Reliability and subject specificity of personalized whole-brain dynamical models

Dynamical whole-brain models were developed to link structural (SC) and functional connectivity (FC) together into one framework. Nowadays, they are used to investigate the dynamical regimes of the brain and how these relate to behavioral, clinical and demographic traits. However, there is no comprehensive investigation on how reliable and subject specific the modeling results are given the variability of the empirical FC. In this study, we show that the parameters of these models can be fitted with a "poor" to "good" reliability depending on the exact implementation of the modeling paradigm. We find, as a general rule of thumb, that enhanced model personalization leads to increasingly reliable model parameters. In addition, we observe no clear effect of the model complexity evaluated by separately sampling results for linear, phase oscillator and neural mass network models. In fact, the most complex neural mass model often yields modeling results with "poor" reliability comparable to the simple linear model, but demonstrates an enhanced subject specificity of the model similarity maps. Subsequently, we show that the FC simulated by these models can outperform the empirical FC in terms of both reliability and subject specificity. For the structure-function relationship, simulated FC of individual subjects may be identified from the correlations with the empirical SC with an accuracy up to 70%, but not vice versa for non-linear models. We sample all our findings for 8 distinct brain parcellations and 6 modeling conditions and show that the parcellation-induced effect is much more pronounced for the modeling results than for the empirical data. In sum, this study provides an exploratory account on the reliability and subject specificity of dynamical whole-brain models and may be relevant for their further development and application. In particular, our findings suggest that the application of the dynamical whole-brain modeling should be tightly connected with an estimate of the reliability of the results.