Large-scale neural models and dynamic causal modelling

Dynamic causal modelling (DCM) is a method for estimating and making inferences about the coupling among small numbers of brain areas, and the influence of experimental manipulations on that coupling [Friston, K.J., Harrison, L., Penny, W., 2003. Dynamic causal modelling. Neuroimage 19, 1273-1302]. Large-scale neural modelling aims to construct neurobiologically grounded computational models with emergent behaviours that inform our understanding of neuronal systems. One such model has been used to simulate region-specific BOLD time-series [Horwitz, B., Friston, K.J., Taylor, J.G., 2000. Neural modeling and functional brain imaging: an overview. Neural Netw. 13, 829-846]. DCM was used to make inferences about effective connectivity using data generated by a model implementing a visual delayed match-to-sample task [Tagamets, M.A., Horwitz, B., 1998. Integrating electrophysiological and anatomical experimental data to create a large-scale model that simulates a delayed match-to-sample human brain imaging study. Cereb. Cortex 8, 310-320]. The aim was to explore the validity of inferences made using DCM about the connectivity structure and task-dependent modulatory effects, in a system with a known connectivity structure. We also examined the effects of misspecifying regions of interest. Models with hierarchical connectivity and reciprocal connections were examined using DCM and Bayesian Model Comparison [Penny, W.D., Stephan, K.E., Mechelli, A., Friston, K.J., 2004. Comparing dynamic causal models. Neuroimage 22, 1157-1172]. This approach revealed strong evidence for those models with correctly specified anatomical connectivity. Furthermore, Bayesian model comparison favoured those models when bilinear effects corresponded to their implementation in the neural model. These findings generalised to an extended model with two additional areas and reentrant circuits. The conditional uncertainty of coupling parameter estimates increased in proportion to the number of incorrectly specified regions. These results highlight the role of neural models in establishing the validity of estimation and inference schemes. Specifically, Bayesian model comparison confirms the validity of DCM in relation to a well-characterised and comprehensive neuronal model. (c) 2005 Elsevier Inc. All rights reserved.