Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans

Significance Major depressive disorder is a significant contributor to the global burden of disease, affecting 350 million people according to an estimation of the World Health Organization. Today, no valid biomarkers of depression, which could predict the efficacy of a certain treatment in a certain group of patients, exist. Sleep deprivation is an effective and rapid-acting antidepressive treatment. However, the biomechanism of this effect is largely unknown. This study shows the effects of sleep deprivation on human brain functional connectivity alterations via the dorsal nexus, an area which is crucial in major depressive disorder. Here, we offer a neurobiological explanation for the known antidepressive action of sleep deprivation. In many patients with major depressive disorder, sleep deprivation, or wake therapy, induces an immediate but often transient antidepressant response. It is known from brain imaging studies that changes in anterior cingulate and dorsolateral prefrontal cortex activity correlate with a relief of depression symptoms. Recently, resting-state functional magnetic resonance imaging revealed that brain network connectivity via the dorsal nexus (DN), a cortical area in the dorsomedial prefrontal cortex, is dramatically increased in depressed patients. To investigate whether an alteration in DN connectivity could provide a biomarker of therapy response and to determine brain mechanisms of action underlying sleep deprivations antidepressant effects, we examined its influence on resting state default mode network and DN connectivity in healthy humans. Our findings show that sleep deprivation reduced functional connectivity between posterior cingulate cortex and bilateral anterior cingulate cortex (Brodmann area 32), and enhanced connectivity between DN and distinct areas in right dorsolateral prefrontal cortex (Brodmann area 10). These findings are consistent with resolution of dysfunctional brain network connectivity changes observed in depression and suggest changes in prefrontal connectivity with the DN as a brain mechanism of antidepressant therapy action.

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