Biology subjects

Khambhati, A. N.

Publications and source records attributed to Khambhati, A. N..

7 recordsLinked to original sources

bioRxiv2018

Dynamic constraints on activity and connectivity during the learning of value

Human learning is a complex process in which future behavior is altered via the modulation of neural activity. Yet, the degree to which brain activity and functional connectivity during learning is constrained across subjects, for example by conserved anatomy and physiology or by the nature of the task, remains unknown. Here, we measured brain activity and functional connectivity in a longitudinal experiment in which healthy adult human participants learned the values of novel objects over the course of four days. We assessed the presence of constraints on activity and functional connectivity using an inter-subject correlation approach. Constraints on activity and connectivity were greater in magnitude than expected in a non-parametric permutation-based null model, particularly in primary sensory and motor systems, as well as in regions associated with the learning of value. Notably, inter-subject connectivity in activity and connectivity displayed marked temporal variations, with inter-subject correlations in activity exceeding those in connectivity during early learning and visa versa in later learning. Finally, individual differences in performance accuracy tracked the degree to which a subjects connectivity, but not activity, tracked subject-general patterns. Taken together, our results support the notion that brain activity and connectivity are constrained across subjects in early learning, with constraints on activity, but not connectivity, decreasing in later learning.

neuroscience↗

bioRxiv2018

Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy

Focal epilepsy is a devastating neurological disorder that affects an overwhelming number of patients world-wide, many of whom prove resistant to medication. The efficacy of current innovative technologies for the treatment of these patients has been stalled by the lack of accurate and effective methods to fuse multimodal neuroimaging data to map anatomical targets driving seizure dynamics. Here we propose a parsimonious model that explains how large-scale anatomical networks and shared genetic constraints shape inter-regional communication in focal epilepsy. In extensive ECoG recordings acquired from a group of patients with medically refractory focal-onset epilepsy, we find that ictal and preictal functional brain network dynamics can be accurately predicted from features of brain anatomy and geometry, patterns of white matter connectivity, and constraints complicit in patterns of gene coexpression, all of which are conserved across healthy adult populations. Moreover, we uncover evidence that markers of non-conserved architecture, potentially driven by idiosyncratic pathology of single subjects, are most prevalent in high frequency ictal dynamics and low frequency preictal dynamics. Finally, we find that ictal dynamics are better predicted by white matter features and more poorly predicted by geometry and genetic constraints than preictal dynamics, suggesting that the functional brain network dynamics manifest in seizures rely on - and may directly propagate along - underlying white matter structure that is largely conserved across humans. Broadly, our work offers insights into the generic architectural principles of the human brain that impact seizure dynamics, and could be extended to further our understanding, models, and predictions of subject-level pathology and response to intervention.

neuroscience↗

bioRxiv2018

White Matter Network Architecture Guides Direct Electrical Stimulation Through Optimal State Transitions

Electrical brain stimulation is currently being investigated as a potential therapy for neurological disease. However, opportunities to optimize and personalize such therapies are challenged by the fact that the beneficial impact (and potential side effects) of focal stimulation on both neighboring and distant regions is not well understood. Here, we use network control theory to build a formal model of brain network function that makes explicit predictions about how stimulation spreads through the brains white matter network and influences large-scale dynamics. We test these predictions using combined electrocorticography (ECoG) and diffusion weighted imaging (DWI) data from patients with medically refractory epilepsy undergoing evaluation for resective surgery, and who volunteered to participate in an extensive stimulation regimen. We posit a specific model-based manner in which white matter tracts constrain stimulation, defining its capacity to drive the brain to new states, including states associated with successful memory encoding. In a first validation of our model, we find that the true pattern of white matter tracts can be used to more accurately predict the state transitions induced by direct electrical stimulation than the artificial patterns of a topological or spatial network null model. We then use a targeted optimal control framework to solve for the optimal energy required to drive the brain to a given state. We show that, intuitively, our model predicts larger energy requirements when starting from states that are farther away from a target memory state. We then suggest testable hypotheses about which structural properties will lead to efficient stimulation for improving memory based on energy requirements. We show that the strength and homogeneity of edges between controlled and uncontrolled nodes, as well as the persistent modal controllability of the stimulated region, predict energy requirements. Our work demonstrates that individual white matter architecture plays a vital role in guiding the dynamics of direct electrical stimulation, more generally offering empirical support for the utility of network control theoretic models of brain response to stimulation.

