Computational Modeling of Resting-State Activity Demonstrates Markers of Normalcy in Children with Prenatal or Perinatal Stroke

Abstract

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.

Fifty shades of The Virtual Brain: Converging optimal working points yield biologically plausible electrophysiological and imaging features

“…In the current study, we conducted a large parameter space exploration with TVB, simulating BOLD fMRI and electrophysiological neural signals for 50 individual human brains. TVB has previously been used to study how neural networks behave in healthy and diseased states (8,10,13,18,21,26). Here, we assert that goodness-of-fit of simulated to empirical data converge at a particular parameter set across multiple tenets of the EEG and fMRI signal, and that there are reliable inter-individual differences in biophysical parameters that lead to optimal functioning.…”

“…In a second set of simulations, we explored a narrower range of global coupling and reproduced alpha frequency (8)(9)(10)(11)(12)(13)(14)(15) Hz) oscillations in the neural signal, a characteristic feature of human empirical EEG (37,38), which has previously been modelled as a function of global coupling in MEG (30). Here, it was shown that transmission delays and global cortical coupling affect the mean power in an MEG model, and the best model fit was found in the alpha band power.…”

“…For example: tuning the network close to a bifurcation point (25), exploration of the dynamical landscape (21), motor recovery in stroke (8)(9)(10), seizure activity (26), Alzheimer's disease (27)(28)(29)) efficiency of the system in the pathological brain (8). Moreover, alpha band power in an MEG model was a function of transmission delays and global cortical coupling (30).…”

“…Another study on exclusively healthy subjects used the same local model and the SC of 9 individuals to fit simulated FCs to their empirical counterpart (18). This procedure was also used in another study when varying global coupling to simulate 42 virtual brains (10). In the study of Kunze et al, the standard SC provided by TVB was used to assess the effect of transcranial direct current stimulation (tDCS) on frequency, FC and postsynaptic potentials of pyramidal cells (16).…”

Resting-State Functional Connectivity and Cognitive Impairment in Children with Perinatal Stroke

“…Therefore, an early childhood stroke that affects immature connections might have a stronger impact on functional reorganization than a stroke that affects more mature networks [29]. However, there exists also the hypothesis that damaged areas continue to support the performance of tasks involving them and the typical functional connections of these regions play an important role in preservation of normalcy after early perinatal stroke [52]. In our study significant changes in DMN and especially in the posterior precuneus part of DMN, which is the main hub within DMN, were found in the children with AIS who had also serious cognitive problems.…”