TY - JOUR
T1 - Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition
AU - Moguilner, Sebastian
AU - Herzog, Rubén
AU - Perl, Yonatan Sanz
AU - Medel, Vicente
AU - Cruzat, Josefina
AU - Coronel, Carlos
AU - Kringelbach, Morten
AU - Deco, Gustavo
AU - Ibáñez, Agustín
AU - Tagliazucchi, Enzo
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - Biophysical modeling
KW - Dementia
KW - Gender
KW - Heterogeneity
KW - Hyperexcitability
KW - Neurodegeneration
KW - Variability
UR - http://www.scopus.com/inward/record.url?scp=85190130623&partnerID=8YFLogxK
U2 - 10.1186/s13195-024-01449-0
DO - 10.1186/s13195-024-01449-0
M3 - Article
C2 - 38605416
AN - SCOPUS:85190130623
SN - 1758-9193
VL - 16
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 79
ER -