| As a common problem in modern society,total or partial sleep deprivation(SD)has been proven to cause mood detriments.Long-term sleep loss can even cause depression.However,as a hallmark symptom of depression,sleep deprivation has a fast-acting antidepressant effect.Due to the fact that depression is one kind of negative mood,in order to investigate the neurobiological mechanism underlying the efficacy of SD as a resistant to negative mood,here we used resting-state blood-oxygen-level-dependent functional magnetic resonance imaging(BOLD fMRI)and artetial spin labling(ASL)perfusion fMRI in both healthy and depressed adults to examine the neural mechanisms that underlies the impact of total sleep deprivation(TSD)on negative mood and depress symptoms,respectively.The results from these two studies addressed a common mechanism of the anti-negative mood effect as well as the antidepressant effect of TSD.In addition,we also used BOLD fMRI and ASL perfusion fMRI to investigate the prediction of TSD-induced negative mood changes by baseline brain functions in healthy subjects.The studies mentioned above were illustrated in 4 chapters.In chapter 3,we examined the behavioral consequences of TSD on negative mood,and the relationship between negative mood change and positive mood change,as well as between negative mood change and psychomotor vigilance test(PVT)performance change after TSD in healthy subjects.In Study 1,we found a significant TSD-induced increase in negative mood and decrease in positive mood.In Study 2,we found that after TSD,neither the correlation between negative mood change and positive mood change,nor the correlation between negative mood change and PVT performance change was significant.The results suggest an increased instability of mood caused by TSD,and differed mechanisms that underly TSD-induced negative mood change and positive mood change.In addition,the uncorelated negative mood change and PVT performance change after TSD might indicate the desynchronized neurobiologyical changes that underly the subjective mood and objective cognitive behavior.In chapter 4,we investigated the mechanism of the TSD-induced negative mood change in healthy subjects.We found increases in resting-state functional connectivity between bilateral dorsal nexus(DN)and right dorsolateral prefrontal gyrus(dlPFC),as well as between bilateral amygdala and bilateral anterior cingulate cortex(ACC)following TSD.However,only the latter connectivity change related significantly and negatively to negative mood change after TSD,suggesting that subjects with stronger amygdala-ACC connectivity had better mood while subjects with weaker amygdala-ACC connectivity had worse mood after TSD.These findings indicated that sleep deprivation improved mood by facilitating the regulatory effect of cortical mood-regulating regions over the limbic areas in healthy subjects.The hyper-connectivity between amygdala and ACC might be the biomarker of the anti-negative mood effect of TSD.Unfortunately,we did not find significant correlations between TSD-induced cerebral blood flow(CBF)change and negative mood change.In chapter 5,we explored the prediction of TSD-induced negative mood changes by baseline brain functions(resting-state functional connectivity and CBF)in healthy subjects.The results showed that the baseline levels of CBF from thalamus and limbic regions such as insula,hippocampus,caudate and ventral striatum correlated negatively with TSD-induced negative mood changes.Subjects with more CBF from thalamus and limbic regions at baseline had better mood after TSD,while subjects with less CBF at baseline had worse mood after TSD.Higer levels of CBF might implicate more cognitive resources,which was resilient to TSD.More cognitive reserve after TSD might represent stronger capacity to maintain better mood states.Unfortunately,we did not find significant correlations between baseline resting-state functional connectivity and TSD-induced negative mood changes.In chapter 6,we did the same functional connectivity analyses for patients with major depressive disorder(MDD)as we did for healthy subjects from chapter 4,to test whether the findings from healthy subjects can be replicated in depressed subjects.We found that about half of the depressed subjects experienced mood improvement after TSD.Both bilateral DN-right dlPFC and bilateral amygdala-bilateral ACC connectivity increased after TSD in depressed subjects.Moreover,relative to the baseline,TSD led to more increases in amygdala-ACC connectivity in subjects with mood improvement while less increases in amygdala-ACC connectivity in subjects with mood detriments.However,only the degree of TSD-induced amygdala-ACC connectivity increases correlated negatively with the degree of depressive mood increases in depressed subjects.These findings indicated that sleep deprivation improved mood by facilitating the regulatory effect of cortical mood-regulating regions over the limbic areas in depressed subjects.The hyper-connectivity between amygdala and ACC might be the biomarker of the antidepressant effect of TSD.In summary,our study demonstrated that TSD led to an increase in negative mood and a decrease in positive mood in healthy subjects.Neither positive mood change nor PVT performance change correlated significantly with negative mood change after TSD.However,about half of depressesd patients experienced mood improvement following TSD.Moreover,we found the same mechanism that underlies the anti-negative mood effect of TSD in healthy subjects and the antidepressant effect of TSD in depressed subjects,that is,sleep deprivation improved mood by increasing functional connectivity between amygdala and ACC,which facilitates the regulatory effect of cortical mood-regulating regions over the limbic areas.In addition,higher levels of CBF from thalamus and limbic regions before TSD might represent higer levels of cognitive resources to prevent the detrimental effect of TSD on negative mood in healthy subjects.These studies replicate previous findings and further our understanding of the neurobiological mechanism of sleep deprivation’s effect on negative mood.These results might provide new insights on the relief of negative mood and on the target for diagnosis and treatment of MDD. |
