Dataset Information

Model-based whole-brain perturbational landscape of neurodegenerative diseases.

ABSTRACT: The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). These models included disease-specific atrophy maps as priors to modulate local parameters, revealing increased stability of hippocampal and insular dynamics as signatures of brain atrophy in AD and bvFTD, respectively. Using variational autoencoders, we visualized different pathologies and their severity as the evolution of trajectories in a low-dimensional latent space. Finally, we perturbed the model to reveal key AD- and bvFTD-specific regions to induce transitions from pathological to healthy brain states. Overall, we obtained novel insights on disease progression and control by means of external stimulation, while identifying dynamical mechanisms that underlie functional alterations in neurodegeneration.

SUBMITTER: Sanz Perl Y

PROVIDER: S-EPMC10063230 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Model-based whole-brain perturbational landscape of neurodegenerative diseases.

Sanz Perl Yonatan Y Fittipaldi Sol S Gonzalez Campo Cecilia C Moguilner Sebastián S Cruzat Josephine J Fraile-Vazquez Matias E ME Herzog Rubén R Kringelbach Morten L ML Deco Gustavo G Prado Pavel P Ibanez Agustin A Tagliazucchi Enzo E

eLife 20230330

The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). These models included disease-specific atrophy maps as priors to modulate local p ...[more]

PMID: 36995213

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Project description:Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. It has been noted that glial cells including astrocytes (which outnumber other cell types in the CNS) essentially contribute more to the BBB integrity, extracellular homeostasis, neurotransmitter release, regulation of neurogenic niches in response to neuroinflammatory stimulus, and synaptic plasticity. In a recent study for NDDs utilizing cellular and molecular biology and genetic and pharmacological tools, the role of reactive astrocytes (RACs) and gliosis was demonstrated, able to trigger pathophysiological/psychopathological detrimental changes during the disease progression. We speculate, in particular, the BBB, the NVU, and changes of the astrocytes (potentially different populations from the RACs) not only interfere with neuronal development and synaptogenesis, but also generate oxidative damages, contribute to beta-amyloid clearances and disrupted vasculature, as well as lead to neuroinflammatory disorders. During the past several decades, stem cell therapy has been investigated with a research focus to target related neuro-/vascular pathologies (cell replacement and repair) and neurological/psychiatric symptoms (paracrine protection and homeostasis). Evidence shows that transplantation of neurogenic or vasculogenic cells could be achieved to pursue differentiation and maturation within the diseased brains as expected. It would be hoped that, via regulating functions of astrocytes, astrocytic involvement, and modulation of the BBB, the NVU and astrocytes should be among major targets for therapeutics against NDDs pathogenesis by drug and cell-based therapies. The non-invasive strategies in combination with stem cell transplantation such as the well-tested intranasal deliveries for drug and stem cells by our and many other groups show great translational potentials in NDDs. Neuroimaging and clinically relevant analyzing tools need to be evaluated in various NDDs brains.

Dataset Information

Model-based whole-brain perturbational landscape of neurodegenerative diseases.

Publications

Model-based whole-brain perturbational landscape of neurodegenerative diseases.

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