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

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.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000F-2F9F-B Version Permalink: https://hdl.handle.net/21.11116/0000-000F-3427-B
Genre: Journal Article

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 Creators:
Moguilner, Sebastian1, 2, 3, 4, 5, Author
Herzog, Rubén1, Author
Perl, Yonatan Sanz3, 6, 7, 8, Author
Medel, Vicente1, 9, Author
Cruzat, Josefina1, Author
Coronel, Carlos1, Author
Kringelbach, Morten10, 11, 12, Author
Deco, Gustavo8, 13, 14, 15, Author           
Ibáñez, Agustín1, 2, 3, 5, 16, Author
Tagliazucchi, Enzo1, 3, 6, 7, Author
Affiliations:
1Latin American Brain Health Institute (BrainLat), Santiago, Chile, ou_persistent22              
2Global Brain Health Institute (GBHI), University of California, San Francisco, CA, USA, ou_persistent22              
3Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina, ou_persistent22              
4Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, ou_persistent22              
5Trinity College Dublin, Ireland, ou_persistent22              
6National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina, ou_persistent22              
7Department of Physics, University of Buenos Aires, Argentina, ou_persistent22              
8Computational Neuroscience Group, Department of Information and Communication Technologies, Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
9Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), University of Valparaiso, Chile, ou_persistent22              
10Centre for Eudaimonia and Human Flourishing, University of Oxford, United Kingdom, ou_persistent22              
11Department of Psychiatry, University of Oxford, United Kingdom, ou_persistent22              
12Department of Clinical Medicine, Center for Music in the Brain, Aarhus University, Denmark, ou_persistent22              
13Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634551              
14Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
15Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, ou_persistent22              
16Institute of Neuroscience, Trinity College Dublin, Ireland, ou_persistent22              

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Free keywords: Biophysical modeling; Dementia; Gender; Heterogeneity; Hyperexcitability; Neurodegeneration; Variability
 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.

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Language(s): eng - English
 Dates: 2023-11-062024-04-022024-04-112024-04-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1186/s13195-024-01449-0
PMID: 38605416
PMC: PMC11008050
 Degree: -

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Project name : -
Grant ID : GBHI ALZ UK-21-721776
Funding program : -
Funding organization : Global Brain Health Institute (GBHI), Alzheimer’s Association, and Alzheimer’s Society
Project name : -
Grant ID : CW2680521
Funding program : -
Funding organization : Takeda
Project name : -
Grant ID : 1210195; 1210176; 1220995; 15150012; ID20I10152; ID22I10029; ACT210096; 1220995
Funding program : -
Funding organization : Agencia Nacional de Investigación y Desarrollo (ANID)
Project name : -
Grant ID : 2017-1818; 2017-1820; 2019–02294
Funding program : -
Funding organization : FONCYT-PICT
Project name : -
Grant ID : R01AG057234
Funding program : -
Funding organization : National Institutes of Health (NIH)
Project name : -
Grant ID : SG-20-725707-ReDLat
Funding program : -
Funding organization : Alzheimer’s Association

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Title: Alzheimer's Research & Therapy
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: BioMed Central
Pages: - Volume / Issue: 16 (1) Sequence Number: 79 Start / End Page: - Identifier: ISSN: 1758-9193
CoNE: https://pure.mpg.de/cone/journals/resource/1758-9193