The Association Between Sleep Problems and Attentional Network Functions in Patients with Self-Limited Epilepsy with Centrotemporal Spikes

Nan Jiang,1,2 Chun Mei Yang,1,2 Jia Le Wang,1,2 Xiao Fei Ye,1 Bin Yang1,2 1Children’s Medical Centre of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2The Fifth Clinical College Affiliated to Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Bin Yang, Children’s Medical Centre of Anhui Medical University, The Fifth Clinical College Affiliated to Anhui Medical University, Hefei, People’s Republic of China, Tel +86-13866127496, Email [email protected]: To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction.Patients and methods: 107 children 6– 14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children’s Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT).Results: Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P< 0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= − 0.253, P< 0.01), while they were positively correlated with total reaction time (ρ=0.367, P< 0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=− 0.344 P< 0.01; ρ=− 0.418 P< 0.01).Conclusion: Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.Keywords: SeLECTS, attention network function, sleep disorders, CSH

Quantitative association of cerebral blood flow, relaxation times and proton density in young and middle-aged primary insomnia patients: A prospective study using three-dimensional arterial spin labeling and synthetic magnetic resonance imaging

ObjectivesTo quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes.MethodsCranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis.ResultsBilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p &lt; 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes.ConclusionInsomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients

Time-on-task and sleep deprivation effects are evidenced in overlapping brain areas

10.1016/j.neuroimage.2013.05.119NeuroImage82326-335NEIM

Exploration of sleep deprivation

103 leaves ; 29 cmIncludes abstract and appendices.Includes bibliographical references (leaves 98-103).Sleep deprivation has been associated with poor vigilance performance. Previous studies have demonstrated performance decrements on the psychomotor vigilance task (PVT) and changes to resting-state EEG (rEEG) power. This study was designed to link diminished vigilance with rEEG after sleep deprivation to identify underlying mechanisms. In this study, rEEG and the 10-minute PVT were used after a full night's sleep or sleep deprivation. Absolute alpha power decreased when eyes were closed for the sleep deprivation condition, but not for the sleep condition. Furthermore, the response times on the PVT increased following sleep deprivation, but not after a normal night of sleep. Interestingly, no correlation was observed between the PVT and changes to rEEG spectral power. These findings suggest that the impairment in vigilance following sleep deprivation may not be directly tied to changes in rEEG spectral power. The findings are discussed within the context of contemporary theories of sleep deprivation

Mental Fatigue and Sleep Deprivation: Effects, Mechanisms and Countermeasures in Endurance Exercise Performance

Mental fatigue and sleep deprivation are two common conditions in our modern societies, affecting millions of healthy people. Whereas mental fatigue is considered a psychobiological state caused by prolonged and demanding cognitive activities, sleep deprivation can be defined as a brain state caused by at least 24 hours of wakefulness. The first aim of this thesis was to investigate the acute effects of mental fatigue, sleep deprivation and subsequent recovery sleep on endurance exercise performance. The second aim was to evaluate the effects of two innovative training interventions, Brain Endurance Training (BET) and Sleep Deprivation Training (SDT) on endurance performance. It was hypothesized that: 1) 50-min of mentally-demanding cognitive task and 25-h of sleep deprivation would impair endurance performance and that the following night of recovery sleep would be enough to restore rested endurance performance; 2) six weeks of BET (alone) and six weeks of SDT (combined with physical training) would improve endurance performance. The first and second study do not provide reliable evidence that mental fatigue and sleep deprivation reduce endurance performance during a half-marathon and a 20-min cycling time trial, respectively. However, an alternative statistical analysis used in study one, suggests that the hypothesis that mental fatigue is harmful cannot be rejected. The third study shows that BET is not effective in physically-inactive males. The fourth study reveals that SDT in combination with physical training might be beneficial to counteract the effects of sleep deprivation on endurance performance. In conclusion, the findings do not provide statistical evidence of a negative effect of mental fatigue and sleep deprivation on endurance performance. However, it might be prudent to avoid them prior to races. The use of BET alone does not enhance endurance performance. Nonetheless, the combination of SDT with a physical training program might be beneficial in preparation for an endurance/ultra-endurance event

