentration is observed after the cognitive session at 4 hours of hypoxia exposure compared to that at 30 minutes, only in the SRHY condition. There are significant positive correlations between reaction time and the corresponding heart rate (a non-invasive marker of physiological stress) for the executive tasks in the two sleep conditions. This was not observed for salivary levels of sAA and cortisol, respective reliable indicators of the sympathoadrenomedullary system and the hypothalamic-pituitary adrenocortical system.
CONCLUSIONS: Exposure to moderate normobaric hypoxia (≃ 3,500 m / ≃ 11,500 ft simulated) after a single night of 3-hour sleep impairs cognitive performance after 30 minutes and 4 hours of exposure. The key determinants and/or mechanism(s) responsible for cognitive impairment when exposed to moderate hypoxia with sleep restriction, particularly on the executive function, have yet to be elucidated.

Most studies of developing visual attention are conducted using screen-based tasks in which infants move their eyes to select where to look. However, real-world visual exploration entails active movements of both eyes and head to bring relevant areas in view. Thus, relatively little is known about how infants coordinate their eyes and heads to structure their visual experiences. Infants were tested every 3 months from 9 to 24 months while they played with their caregiver and three toys while sitting in a highchair at a table. Infants wore a head-mounted eye tracker that measured eye movement toward each of the visual targets (caregiver\'s face and toys) and how targets were oriented within the head-centered field of view (FOV). With age, infants increasingly aligned novel toys in the center of their head-centered FOV at the expense of their caregiver\'s face. Both faces and toys were better centered in view during longer looking events, suggesting that infants of all ages aligned their eyes and head to sustain attention. The bias in infants\' head-centered FOV could not be accounted for by manual action: Held toys were more poorly centered compared with non-held toys. We discuss developmental factors-attentional, motoric, cognitive, and social-that may explain why infants increasingly adopted biased viewpoints with age.

Sustained attention, as the basis of general cognitive ability, naturally varies across different time scales, spanning from hours, e.g. from wakefulness to drowsiness state, to seconds, e.g. trial-by-trail fluctuation in a task session. Whether there is a unified mechanism underneath such trans-scale variability remains unclear. Here we show that fluctuation of cortical excitation/inhibition (E/I) is a strong modulator to sustained attention in humans across time scales. First, we observed the ability to attend varied across different brain states (wakefulness, postprandial somnolence, sleep deprived), as well as within any single state with larger swings. Second, regardless of the time scale involved, we found highly attentive state was always linked to more balanced cortical E/I characterized by electroencephalography (EEG) features, while deviations from the balanced state led to temporal decline in attention, suggesting the fluctuation of cortical E/I as a common mechanism underneath trans-scale attentional variability. Furthermore, we found the variations of both sustained attention and cortical E/I indices exhibited fractal structure in the temporal domain, exhibiting features of self-similarity. Taken together, these results demonstrate that sustained attention naturally varies across different time scales in a more complex way than previously appreciated, with the cortical E/I as a shared neurophysiological modulator.

The first therapeutical goal followed by neurooncological surgeons dealing with prefrontal gliomas is attempting supramarginal tumor resection preserving relevant neurological function. Therefore, advanced knowledge of the frontal aslant tract (FAT) functional neuroanatomy in high-order cognitive domains beyond language and speech processing would help refine neurosurgeries, predicting possible relevant cognitive adverse events and maximizing the surgical efficacy. To this aim we performed the recently developed correlational tractography analyses to evaluate the possible relationship between FAT\'s microstructural properties and cognitive functions in 27 healthy subjects having ultra-high-field (7-Tesla) diffusion MRI. We independently assessed FAT segments innervating the dorsolateral prefrontal cortices (dlPFC-FAT) and the supplementary motor area (SMA-FAT). FAT microstructural robustness, measured by the tract\'s quantitative anisotropy (QA), was associated with a better performance in episodic memory, visuospatial orientation, cognitive processing speed and fluid intelligence but not sustained selective attention tests. Overall, the percentual tract volume showing an association between QA-index and improved cognitive scores (pQACV) was higher in the SMA-FAT compared to the dlPFC-FAT segment. This effect was right-lateralized for verbal episodic memory and fluid intelligence and bilateralized for visuospatial orientation and cognitive processing speed. Our results provide novel evidence for a functional specialization of the FAT beyond the known in language and speech processing, particularly its involvement in several higher-order cognitive domains. In light of these findings, further research should be encouraged to focus on neurocognitive deficits and their impact on patient outcomes after FAT damage, especially in the context of glioma surgery.

