Altered network stability in progressive supranuclear palsy

David J Whiteside,P Simon Jones,Boyd C P Ghosh,Ian Coyle-Gilchrist,Alexander Gerhard,Michele T Hu,Johannes C Klein,P Nigel Leigh,Alistair Church,David J Burn,Huw R Morris,James B Rowe,Timothy Rittman

doi:10.1016/j.neurobiolaging.2021.07.007

Abstract

The clinical syndromes of Progressive Supranuclear Palsy (PSP) may be mediated by abnormal temporal dynamics of brain networks, due to the impact of atrophy, synapse loss and neurotransmitter deficits. We tested the hypothesis that alterations in signal complexity in neural networks influence short-latency state transitions. Ninety-four participants with PSP and 64 healthy controls were recruited from two independent cohorts. All participants underwent clinical and neuropsychological testing and resting-state functional MRI. Network dynamics were assessed using hidden Markov models and neural signal complexity measured in terms of multiscale entropy. In both cohorts, PSP increased the proportion of time in networks associated with higher cognitive functions. This effect correlated with clinical severity as measured by the PSP-rating-scale, and with reduced neural signal complexity. Regional atrophy influenced abnormal brain-state occupancy, but abnormal network topology and dynamics were not restricted to areas of atrophy. Our findings show that the pathology of PSP causes clinically relevant changes in neural temporal dynamics, leading to a greater proportion of time in inefficient brain-states.

Highlights

The human brain optimises efficiency by balancing integration and segregation of information transfer among neural assemblies
To test our hypothesis that changes in network dynamics were related cortical network topological remodelling in progressive supranuclear palsy (PSP) in response to subcortical tau burden, we focused on the following metrics: weighted degree, measuring the number and strength of nodal functional connections; clustering coefficient, the proportion of triangular connections formed by each node over the proportion of all possible such connections; and path length, the average shortest topological distance between nodes of the graph
The principal results of this study are that (i) the exemplar tauopathy of PSP changes network dynamics, with a higher proportion of time spent in frontoparietal activation states; (ii) these changes in network dynamics are related to complexity as measured by multi-scale entropy, (iii) the changes in network dynamics correlated with clinical severity and regional atrophy; and (iv) altered network dynamics occur in the context of widespread changes to network topology

Summary

Introduction

The human brain optimises efficiency by balancing integration and segregation of information transfer among neural assemblies. The activity and connectivity of regional specialisation is dynamic (Deco et al, 2017; Friston et al, 2012; Honey et al, 2007; Shine et al, 2019; Tognoli and Kelso, 2014), even on the suprasec-. The pattern of spread of tau-pathology is dictated in part by the brain’s topology and connectivity (Ahmed et al, 2014; Clavaguera et al, 2009; Seeley et al, 2009), leading to reductions in effective information processing and cognition. We proposed that alterations in large-scale network dynamics contribute to the severity of neurodegenerative syndromes. We test this using the tau-associated disease progressive supranuclear palsy (PSP), as a demonstrator condition because of its high clinicopathological correlation.

Methods

Results

Discussion

Conclusion