The Cingulate as a Catalyst Region for Global Dysfunction: a Dynamical Modelling Paradigm

The anterior cingulate (AC) often exhibits both structural and functional abnormalities in affective disorders. Neither the cause for this vulnerability nor its effect on behaviour is known. Due to its extensive connectivity, minor output changes from the AC may exert widespread consequences. A causal model describing coupling coefficients (effective connectivity) among several brain regions in healthy subjects performing a memory task inspired our work. This stationary causal analysis provides a theoretical framework for our nonlinear dynamical models. We tested the effects of global and local perturbations upon stability of a systems-level neural network of interconnected brain regions. Interactions between regions, represented by path coefficients, were modelled using connectivity matrices. We found that both characteristic behaviour and response to perturbation differed in networks representing perceptual matching and long-delay conditions. Owing to the highly interconnected character of the networks, activation of a few areas was sufficient to trigger characteristic patterns of behaviour. However, only perturbation of key regions resulted in global dysfunction. Likewise, recovery of function was possible by increasing output from some, but not all, regions. We suggest for this recovery to be context specific, conditional on the task, integrity of other regions and global properties such as neuronal excitability.