The Continuous Visual Attention Test (CVAT) is a test that detects visuomotor reaction time (RT, alertness), variability of reaction time (VRT, sustained attention), omission errors (OE, focused attention), and commission errors (CE, response inhibition). The standard test takes 15 min, while the ultrafast version only 90 s. Besides overall task length, the two versions differ by target probability (20% and 80% in the 15-min vs. only 80% in the 90-s test) and stimulus-onset asynchrony (SOA) (1, 2, and 4 s in the 15-min vs. only 1 s in the 90-s test. We aimed to analyze the effect of target probability, SOA, and time length on the CVAT variables across the 15-min task and to verify correlations and agreements between the 15-min and the 90-s CVATs. 205 healthy participants performed the two CVATs on the same day. Considering the 15-min task, RT and CE were strongly affected by target probability. Conversely, VRT was not affected. When the 15-min task was compared to the 90-s task, we found no significant difference in the VRT variable. Additionally, a significant agreement between the two tasks was found for the VRT variable. We concluded that sustained attention can be measured with the 90-s CVAT.

People with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) often report cognitive impairment which can be quite burdensome but is rarely evaluated in routine clinical practice. In this systematic review and meta-analysis, we assessed the nature and magnitude of cognitive impairment in NT1, NT2, and IH in studies conducted from January 2000 to October 2022. We classified cognitive tests assessing memory, executive function, and attention by cognitive domain. Between-group differences were analyzed as standardized mean differences (Cohen\'s d), and Cohen\'s d for individual tests were integrated according to cognitive domain and clinical disease group. Eighty-seven studies were screened for inclusion; 39 satisfied inclusion criteria, yielding 73 comparisons (k): NT1, k = 60; NT2, k = 8; IH, k = 5. Attention showed large impairment in people with NT1 (d = -0.90) and IH (d = -0.97), and moderate impairment in NT2 (d = -0.60). Executive function was moderately impaired in NT1 (d = -0.30) and NT2 (d = -0.38), and memory showed small impairments in NT1 (d = -0.33). A secondary meta-analysis identified sustained attention as the most impaired domain in NT1, NT2, and IH (d ≈ -0.5 to -1). These meta-analyses confirm that cognitive impairments are present in NT1, NT2, and IH, and provide quantitative confirmation of reports of cognitive difficulties made by patients and clinicians. These findings provide a basis for the future design of studies to determine whether cognitive impairments can improve with pharmacologic and nonpharmacologic treatments for narcolepsy and IH.

Cholinergic disruptions underlie attentional deficits following traumatic brain injury (TBI). Yet, drugs specifically targeting acetylcholinesterase (AChE) inhibition have yielded mixed outcomes. Therefore, we hypothesized that galantamine (GAL), a dual-action competitive AChE inhibitor and α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator, provided chronically after injury, will attenuate TBI-induced deficits of sustained attention and enhance ACh efflux in the medial prefrontal cortex (mPFC), as assessed by in vivo microdialysis. In Experiment 1, adult male rats (n = 10-15/group) trained in the 3-choice serial reaction time (3-CSRT) test were randomly assigned to controlled cortical impact (CCI) or sham surgery and administered GAL (0.5, 2.0, or 5.0 mg/kg; i.p.) or saline vehicle (VEH; 1 mL/kg; i.p) beginning 24-h post-surgery and once daily thereafter for 27 days. Measures of sustained attention and distractibility were assessed on post-operative days 21-25 in the 3-CSRT, following which cortical lesion volume and basal forebrain cholinergic cells were quantified on day 27. In Experiment 2, adult male rats (n = 3-4/group) received a CCI and 24 h later administered (i.p.) one of the three doses of GAL or VEH for 21 days to quantify the dose-dependent effect of GAL on in vivo ACh efflux in the mPFC. Two weeks after the CCI, a guide cannula was implanted in the right mPFC. On post-surgery day 21, baseline and post-injection dialysate samples were collected in a temporally matched manner with the cohort undergoing behavior. ACh levels were analyzed using reverse phase high-performance liquid chromatography (HPLC) coupled to an electrochemical detector. Cortical lesion volume was quantified on day 22. The data were subjected to ANOVA, with repeated measures where appropriate, followed by Newman-Keuls post hoc analyses. All TBI groups displayed impaired sustained attention versus the pooled SHAM controls (p\'s < 0.05). Moreover, the highest dose of GAL (5.0 mg/kg) exacerbated attentional deficits relative to VEH and the two lower doses of GAL (p\'s < 0.05). TBI significantly reduced cholinergic cells in the right basal forebrain, regardless of treatment condition, versus SHAM (p < 0.05). In vivo microdialysis revealed no differences in basal ACh in the mPFC; however, GAL (5.0 mg/kg) significantly increased ACh efflux 30 min following injection compared to the VEH and the other GAL (0.5 and 2.0 mg/kg) treated groups (p\'s < 0.05). In both experiments, there were no differences in cortical lesion volume across treatment groups (p\'s > 0.05). In summary, albeit the higher dose of GAL increased ACh release, it did not improve measures of sustained attention or histopathological markers, thereby partially supporting the hypothesis and providing the impetus for further investigations into alternative cholinergic pharmacotherapies such as nAChR positive allosteric modulators.