PERIOD3 variable number tandem repeat genotype associations with performance, injury, illness and re-entrainment

Background: Circadian rhythms are internally driven biological variations that fluctuate with a period of approximately 24 hours, even in the absence of external environmental time cues. These rhythms enable organisms to synchronise their internal clock time with external environmental time. This ensures appropriate timing of biological and metabolic processes, and allows anticipation of daily changes in the environment. Circadian rhythms also play an important role in sports in terms of optimising performance time-of-day and aiding adjustment to global time zone changes. Thus, performance, which is under the control of the athlete, may be impacted by event time-of-day scheduling in the new time zone. It has previously been shown that individual sport athletes in South Africa tend to be morning-types and carry the PERIOD3 (PER3) Variable Number Tandem Repeat (VNTR) 5-repeat allele, which has been associated with a preference for mornings. The distribution of the PER3 VNTR polymorphism in combination with an individual's preference for mornings or evenings has not yet been described in team sports. Differences in the PER3 VNTR genotype between team and individual sport athletes are expected, given that individual sport athletes may be free to choose the time-of-day at which they train. In contrast, team sport athletes usually train in groups, thus these individuals may not have the flexibility to choose their preferred training times. There are notable inter-individual differences in adjustment to jet-lag after time zone changes. A possible genetic candidate that may be responsible for some of this variation is the PER3 VNTR gene. This gene consist of two alleles corresponding in size to 4-repeats (PER34) or 5-repeats (PER35). Individuals are either homozygous for the 4-repeat allele (PER⁴⁄⁴) or the 5-repeat allele (PER3⁵⁄⁵), while others are heterozygous for the PER3 gene (PER34/5). The PER3 VNTR genotype might explain individual sensitivity to bright light and has been reported to be associated with sleep pressure- an increase in the brain's pressure and need for sleep, following an extended period of awakening. Individuals homozygous for the longer variant of the gene (i.e. PER3⁵⁄⁵) experience a higher sleep pressure during extended wakefulness. The PER3⁵⁄⁵ genotype has been reported to be more sensitive to the alerting and melatonin suppression effects of blue enriched light than the PER⁴⁄⁴ genotype. Aims: Therefore, the aim of Study 1 was to compare the chronotype and PER3 VNTR genotype distribution of South African Super Rugby players to individuals of low physical activity (i.e. those who are physically active ≤2 times per week). The aim of Study 2 was to determine whether PER3 VNTR genotype might contribute to inter-individual variation in the extent to which game involvement and quality of play are affected following trans-meridian travel. Further, the aim of Study 3 was to compare the impact of time zone travel during the 2012 Super Rugby competition in South African players genotyped as PER⁴⁄⁴, PER34/5 and PER3⁵⁄⁵ on the incidence of illnesses and injuries. Lastly, the aim of Study 4 was to compare the extent to which individuals genotyped as PER⁴⁄⁴ or PER3⁵⁄⁵ respond to appropriately-timed blue light exposure in order to resynchronise their circadian rhythm, following simulated eastward travel, based on changes in dim-light melatonin onset and cortisol circadian phases

Cognitive fatigue in young, middle-aged, and older people: behavioral and functional neuroimaging investigations

