Connectome | EPFL Graph Search

A connectome (kəˈnɛktoʊm) is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". An organism's nervous system is made up of neurons which communicate through synapses. A connectome is constructed by tracing the neuron in a nervous system and mapping where neurons are connected through synapses. The significance of the connectome stems from the realization that the structure and function of the human brain are intricately linked, through multiple levels and modes of brain connectivity. There are strong natural constraints on which neurons or neural populations can interact, or how strong or direct their interactions are. Indeed, the foundation of human cognition lies in the pattern of dynamic interactions shaped by the connectome. Despite such complex and variable structure-function mappings, the connectome is an indispensable basis for the mechanistic interpretation of dynamic brain data, from single-cell r

Investigating cognitive ability using action-based models of structural brain networks

Enrico Amico

Recent developments in network neuroscience have highlighted the importance of developing techniques for analysing and modelling brain networks. A particularly powerful approach for studying complex neural systems is to formulate generative models that use wiring rules to synthesize networks closely resembling the topology of a given connectome. Successful models can highlight the principles by which a network is organized (identify structural features that arise from wiring rules versus those that emerge) and potentially uncover the mechanisms by which it grows and develops. Previous research has shown that such models can validate the effectiveness of spatial embedding and other (non-spatial) wiring rules in shaping the network topology of the human connectome. In this research, we propose variants of the action-based model that combine a variety of generative factors capable of explaining the topology of the human connectome. We test the descriptive validity of our models by evaluating their ability to explain between-subject variability. Our analysis provides evidence that geometric constraints are vital for connectivity between brain regions, and an action-based model relying on both topological and geometric properties can account for between-subject variability in structural network properties. Further, we test correlations between parameters of subject-optimized models and various measures of cognitive ability and find that higher cognitive ability is associated with an individual's tendency to form long-range or non-local connections.

OXFORD UNIV PRESS2022

The progressive loss of brain network fingerprints in Amyotrophic Lateral Sclerosis predicts clinical impairment

Enrico Amico

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by functional connectivity alterations in both motor and extra-motor brain regions. Within the framework of network analysis, fingerprinting represents a reliable approach to assess subject-specific connectivity features within a given population (healthy or diseased). Here, we applied the Clinical Connectome Fingerprint (CCF) analysis to source-reconstructed magnetoencephalography (MEG) signals in a cohort of seventy-eight subjects: thirty-nine ALS patients and thirty-nine healthy controls. We set out to develop an identifiability matrix to assess the extent to which each patient was recognisable based on his/her connectome, as compared to healthy controls. The analysis was performed in the five canonical frequency bands. Then, we built a multilinear regression model to test the ability of the "clinical fingerprint" to predict the clinical evolution of the disease, as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r), the King's disease staging system, and the Milano-Torino Staging (MiToS) disease staging system. We found a drop in the identifiability of patients in the alpha band compared to the healthy controls. Furthermore, the "clinical fingerprint" was predictive of the ALSFRS-r (p = 0.0397; beta = 32.8), the King's (p = 0.0001; beta = -7.40), and the MiToS (p = 0.0025; beta = -4.9) scores. Accordingly, it negatively correlated with the King's (Spearman's rho = -0.6041, p = 0.0003) and MiToS scales (Spearman's rho = -0.4953, p = 0.0040). Our results demonstrated the ability of the CCF approach to predict the individual motor impairment in patients affected by ALS. Given the subject-specificity of our approach, we hope to further exploit it to improve disease management.

ELSEVIER SCI LTD2022

A Brief History of Simulation Neuroscience

Xue Fan, Henry Markram

Our knowledge of the brain has evolved over millennia in philosophical, experimental and theoretical phases. We suggest that the next phase is simulation neuroscience. The main drivers of simulation neuroscience are big data generated at multiple levels of brain organization and the need to integrate these data to trace the causal chain of interactions within and across all these levels. Simulation neuroscience is currently the only methodology for systematically approaching the multiscale brain. In this review, we attempt to reconstruct the deep historical paths leading to simulation neuroscience, from the first observations of the nerve cell to modern efforts to digitally reconstruct and simulate the brain. Neuroscience began with the identification of the neuron as the fundamental unit of brain structure and function and has evolved towards understanding the role of each cell type in the brain, how brain cells are connected to each other, and how the seemingly infinite networks they form give rise to the vast diversity of brain functions. Neuronal mapping is evolving from subjective descriptions of cell types towards objective classes, subclasses and types. Connectivity mapping is evolving from loose topographic maps between brain regions towards dense anatomical and physiological maps of connections between individual genetically distinct neurons. Functional mapping is evolving from psychological and behavioral stereotypes towards a map of behaviors emerging from structural and functional connectomes. We show how industrialization of neuroscience and the resulting large disconnected datasets are generating demand for integrative neuroscience, how the scale of neuronal and connectivity maps is driving digital atlasing and digital reconstruction to piece together the multiple levels of brain organization, and how the complexity of the interactions between molecules, neurons, microcircuits and brain regions is driving brain simulation to understand the interactions in the multiscale brain.

FRONTIERS MEDIA SA2019

A Brief History of Simulation Neuroscience

Xue Fan, Henry Markram

FRONTIERS MEDIA SA2019