Insufficient sleep is a known trigger of anxiety. Nevertheless, not everyone experiences these effects to the same extent. One determining factor is sex, wherein women experience a greater anxiogenic impact in response to sleep loss than men. However, the underlying brain mechanism(s) governing this sleep-loss-induced anxiety increase, including the markedly different reaction in women and men, is unclear. Here, we tested the hypothesis that structural brain morphology in a discrete network of emotion-relevant regions represents one such explanatory factor. Healthy participants were assessed across sleep-rested and sleep-deprived conditions, with brain structure quantified using gray matter volume measures. Sleep loss triggered greater levels of anxiety in women compared with men. Reduced gray matter volume in the anterior insula and lateral orbitofrontal cortex predicted the anxiogenic impact of sleep loss in women, yet predicted resilience in men, and did so with high discrimination accuracy. In contrast, gray matter volume in ventromedial prefrontal cortex predicted the anxiogenic impact of sleep loss in both men and women. Structural human brain morphology therefore appears to represent one mechanistic pathway (and possible biomarker) determining anxiety vulnerability to sleep loss—a discovery that may help explain the higher prevalence of sleep disruption and anxiety in women.

Despite an emerging link between alterations in motivated behavior and a lack of sleep, the impact of sleep deprivation on human brain mechanisms of reward and punishment remain largely unknown, as does the role of trait dopamine activity in modulating such effects in the mesolimbic system. Combining fMRI with an established incentive paradigm and individual genotyping, here, we test the hypothesis that trait differences in the human dopamine transporter (DAT) gene—associated with altered synaptic dopamine signalling—govern the impact of sleep deprivation on neural sensitivity to impending monetary gains and losses. Consistent with this framework, markedly different striatal reward responses were observed following sleep loss depending on the DAT functional polymorphisms. Only participants carrying a copy of the nine-repeat DAT allele—linked to higher phasic dopamine activity—expressed amplified striatal response during anticipation of monetary gain following sleep deprivation. Moreover, participants homozygous for the ten-repeat DAT allele—linked to lower phasic dopamine activity—selectively demonstrated an increase in sensitivity to monetary loss within anterior insula following sleep loss. Together, these data reveal a mechanistic dependency on human of trait dopaminergic function in determining the interaction between sleep deprivation and neural processing of rewards and punishments. Such findings have clinical implications in disorders where the DAT genetic polymorphism presents a known risk factor with comorbid sleep disruption, including attention hyperactive deficit disorder and substance abuse.

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network. Indeed, deactivation within these regions alone discriminated sleep-deprived from sleep-control subjects with a 93% degree of sensitivity and 92% specificity. In addition, the relative balance of deactivation within these default nodes significantly correlated with the amount of prior sleep in the control group (and not extended time awake in the deprivation group). Therefore, the stability and the balance of task-related deactivation in key default-mode regions may be dependent on prior sleep, such that a lack thereof disrupts this signature pattern of brain activity, findings that may offer explanatory insights into conditions associated with sleep loss at both a clinical as well as societal level.