Sleep deprivation biases the neural mechanisms underlying economic preferences.

A single night of sleep deprivation (SD) evoked a strategy shift during risky decision making such that healthy human volunteers moved from defending against losses to seeking increased gains. This change in economic preferences was correlated with the magnitude of an SD-driven increase in ventromedial prefrontal activation as well as by an SD-driven decrease in anterior insula activation during decision making. Analogous changes were observed during receipt of reward outcomes: elevated activation to gains in ventromedial prefrontal cortex and ventral striatum, but attenuated anterior insula activation following losses. Finally, the observed shift in economic preferences was not correlated with change in psychomotor vigilance. These results suggest that a night of total sleep deprivation affects the neural mechanisms underlying economic preferences independent of its effects on vigilant attention.

Sleep deprivation and interference by emotional distracters.

STUDY OBJECTIVES: We determined if sleep deprivation would amplify the effect of negative emotional distracters on working memory. DESIGN: A crossover design involving 2 functional neuroimaging scans conducted at least one week apart. One scan followed a normal night of sleep and the other followed 24 h of sleep deprivation. Scanning order was counterbalanced across subjects. SETTING: The study took place in a research laboratory. PARTICIPANTS: 24 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Study participants were scanned while performing a delayed-response working memory task. Two distracters were presented during the maintenance phase, and these differed in content: highly arousing, negative emotional scenes; low-arousing, neutral scenes; and digitally scrambled versions of the pictures. Irrespective of whether volunteers were sleep deprived, negative emotional (relative to neutral) distracters elicited greater maintenance-related activity in the amygdala, ventrolateral prefrontal cortex, and fusiform gyri, while concurrently depressing activity in cognitive control regions. Individuals who maintained or increased distracter-related amygdala activation after sleep deprivation showed increased working memory disruptions by negative emotional distracters. These individuals also showed reduced functional connectivity between the amygdala and the ventromedial and dorsolateral prefrontal cortices, regions postulated to mediate cognitive control against emotional distraction. CONCLUSIONS: Increased distraction by emotional stimuli following sleep deprivation is accompanied by increases in amygdala activation and reduced functional connectivity between the amygdala and prefrontal cognitive control regions. These findings shed light on the neural basis for interindividual variation in how negative emotional stimuli might distract sleep deprived persons.

Hippocampal region-specific contributions to memory performance in normal elderly.

To investigate the relationship between regional hippocampal volume and memory in healthy elderly, 147 community-based volunteers, aged 55-83years, were evaluated using magnetic resonance imaging, the Groton Maze Learning Test, Visual Reproduction and the Rey Auditory Verbal Learning Test. Hippocampal volumes were determined by interactive volumetry. We found greater age-related reduction in the volume of the hippocampal head relative to the tail. Right hippocampal tail volume correlated with spatial memory on the Groton Maze Learning Test while left hippocampal body volume was associated with delayed verbal memory. These associations were independent of age, sex, education and speed of processing and support the notion of functional differentiation along the long axis of the hippocampus.

Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation.

STUDY OBJECTIVES: We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation. DESIGN: Double-blind, placebo-controlled, crossover study involving 7 laboratory visits over 2 months. Participants underwent 4 functional MRI scans; 2 sessions (donepezil or placebo) followed a normal night's sleep, and 2 sessions followed a night of sleep deprivation. SETTING: The study took place in a research laboratory. PARTICIPANTS: 26 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders. INTERVENTIONS: 5 mg of donepezil was taken once daily for approximately 17 days. MEASUREMENTS AND RESULTS: Subjects were scanned while performing a semantic judgment task and tested for word recognition outside the scanner 45 minutes later. Sleep deprivation increased the frequency of non-responses at encoding and impaired delayed recognition. No benefit of donepezil was evident when participants were well rested. When sleep deprived, individuals who showed greater performance decline improved with donepezil, whereas more resistant individuals did not benefit. Accompanying these behavioral effects, there was corresponding modulation of task-related activation in functionally relevant brain regions. Brain regions identified in relation to donepezil-induced alteration in non-response rates could be distinguished from regions relating to improved recognition memory. This suggests that donepezil can improve delayed recognition in sleep-deprived persons by improving attention as well as enhancing memory encoding. CONCLUSIONS: Donepezil reduced decline in recognition performance in individuals vulnerable to the effects of sleep deprivation. Additionally, our findings demonstrate the utility of combined fMRI-behavior evaluation in psychopharmacological studies.

Cognitive function and brain structure correlations in healthy elderly East Asians.

