Related Experiment Video
Updated: May 11, 2026
Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
The neuroimaging signature of frontotemporal lobar degeneration associated with Granulin mutations: an effective
Enrico Premi1, Mario Grassi, Stefano Gazzina
1Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Italy.
Unlabelled:
It has been suggested that monogenic frontotemporal lobar degeneration (FTLD) due to Granulin (GRN) mutations might present a specific pattern of atrophy, as compared with FTLD GRN-negative disease. Recent literature has suggested that the study of functional neural networks, rather than regional structural damage, might better elucidate the pathogenic mechanisms, showing complex relationships among structural alterations observed with conventional neuroimaging. The aim of this study was to evaluate effective brain connectivity in FTLD patients carrying GRN mutations (GRN+), compared with FTLD patients without pathogenetic GRN mutations (GRN-) and healthy controls (HCs).
Methods:
Twenty-six FTLD patients (13 GRN+ and 13 GRN- matched for age, sex, and phenotype) and 13 age- and sex-matched HCs underwent brain perfusion SPECT. Brain regions involved in FTLD (dorsolateral, anterior cingulate, orbitofrontal, posterior temporal, temporal pole, and parietal) were used as regions of interest to identify functionally interconnected areas. An effective connectivity (path) analysis was defined with a PC algorithm (named after its inventors Peter Spirtes and Clark Glymour) search procedure and structural equation fitting. Statistically significant differences among the 3 groups were determined.
Results:
The best-fitting model was obtained by the data-driven approach, and brain connectivity pathways resembling state-of-the-art anatomic knowledge were obtained. When GRN+ and GRN- groups were considered, the former presented a selective bilateral parietotemporal disconnection, compared with GRN- patients. Furthermore, in FTLD GRN+ patients an increased compensative connectivity of the temporal regions (temporal pole and posterior temporal cortices) was observed.
Conclusion:
The present work suggests that impairment of effective functional connectivity of the parietotemporal regions is the hallmark of GRN-related FTLD. However, compensative mechanisms--which should be further investigated-may occur.