In our modern societies, humans are constantly cognitively solicited until a relatively advanced age. This continuous cognitive stimulation can obviously be experienced at work but it can also more insidiously come from overcrowded environments, social networks, or constant advertisement on the internet, which eventually bury people in an uninterrupted flow of information. Cognitive fatigue has progressively become one of the most prevalent causes of accidents in everyday life (Dinges, 1995; Shen et al., 2008) but also in the workplace (McCormick et al., 2012). If cognitive fatigue can be considered a normal and adaptive response to long-lasting tasks (Boksem & Tops, 2008), it can also lead to tragic consequences in certain professions. For example, studies have already found evidence of attention drops in airplane pilots (Bartlett, 1943) or large speed variation in car or train drivers under cognitive fatigue (Brown, 1994; Campagne et al., 2004; Kecklund & Akerstedt, 1993; Torsvall & Akerstedt, 1987). This phenomenon is also striking in emergency services like in firefighters (Aisbett & Nichols, 2007; Aisbett et al., 2012; Ferguson et al., 2016) and in intensive care unit physicians (Maltese et al., 2016). When continuously exposed to cognitive fatigue, some individuals can unfortunately develop the so-called burnout condition (Maslach et al., 2001) with its inherent costs for the public health care system but also for the employer (Ricci et al., 2007), in addition to the burden for the individual.Cognitive fatigue can be observed in various domains: Blain et al. (2016) showed that daylong intense cognitive work tends to enhance impulsivity in economic decisions. Likewise, cognitive fatigue has been shown to impair economic decisions, preferences, strategies (Mullette-Gillman et al., 2015), emotion regulation (Grillon et al., 2015), as well as cognitive flexibility in university students (Plukaard et al., 2015). In the sport domain, cognitive fatigue has also been found to alter soccer-specific decision-making (Smith et al., 2016), intermittent running performance (Smith et al., 2015) as well as table tennis performance (Le Mansec et al., 2018).In more severe cases, cognitive fatigue can further develop into a permanent condition, such as Chronic Fatigue Syndrome (CFS; Tanaka & Watanabe, 2010). Cognitive fatigue is also frequently reported in psychological conditions such as depression (Demyttenaere et al., 2005; Lavidor et al., 2002) and neurological illnesses such as Parkinson’s disease (PD), Multiple Sclerosis (MS), traumatic brain injury, stroke, myasthenia gravis, amyotrophic lateral sclerosis, or postpolio syndrome (Chaudhuri & Behan, 2000; Kluger et al., 2013). Obviously, given the potentially tragic consequences of cognitive fatigue, studies are needed to better understand this phenomenon. On the other hand, medical progress has radically increased life expectancy in the last decades, reaching the age of 81.44 in Belgium (in 2017). At the same time, people have been progressively required to work until a more advanced age although diminished cognitive functioning efficiency has been found in older age (Collette & Salmon, 2014; Crawford et al., 2000; Salthouse et al., 2003; West, 1996, 2000). Therefore, it seems crucial to become aware of how cognitive fatigue manifests in advancing age. Surprisingly, very few studies have investigated cognitive fatigue, behaviorally or at the cerebral level, in aging populations.In addition to older age, the middle-aged population also seems particularly at risk for cognitive fatigue. Indeed, midlife has sometimes been considered as the most challenging life period due to the presence of many cognitive requirements (children to care for, work, social life, everyday duties). However, middle-aged people