Optimal control based seizure abatement using patient derived connectivity.
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ABSTRACT:
SUBMITTER: Taylor PN
PROVIDER: S-EPMC4453481 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description:Active brain stimulation to abate epileptic seizures has shown mixed success. In spike-wave (SW) seizures, where the seizure and background state were proposed to coexist, single-pulse stimulations have been suggested to be able to terminate the seizure prematurely. However, several factors can impact success in such a bistable setting. The factors contributing to this have not been fully investigated on a theoretical and mechanistic basis. Our aim is to elucidate mechanisms that influence the success of single-pulse stimulation in noise-induced SW seizures. In this work, we study a neural population model of SW seizures that allows the reconstruction of the basin of attraction of the background activity as a four dimensional geometric object. For the deterministic (noise-free) case, we show how the success of response to stimuli depends on the amplitude and phase of the SW cycle, in addition to the direction of the stimulus in state space. In the case of spontaneous noise-induced seizures, the basin becomes probabilistic introducing some degree of uncertainty to the stimulation outcome while maintaining qualitative features of the noise-free case. Additionally, due to the different time scales involved in SW generation, there is substantial variation between SW cycles, implying that there may not be a fixed set of optimal stimulation parameters for SW seizures. In contrast, the model suggests an adaptive approach to find optimal stimulation parameters patient-specifically, based on real-time estimation of the position in state space. We discuss how the modelling work can be exploited to rationally design a successful stimulation protocol for the abatement of SW seizures using real-time SW detection.
| S-EPMC4273970 | biostudies-literature
Project description:Recent studies have shown that mathematical models can be used to analyze brain networks by quantifying how likely they are to generate seizures. In particular, we have introduced the quantity termed brain network ictogenicity (BNI), which was demonstrated to have the capability of differentiating between functional connectivity (FC) of healthy individuals and those with epilepsy. Furthermore, BNI has also been used to quantify and predict the outcome of epilepsy surgery based on FC extracted from pre-operative ictal intracranial electroencephalography (iEEG). This modeling framework is based on the assumption that the inferred FC provides an appropriate representation of an ictogenic network, i.e., a brain network responsible for the generation of seizures. However, FC networks have been shown to change their topology depending on the state of the brain. For example, topologies during seizure are different to those pre- and post-seizure. We therefore sought to understand how these changes affect BNI. We studied peri-ictal iEEG recordings from a cohort of 16 epilepsy patients who underwent surgery and found that, on average, ictal FC yield higher BNI relative to pre- and post-ictal FC. However, elevated ictal BNI was not observed in every individual, rather it was typically observed in those who had good post-operative seizure control. We therefore hypothesize that elevated ictal BNI is indicative of an ictogenic network being appropriately represented in the FC. We evidence this by demonstrating superior model predictions for post-operative seizure control in patients with elevated ictal BNI.
| S-EPMC5837986 | biostudies-literature
Project description:ObjectiveCurrent 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.ApproachInspired 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 resultsAlthough 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.SignificanceOur integrative study informs the development of modulation and control algorithms for neurostimulation that could improve the effectiveness of implantable, closed-loop anti-epileptic devices.
| S-EPMC8341467 | biostudies-literature
Project description:Automated seizure detection is a valuable asset to health professionals, which makes adequate treatment possible in order to minimize brain damage. Most research focuses on two separate aspects of automated seizure detection: EEG feature computation and classification methods. Little research has been published regarding optimal training dataset composition for patient-independent seizure detection. This paper evaluates the performance of classifiers trained on different datasets in order to determine the optimal dataset for use in classifier training for automated, age-independent, seizure detection. Three datasets are used to train a support vector machine (SVM) classifier: (1) EEG from neonatal patients, (2) EEG from adult patients and (3) EEG from both neonates and adults. To correct for baseline EEG feature differences among patients feature, normalization is essential. Usually dedicated detection systems are developed for either neonatal or adult patients. Normalization might allow for the development of a single seizure detection system for patients irrespective of their age. Two classifier versions are trained on all three datasets: one with feature normalization and one without. This gives us six different classifiers to evaluate using both the neonatal and adults test sets. As a performance measure, the area under the receiver operating characteristics curve (AUC) is used. With application of FBC, it resulted in performance values of 0.90 and 0.93 for neonatal and adult seizure detection, respectively. For neonatal seizure detection, the classifier trained on EEG from adult patients performed significantly worse compared to both the classifier trained on EEG data from neonatal patients and the classier trained on both neonatal and adult EEG data. For adult seizure detection, optimal performance was achieved by either the classifier trained on adult EEG data or the classifier trained on both neonatal and adult EEG data. Our results show that age-independent seizure detection is possible by training one classifier on EEG data from both neonatal and adult patients. Furthermore, our results indicate that for accurate age-independent seizure detection, it is important that EEG data from each age category are used for classifier training. This is particularly important for neonatal seizure detection. Our results underline the under-appreciated importance of training dataset composition with respect to accurate age-independent seizure detection.
