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Updated: Feb 17, 2026
Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
Disruption of Semantic Network in Mild Alzheimer's Disease Revealed by Resting-State fMRI
Daniele Mascali1, Mauro DiNuzzo2, Laura Serra3
1Centro Fermi - Museo Storico della Fisica e Centro Studi e Ricerche "Enrico Fermi", Piazza del Viminale 1, 00184 Rome, Italy.
Abstract:
Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean mini-mental state examination = 20.5) and in a group of age-matched healthy controls (n = 19). Voxel-wise analysis spatially constrained in the left fronto-temporal semantic control network identified two regions with altered functional connectivity (FC) in AD patients, specifically in the pars opercularis (POp, BA44) and in the posterior middle temporal gyrus (pMTG, BA21). Using whole-brain seed-based analysis, we demonstrated that these two regions have altered FC even beyond the semantic control network. In particular, the pMTG displayed a wide-distributed pattern of lower connectivity to several brain regions involved in language-semantic processing, along with a possibly compensatory higher connectivity to the Wernicke's area. We conclude that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing.
Insights
Early Alzheimer's disease (AD) disrupts the brain's semantic control network. Mild AD patients show altered functional connectivity in key language areas, impacting semantic processing.
Area of Science:
- Neuroscience
- Cognitive Neurology
- Medical Imaging
Background:
- Subtle semantic deficits are early indicators in Alzheimer's disease (AD).
- The semantic control network's role in language processing is crucial.
- Understanding early AD-related brain network changes is vital for timely intervention.
Purpose of the Study:
- To test the hypothesis that the semantic control network is deregulated in mild AD.
- To investigate alterations in functional connectivity within the semantic control network in mild AD patients.
Main Methods:
- Resting-state functional magnetic resonance imaging (fMRI) was used.
- A cohort of mild AD patients (n=38) and healthy controls (n=19) were studied.
- Voxel-wise and seed-based analyses were performed on the left fronto-temporal semantic control network.
Main Results:
- Altered functional connectivity (FC) was identified in the pars opercularis (POp) and posterior middle temporal gyrus (pMTG) in AD patients.
- The pMTG showed widespread decreased connectivity to language-semantic regions.
- A potential compensatory increase in FC between pMTG and Wernicke's area was observed.
Conclusions:
- The semantic control network is abnormally connected in mild AD.
- These connectivity changes extend beyond the semantic control network to other language-critical areas.
- Abnormal connectivity in mild AD impacts language processing and semantic control.
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