Nonmedical use of prescription opioids peaks during late adolescence, a developmental period associated with the maturation of higher-order cognitive processes. To date, however, how chronic adolescent oxycodone (OXY) self-administration alters neurobehavioral (i.e., locomotion, startle reactivity) and/or neurocognitive (i.e., preattentive processes, intrasession habituation, stimulus-reinforcement learning, sustained attention) function has not yet been systematically evaluated. Hence, the rationale was built for establishing the dose-dependency of adolescent OXY self-administration on the trajectory of neurobehavioral and neurocognitive development. From postnatal day (PD) 35 to PD 105, an age in rats that corresponds to the adolescent and young adult period in humans, male and female F344/N rats received access to either oral OXY (0, 2, 5, or 10 mg/kg) or water under a two-bottle choice experimental paradigm. Independent of biological sex or dose, rodents voluntarily escalated their OXY intake across ten weeks. A longitudinal experimental design revealed prominent OXY-induced impairments in neurobehavioral development, characterized by dose-dependent increases in locomotion and sex-dependent increases in startle reactivity. Systematic manipulation of the interstimulus interval in prepulse inhibition supports an OXY-induced impairment in preattentive processes. Despite the long-term cessation of OXY intake, rodents with a history of chronic adolescent oral OXY self-administration exhibited deficits in sustained attention; albeit no alterations in stimulus-reinforcement learning were observed. Taken together, adolescent oral OXY self-administration induces selective long-term alterations in neurobehavioral and neurocognitive development enjoining the implementation of safer prescribing guidelines for this population.

Researchers dispute the cause of errors in high Go, low No Go target detection tasks, like the Sustained Attention to Response Task (SART). Some researchers propose errors in the SART are due to perceptual decoupling, where a participant is unaware of stimulus identity. This lack of external awareness causes an erroneous response. Other researchers suggest the majority of the errors in the SART are instead due to response leniency, not perceptual decoupling. Response delays may enable a participant who is initially unaware of stimulus identity, perceptually decoupled, to become aware of stimulus identity, or perceptually recoupled. If, however, the stimulus presentation time is shortened to the minimum necessary for stimulus recognition and the stimulus is disrupted with a structured mask, then there should be no time to enable perception to recouple even with a response delay. From the perceptual decoupling perspective, there should be no impact of a response delay on performance in this case. Alternatively if response bias is critical, then even in this case a response delay may impact performance. In this study, we shortened stimulus presentation time and added a structured mask. We examined whether a response delay impacted performance in the SART and tasks where the SART\'s response format was reversed. We expected a response delay would only impact signal detection theory bias, c, in the SART, where response leniency is an issue. In the reverse formatted SART, since bias was not expected to be lenient, we expected no impact or minimal impact of a response delay on response bias. These predictions were verified. Response bias is more critical in understanding SART performance, than perceptual decoupling, which is rare if it occurs at all in the SART.

The vigilance decrement, a temporal decline in detection performance, has been observed across multiple sensory modalities. Spatial uncertainty about the location of task-relevant stimuli has been demonstrated to increase the demands of vigilance and increase the severity of the vigilance decrement when attending to visual displays. The current study investigated whether spatial uncertainty also increases the severity of the vigilance decrement and task demands when an auditory display is used. Individuals monitored an auditory display to detect critical signals that were shorter in duration than non-target stimuli. These auditory stimuli were presented in either a consistent, predictable pattern that alternated sound presentation from left to right (spatial certainty) or an inconsistent, unpredictable pattern that randomly presented sounds from the left or right (spatial uncertainty). Cerebral blood flow velocity (CBFV) was measured to assess the neurophysiological demands of the task. A decline in performance and CBFV was observed in both the spatially certain and spatially uncertain conditions, suggesting that spatial auditory vigilance tasks are demanding and can result in a vigilance decrement. Spatial uncertainty resulted in a more severe vigilance decrement in correct detections compared to spatial certainty. Reduced right-hemispheric CBFV was also observed during spatial uncertainty compared to spatial certainty. Together, these results suggest that auditory spatial uncertainty hindered performance and required greater attentional demands compared to spatial certainty. These results concur with previous research showing the negative impact of spatial uncertainty in visual vigilance tasks, but the current results contrast recent research showing no effect of spatial uncertainty on tactile vigilance.