Work

High-order functional redundancy in ageing explained via alterations in the connectome in a whole-brain model

Year: 2022

Type: article

Abstract: The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain’s connectomics that occurs along the lifespan. However, the precise relationship between high-order functional interactions and connnectomics, as well as their variations with age are largely unknown, in part due to the absence of mechanistic models that can efficiently map brain connnectomics to functional connectivity in aging. To investigate this issue, we have built a neurobiologically-realistic whole-brain computational model using both anatomical and functional MRI data from 161 participants ranging from 10 to 80 years old. We show that the age differences in high-order functional interactions can be largely explained by variations in the connectome. Based on this finding, we propose a simple neurodegeneration model that is representative of normal physiological aging. As such, when applied to connectomes of young participant it reproduces the age-variations that occur in the high-order structure of the functional data. Overall, these results begin to disentangle the mechanisms by which structural changes in the connectome lead to functional differences in the ageing brain. Our model can also serve as a starting point for modelling more complex forms of pathological ageing or cognitive deficits. Author summary Modern neuroimaging techniques allow us to study how the human brain’s anatomical architecture (a.k.a. structural connectome) changes under different conditions or interventions. Recently, using functional neuroimaging data, we have shown that complex patterns of interactions between brain areas change along the lifespan, exhibiting increased redundant interactions in the older population. However, the mechanisms that underlie these functional differences are still unclear. Here, we extended this work and hypothesized that the variations of functional patterns can be explained by the dynamics of the brain’s anatomical networks, which are known to degenerate as we age. To test this hypothesis, we implemented a whole-brain model of neuronal activity, where different brain regions are anatomically wired using real connectomes from 161 participants with ages ranging from 10 to 80 years old. Analyzing different functional aspects of brain activity when varying the empirical connectomes, we show that the increased redundancy found in the older group can indeed be explained by precise rules affecting anatomical connectivity, thus emphasizing the critical role that the brain connectome plays for shaping complex functional interactions and the efficiency in the global communication of the human brain.

Source: PLoS Computational Biology

DOI: 10.1371/journal.pcbi.1010431