We investigated the effect of age and health variables known to modulate cognitive aging on several measures of cognitive performance and brain volume in a cohort of healthy, non-demented persons of Chinese descent aged between 55 and 86 years. 248 subjects contributed combined neuropsychological, MR imaging, health and socio-demographic information. Speed of processing showed the largest age-related decline. Education and plasma homocysteine levels modulated age-related decline in cognitive performance. Total cerebral volume declined at an annual rate of 0.4%/yr. Gray and white matter volume loss was comparable in magnitude. Regionally, there was relatively greater volume loss in the lateral prefrontal cortex bilaterally, around the primary visual cortex as well as bilateral superior parietal cortices. Speed of processing showed significant positive correlation with gray matter volume in several frontal, parietal and midline occipital regions bilaterally. In spite of differences in diet, lifestyle and culture, these findings are broadly comparable to studies conducted in Caucasian populations and suggest generalizability of processes involved in age-related decline in cognition and brain volume.

Cholinergic augmentation modulates visual task performance in sleep-deprived young adults.

Using 24 h of total sleep deprivation to perturb normal cognitive function, we conducted a double-blind, placebo-controlled crossover study to evaluate the effect of the acetylcholinesterase inhibitor, donepezil, on behavioral performance and task-related brain activation in 28 healthy, young, adult volunteers. The behavioral tasks involved the parametric manipulation of visual short-term memory load and perceptual load in separate experiments indirectly evaluating attention. Sleep deprivation significantly reduced posterior cortical activation (intraparietal sulcus and extrastriate cortex) at all levels of visual memory as well as perceptual load. Donepezil modulated an individual's performance in both tasks in accordance to whether accuracy declined after sleep deprivation without treatment. Critically, there were significant correlations between donepezil-induced increases in neural activation in the posterior cortical areas and improvement in accuracy. Reduced visual short-term memory after sleep deprivation may thus originate from a decline in visual attention and/or visual processing. Cholinergic augmentation can alleviate these deficits in individuals vulnerable to the effects of sleep deprivation, but it may have neutral or negative effects on those resistant to sleep deprivation.

Functional neuroimaging of sleep deprived healthy volunteers and persons with sleep disorders: a brief review.

Sleep loss can severely impact on the integrity of cognitive functions. This review highlights the recent functional neuroimaging studies on the brain's response while performing cognitive tasks when deprived of sleep. Among sleep-deprived healthy volunteers, reduced attention, accompanied by lowered parieto-occipital activation, may underlie performance decrements seen in other "higher cognitive domains". Functional neuroimaging in this setting has increased our understanding of how the brain responds to, and compensates for, sleep loss. Functional neuroimaging may also provide a safe, reproducible and non-invasive means to evaluate the cognitive and neural impact of therapeutic interventions designed to treat sleep disorders and/ or to reduce the negative cognitive impact of sleep loss.

Functional neuroimaging insights into how sleep and sleep deprivation affect memory and cognition.

PURPOSE OF REVIEW: The review summarizes current knowledge about what fMRI has revealed regarding the neurobehavioral correlates of sleep deprivation and sleep-dependent memory consolidation. RECENT FINDINGS: Functional imaging studies of sleep deprivation have characterized its effects on a number of cognitive domains, the best studied of these being working memory. There is a growing appreciation that it is important to consider interindividual differences in vulnerability to sleep deprivation, task and task difficulty when interpreting imaging results. Our understanding of the role of sleep and the dynamic evolution of offline memory consolidation has benefited greatly from human imaging studies. Both hippocampal-dependent and hippocampal-independent memory systems have been studied. SUMMARY: Functional imaging studies contrasting sleep-deprived and well-rested brains provide substantial evidence that sleep is highly important for optimal cognitive function and learning. The experimental paradigms developed to date merit evaluation in clinical settings to determine the impact of sleep disruption in sleep disorders.

Functional imaging of working memory following normal sleep and after 24 and 35 h of sleep deprivation: Correlations of fronto-parietal activation with performance.

Working memory was evaluated after normal sleep, and at 24 and 35 h of sleep deprivation (SD) in 26 healthy young adults to examine the neural correlates of inter-individual differences in performance. The extent of performance decline was not significantly different between the two SD test periods although there was greater variability in performance at SD35. In both SD sessions, there was reduced task-related activation (relative to normal sleep) in both superior parietal regions and the left thalamus. Activation of the left parietal and left frontal regions after normal sleep was negatively correlated with performance accuracy decline from normal sleep to SD24 thus differentiating persons who maintained working memory performance following SD from those who were vulnerable to its effects.