Biophysical models applied to dementia patients reveal links between 
geographical origin, gender, disease duration, and loss of neural inhibition

Moguilner, Sebastian; Herzog, Rubén; Perl, Yonatan Sanz; Medel, Vicente; Cruzat, Josefina; Coronel, Carlos; Kringelbach, Morten; Deco, Gustavo; Ibáñez, Agustín; Tagliazucchi, Enzo

doi:10.1186/s13195-024-01449-0

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Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition

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Deco, Gustavo
Computational Neuroscience Group, Department of Information and Communication Technologies, Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain;
Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain;
Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia;

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Citation

Moguilner, S., Herzog, R., Perl, Y. S., Medel, V., Cruzat, J., Coronel, C., et al. (2024). Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition. Alzheimer's Research & Therapy, 16(1): 79. doi:10.1186/s13195-024-01449-0.

Cite as: https://hdl.handle.net/21.11116/0000-000F-2F9F-B

Abstract

Background: The hypothesis of decreased neural inhibition in dementia has been sparsely studied in functional magnetic resonance imaging (fMRI) data across patients with different dementia subtypes, and the role of social and demographic heterogeneities on this hypothesis remains to be addressed.

Methods: We inferred regional inhibition by fitting a biophysical whole-brain model (dynamic mean field model with realistic inter-areal connectivity) to fMRI data from 414 participants, including patients with Alzheimer's disease, behavioral variant frontotemporal dementia, and controls. We then investigated the effect of disease condition, and demographic and clinical variables on the local inhibitory feedback, a variable related to the maintenance of balanced neural excitation/inhibition.

Results: Decreased local inhibitory feedback was inferred from the biophysical modeling results in dementia patients, specific to brain areas presenting neurodegeneration. This loss of local inhibition correlated positively with years with disease, and showed differences regarding the gender and geographical origin of the patients. The model correctly reproduced known disease-related changes in functional connectivity.

Conclusions: Results suggest a critical link between abnormal neural and circuit-level excitability levels, the loss of grey matter observed in dementia, and the reorganization of functional connectivity, while highlighting the sensitivity of the underlying biophysical mechanism to demographic and clinical heterogeneities in the patient population.