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.

Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness.

Severe traumatic brain injury can lead to disorders of consciousness (DOC) characterized by deficit in conscious awareness and cognitive impairment including coma, vegetative state, minimally consciousness, and lock-in syndrome. Of crucial importance is to find objective markers that can account for the large-scale disturbances of brain function to help the diagnosis and prognosis of DOC patients and eventually the prediction of the coma outcome. Following recent studies suggesting that the functional organization of brain networks can be altered in comatose patients, this work analyzes brain functional connectivity (FC) networks obtained from resting-state functional magnetic resonance imaging (rs-fMRI). Two approaches are used to estimate the FC: the Partial Correlation (PC) and the Transfer Entropy (TE). Both the PC and the TE show significant statistical differences between the group of patients and control subjects; in brief, the inter-hemispheric PC and the intra-hemispheric TE account for such differences. Overall, these results suggest two possible rs-fMRI markers useful to design new strategies for the management and neuropsychological rehabilitation of DOC patients.