Characteristic changes in the default mode network in hypertensive patients with cognitive impairment

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Abstract

Hypertension has a close affinity to brain degeneration and cognitive decline during the aging process. The default mode network (DMN) is usually affected in various diseases related to cognitive impairment (CI). The present research aimed to explore the alterations in the DMN and its subcomponents in hypertensive patients with and without CI and to investigate the associations between cognitive performance and network abnormalities. Resting-state functional magnetic resonance imaging and neuropsychological tests were performed in 74 subjects, namely, 30 hypertensive patients with normal cognition (HTN-NC), 25 hypertensive patients with CI (HTN-CI), and 19 healthy controls. Seed-based functional connectivity (FC) analysis was performed to identify the DMN patterns. The group differences in the DMN were mainly shown in brain regions related to the core subsystem and the dorsal medial subsystem of the DMN. Post hoc analysis revealed a trend of dissociation among the DMN subsystems in the HTN-NC group. In contrast, the HTN-CI group displayed extensively increased FC in both subsystems. Importantly, increased FC of the dorsal medial subsystem in the HTN-CI patients was associated with poor cognitive performance, such as scores on Mini-Mental State Examination (ρ = -0.438, P = 0.029) and Montreal Cognitive Assessment (ρ = -0.449, P = 0.025). The findings suggest that extensively increased connectivities in the core subsystem and the dorsal media subsystem of the DMN may distinguish hypertension with CI from hypertension with normal cognition. The characteristic change in the dorsal medial subsystem may become an early imaging biomarker for the diagnosis and treatment of cognitive impairment associated with hypertension.

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Functional connectivity of default mode network components: correlation, anticorrelation, and causality.

Lucina Q Uddin, A. M. Kelly, Bharat Biswal … (2009)

The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), exhibits higher metabolic activity at rest than during performance of externally oriented cognitive tasks. Recent studies have suggested that competitive relationships between the DMN and various task-positive networks involved in task performance are intrinsically represented in the brain in the form of strong negative correlations (anticorrelations) between spontaneous fluctuations in these networks. Most neuroimaging studies characterize the DMN as a homogenous network, thus few have examined the differential contributions of DMN components to such competitive relationships. Here, we examined functional differentiation within the DMN, with an emphasis on understanding competitive relationships between this and other networks. We used a seed correlation approach on resting-state data to assess differences in functional connectivity between these two regions and their anticorrelated networks. While the positively correlated networks for the vmPFC and PCC seeds largely overlapped, the anticorrelated networks for each showed striking differences. Activity in vmPFC negatively predicted activity in parietal visual spatial and temporal attention networks, whereas activity in PCC negatively predicted activity in prefrontal-based motor control circuits. Granger causality analyses suggest that vmPFC and PCC exert greater influence on their anticorrelated networks than the other way around, suggesting that these two default mode nodes may directly modulate activity in task-positive networks. Thus, the two major nodes comprising the DMN are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated.

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Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.

Martijn P. van den Heuvel, René C.W. Mandl, René S Kahn … (2009)

During rest, multiple cortical brain regions are functionally linked forming resting-state networks. This high level of functional connectivity within resting-state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting-state functional magnetic resonance imaging time-series with diffusion tensor imaging scans. Nine consistently found functionally linked resting-state networks were retrieved from the resting-state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting-state networks. Our results show that well-known anatomical white matter tracts interconnect at least eight of the nine commonly found resting-state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal-frontal networks. Our results suggest that the functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.

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Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state fMRI.

Liang Wang, Yufeng Zang, Yong Zhu He … (2006)

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in "default mode network" previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.