Spike sorting in the presence of stimulation artifacts: a dynamical control systems approach.

Objective. Bi-directional electronic neural interfaces, capable of both electrical recording and stimulation, communicate with the nervous system to permit precise calibration of electrical inputs by capturing the evoked neural responses. However, one significant challenge is that stimulation artifacts often mask the actual neural signals. To address this issue, we introduce a novel approach that employs dynamical control systems to detect and decipher electrically evoked neural activity despite the presence of electrical artifacts.Approach. Our proposed method leverages the unique spatiotemporal patterns of neural activity and electrical artifacts to distinguish and identify individual neural spikes. We designed distinctive dynamical models for both the stimulation artifact and each neuron observed during spontaneous neural activity. We can estimate which neurons were active by analyzing the recorded voltage responses across multiple electrodes post-stimulation. This technique also allows us to exclude signals from electrodes heavily affected by stimulation artifacts, such as the stimulating electrode itself, yet still accurately differentiate between evoked spikes and electrical artifacts.Main results. We applied our method to high-density multi-electrode recordings from the primate retina in anex vivosetup, using a grid of 512 electrodes. Through repeated electrical stimulations at varying amplitudes, we were able to construct activation curves for each neuron. The curves obtained with our method closely resembled those derived from manual spike sorting. Additionally, the stimulation thresholds we estimated strongly agreed with those determined through manual analysis, demonstrating high reliability (R2=0.951for human 1 andR2=0.944for human 2).Significance. Our method can effectively separate evoked neural spikes from stimulation artifacts by exploiting the distinct spatiotemporal propagation patterns captured by a dense, large-scale multi-electrode array. This technique holds promise for future applications in real-time closed-loop stimulation systems and for managing multi-channel stimulation strategies.

The role of long-term power-law memory in controlling large-scale dynamical networks.

Controlling large-scale dynamical networks is crucial to understand and, ultimately, craft the evolution of complex behavior. While broadly speaking we understand how to control Markov dynamical networks, where the current state is only a function of its previous state, we lack a general understanding of how to control dynamical networks whose current state depends on states in the distant past (i.e. long-term memory). Therefore, we require a different way to analyze and control the more prevalent long-term memory dynamical networks. Herein, we propose a new approach to control dynamical networks exhibiting long-term power-law memory dependencies. Our newly proposed method enables us to find the minimum number of driven nodes (i.e. the state vertices in the network that are connected to one and only one input) and their placement to control a long-term power-law memory dynamical network given a specific time-horizon, which we define as the 'time-to-control'. Remarkably, we provide evidence that long-term power-law memory dynamical networks require considerably fewer driven nodes to steer the network's state to a desired goal for any given time-to-control as compared with Markov dynamical networks. Finally, our method can be used as a tool to determine the existence of long-term memory dynamics in networks.

External drivers of BOLD signal's non-stationarity.

A fundamental challenge in neuroscience is to uncover the principles governing how the brain interacts with the external environment. However, assumptions about external stimuli fundamentally constrain current computational models. We show in silico that unknown external stimulation can produce error in the estimated linear time-invariant dynamical system. To address these limitations, we propose an approach to retrieve the external (unknown) input parameters and demonstrate that the estimated system parameters during external input quiescence uncover spatiotemporal profiles of external inputs over external stimulation periods more accurately. Finally, we unveil the expected (and unexpected) sensory and task-related extra-cortical input profiles using functional magnetic resonance imaging data acquired from 96 subjects (Human Connectome Project) during the resting-state and task scans. This dynamical systems model of the brain offers information on the structure and dimensionality of the BOLD signal's external drivers and shines a light on the likely external sources contributing to the BOLD signal's non-stationarity. Our findings show the role of exogenous inputs in the BOLD dynamics and highlight the importance of accounting for external inputs to unravel the brain's time-varying functional dynamics.

Model-based stationarity filtering of long-term memory data applied to resting-state blood-oxygen-level-dependent signal.