neuroscience↗

bioRxiv2018

Predictive control of electrophysiological network architecture using direct, single-node neurostimulation in humans

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multi-modal intracranial recordings and diffusion tensor imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition.

neuroscience↗

bioRxiv2017

Modelling And Interpreting Network Dynamics

Recent advances in brain imaging techniques, measurement approaches, and storage capacities have provided an unprecedented supply of high temporal resolution neural data. These data present a remarkable opportunity to gain a mechanistic understanding not just of circuit structure, but also of circuit dynamics, and its role in cognition and disease. Such understanding necessitates a description of the raw observations, and a delineation of computational models and mathematical theories that accurately capture fundamental principles behind the observations. Here we review recent advances in a range of modeling approaches that embrace the temporally-evolving interconnected structure of the brain and summarize that structure in a dynamic graph. We describe recent efforts to model dynamic patterns of connectivity, dynamic patterns of activity, and patterns of activity atop connectivity. In the context of these models, we review important considerations in statistical testing, including parametric and non-parametric approaches. Finally, we offer thoughts on careful and accurate interpretation of dynamic graph architecture, and outline important future directions for method development.

neuroscience↗

bioRxiv2017

Beyond modularity: Fine-scale mechanisms and rules for brain network reconfiguration

The human brain is in constant flux, as distinct areas engage in transient communication to support basic behaviors as well as complex cognition. The collection of interactions between cortical and subcortical areas forms a functional brain network whose topology evolves with time. Despite the nontrivial dynamics that are germaine to this networked system, experimental evidence demonstrates that functional interactions organize into putative brain systems that facilitate different facets of cognitive computation. We hypothesize that such dynamic functional networks are organized around a set of rules that constrain their spatial architecture - which brain regions may functionally interact - and their temporal architecture - how these interactions fluctuate over time. To objectively uncover these organizing principles, we apply an unsupervised machine learning approach called nonnegative matrix factorization to time-evolving, resting state functional networks in 20 healthy subjects. This machine-learning approach automatically clusters temporally co-varying functional interactions into subgraphs that represent putative topological modes of dynamic functional architecture. We find that subgraphs are stratified based on both the underlying modular organization and the topographical distance of their strongest interactions: while many subgraphs are largely contained within modules, others span between modules and are expressed differently over time. The relationship between dynamic subgraphs and modular architecture is further highlighted by the ability of time-varying subgraph expression to explain inter-individual differences in module reorganization. Collectively, these results point to the critical role subgraphs play in constraining the topography and topology of functional brain networks. More broadly, this machine learning approach opens a new door for understanding the architecture of dynamic functional networks during both task and rest states, and for probing alterations of that architecture in disease.

neuroscience↗

bioRxiv2016

Recurring functional interactions predict network architecture of interictal and ictal states in neocortical epilepsy

Human epilepsy patients suffer from spontaneous seizures, which originate in brain regions that also subserve normal function. Prior studies demonstrate focal, neocortical epilepsy is associated with dysfunction, several hours before seizures. How does the epileptic network perpetuate dysfunction during baseline periods? To address this question, we developed an unsupervised machine learning technique to disentangle patterns of functional interactions between brain regions, or subgraphs, from dynamic functional networks constructed from approximately 100 hours of intracranial recordings in each of 22 neocortical epilepsy patients. Using this approach, we found: (i) subgraphs from ictal (seizure) and interictal (baseline) epochs are topologically similar, (ii) interictal subgraph topology and dynamics can predict brain regions that generate seizures, and (iii) subgraphs undergo slower and more coordinated fluctuations during ictal epochs compared to interictal epochs. Our observations suggest that the epileptic network drives dysfunction by controlling dynamics of functional interactions between brain regions that generate seizures and those that underlie normal function.

neuroscience↗