Individualized time windows enhance TMS-EEG signal characterization and improve assessment of cortical function in schizophrenia.

Transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings are crucial to directly assess cortical excitability and inhibition in a non-invasive and task-free manner. TMS-EEG signals are characterized by TMS-evoked potentials (TEPs), which are employed to evaluate cortical function. Nonetheless, different time windows (TW) have been used to compute them over the years. Moreover, these TWs tend to be the same for all participants omitting the intersubject variability. Therefore, the objective of this study is to assess the effect of using different TWs to compute the TEPs, moving from a common fixed TW to more adaptive individualized TWs. Twenty-nine healthy (HC) controls and twenty schizophrenia patients (SCZ) underwent single-pulse (SP) TMS-EEG protocol. Firstly, only the HC were considered to evaluate the TEPs for three different TWs in terms of amplitude and topographical distribution. Secondly, the SCZ patients were included to determine which TW is better to characterize the brain alterations of SCZ. The results indicate that a more individualized TW provides a better characterization of the SP TMS-EEG signals, although all of them show the same tendency. Regarding the comparison between groups, the individualized TW is the one that provides a better differentiation between populations. They also provide further support to the possible imbalance of cortical excitability/inhibition in the SCZ population due to its reduced activity in the N45 TEP and greater amplitude values in the N100. Results also suggest that the SCZ brain has a baseline hyperactive state since the TEPs of the SCZ appear earlier than those of the HC.

A Dynamic Fitting Strategy for Physiological Models: A Case Study of a Cardiorespiratory Model for the Simulation of Incremental Aerobic Exercise.

Using mathematical models of physiological systems in medicine has allowed for the development of diagnostic, treatment, and medical educational tools. However, their complexity restricts, in most cases, their application for predictive, preventive, and personalized purposes. Although there are strategies that reduce the complexity of applying models based on fitting techniques, most of them are focused on a single instant of time, neglecting the effect of the system's temporal evolution. The objective of this research was to introduce a dynamic fitting strategy for physiological models with an extensive array of parameters and a constrained amount of experimental data. The proposed strategy focused on obtaining better predictions based on the temporal trends in the system's parameters and being capable of predicting future states. The study utilized a cardiorespiratory model as a case study. Experimental data from a longitudinal study of healthy adult subjects undergoing aerobic exercise were used for fitting and validation. The model predictions obtained in a steady state using the proposed strategy and the traditional single-fit approach were compared. The most successful outcomes were primarily linked to the proposed strategy, exhibiting better overall results regarding accuracy and behavior than the traditional population fitting approach at a single instant in time. The results evidenced the usefulness of the dynamic fitting strategy, highlighting its use for predictive, preventive, and personalized applications.

A Novel Strategy to Fit and Validate Physiological Models: A Case Study of a Cardiorespiratory Model for Simulation of Incremental Aerobic Exercise.

Applying complex mathematical models of physiological systems is challenging due to the large number of parameters. Identifying these parameters through experimentation is difficult, and although procedures for fitting and validating models are reported, no integrated strategy exists. Additionally, the complexity of optimization is generally neglected when the number of experimental observations is restricted, obtaining multiple solutions or results without physiological justification. This work proposes a fitting and validation strategy for physiological models with many parameters under various populations, stimuli, and experimental conditions. A cardiorespiratory system model is used as a case study, and the strategy, model, computational implementation, and data analysis are described. Using optimized parameter values, model simulations are compared to those obtained using nominal values, with experimental data as a reference. Overall, a reduction in prediction error is achieved compared to that reported for model building. Furthermore, the behavior and accuracy of all the predictions in the steady state were improved. The results validate the fitted model and provide evidence of the proposed strategy's usefulness.

Spinal Cord Injury Patients Exhibit Changes in Motor-Related Activity and Topographic Distribution.