Resting-state blood-oxygen-level-dependent (BOLD) signal acquired through functional magnetic resonance imaging is a proxy of neural activity and a key mechanism for assessing neurological conditions. Therefore, practical tools to filter out artefacts that can compromise the assessment are required. On the one hand, a variety of tailored methods to preprocess the data to deal with identified sources of noise (e.g., head motion, heart beating, and breathing, just to mention a few) are in place. But, on the other hand, there might be unknown sources of unstructured noise present in the data. Therefore, to mitigate the effects of such unstructured noises, we propose a model-based filter that explores the statistical properties of the underlying signal (i.e., long-term memory). Specifically, we consider autoregressive fractional integrative process filters. Remarkably, we provide evidence that such processes can model the signals at different regions of interest to attain stationarity. Furthermore, we use a principled analysis where a ground-truth signal with statistical properties similar to the BOLD signal under the injection of noise is retrieved using the proposed filters. Next, we considered preprocessed (i.e., the identified sources of noise removed) resting-state BOLD data of 98 subjects from the Human Connectome Project. Our results demonstrate that the proposed filters decrease the power in the higher frequencies. However, unlike the low-pass filters, the proposed filters do not remove all high-frequency information, instead they preserve process-related higher frequency information. Additionally, we considered four different metrics (power spectrum, functional connectivity using the Pearson's correlation, coherence, and eigenbrains) to infer the impact of such filter. We provided evidence that whereas the first three keep most of the features of interest from a neuroscience perspective unchanged, the latter exhibits some variations that could be due to the sporadic activity filtered out.

A time-reversed model selection approach to time series forecasting.

In this paper, we introduce a novel model selection approach to time series forecasting. For linear stationary processes, such as AR processes, the direction of time is independent of the model parameters. By combining theoretical principles of time-reversibility in time series with conventional modeling approaches such as information criteria, we construct a criterion that employs the backwards prediction (backcast) as a proxy for the forecast. Hereby, we aim to adopt a theoretically grounded, data-driven approach to model selection. The novel criterion is named the backwards validated information criterion (BVIC). The BVIC identifies suitable models by trading off a measure of goodness-of-fit and a models ability to predict backwards. We test the performance of the BVIC by conducting experiments on synthetic and real data. In each experiment, the BVIC is examined in contrast to conventionally employed criteria. Our experimental results suggest that the BVIC has comparable performance as conventional information criteria. Specifically, in most of the experiments performed, we did not find statistically significant differences between the forecast error of the BVIC under certain parameterizations and that of the different information criteria. Nonetheless, it is worth emphasizing that the BVIC guarantees are established by design where the model order penalization term depends on strong mathematical properties of time-reversible time series forecasting properties and a finite data assessment. In particular, the penalization term is replaced by a weighted trade-off between functional dimensions pertaining to forecasting.That said, we observed that the BVIC recovered more accurately the real order of the underlying process than the other criteria, which rely on a static penalization of the model order. Lastly, leveraging the latter property we perform the assessment of the order model (or, memory) of time series pertaining to epileptic seizures recorded using electrocorticographic data. Our results provide converging evidence that the order of the model increases during the epileptic events.

NEO: NEuro-Inspired Optimization-A Fractional Time Series Approach.

Solving optimization problems is a recurrent theme across different fields, including large-scale machine learning systems and deep learning. Often in practical applications, we encounter objective functions where the Hessian is ill-conditioned, which precludes us from using optimization algorithms utilizing second-order information. In this paper, we propose to use fractional time series analysis methods that have successfully been used to model neurophysiological processes in order to circumvent this issue. In particular, the long memory property of fractional time series exhibiting non-exponential power-law decay of trajectories seems to model behavior associated with the local curvature of the objective function at a given point. Specifically, we propose a NEuro-inspired Optimization (NEO) method that leverages this behavior, which contrasts with the short memory characteristics of currently used methods (e.g., gradient descent and heavy-ball). We provide evidence of the efficacy of the proposed method on a wide variety of settings implicitly found in practice.

Risk sensitivity and theory of mind in human coordination.

