Multimodal Imaging Study Of Neural Correlates To Individual Differences In Vulnerability Toward Total Sleep Deprivation Induced Changes In Cognitive Function

A single night of total sleep deprivation(TSD)produces a range of fundamental neurocognitive deficits and is associated with serious outcomes.However,the performance impairments from TSD have shown large inter-individual differences that were stable and trait-like.Examination of neural correlates and other potential biomarkers underlying the individual differences in response to TSD is currently underway,but the clear mechanisms were still not well elucidated.Therefore,the current study thoroughly investigated the neural mechanisms of individual differences in vulnerability toward total sleep deprivation using multimodal imaging techniques(PET,MRI,resting-f MRI and task-related-f MRI).The main findings and the innovation points are as follows:We firstly investigate the effects of TSD on interhemispheric interactions.We used a recently validated approach,voxel-mirrored homotopic connectivity(VMHC),to directly examine the changes in interhemispheric homotopic resting-state functional connectivity(RSFC)after SD.The between-condition differences in interhemispheric RSFC were then examined at global and voxelwise levels separately.Significantly increased global VMHC was found after sleep deprivation;specifically,a significant increase in VMHC was found in specific brain regions,including the thalamus,paracentral lobule,supplementary motor area,postcentral gyrus and lingual gyrus.No regions showed significantly reduced VMHC after sleep deprivation.Further analysis indicates that these findings did not depend on the various sizes of smoothing kernels that were adopted in the preprocessing steps and that the differences in these regions were still significant with or without global signal regression.Our data suggest that the increased VMHC might reflect the compensatory involvement of bilateral brain areas,especially the bilateral thalamus,to prevent cognitive performance deterioration when sleep pressure is elevated after sleep deprivation.We then used Fluorine-18 fluorodeoxyglucose positron emission tomography–computed tomography(18F-PET-CT)to investigate whether the cerebral metabolism in the resting state play an important role in the individual differences of a mathematical processing task.Large inter-individual differences were found in the throughput changes of the mathematical processing task,while the inter-individual differences were not associated with baseline or post-deprivation performance levels.Specifically,deterioration of throughput on the mathematical processing task was significantly correlated with metabolism changes in the superior frontal medial gyrus.These findings suggested that frontal metabolic activity contributes to individual differences in waking-induced impairment of cognitive performance.The effect of TSD on cognition is characterized by destabilized performance rather than by eliminated capability to perform.Cognitive instability in TSD can be assayed by one leading paradigm,i.e.,the psychomotor vigilance task(PVT),which is a test of reaction times(RTs)to a cue that occurs at random inter-stimulus intervals.PVT lapses induced by TSD have been found to exhibit substantial differences between individuals who range from apparent cognitive resistance to severe cognitive impairment.In this study,participants were divided into resilient and vulnerable groups according to mean number of PVT lapses during the final 3 hours of a TSD session.Tract-based spatial statistical analyses with multiple diffusion tensor imaging-derived characteristics(i.e.,fractional anisotropy(FA),mean diffusivity,radial diffusivity,and axial diffusivity)were employed to investigate differences in white matter(WM)integrity between the resilient and vulnerable groups and to test the linear relationship between the number of PVT lapses and the diffusion characteristics.Finally,hierarchical linear regression was used to assess relative contributions of tract-specific FA values in predicting PVT lapses.Compared with the vulnerable group,the resistant group exhibited significantly higher FA in multiple WM tracts.Significant negative correlations were found between numbers of PVT lapses and FA in multiple WM tracts.Our results also showed that >50% of individual variability in PVT lapses may be explained by variations in FA within the superior longitudinal fasciculus and splenium of the corpus callosum.These findings suggest that cognitive instability after TSD was closely associated with individual differences in WM integrity.In an attempt to understand the neural underpinnings of TSD-related impairment within a specific cognitive domain,most imaging studies of TSD typically conduct two imaging sessions in each subject,One session is performed after rested wakefulness and the other after TSD.By comparing the differences in neural activation between these two sessions,researchers have proposed many theories,expanding our understanding of the neurocognitive consequences of TSD.However,the observed alterations in neural activation after TSD describe the modulated cerebral responses rather than the process of modulation.A clearer and more complete understanding of neural changes associated with the process ofTSD can be obtained by increasing observation sessions during TSD.The present study extends the investigation of neural correlates of a PVT from obtaining only one f MRI measurement after TSD to obtaining five repeated f MRI measurements during TSD.PVT trials(fastest and slowest)elicited different overall activation patterns in the different sessions,which suggested dynamic properties of cerebral activation.Repeated ANOVA analysis showed significant activation differences in brain regions within the cognitive control network and DMN for the fastest and slowest PVT trials,respectively.The time course of activation in these regions was homogeneous within each trial type,but heterogeneous between trial types.These results advance our understanding of the dynamic process of sustained attention activation during one night of TSD.Our findings also add information regarding the effect of circadian rhythmicity and homeostatic sleep pressure on regional brain responses.Performance on the PVT and neuronal responses in high-order association cortex have both been found to gradually decrease as TSD progresses.However,how task performance and cerebral responses related to working memory—another important element of many neurobehavioral tasks—are modulated during TSD is still not well understood.The present study investigated dynamic changes in Sternberg working-memory task(SWMT)performance and the accompanying cerebral responses by obtaining repeated f MRI measurements during one night of TSD.Unlike the PVT outcomes that showed gradual deteriorations,RTs for the SWMT in participants with intermediate chronotypes improved in session 5(6:00 am)compared with session 4(4:00 am).Cerebral responses during the SWMT showed distinct differences across the three sessions,indicating a clear modulation of circadian rhythm and homeostatic sleep pressure on working memory brain responses.Finally,RTs for the SWMT were found to be strongly correlated with task-related activation in the angular gyrus and with the degree of negative correlation between the control and default networks.