Drug-resistant focal epilepsy in children is associated with increased modal controllability of the whole brain and epileptogenic regions

Network control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states. In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery. Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function

Interictal Network Dynamics in Paediatric Epilepsy Surgery

Epilepsy is an archetypal brain network disorder. Despite two decades of research elucidating network mechanisms of disease and correlating these with outcomes, the clinical management of children with epilepsy does not readily integrate network concepts. For example, network measures are not used in presurgical evaluation to guide decision making or surgical management plans. The aim of this thesis was to investigate novel network frameworks from the perspective of a clinician, with the explicit aim of finding measures that may be clinically useful and translatable to directly benefit patient care. We examined networks at three different scales, namely macro (whole brain diffusion MRI), meso (subnetworks from SEEG recordings) and micro (single unit networks) scales, consistently finding network abnormalities in children being evaluated for or undergoing epilepsy surgery. This work also provides a path to clinical translation, using frameworks such as IDEAL to robustly assess the impact of these new technologies on management and outcomes. The thesis sets up a platform from which promising computational technology, that utilises brain network analyses, can be readily translated to benefit patient care

Small-World Brain Networks Revisited.

It is nearly 20 years since the concept of a small-world network was first quantitatively defined, by a combination of high clustering and short path length; and about 10 years since this metric of complex network topology began to be widely applied to analysis of neuroimaging and other neuroscience data as part of the rapid growth of the new field of connectomics. Here, we review briefly the foundational concepts of graph theoretical estimation and generation of small-world networks. We take stock of some of the key developments in the field in the past decade and we consider in some detail the implications of recent studies using high-resolution tract-tracing methods to map the anatomical networks of the macaque and the mouse. In doing so, we draw attention to the important methodological distinction between topological analysis of binary or unweighted graphs, which have provided a popular but simple approach to brain network analysis in the past, and the topology of weighted graphs, which retain more biologically relevant information and are more appropriate to the increasingly sophisticated data on brain connectivity emerging from contemporary tract-tracing and other imaging studies. We conclude by highlighting some possible future trends in the further development of weighted small-worldness as part of a deeper and broader understanding of the topology and the functional value of the strong and weak links between areas of mammalian cortex.DSB acknowledges support from the John D. and Catherine T. MacArthur Foundation, the Alfred P. Sloan Foundation, the Army Research Laboratory and the Army Research Office through contract numbers W911NF-10-2-0022 and W911NF-14-1-0679, the National Institute of Health (2-R01-DC-009209-11, 1R01HD086888-01, R01-MH107235, R01-MH107703, and R21-M MH-106799), the Office of Naval Research, and the National Science Foundation (BCS-1441502, CAREER PHY-1554488, and BCS-1631550).This is the final version of the article. It first appeared from Sage at http://dx.doi.org/10.1177/1073858416667720

Control Theoretic Analysis of Human Brain Networks

The brain is a complex system with complicated structures and entangled dynamics. Among the various approaches to investigating the brain\u27s mechanics, the graphical method provides a successful framework for understanding the topology of both the structural and functional networks, and discovering efficient diagnostic biomarkers for cognitive behaviors, brain disorders and diseases. Yet it cannot explain how the structure affects the functionality and how the brain tunes its transition among multiple states to manipulate the cognitive control. In my dissertation, I propose a novel framework of modeling the mechanics of the cognitive control, which involves in applying control theory to analyzing the brain networks and conceptually connecting the cognitive control with the engineering control. First, I examine the energy distribution among different states via combining the energetic and structural constraints of the brain\u27s state transition in a free energy model, where the interaction between regions is explicitly informed by structural connectivity. This work enables the possibility of achieving a whole view of the brain\u27s energy landscape and preliminarily indicates the feasibility of control theory to model the dynamics of cognitive control. In the following work, I exploit the network control theory to address two questions about how the large-scale circuitry of the human brain constrains its dynamics. First, is the human brain theoretically controllable? Second, which areas of the brain are most influential in constraining or facilitating changes in brain state trajectories? Further, I seek to examine the structural effect on the control actions through solving the optimal control problem under different boundary conditions. I quantify the efficiency of regions in terms of the energy cost for the brain state transition from the default mode to task modes. This analysis is extended to the perturbation analysis of trajectories and is applied to the comparison between the group with mild traumatic brain injury(mTBI) and the healthy group. My research is the first to demonstrate how control theory can be used to analyze human brain networks

The Topology and Geometry of Neural Representations

A central question for neuroscience is how to characterize brain representations of perceptual and cognitive content. An ideal characterization should distinguish different functional regions with robustness to noise and idiosyncrasies of individual brains that do not correspond to computational differences. Previous studies have characterized brain representations by their representational geometry, which is defined by the representational dissimilarity matrix (RDM), a summary statistic that abstracts from the roles of individual neurons (or responses channels) and characterizes the discriminability of stimuli. Here we explore a further step of abstraction: from the geometry to the topology of brain representations. We propose topological representational similarity analysis (tRSA), an extension of representational similarity analysis (RSA) that uses a family of geo-topological summary statistics that generalizes the RDM to characterize the topology while de-emphasizing the geometry. We evaluate this new family of statistics in terms of the sensitivity and specificity for model selection using both simulations and functional MRI (fMRI) data. In the simulations, the ground truth is a data-generating layer representation in a neural network model and the models are the same and other layers in different model instances (trained from different random seeds). In fMRI, the ground truth is a visual area and the models are the same and other areas measured in different subjects. Results show that topology-sensitive characterizations of population codes are robust to noise and interindividual variability and maintain excellent sensitivity to the unique representational signatures of different neural network layers and brain regions.Comment: codes: https://github.com/doerlbh/TopologicalRS

Development Of Human Brain Network Architecture Underlying Executive Function

The transition from late childhood to adulthood is characterized by refinements in brain structure and function that support the dynamic control of attention and goal-directed behavior. One broad domain of cognition that undergoes particularly protracted development is executive function, which encompasses diverse cognitive processes including working memory, inhibitory control, and task switching. Delineating how white matter architecture develops to support specialized brain circuits underlying individual differences in executive function is critical for understanding sources of risk-taking behavior and mortality during adolescence. Moreover, neuropsychiatric disorders are increasingly understood as disorders of brain development, are marked by failures of executive function, and are linked to the disruption of evolving brain connectivity. Network theory provides a parsimonious framework for modeling how anatomical white matter pathways support synchronized fluctuations in neural activity. However, only sparse data exists regarding how the maturation of white matter architecture during human brain development supports coordinated fluctuations in neural activity underlying higher-order cognitive ability. To address this gap, we capitalize on multi-modal neuroimaging and cognitive phenotyping data collected as part of the Philadelphia Neurodevelopmental Cohort (PNC), a large community-based study of brain development. First, diffusion tractography methods were applied to characterize how the development of structural brain network topology supports domain-specific improvements in cognitive ability (n=882, ages 8-22 years old). Second, structural connectivity and task-based functional connectivity approaches were integrated to describe how the development of anatomical constraints on functional communication support individual differences in executive function (n=727, ages 8-23 years old). Finally, the systematic impact of head motion artifact on measures of structural connectivity were characterized (n=949, ages 8-22 years old), providing important guidelines for studying the development of structural brain network architecture. Together, this body of work expands our understanding of how developing white matter connectivity in youth supports the emergence of functionally specialized circuits underlying executive processing. As diverse types of psychopathology are increasingly linked to atypical brain maturation, these findings could collectively lead to earlier diagnosis and personalized interventions for individuals at risk for developing mental disorders