What humans do when exposed to uncertainty, incomplete information, and a dynamic environment influenced by other agents remains an open scientific challenge with important implications in both science and engineering applications. In these contexts, humans handle social situations by employing elaborate cognitive mechanisms such as theory of mind and risk sensitivity. Here we resort to a novel theoretical model, showing that both mechanisms leverage coordinated behaviors among self-regarding individuals. Particularly, we resort to cumulative prospect theory and level-k recursions to show how biases towards optimism and the capacity of planning ahead significantly increase coordinated, cooperative action. These results suggest that the reason why humans are good at coordination may stem from the fact that we are cognitively biased to do so.

Fractional-order model predictive control as a framework for electrical neurostimulation in epilepsy.

Objective.Electrical neurostimulation is an increasingly adopted therapeutic methodology for neurological conditions such as epilepsy. Electrical neurostimulation devices are commonly characterized by their limited sensing, actuating, and computational capabilities. However, the sensing mechanisms are often used only for their detection potential (e.g. to detect seizures), which automatically and dynamically trigger the actuation capabilities, but ultimately deploy prespecified stimulation doses that resulted from a period of manual (and empirical) calibration. The potential information contained in the measurements acquired by the sensing mechanisms is, therefore, considerably underutilized, given that this type of stimulation strategy only entails an event-triggered relationship between the sensors and actuators of the device. Such stimulation strategies are suboptimal in general and lack theoretical guarantees regarding their performance.Approach.In order to leverage the aforementioned information, harvested during normal sensing-actuating operation, we must consider a real-time feedback (closed-loop) strategy. More precisely, the stimulation signal itself should automatically adapt based upon the state of the neurophysiological system at hand, estimated from data collected in real-time through sensors in the device.Main results.In this work, we propose a model-based approach for (real-time) closed-loop electrical neurostimulation, in which the evolution of the system is captured by a fractional-order system (FOS). More precisely, we propose amodel predictive control(MPC) approach with an underlying FOS predictive model, due to the ability of fractional-order dynamics to more accurately capture the long-term dependence present in biological systems, compared to the standard linear time-invariant models. Furthermore, MPC offers, by design, an additional layer of robustness to compensate for system-model mismatch, which the more traditional strategies lack. To establish the potential of our framework, we focus on epileptic seizure mitigation by computational simulation of our proposed strategy upon seizure-like events. Lastly, we provide evidence of the effectiveness of our method on seizures simulated by commonly adopted models in the neuroscience and medical community present in the literature, as well as real seizure data as obtained from subjects with epilepsy.SignificanceOur study thus paves the way for the development and implementation of robust real-time closed-loop electrical neurostimulation which can then be used for the construction of more effective devices for epileptic seizure mitigation.

On the effects of memory and topology on the controllability of complex dynamical networks.

Recent advances in network science, control theory, and fractional calculus provide us with mathematical tools necessary for modeling and controlling complex dynamical networks (CDNs) that exhibit long-term memory. Selecting the minimum number of driven nodes such that the network is steered to a prescribed state is a key problem to guarantee that complex networks have a desirable behavior. Therefore, in this paper, we study the effects of long-term memory and of the topological properties on the minimum number of driven nodes and the required control energy. To this end, we introduce Gramian-based methods for optimal driven node selection for complex dynamical networks with long-term memory and by leveraging the structure of the cost function, we design a greedy algorithm to obtain near-optimal approximations in a computationally efficiently manner. We investigate how the memory and topological properties influence the control effort by considering Erdos-Rényi, Barabási-Albert and Watts-Strogatz networks whose temporal dynamics follow a fractional order state equation. We provide evidence that scale-free and small-world networks are easier to control in terms of both the number of required actuators and the average control energy. Additionally, we show how our method could be applied to control complex networks originating from the human brain and we discover that certain brain cortex regions have a stronger impact on the controllability of network than others.

Generating complex networks with time-to-control communities.