have scarcely been the focus of interest in the literature, probably because of the difficulty reaching this busy population. In an attempt to understand cognitive fatigue at different life stages, studies presented in this Thesis work have systematically focused on three age groups: young, middle-aged, and older people. The first chapter of this Thesis work starts by presenting definitions and models of cognitive fatigue, from those emphasizing energy depletion as the consequence of long-lasting work to those integrating notions that more particularly focus on the voluntarily controlled effort (e.g., executive function, costs/benefits or effort/reward calculation, opportunity cost) invested by the individual into a cognitive activity. For the sake of completeness, this chapter ends by the presentation of some pathological fatigue models. The second chapter describes studies investigating cognitive fatigue in young people. This chapter makes the distinction between experimental protocols based on the Time-on-Task approach (i.e., performing a unique long-lasting task) and those based on the Probe approach (i.e., performing two consecutive tasks in order to test transfer fatigue effects from the first to the second). The presentation of studies also distinguishes between objective (behavioral, electrophysiologic, neuroimaging, connectivity, motivation-related) and subjective (self-reported scales) assessment of cognitive fatigue.The third chapter is dedicated to the presentation of models of cognitive and cerebral aging. It starts by describing cognitive functions that are known to decline with age as well as potential mediators (i.e., processing speed and inhibition) of age-related declines. It presents the well-recognized patterns of cognitive reserve (Stern, 2002, 2009) as well as cerebral compensation postulated in the PASA, ELSA, CRUNCH, and HAROLD hypotheses. It also presents models that more largely integrate factors potentially influencing cognitive aging (Dennis & Cabeza, 2013; STAC; STAC-R) as well as the hypothesis of the declining dopaminergic system. This chapter ends by describing cognitive efficiency in the middle-aged population. The last introductory chapter is dedicated to the presentation of studies about cognitive fatigue in older as well as in middle-aged population. Regarding the experimental part of the Thesis, the first study was based on a Time-on-Task approach in which a 160-minute Stroop task was continuously administrated to young, middle-aged, and older people in order to test performance decrement (increase in extreme reaction times (RTs)) as a function of both the time spent on task and age. The second study was based on the same protocol as the first one, except that rest breaks were given every 40 minutes. This study allowed us to test whether periodically interrupting the task with short breaks (5 minutes) might relieve cognitive fatigue and allow people to maintain performance. The extent to which the three age groups benefit from breaks was also investigated.The third study used a Probe approach in which a fatigue condition (i.e., a long-lasting Stroop task) or a control condition (i.e., watching videos) was directly followed by an N-Back task during functional magnetic resonance imaging (fMRI) acquisition. This procedure allowed us to test whether cerebral activity is differentially modulated by a fatigue state as a function of age. This work ends by a general discussion of the results of the three studies and proposes future lines of investigation in this research field.We hope our results will contribute to advance knowledge about cognitive fatigue in aging and will be the starting point of many other studies afterwards. We already thank all readers for their interest and wish them a compelling reading

