Exploration of functional brain networks in neurodegenerative disease

Abstract

Neurodegenerative diseases target specific anatomical and functional brain networks. A number of intrinsic functional brain networks can be identified in individuals at rest, that correspond to networks found in task-based functional MRI studies. However, the impact of pathological changes and relation to disease severity remains unclear.We examined three networks of interest in patients with progressive supranuclear palsy (PSP) and the neurodegenerative corticobasal syndrome (CBS). These two diseases share features of cognitive decline and a movement disorder, although they have important phenotypic differences. They are both associated with accumulation of tau protein in neuronal and glial cells. We examined the default mode network, which is deactivated during tasks and has been consistently implicated in Alzheimer's disease; the salience network, often activated during tasks and affected in frontotemporal dementia; and the basal ganglia network, since both PSP and CBS pathology affects the basal ganglia.Using resting state functional MRI scanning, we applied independent component analysis and template matching to identify networks of interest. Spatiotemporal group differences in network architecture were identified with dual regression to extract spatial maps for each network in individuals and perform group-wise t tests. In addition, clinical test scores were added as covariates to group comparisons.Increased functional connectivity was seen within all three networks in disease groups. Decreased connectivity was seen between the basal ganglia network and cortical regions in PSP. Network changes correlated with worse scores on clinical measures of disease.Increased connectivity in relevant functional brain networks identify neurodegenerative diseases and mirror clinical disease features. FundingUK Medical Research Council.