| S-EPMC4958398 | biostudies-literature
Project description:The architecture of the human connectome changes with brain maturation. Pivotal to understanding these changes is defining developmental periods when transitions in network topology occur. Here, using 110 resting-state functional connectivity data sets from healthy fetuses between 19 and 40 gestational weeks, we estimated optimal gestational-age (GA) cut points for dichotomizing fetuses into 'young' and 'old' groups based on global network features. We computed the small-world index, normalized clustering and path length, global and local efficiency, and modularity from connectivity matrices comprised 200 regions and their corresponding pairwise connectivity. We modeled the effect of GA at scan on each metric using separate repeated-measures generalized estimating equations. Our modeling strategy involved stratifying fetuses into 'young' and 'old' based on the scan occurring before or after a selected GA (i.e., 28 to 33). We then used the quasi-likelihood independence criterion statistic to compare model fit between 'old' and 'young' cohorts and determine optimal cut points for each graph metric. Trends for all metrics, except for global efficiency, decreased with increasing gestational age. Optimal cut points fell within 30-31 weeks for all metrics coinciding with developmental events that include a shift from endogenous neuronal activity to sensory-driven cortical patterns.
| S-EPMC8304646 | biostudies-literature
Project description:BackgroundOptimality principles have been used to explain the structure and behavior of living matter at different levels of organization, from basic phenomena at the molecular level, up to complex dynamics in whole populations. Most of these studies have assumed a single-criteria approach. Such optimality principles have been justified from an evolutionary perspective. In the context of the cell, previous studies have shown how dynamics of gene expression in small metabolic models can be explained assuming that cells have developed optimal adaptation strategies. Most of these works have considered rather simplified representations, such as small linear pathways, or reduced networks with a single branching point, and a single objective for the optimality criteria.ResultsHere we consider the extension of this approach to more realistic scenarios, i.e. biochemical pathways of arbitrary size and structure. We first show that exploiting optimality principles for these networks poses great challenges due to the complexity of the associated optimal control problems. Second, in order to surmount such challenges, we present a computational framework which has been designed with scalability and efficiency in mind, including mechanisms to avoid the most common pitfalls. Third, we illustrate its performance with several case studies considering the central carbon metabolism of S. cerevisiae and B. subtilis. In particular, we consider metabolic dynamics during nutrient shift experiments.ConclusionsWe show how multi-objective optimal control can be used to predict temporal profiles of enzyme activation and metabolite concentrations in complex metabolic pathways. Further, we also show how to consider general cost/benefit trade-offs. In this study we have considered metabolic pathways, but this computational framework can also be applied to analyze the dynamics of other complex pathways, such as signal transduction or gene regulatory networks.
| S-EPMC7579911 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to investigate functional connectivity (FC) changes in epileptogenic networks in intractable partial epilepsy obtained from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel-based network measure of degree that reflects the number of connections to each voxel.MethodsWe measured differences between intrahemispheric- and interhemispheric-ICC (ICCintra-inter) that could reveal localized connectivity abnormalities in epileptogenic zones while more global network changes would be eliminated when subtracting these values. The ICCintra-inter map was compared with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in 29 patients with at least 1 year of postsurgical follow-up. Two independent reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates were compared for various clinical factors.ResultsConcordance between the icEEG SOZ and ICCintra-inter map was observed in 72.4% (21/29) of the patients, which was higher in patients with good surgical outcome, especially in those patients with temporal lobe epilepsy (TLE) or lateral temporal seizure localization. Concordance was also better in the extratemporal lobe epilepsy than the TLE group. In 85.7% (18/21) of the cases, the ICCintra-inter values were negative in the SOZ, indicating decreased FC within the epileptic hemisphere relative to between hemispheres.ConclusionsAssessing alterations in FC using fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive presurgical diagnostic tool to improve surgical outcome. In addition, the method reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC may be altered, in the presence of both regional as well as global network abnormalities.
