Long-term total sleep deprivation reduces thalamic gray matter volume in healthy men

Sleep loss can alter extrinsic, task-related functional MRI signals involved in attention, memory, and executive function. However, the effects of sleep loss on brain structure have not been well characterized. Recent studies with patients with sleep disorders and animal models have demonstrated reduction of regional brain structure in the hippocampus and thalamus. In this study, using T1-weighted MRI, we examined the change of regional gray matter volume in healthy adults after long-term total sleep deprivation (∼72 h). Regional volume changes were explored using voxel-based morphometry with a paired two-sample t-test. The results revealed significant loss of gray matter volume in the thalamus but not in the hippocampus. No overall decrease in whole brain gray matter volume was noted after sleep deprivation. As expected, sleep deprivation significantly reduced visual vigilance as assessed by the continuous performance test, and this decrease was correlated significantly with reduced regional gray matter volume in thalamic regions. This study provides the first evidence for sleep loss-related changes in gray matter in the healthy adult brain

DEVELOPMENT OF NEUROPHYSIOLOGICAL APPROACHES FOR MONITORING AND INTERVENING MENTAL FATIGUE

Ph.DDOCTOR OF PHILOSOPH

A Short Window Granger Causality Approach to Identify Brain Functional Pattern Associated with Changes of Performance Induced by Sleep Deprivation

The comprehensive effect of sleep deprivation on biological and behavioral functions largely remains unknown. There is evidence to support that human sleep must be of sufficient duration and physiological continuity to ensure neurocognitive performance while we are waking. Insufficient sleep would lead to high risk of human-error related to accidents, injuries or even fatal outcomes. However, in modern society, more and more people suffer from sleep deprivation because of the increasing social, academic or occupational demand. It is important to study the effect of sleep deprivation, not only on task performance, but also on neurocognitive functions. Recent research that has explored brain effective connectivity has demonstrated the directed inference interaction among pairs of brain areas, which may bring important insight to understand how brain works to support neurocognitive function. This research aimed to identify the brain effective connectivity pattern associated with changes of a task performance, response time, following sleep deprivation. Experiments were conducted by colleagues at Neuroergonomics Department at Jagiellonian University, Krakow, Poland. Ten healthy young women, with an average age of 23-year-old, performed visual spatial sustained-attention tasks under two conditions: (1) the rest-wakeful (RW) condition, where participants had their usual sleep and (2) the sleep-deprived (SD) condition, where participants had 3 hours less sleep than their usual sleep, for 7 nights (amounting to 21 h of sleep debt). Measures included eye tracking performance and functional magnetic resonance imaging (fMRI). In each condition, each subject*s eye-position was monitored through 13 sessions, each with 46 trials, while fMRI data was recorded. There were two task performance measures, accuracy and response time. Accuracy measured the proportion of correct responses of all trials in each session. Response time measured the average amount of milliseconds until participants gazed at the target stimuli in each session. An experimental session could be treated as a short window. By splitting long trials of fMRI data into consecutive windows, Granger causality was applied based on short trials of fMRI data. This procedure helped to calculate pairwise causal influences with respect to time-varying property in brain causal interaction. Causal influence results were then averaged across sessions to create one matrix for each participant. This matrix was averaged within each condition to formulate a model of brain effective connectivity, which also served as a basis of comparison. In conclusion, significant effect of sleep deprivation was found on response time and brain effective connectivity. In addition, the change of brain effective connectivity after sleep deprivation was linked to the change of response time. First, an analysis of variance (ANOVA) showed significant difference for response time between the RW condition and the SD condition. No significant changes for accuracy were found. A paired t-test showed that response time was significantly shorter in sleep deprivation for the visual spatial sustained-attention task. Second, Granger causality analysis demonstrated a reduction of bidirectional connectivity and an increase of directed influences from low-level brain areas to high-level brain areas after sleep deprivation. This observation suggested that sleep deprivation provoked the effective connectivity engaged in salient stimuli processing, but inhibited the effective connectivity in biasing selection of attention on task and in maintaining self-awareness in day time. Furthermore, in the SD condition, attention at the visual spatial task seemed to be driven by a bottom-up modulation mechanism. Third, a relationship was found between brain effective connectivity with response time. Decreases of Granger causal influences in two directions, from medial frontal lobe to sub cortical gray nuclei and from medial parietal lobe to sub cortical gray nuclei, were associated with shorter response time in the SD condition. Additionally, an increase of Granger causal influence from medial parietal lobe to cerebellum was associated with longer response time in the SD condition

Exploring the Role of the Dorsal Attention Network in Sustained Attention With rTMS

