Thus, there appears to be a reduction in the number of functional cortical circuits available to process visual information during SD. A ‘functional circuit’, refers to the assembly

of neurons activated during the performance of a particular task. It could include neurons in close proximity, for example, those in visual cortex, as well as clusters connected by long-range fibers, such as those OSI906 in frontal and parietal areas mediating attention. Sustained wakefulness results in an increase in homeostatic sleep pressure resulting in ‘local sleep’ where circumscribed patches of cerebral cortex demonstrate physiological features of sleep in drowsy but still responsive animals 44 and 74]. Goal directed behavior like reaching, is more likely to fail during periods when clusters of frontal and parietal neurons show transient reductions in multi-unit activity [43••]. In human volunteers, correct responses elicit lower BOLD signal changes in the sleep-deprived state than in the rested state. This suggests that in the rested state, there may be some redundancy in circuit activation allowing for random failures without compromising behavioral performance. When sleep-deprived, this reserve is reduced, leading to occasional behavioral lapses. This

‘local sleep’ account of neurobehavioral degradation in SD is attractive in that it is relevant in both top-down or bottom-up sensory system failure accounts of degraded performance as well as time-on-task effects. However, at the present time, it is unclear whether ‘local sleep’ GSI-IX in vitro triggers altered connectivity or, if brainstem, hypothalamic and basal forebrain structures are the originators of lower cortical connectivity and reduced cortical activation 9 and 75]. Newer methods to evaluate ‘dynamic functional connectivity’ [76••] over temporal windows spanning seconds instead of minutes using both fMRI and EEG promise to shed light on this open question. Deficits in visual perception or visual processing capacity are central to explaining neurobehavioral changes in sleep deprivation. Reduced engagement of fronto-parietal regions that mediate top-down control of attention

has been demonstrated in multiple experiments evaluating different facets of attention and visual processing capacity. Independently of, or consequent to this, visual extrastriate cortex activation is markedly reduced. AZD9291 molecular weight The onset of ‘local sleep’ at random intervals in these heavily engaged brain areas following sustained wakefulness could account for the observed reduction in task-related activation. Concurrently, several changes in cortical-cortical as well as thalamo-cortical connectivity can disrupt the normal passage of sensory information to association cortex. Over minutes, these physiological changes can be reliably distinguished from rested wakefulness. However, from trial-to-trial, on a temporal scale of seconds, they appear more stochastic, having the characteristics of ‘wake-state’ instability.