Driver fatigue and performance decrements over time-on-task: Effects and mitigation

Road crashes are a leading cause of death by injury globally (WHO, 2018), with fatigue estimated to contribute to 17% of fatal crashes (Tefft, 2012; TfNSW, 2017). A century of research has advanced our knowledge regarding the causes and effects of fatigue, but much remains unknown. In particular, while there is evidence that both heightened sleep-need and characteristics of the driving task can give rise to fatigue, the relative and combined effects of these factors are not sufficiently understood. Also, while several potential task-based fatigue interventions have been suggested, the effectiveness of these potential interventions is not well established. The present research is comprised of three empirical, driving simulator-based studies that aim to enhance our current understanding of the causes and possible mitigators of driver fatigue. The first study aimed to determine the contributions of time-on-task and sleep restriction, individually and combined, on the development of driver fatigue and performance impairment, and to investigate the potentially protective effects of a simple task modification. Sixty participants drove a simulated, monotonous route for 2 hours, under conditions of either prior sleep restriction or no sleep restriction, and with either normal speed limit signs or signs that required calculation of a mathematical problem, which has previously been shown to protect performance (Dunn & Williamson, 2012). Results clearly demonstrate that both sleep restriction and time-on-task contribute independently to driver fatigue, but there was some indication that sleep-restricted drivers could initially protect their performance, perhaps through the exertion of greater effort. The speed sign manipulation failed to show any protective effects. The second study was designed to further examine the effect of task-factors on driver state and performance over time-on-task. Exposure to a secondary cognitive task has been found to improve driving performance during the period of exposure, but the effects of this intervention over the duration of a drive has received limited attention. This study specifically investigated whether repeated exposures to a secondary task can overcome the degradation of performance and subjective state that occurs over time-on-task, whether any such benefits are dependent on the cognitive workload imposed by the task, and whether these beneficial effects might be attributable to increased effort. This study (N = 17, fully within participants design) employed a secondary cognitive task commonly found to elicit temporally limited beneficial effects in driving performance (n-back task), presenting it three times during an otherwise monotonous 90-minute simulated drive. Each participant performed three drives, one in each of three conditions, with order of condition counterbalanced between participants. The three conditions involved either three periods of 2-back (higher cognitive workload), three periods of 0-back (lower cognitive workload), or no n-back task (control). Results demonstrated that the 2-back condition marginally improved driving performance during exposure but neither condition reduced the degradation of performance or subjective state over time-on-task. The third study built upon study two by exploring whether increasing the frequency of secondary-task exposures would result in reduced performance decrements over time and also by comparing the effect of secondary-task exposure to the effect of taking breaks from driving, which is currently the typical advice provided to drivers to counteract fatigue and performance decrements. This study involved ninety-two participants driving a simulated, monotonous route for 90 minutes in one of six conditions: Driving only (control); infrequent 2-back exposure (three exposures, as per study 2); frequent 2-back exposure (five exposures); continuous 2-back exposure throughout the drive; infrequent breaks (three breaks); or frequent breaks (five breaks). Results indicate that infrequent exposure to a secondary task sustained driving performance over 90-minutes of time-on-task, which is inconsistent with the findings of study 2. Contrary to expectations, frequent secondary-task exposure was less beneficial than infrequent exposure, providing no benefit over the control condition. Continuous secondary-task exposure was detrimental to performance over time-on-task. The provision of breaks from driving also sustained driving performance over time-on-task, with more frequent breaks providing marginally greater benefit than less frequent breaks. Providing participants with breaks from driving was also beneficial for subjective states, measured as sleepiness, fatigue and effort. Results also confirmed that performance improvements in the secondary-task conditions were not solely a result of increased effort. These studies demonstrate that continuous time-on-task driving in highway-like conditions has a robust fatiguing effect. This effect is independent of, but exacerbated by, receiving insufficient sleep, highlighting the importance of taking continuous operating time into consideration, even in the context of seemingly simple tasks and when drivers are well-slept. Additionally, these studies demonstrate that repeated exposure to a secondary task might be an effective intervention for sustaining performance during monotonous drives of at least 90-minutes duration, but the nature and frequency of such interventions appear to be a key factor in their effectiveness. Results also suggest that performance might be best sustained by taking very frequent breaks, and although this might be impractical in the context of driving, this finding might be applied to a broad range of tasks that require sustained attention, including operations in security and quality control

Examining Resting-state Functional and Structural Connectivity of the Attention Networks after Early Brain Insults

Brain insults that occur early in life often lead to cognitive impairments, and sustained attention is highly vulnerable to the initial event as well as to the altered structural and functional brain development that follows. Sustained attention impairments are associated with neural changes in specific brain networks – default mode network (DMN) and central executive network (CEN) – that are crucial for proper attention functioning in healthy populations. Prior studies have, however, typically focused on adult cohorts, which is not applicable to understanding structural and functional changes in the developing brain. There are relatively few studies that have examined these networks in children with an early life injury with advanced quantitative neuroimaging techniques (structural magnetic resonance imaging (MRI) and functional MRI). Thus, the current thesis used these methods to investigate DMN and CEN changes following an early life brain insult in children with traumatic brain injury (TBI), epilepsy, or heterogeneous brain insults with the aim to identify shared neural changes in heterogeneous patient cohorts that underpin common attention impairments. The current thesis has reported reduced functional connectivity in the DMN regions (posterior cingulate cortex and medial prefrontal cortex) in children with TBI, and in the left parietal lobe in children with focal epilepsy as compared to controls at 2-years post-injury. Children with epilepsy however showed no differences in the structural covariance network when compared to controls. Children with heterogeneous brain insults also showed no significant functional and structural connectivity changes when imaging data were acquired in the acute post-insult period. This thesis is however limited by the lack of behavioural measures, and future studies should integrate neuropsychology and neuroimaging to better understand the relationships between the brain connectivity changes and attention deficits, therefore allowing the identification of children who would benefit most from early interventions that could improve their long-term neurocognitive outcomes