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Keynote: Network-based Neurodegeneration

Description

The anatomy of neurodegenerative disease can be understood in terms of two key aspects: onset and progression. Mechanisms controlling onset timing and location remain mysterious, and each disease features striking heterogeneity in its onset sites. Regarding progression, network analyses have revealed that each clinical syndrome reflects degeneration of a specific large-scale network. Each vulnerable network, in turn, is anchored by a pivotal “epicenter” whose functional-anatomical connections govern the vulnerability of other regions, perhaps because prion-like corruptive templating begets trans-synaptic disease protein spread. I will illustrate these principles with a focus on the behavioral variant of frontotemporal dementia (bvFTD). BvFTD begins within the “salience network,” a system anchored by the anterior cingulate and frontoinsular cortices and specialized for social-emotional-autonomic processing. Patients with bvFTD lose the capacity for adaptive, real-time behavioral guidance, possibly in part because salience-driven viscero-autonomic cues and responses are late, degraded, or improperly modulated. Within the salience network hubs, Layer 5 von Economo neurons and fork cells show a particular predilection for disease protein aggregation and cell death, providing a cellular focus for bvFTD selective vulnerability research and a potential window into the neural computations that contribute to sophisticated human social-emotional functions.

Contributors

  • William Seeley