The Research On Mechanism Of Association Of Brain Connectivity With Microvascular Characteristics Based On Functional Magnetic Resonance Imaging

Brain functional connectivity based on magnetic resonance imaging(MRI)has been widely used to investigate the brain function and the network mechanism of brain diseases,its methodological basis is performing the correlation or synchronization analysis for the blood oxygen level-dependent signal(BOLD).Brain functional connectivity can realize the characterization of brain networks and organization.However,the BOLD signal obtained by MRI reflects the microvascular characteristics in local brain regions and the relative content of altered deoxyhemoglobin in blood,so the characteristics of brain connectivity based on MRI will be affected by the microvascular characteristics of organisms.However,the relationship between the altered brain connectivity characteristics and the altered microvascular characteristics is still unclear,which may lead to a quite deviation interpretation of the brain network mechanism.Thus,combining the microvascular imaging features to interpret the brain connectivity characteristics characterized by the BOLD signal will be more accurate.The main objective of this dissertation was to explore the relationship between altered brain connectivity and microvascular characteristics,and carried out a more systematic study from the perspectives of internal disturbance and external stimulation.In this dissertation,healthy aging was chosen as an internal disturbance condition,because aging is accompanied by changed brain function and vascular features but without altered pathological characteristics.Transcranial direct current stimulation(t DCS)was selected as the condition of external stimulation because it is noninvasive and can induce changes in brain activity and blood supply at the same time.In this dissertation,the functional f MRI(f MRI)was used to depict the brain connectivity features,renal BOLD signal was used to reflect systemic microvascular oxygenation features,and the cerebral blood flow(CBF)based on arterial spin labeling(ASL)was utilized to describe cerebral perfusion.To reveal the mechanism of association of brain connectivity with microvascular characteristics,we investigated the relationship between different brain connectivity characteristics and systemic microvascular oxygenation characteristics or cerebral perfusion with the help of multimodal imaging technology.The main work of this dissertation included the following five parts:1.In this part,healthy aging was chosen as the condition of internal disturbance,and then the brain spontaneous brain activity from f MRI and cerebral perfusion features were fused.Next,the indexes of the global and local neurovascular couple were constructed to explore the influence of healthy aging on neurovascular coupling.The results showed that the global neurovascular coupling decoupling in healthy aging and this decoupling was significantly associated with cognitive function decline.At the same time,healthy aging induced increased local neurovascular coupling in the cognitive-related cortex and motor cortex,and decreased local neurovascular coupling in the visual and auditory cortex,indicating that healthy aging needed more supply in the cognitive and motor cortex to maintain neuronal activity.These results emphasized the importance of neurovascular coupling on cognition and further demonstrated the alteration of functional features in cortical hubs was associated with altered cerebral perfusion.2.In this part,the functional connectivity density(FCD)was utilized to depict the alteration of brain functional connectivity caused by healthy aging at the voxel level.To study the relationship between altered brain functional connectivity and renal oxygenation,the coupling analysis of brain FCD and renal oxygenation was performed.The results showed that the increased FCD in the motor cortex and decreased FCD in the default mode network(DMN)caused by healthy aging were associated with decreased systemic microvascular oxygenation.And we found the altered FCD in brain watershed regions was also associated with decreased systemic microvascular oxygenation.These results indicated that the connectivity of brain regions which susceptible to aging was related to systemic microvascular oxygenation.This part revealed that the altered brain connectivity is closely related to vascular oxygenation,and provided a new perspective for studying the physiological basis of functional connectivity.3.In this part,the stepwise functional connectivity(SFC)analysis was used to investigate the changed functional hierarchical functional structure from unimodal regions to transmodal regions caused by healthy aging.And then we constructed the research model of systemic microvascular oxygenation-cerebral hierarchical functional connectivity-behavior.The results showed that healthy aging induced the transformation of cerebral cortical hubs.And the greater the changes in the hierarchical functional connectivity caused by healthy aging,the more severe the systemic microvascular oxygenation,and the lower the cognitive function.This part revealed the relationships among systemic microvascular oxygenation,brain hierarchical connection,and behavior through the research model of systemic microvascular oxygenation-brain hierarchical connection – behavior,which confirmed the importance of systemic microvascular oxygenation features on brain connectivity features.4.In this part,we combined three imaging technology(brain f MRI,brain ASL,and renal BOLD)and utilized functional gradient analysis to construct the functional hierarchical structure in different states(resting state and naturalistic stimuli state).And then using the moderation analysis to explore the influence of different vascular features(cerebral perfusion and systemic microvascular oxygenation characteristics)on the relationship between brain functional features and behavior.The results showed that healthy aging induced the compression of the sensory-sensorimotor system and transmodal regions in the resting state,and these regions would be further compressed in the naturalistic stimulus state.Moderation results confirmed that the better the microvascular features,the closer the relationship between the cerebral functional gradient of the insula and behavioral performance.This part revealed the relationship between brain connectivity characteristics and behavioral performance could be regulated by the microvascular state,which provided a new framework for studying the physiological mechanism of functional connectivity.5.In this part,to detect the relationship between the stimulation-induced alteration of brain functional features and cerebral perfusion,t DCS was selected as the condition of external stimulation.The brain spontaneous brain activity and the functional gradient were utilized to describe the brain functional characteristics,and the coupling analysis between the brain function characteristics and cerebral perfusion was carried out.The results showed that t DCS caused the altered functional characteristics in the target network,visual network,and high-level cognitive network.And the t DCS also caused a decreased blood supply in the thalamus and temporal pole but enhanced the neurovascular coupling.In addition,t DCS-induced alteration of thalamic blood supply was positively correlated with the t DCS-induced altered functional gradient in SMN and was negatively correlated with the altered functional gradient in the high-level cognitive network,suggesting that the changed thalamic blood supply was related to the alteration of functional characteristics in primary sensory network and high-level cognitive network.This part confirmed that thalamic blood supply plays an important role in brain functional characteristics,and emphasized again the importance of altered blood supply on brain functional characteristics from the perspective of external stimulation.In general,this dissertation mainly explored the correlation mechanism between the changed different brain connectivity characteristics and microvascular features under different research conditions.From the point of view of internal disturbance,we found that the altered brain spontaneous activity,the altered FCD,and altered brain hierarchical connectivity structure caused by healthy aging were related to the declined systemic microvascular oxygenation,and different microvascular features regulated the relationship between brain functional characteristics and behavioral performance.From the perspective of external stimulation,we found that stimulation enhanced neurovascular coupling,and the stimulation-induced changes in the functional gradients of primary sensory and high-level cognitive networks were related to the changes in thalamic perfusion.These results confirmed that the alteration of connectivity characteristics in brain regions susceptible to disturbance was closely related to the changed blood supply,which revealed the importance of blood supply on the characteristics of brain connectivity,and provided an explanatory framework for the physiological mechanism of brain connectivity.