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Project description:Predicting the movements, ground reaction forces and neuromuscular activity during gait can be a valuable asset to the clinical rehabilitation community, both to understand pathology, as well as to plan effective intervention. In this work we use an optimal control method to generate predictive simulations of pathological gait in the sagittal plane. We construct a patient-specific model corresponding to a 7-year old child with gait abnormalities and identify the optimal spring characteristics of an ankle-foot orthosis that minimizes muscle effort. Our simulations include the computation of foot-ground reaction forces, as well as the neuromuscular dynamics using computationally efficient muscle torque generators and excitation-activation equations. The optimal control problem (OCP) is solved with a direct multiple shooting method. The solution of this problem is physically consistent synthetic neural excitation commands, muscle activations and whole body motion. Our simulations produced similar changes to the gait characteristics as those recorded on the patient. The orthosis-equipped model was able to walk faster with more extended knees. Notably, our approach can be easily tuned to simulate weakened muscles, produces physiologically realistic ground reaction forces and smooth muscle activations and torques, and can be implemented on a standard workstation to produce results within a few hours. These results are an important contribution toward bridging the gap between research methods in computational neuromechanics and day-to-day clinical rehabilitation.
| S-EPMC5390028 | biostudies-literature
Project description:Localization of epileptogenic zone currently requires prolonged intracranial recordings to capture seizure, which may take days to weeks. The authors developed a novel method to identify the seizure onset zone (SOZ) and predict seizure outcome using short-time resting-state stereotacticelectroencephalography (SEEG) data. In a cohort of 27 drug-resistant epilepsy patients, the authors estimated the information flow via directional connectivity and inferred the excitation-inhibition ratio from the 1/f power slope. They hypothesized that the antagonism of information flow at multiple frequencies between SOZ and non-SOZ underlying the relatively stable epilepsy resting state could be related to the disrupted excitation-inhibition balance. They found flatter 1/f power slope in non-SOZ regions compared to the SOZ, with dominant information flow from non-SOZ to SOZ regions. Greater differences in resting-state information flow between SOZ and non-SOZ regions are associated with favorable seizure outcome. By integrating a balanced random forest model with resting-state connectivity, their method localized the SOZ with an accuracy of 88% and predicted the seizure outcome with an accuracy of 92% using clinically determined SOZ. Overall, this study suggests that brief resting-state SEEG data can significantly facilitate the identification of SOZ and may eventually predict seizure outcomes without requiring long-term ictal recordings.
| S-EPMC9218648 | biostudies-literature
Project description:Motivational influences on cognitive control play an important role in shaping human behavior. Cognitive facilitation through motivators such as prospective reward or punishment is thought to depend on regions from the dopaminergic mesocortical network, primarily the ventral tegmental area (VTA), inferior frontal junction (IFJ), and anterior cingulate cortex (ACC). However, how interactions between these regions relate to motivated control remains elusive. In the present functional magnetic resonance imaging study, we used dynamic causal modeling (DCM) to investigate effective connectivity between left IFJ, ACC, and VTA in a task-switching paradigm comprising three distinct motivational conditions (prospective monetary reward or punishment and a control condition). We found that while prospective punishment significantly facilitated switching between tasks on a behavioral level, interactions between IFJ, ACC, and VTA were characterized by modulations through prospective reward but not punishment. Our DCM results show that IFJ and VTA modulate ACC activity in parallel rather than by interaction to serve task demands in reward-based cognitive control. Our findings further demonstrate that prospective reward and punishment differentially affect neural control mechanisms to initiate decision-making.
| S-EPMC8410574 | biostudies-literature