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Patterns of neurodegeneration in dementia reflect a global functional state space

Jones, D. T.; Lowe, V.; Graff-Radford, J.; Botha, H.; Wiepert, D.; Murphy, M. C.; Murray, M. E.; Senjem, M. L.; Gunter, J. L.; Wiste, H. J.; Boeve, B. F.; Knopman, D. S.; Petersen, R. C.; Jack, C. R.

2020-11-12 neurology
10.1101/2020.11.09.20228676 medRxiv
Show abstract

Disruption of mental functions in Alzheimers disease (AD) and related disorders is accompanied by selective degeneration of brain regions for unknown reasons. These regions comprise large-scale ensembles of cells organized into networks required for mental functioning. A mechanistic framework does not exist to explain the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and the functional connectome. The association between dementia symptoms and degenerative brain anatomy encodes a mapping between mental functions and neuroanatomy. We isolated this mapping through unsupervised decoding of neurodegeneration in humans. This reflected a simple information processing-based functional description of macroscale brain anatomy, the global functional state space (GFSS). We then linked the GFSS to AD physiology, functional networks, and mental abilities. We extended the GFSS framework to normal aging and seven degenerative diseases of mental functions. One Sentence SummaryA global information processing framework for mental functions links neuroanatomy, cognitive neuroscience and clinical neurology.

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