Dynamical networks are pervasive in a multitude of natural and human-made systems. Often, we seek to guarantee that their state is steered to the desired goal within a specified number of time steps. Different network topologies lead to implicit trade-offs between the minimum number of driven nodes and the time-to-control. In this study, we propose a generative model to create artificial dynamical networks with trade-offs similar to those of real networks. Remarkably, we show that several centrality and non-centrality measures are not necessary nor sufficient to explain the trade-offs, and as a consequence, commonly used generative models do not suffice to capture the dynamical properties under study. Therefore, we introduce the notion of time-to-control communities, that combine networks' partitions and degree distributions, which is crucial for the proposed generative model. We believe that the proposed methodology is crucial when invoking generative models to investigate dynamical network properties across science and engineering applications. Lastly, we provide evidence that the proposed generative model can generate a variety of networks with statistically indiscernible trade-offs (i.e., the minimum number of driven nodes vs. the time-to-control) from those steaming from real networks (e.g., neural and social networks).

Model-based design for seizure control by stimulation.

OBJECTIVE: Current brain stimulation paradigms are largely empirical rather than theoretical. An opportunity exists to improve upon their modest effectiveness in closed-loop control strategies with the development of theoretically grounded, model-based designs. APPROACH: Inspired by this need, here we couple experimental data and mathematical modeling with a control-theoretic strategy for seizure termination. We begin by exercising a dynamical systems approach to model seizures (n = 94) recorded using intracranial EEG (iEEG) from 21 patients with medication-resistant, localization-related epilepsy. MAIN RESULTS: Although each patient's seizures displayed unique spatial and temporal patterns, their evolution can be parsimoniously characterized by the same model form. Idiosyncracies of the model can inform individualized intervention strategies, specifically in iEEG samples with well-localized seizure onset zones. Temporal fluctuations in the spatial profiles of the oscillatory modes show that seizure onset marks a transition into a regime in which the underlying system supports prolonged rhythmic and focal activity. Based on these observations, we propose a control-theoretic strategy that aims to stabilize ictal activity using static output feedback for linear time-invariant switching systems. Finally, we demonstrate in silico that our proposed strategy allows us to dampen the emerging focal oscillatory sources using only a small set of electrodes. SIGNIFICANCE: Our integrative study informs the development of modulation and control algorithms for neurostimulation that could improve the effectiveness of implantable, closed-loop anti-epileptic devices.

Spectral mapping of brain functional connectivity from diffusion imaging.

Understanding the relationship between the dynamics of neural processes and the anatomical substrate of the brain is a central question in neuroscience. On the one hand, modern neuroimaging technologies, such as diffusion tensor imaging, can be used to construct structural graphs representing the architecture of white matter streamlines linking cortical and subcortical structures. On the other hand, temporal patterns of neural activity can be used to construct functional graphs representing temporal correlations between brain regions. Although some studies provide evidence that whole-brain functional connectivity is shaped by the underlying anatomy, the observed relationship between function and structure is weak, and the rules by which anatomy constrains brain dynamics remain elusive. In this article, we introduce a methodology to map the functional connectivity of a subject at rest from his or her structural graph. Using our methodology, we are able to systematically account for the role of structural walks in the formation of functional correlations. Furthermore, in our empirical evaluations, we observe that the eigenmodes of the mapped functional connectivity are associated with activity patterns associated with different cognitive systems.

Trade-offs between driving nodes and time-to-control in complex networks.

Recent advances in control theory provide us with efficient tools to determine the minimum number of driving (or driven) nodes to steer a complex network towards a desired state. Furthermore, we often need to do it within a given time window, so it is of practical importance to understand the trade-offs between the minimum number of driving/driven nodes and the minimum time required to reach a desired state. Therefore, we introduce the notion of actuation spectrum to capture such trade-offs, which we used to find that in many complex networks only a small fraction of driving (or driven) nodes is required to steer the network to a desired state within a relatively small time window. Furthermore, our empirical studies reveal that, even though synthetic network models are designed to present structural properties similar to those observed in real networks, their actuation spectra can be dramatically different. Thus, it supports the need to develop new synthetic network models able to replicate controllability properties of real-world networks.