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

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 differences in high-order functional interactions between age groups 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 modeling more complex forms of pathological ageing or cognitive deficits.

High-Order Interdependencies in the Aging Brain.

Background: Brain interdependencies can be studied from either a structural/anatomical perspective ("structural connectivity") or by considering statistical interdependencies ("functional connectivity" [FC]). Interestingly, while structural connectivity is by definition pairwise (white-matter fibers project from one region to another), FC is not. However, most FC analyses only focus on pairwise statistics and they neglect higher order interactions. A promising tool to study high-order interdependencies is the recently proposed O-Information, which can quantify the intrinsic statistical synergy and the redundancy in groups of three or more interacting variables. Methods: We analyzed functional magnetic resonance imaging (fMRI) data obtained at rest from 164 healthy subjects with ages ranging in 10 to 80 years and used O-Information to investigate how high-order statistical interdependencies are affected by age. Results: Older participants (from 60 to 80 years old) exhibited a higher predominance of redundant dependencies compared with younger participants, an effect that seems to be pervasive as it is evident for all orders of interaction. In addition, while there is strong heterogeneity across brain regions, we found a "redundancy core" constituted by the prefrontal and motor cortices in which redundancy was evident at all the interaction orders studied. Discussion: High-order interdependencies in fMRI data reveal a dominant redundancy in functions such as working memory, executive, and motor functions. Our methodology can be used for a broad range of applications, and the corresponding code is freely available. Impact statement Past research has showcased multiple changes to the brain's structural and functional properties caused by aging. Here we expand prior work through recent advancements in multivariate information theory, which provide richer and more theoretically principled analyses than existing alternatives. We show that the brains of older participants contain more redundant information at multiple spatial scales-that is, activation in different brain regions is less diverse, compared with younger participants-and identify a "redundancy core" constituted by prefrontal and motor cortices, which might explained impaired performance in the old population in functions such as working memory and executive control.

Chaos versus noise as drivers of multistability in neural networks.

The multistable behavior of neural networks is actively being studied as a landmark of ongoing cerebral activity, reported in both functional Magnetic Resonance Imaging (fMRI) and electro- or magnetoencephalography recordings. This consists of a continuous jumping between different partially synchronized states in the absence of external stimuli. It is thought to be an important mechanism for dealing with sensory novelty and to allow for efficient coding of information in an ever-changing surrounding environment. Many advances have been made to understand how network topology, connection delays, and noise can contribute to building this dynamic. Little or no attention, however, has been paid to the difference between local chaotic and stochastic influences on the switching between different network states. Using a conductance-based neural model that can have chaotic dynamics, we showed that a network can show multistable dynamics in a certain range of global connectivity strength and under deterministic conditions. In the present work, we characterize the multistable dynamics when the networks are, in addition to chaotic, subject to ion channel stochasticity in the form of multiplicative (channel) or additive (current) noise. We calculate the Functional Connectivity Dynamics matrix by comparing the Functional Connectivity (FC) matrices that describe the pair-wise phase synchronization in a moving window fashion and performing clustering of FCs. Moderate noise can enhance the multistable behavior that is evoked by chaos, resulting in more heterogeneous synchronization patterns, while more intense noise abolishes multistability. In networks composed of nonchaotic nodes, some noise can induce multistability in an otherwise synchronized, nonchaotic network. Finally, we found the same results regardless of the multiplicative or additive nature of noise.