Functional Relevance And Clinical Application In Bipolar Disorder Of Global Signal In FMRI

How global and local activity interact with each other is a common question in complex systems.Recent evidence suggests that,as other complex systems,the brain,analogously,displays ‘global' activity that interacts with its local-regional activity and modulates behavior.The brain's global activity can be measured by the global signal(GS)in f MRI which,so far,has mainly been conceived in methodological terms as artifact or noise that is to be eliminated(i.e.,regressed)from the data during functional connectivity analyses.Extending beyond its methodological relevance,this thesis aims to investigate the informative nature(i.e.,its functions and clinical application)of global signal.In terms of its informative nature,this thesis aims to investigate the four following issues:1)The functional relevance of GS during cognitive tasks.As most of the previous studies about global signal are undertaken in resting state,it is largely unknown how the GS is mediated by tasks.By comparing the GS and its topography during rest and task states from the data set of human connectome project(HCP)(n = 837),the results demonstrated that the GS topography(i.e.,the weighted relationship between global and local)was modulated by tasks.More specifically,the results showed that the GS topography was changed during the seven tasks,with mainly decreased GS topography in sensorimotor cortex and increased GS topography in task-involved cortex.Importantly,this rest-task modulation of GS topography could be traced to transient coactivation patterns at the peak period of global signal(GS-peak).Finally,rest-task modulation of GS topography could not be exclusively explained by other sources of physiological noise.2)The relationship between GS and respiration.Previous studies under resting state observed a close relationship between the topography of GS and respiration effect,which made the researchers assuming that GS was merely response of physiological noise.By comparing the topography of GS and respiration,the results showed that the topography of respiration mimicked the topography of global signal in the resting-state whereas both differed during the task states;such partial dissociation suggested that GS could not be equated with a respiration effect.3)The clinical application of GS.One major topic of resting state is its clinical application.This session used bipolar disorder to investigate the relationship between abnormal GS topography and clinical symptoms.Results demonstrated that GS topography was significantly altered in the different phases of bipolar disorder,i.e.,the regions showing abnormally strong topographical GS contribution changed from hippocampus(and parahippocampus/fusiform gyrus)in depression to motor cortex in mania.Additionally,topographical GS changes in these regions correlated with psychopathological measures in both depression and mania.4)Amplitude-or phase-driven mechanism of global signal topography.In the final part,this study investigated the mechanism about the state modulation of GS topography.Results demonstrated that level of synchronization,rather than amplitude variation,served as the neural basis for the changes of GS topography in both rest-task modulation and bipolar disorder alternation.In sum,this thesis investigated the informative nature of GS and its topography in healthy and clinical population,not only in resting state but also in task state.The findings support the informative nature of GS and also offer novel insight into the neural basis of global signal regression.