Different Features of a Metabolic Connectivity Map and the Granger Causality Method in Revealing Directed Dopamine Pathways: A Study Based on Integrated PET/MR Imaging.

Background And Purpose: Exploring the directionality of neural information in the brain is important for understanding brain mechanisms and neurodisease development. Granger causality analysis and the metabolic connectivity map can be used to investigate directional transmission of information between brain regions, but their differences in depicting functional effective connectivity are not clear.

Materials And Methods: Using the Monash rs-PET/MR imaging data set, we conducted Granger causality and metabolic connectivity map analyses of the dopamine reward circuit in the brain. The dopamine reward circuit is a well-known system consisting primarily of the bilateral orbital frontal cortex, caudate, nucleus accumbens, thalamus, and substantia nigra. We validated these circuit pathways using Granger causality and the metabolic connectivity map for identifying effective connectivities against a priori knowledge by testing the significance of directed pathways (< .05, false discovery rate-corrected).

Results: We found 3 types of effective connectivities in the dopamine reward circuit: long-range, neighborhood, and symmetric. Granger causality analysis revealed long-range connections in the orbital frontal cortex-caudate and orbital frontal cortex-nucleus accumbens regions. Metabolic connectivity map analysis revealed neighborhood connections in the nucleus accumbens-caudate, substantia nigra-thalamus, and thalamus-caudate regions. Metabolic connectivity map analysis also found symmetric connections in each of the bilateral nucleus accumbens, caudate, thalamus, and orbital frontal cortex-caudate regions. Different patterns in directional networks of the dopamine reward circuit were revealed by Granger causality and metabolic connectivity map analyses.

Conclusions: Granger causality analysis primarily identified bidirectional cortico-nucleus connections, while the metabolic connectivity map primarily identified direct connections among neighborhood and symmetric regions. The results of this study indicated that investigations of effective connectivities should use an appropriate analysis method depending on the purpose of the study.