Sustained attention that is effortful during challenging cognitive tasks has been associated with robust activity in brain areas involved with cognitive control, collectively referred to as the dorsal attention network (DAN). In contrast, the periods of optimal sustained attention have been associated with relatively less DAN activity than periods of struggle. Optimal sustained attention may be less dependent on DAN function and more dependent on brain networks related to task automation such as the default mode network (DMN). Alternatively, optimal sustained attention may be recruiting DAN function efficiently, thus resulting in less overall activity. These two hypotheses were examined by temporarily disrupting DAN activity by applying repetitive transcranial magnetic stimulation (rTMS) to the frontal eye fields (FEF) in the DAN and then measuring sustained attention to a cognitive task. Subjects randomly received real or sham rTMS to the left or right FEF and then performed a modified go/no-go sustained attention task referred to as the gradCPT. For subjects receiving real rTMS to the right FEF, response accuracy decreased and reaction time variability increased on the gradCPT during periods of optimal sustained attention. The findings suggest that optimal sustained attention to cognitive tasks is supported by the refined, economical recruitment of right hemisphere DAN function

Nocturnal oscillations: Understanding the brain through sleep

This thesis explores the nature of sleep oscillations using behavioral and neurophysiological measures. The first experiment examines how the magnitude of different spectral frequencies in the sleep electroencephalography affect individual’s subjective emotional experience of positive and negative moods, as well as the emotional detriment associated with a full night of sleep deprivation, and its recovery after a daytime nap. The change in positive and negative moods across a night’s sleep is predicted by the magnitude of different oscillatory activity during rapid-eye-movement (REM) and non-REM (NREM) sleep. Experiment 2 uses EEG with simultaneous functional magnetic resonance imaging (fMRI) to examine the blood oxygen level dependent (BOLD) signal changes associated with sleep stage changes, and specifically investigates the functional connectivity changes within the basal ganglia network that occur across an early, slow-wave-rich sleep cycle. In NREM sleep, the functional connectivity of the globus pallidus and the striatum (composed of the putamen and caudate nucleus) show patterns supporting the tripartite division model, and lend support to existing studies of information processing during sleep, especially in the motor domain. Experiment 3 seeks to validate the hypothesis that different frequencies of oscillatory activity within the brain will differentially modulate the spatial profile of BOLD activity. This is achieved with applying transcranial alternating current stimulation (tACS) during fMRI acquisition, by artificially inducing oscillations of different frequencies in the brain while measuring the BOLD signal changes associated with the oscillatory activity. Stimulation to the primary visual cortex led to BOLD activity increases, relative to baseline, in different neural networks depending on the frequency of stimulation. The three experiments presented in the thesis shed light on the nature of neural network modulations caused by ongoing oscillatory activity, and bridge the gap between electrophysiological and haemodynamic findings of sleep-dependent information processing

How sleep deprivation degrades task performance: combining experimental analysis with simulations of adenosinergic effects of basal ganglia and cortical circuits

Thesis (Ph.D.)--Boston UniversityHumans configure themselves into "neural machines" to perform optimally on distinct tasks, and they excel at maintaining such configurations for brief episodes. The neural configuration needed for peak performance, however, is subject to perturbations on multiple time scales. This thesis reports new empirical analyses and computational modeling to advance understanding of the variations in reaction time (RT) on simple RT tasks that are associated with the duration of the preceding inter-stimulus interval (order of seconds); the time-on-task duration (order of minutes); and sleep deprivation duration (order of hours to days). Responses from the psychomotor vigilance task (PVT), including anticipations (false alarms), normal RTs, and very long RTs (lapses in attention), were analyzed to discover the effects of: the 1 - 9 second inter-stimulus interval (ISI); the 10-minute task session; up to 50 hours of sleep deprivation (SD); and wake-promoting agents, caffeine and modafinil. Normal RTs and lapses in attention were negatively correlated with ISI length, whereas anticipations were positively correlated. Anticipations, normal RTs, and lapses increased as time-on-task increased, and during SD. Both caffeine and modafinil reduced lapses and anticipations during SD and decreased RT variability. A simple neural network model incorporating both a time-dependent inhibitory process and a time-dependent excitatory process was developed. The model robustly simulated the ISI effect on behavior. The SD effects were reproducible with two parameter adjustments. Informed modeling of drug effects required greater neurobiological detail. In the basal ganglia (BG), adenosine accumulation during SD has two notable effects: it antagonizes dopamine to reduce BG responsiveness to incoming cortical signals, and it reduces cholinergic transmission to parietal and prefrontal cortices, thus reducing attention to visual signals. A detailed computational model of interactions between BG and cortex during PVT was developed to simulate effects of adenosine and their amelioration by caffeine. The model simulates drug, ISI and SD effects on anticipations, RTs, and lapses. This model can be used to describe the effects of SD over a wide range of tasks requiring planned and reactive movements, and can predict and model effects of pharmacological agents acting on the adenosinergic, cholinergic and dopaminergic systems