Imaging the Sleep Deprived Brain: A Brief Review

Abstract

Functional magnetic resonance imaging (fMRI) is a highly versatile tool used to study neurobehavioral alterations associated with sleep deprivation (SD). Task-related fMRI is the most widely used technique and an impressive list of cognitive domains has been evaluated using this technique (Table 1). fMRI measures relative change in blood oxygenation level dependant (BOLD) signal in capillaries and venules adjacent to neuronal clusters whose firing rate and consequently, synaptic potentials are modulated by task performance. An increase in MR signal occurs as a result of a relatively disproportionate elevation in blood flow relative to oxygen consumption in response to sensory stimulation and/or task performance. In addition to task-related activation, the evaluation of task-related deactivation where signal changes fall below baseline levels can be evaluated. Blood oxygenation level dependant imaging measures relative changes in blood flow, but does not ascertain absolute blood flow. Quantification of blood flow may occasionally be useful, for example, to study time-on-task effects, and other phenomena whose observation requires signal stability over several minutes as opposed to several seconds. Such measurements can be obtained using a variety of arterial spin labeling (ASL) techniques that have different levels of precision. A disadvantage of ASL is its inferior signal to noise ratio relative to BOLD imaging. Additionally, the requirement for block sampling also makes it impossible to perform event-related designs that are important in separating out trials where the subject may have been asleep. The evaluation of functional connectivity, conducted by assessing signal covariation in pairs of regions, or by determining the extent to which signal in a ‘target’ region interacts with that of a ‘seed’ region according to state/task context provides additional characterization of altered physiology. The latter method, known as psychophysiological Interaction-PPI has been applied in studies evaluating selective attention, the processing of emotional pictures as well as executive function/working memory. In addition to fMRI studies designed to evaluate signal changes in response to task performance, it may be informative to evaluate ‘resting-state’ activity or intrinsic functional connectivity. This refers to the identification of regions showing synchronous low frequency oscillations (0.1-0.01 Hz) in BOLD signal that are not time locked to task performance or sensory stimulation. Studies of this type in sleeping individuals have shown changes in connectivity within the default mode network (DMN) alluded to earlier. The first study evaluating resting state networks in the setting of SD found selective reductions in DMN functional connectivity and reduced anti-correlation with low frequency oscillations in the ‘task-positive’ network (Fig. 1). Analyses of resting state data hold promise of being informative of alterations in brain function without requiring motivated performance on the part of a participant. Related to functional connectivity, MRI in the form of diffusion tensor imaging (DTI) can be used to evaluate white matter connectivity. Strangely, only one study to date has used DTI to study sleep deprived individuals. Combining electroencephalography (EEG) and fMRI in SD or sleep related studies is primarily motivated by the need to monitor sleep stage although the high temporal resolution of EEG is also well suited to study transient phenomena like lapsing. The neural correlates of spindles and slow waves have been studied using this technique. In addition, fMRI guided repetitive transcranial magnetic stimulation has been used Received June 12, 2013 Revised June 18, 2013 Accepted June 18, 2013