ASL Imaging of Brain Function Changes During Sleep Restriction

Insufficient or inadequate sleep occurs in millions of people in contemporary societies due to medical conditions or lifestyles. It is estimated that 20% to 40% of the adult US population sleep less than 7-8 hours per night,¹ which is the minimum sleep duration to prevent cumulative deterioration in performance on a range of cognitive tasks.² Insufficient sleep is also a risk factor for multiple diseases and prospective mortality.³ Reduced sleep duration increases sleep propensity, destabilizes the wake state, impairs cognition and behavior, and causes considerable social, financial, and health-related costs.^4–6 Growing evidence suggests large and highly replicable (trait-like) individual differences in the magnitude of sleepiness and cognitive performance vulnerability to sleep deprivation.⁷ While some healthy adults show substantial cognitive deficits and drowsiness without sufficient sleep, others show little cognitive changes and maintain alertness during sleep loss. However, little is known about the neural mechanisms underlying such differential vulnerability to sleep deprivation.

In this issue of SLEEP, Poudel and colleagues⁸ use a relatively new neuroimaging technique—arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI)—to measure brain function and provide an important new clue regarding the effects of sleep restriction on neural activity and drowsiness. In their study, a cohort of healthy adults were restricted to 4 hours time-in-bed and underwent ASL scans after both sleep-restricted and rested nights. Sleep restriction significantly reduced regional cerebral blood flow (CBF) in the right frontoparietal attentional network. However, these CBF changes were mainly observed in participants with strong signs of drowsiness (i.e., vulnerable to sleep restriction), while nondrowsy participants (i.e., resistant to sleep restriction) demonstrated robust regional CBF increases in the basal forebrain and cingulate cortex.

The detrimental effects of sleep loss on regional brain activity and cognitive performance have been reported and replicated by a number of studies. For example, Chee and colleagues reported decreased activity in the frontoparietal regions for overall mean activation as well as during lapses.⁹ However, most of these studies utilized traditional fMRI based on the blood oxygen level dependent (BOLD) contrast, which only measures relative signal changes between task and baseline conditions. BOLD contrast lacks absolute quantification of neural activity, making the accurate interpretation of brain activation changes very difficult. It is hard to determine whether changes in BOLD activation following sleep restriction are due to changes in baseline neural activity, or during specific tasks, or both. It is also hard to dissociate the effects of sleep loss on brain function per se and the effects of sleep loss on task performance that subsequently contaminates brain activation.

Unlike BOLD signal, which reflects a complex interaction among a number of physiological variables including CBF, cerebral blood volume (CBV), and cerebral oxygenation metabolic rate, ASL provides absolute and noninvasive quantification of CBF in physiological units (mL/min/100 g tissue) by using magnetically labeled arterial blood water as an endogenous tracer in a manner analogous to that used for PET scanning.¹⁰ Because ASL utilizes standard MRI hardware and does not require administration of contrast agents or radioactive tracer, it is much safer, more economical, and more widely available compared to PET. ASL scans can also be repeated as often as required during the same session without cumulative effects. In addition, ASL perfusion measurements have been demonstrated to be reliable and reproducible across intervals varying from a few minutes to a few days.^11–13 Therefore, ASL provides the unique opportunity to directly compare brain function before and after sleep restriction without the contamination of task performance declines, which makes ASL well-suited for functional imaging studies of sleep loss.

The study by Poudel and colleagues⁸ provides an example of using ASL to successfully overcome the essential shortcomings of conventional task-correlated BOLD fMRI in imaging brain function following sleep restriction. Although the study recruited a relatively small sample of twenty subjects, the findings of differential patterns of CBF changes in drowsy and nondrowsy participants following sleep loss provide new insights into an understanding of the neural mechanisms underlying the large individual differences in vulnerability to sleep deprivation. Nondrowsy individuals who maintained alertness after sleep restriction also maintained regional CBF levels in the frontoparietal attentional network as opposed to reduced CBF in drowsy individuals. These results suggest that trait-like individual differences in the magnitude of sleepiness and cognitive performance vulnerability (behavior phenotype) to sleep deprivation may due to the differential resistance or sensitivity of regional neural activity (brain phenotype) to sleep deprivation.

The resting baseline CBF changes observed by Poudel et al. pose important questions regarding the interpretation of relative activation changes reported by previous BOLD fMRI studies. As mentioned above, BOLD activation changes reflect the combination effects of sleep restriction on baseline and task conditions. It is still unclear how the resting activity alterations contribute to the task-related activation decrements. Unfortunately, the study by Poudel and colleagues did not involve any specific cognitive tasks. However, ASL is capable of determining task-related brain activation patterns in a way similar to traditional BOLD fMRI studies. For example, we have used ASL and revealed the CBF activation patterns during the psychomotor vigilance test (PVT), a simple but highly sensitive task for measuring attentional and performance deficits due to sleep deprivation. Our results also demonstrated reductions in frontoparietal activity and performance even in a non-sleep deprived cohort following a 20-min continuous PVT.¹⁴ Ongoing studies in our group as well as other laboratories are using ASL to quantify regional neural activity both at rest and during the PVT and other cognitive tasks before and after sleep deprivation, which will enable us to dissociate the differential effects of sleep deprivation on resting brain function and on task activation.¹⁵

DISCLOSURE STATEMENT

Dr. Rao has indicated no financial conflicts of interest.

CITATION

Rao H. ASL imaging of brain function changes during sleep restriction. SLEEP 2012;35(8):1027–1028.