Functional Mechanisms of Recovery after Chronic Stroke: Modeling with the Virtual Brain.

We have seen important strides in our understanding of mechanisms underlying stroke recovery, yet effective translational links between basic and applied sciences, as well as from big data to individualized therapies, are needed to truly develop a cure for stroke. We present such an approach using The Virtual Brain (TVB), a neuroinformatics platform that uses empirical neuroimaging data to create dynamic models of an individual's human brain; specifically, we simulate fMRI signals by modeling parameters associated with brain dynamics after stroke. In 20 individuals with stroke and 11 controls, we obtained rest fMRI, T1w, and diffusion tensor imaging (DTI) data. Motor performance was assessed pre-therapy, post-therapy, and 6-12 months post-therapy. Based on individual structural connectomes derived from DTI, the following steps were performed in the TVB platform: (1) optimization of local and global parameters (conduction velocity, global coupling); (2) simulation of BOLD signal using optimized parameter values; (3) validation of simulated time series by comparing frequency, amplitude, and phase of the simulated signal with empirical time series; and (4) multivariate linear regression of model parameters with clinical phenotype. Compared with controls, individuals with stroke demonstrated a consistent reduction in conduction velocity, increased local dynamics, and reduced local inhibitory coupling. A negative relationship between local excitation and motor recovery, and a positive correlation between local dynamics and motor recovery were seen. TVB reveals a disrupted post-stroke system favoring excitation-over-inhibition and local-over-global dynamics, consistent with existing mammal literature on stroke mechanisms. Our results point to the potential of TVB to determine individualized biomarkers of stroke recovery.

The Virtual Brain: Modeling Biological Correlates of Recovery after Chronic Stroke.

There currently remains considerable variability in stroke survivor recovery. To address this, developing individualized treatment has become an important goal in stroke treatment. As a first step, it is necessary to determine brain dynamics associated with stroke and recovery. While recent methods have made strides in this direction, we still lack physiological biomarkers. The Virtual Brain (TVB) is a novel application for modeling brain dynamics that simulates an individual's brain activity by integrating their own neuroimaging data with local biophysical models. Here, we give a detailed description of the TVB modeling process and explore model parameters associated with stroke. In order to establish a parallel between this new type of modeling and those currently in use, in this work we establish an association between a specific TVB parameter (long-range coupling) that increases after stroke with metrics derived from graph analysis. We used TVB to simulate the individual BOLD signals for 20 patients with stroke and 10 healthy controls. We performed graph analysis on their structural connectivity matrices calculating degree centrality, betweenness centrality, and global efficiency. Linear regression analysis demonstrated that long-range coupling is negatively correlated with global efficiency (P = 0.038), but is not correlated with degree centrality or betweenness centrality. Our results suggest that the larger influence of local dynamics seen through the long-range coupling parameter is closely associated with a decreased efficiency of the system. We thus propose that the increase in the long-range parameter in TVB (indicating a bias toward local over global dynamics) is deleterious because it reduces communication as suggested by the decrease in efficiency. The new model platform TVB hence provides a novel perspective to understanding biophysical parameters responsible for global brain dynamics after stroke, allowing the design of focused therapeutic interventions.