Spinal Cord Injury (SCI) is a common disease that usually limits the patient's independence by affecting their motor function. SCI patients usually present neuroplasticity, which allows brain signals transmission through spread pathways. Some innovative rehabilitation therapies, such as functional electrical stimulation (FES) or Brain-computer interfaces (BCIs) jointly with motor neuroprostheses, provide hope for functional restoration. BCIs require the analysis of event-related EEG potentials (ERPs). Movement-related cortical potentials (MRCPs) and event-related desynchroni-zation and synchronization (ERD/ERS) are the most commonly studied ERPs during motor activity. ERPs of healthy subjects may vary from SCI patients. Thus, this study aimed to compare ERPs between healthy subjects and SCI patients during upper-limb movements (forearm supination and pronation, and hand open). Differences between controls and SCI patients were shown in terms of ERPs' amplitude as well as in topographic maps. Changes in amplitude were more substantial in ERD potentials than in MRCPs, while topographic maps showed better localization of all features in healthy patients. The level of SCI injury determines the patients' mobility. A comparison between complete, partial and no motor function subjects showed lower values of feature's amplitudes in the latter group.Clinical Relevance- This demonstrates the existence of significant statistical differences between healthy and SCI subjects, and might be helpful when performing SCI rehabilitation techniques such as designing BCI and neuroprostheses, or analyzing and understanding the brain plasticity process.

Influence of the number of trials on evoked motor cortical activity in EEG recordings.

Objective. Improvements in electroencephalography enable the study of the localization of active brain regions during motor tasks. Movement-related cortical potentials (MRCPs), and event-related desynchronization (ERD) and synchronization are the main motor-related cortical phenomena/neural correlates observed when a movement is elicited. When assessing neurological diseases, averaging techniques are commonly applied to characterize motor related processes better. In this case, a large number of trials is required to obtain a motor potential that is representative enough of the subject's condition. This study aimed to assess the effect of a limited number of trials on motor-related activity corresponding to different upper limb movements (elbow flexion/extension, pronation/supination and hand open/close).Approach. An open dataset consisting on 15 healthy subjects was used for the analysis. A Monte Carlo simulation approach was applied to analyse, in a robust way, different typical time- and frequency-domain features, topography, and low-resolution electromagnetic tomography.Main results. Grand average potentials, and topographic and tomographic maps showed few differences when using fewer trials, but shifts in the localization of motor-related activity were found for several individuals. MRCP and beta ERD features were more robust to a limited number of trials, yielding differences lower than 20% for cases with 50 trials or more. Strong correlations between features were obtained for subsets above 50 trials. However, the inter-subject variability increased as the number of trials decreased. The elbow flexion/extension movement showed a more robust performance for a limited number of trials, both in population and in individual-based analysis.Significance. Our findings suggested that 50 trials can be an appropriate number to obtain stable motor-related features in terms of differences in the averaged motor features, correlation, and changes in topography and tomography.

An Improved Dynamic Model for the Respiratory Response to Exercise.

Respiratory system modeling has been extensively studied in steady-state conditions to simulate sleep disorders, to predict its behavior under ventilatory diseases or stimuli and to simulate its interaction with mechanical ventilation. Nevertheless, the studies focused on the instantaneous response are limited, which restricts its application in clinical practice. The aim of this study is double: firstly, to analyze both dynamic and static responses of two known respiratory models under exercise stimuli by using an incremental exercise stimulus sequence (to analyze the model responses when step inputs are applied) and experimental data (to assess prediction capability of each model). Secondly, to propose changes in the models' structures to improve their transient and stationary responses. The versatility of the resulting model vs. the other two is shown according to the ability to simulate ventilatory stimuli, like exercise, with a proper regulation of the arterial blood gases, suitable constant times and a better adjustment to experimental data. The proposed model adjusts the breathing pattern every respiratory cycle using an optimization criterion based on minimization of work of breathing through regulation of respiratory frequency.

A synchronization system for the analysis of biomedical signals recorded with different devices from mechanically ventilated patients.

Conducting research associated with mechanically ventilated patients often requires the recording of several biomedical signals to dispose of multiple sources of information to perform a robust analysis. This is especially important in the analysis of the relationship between pressure, volume and flow, signals available from mechanical ventilators, and other biopotentials such as the electromyogram of respiratory muscles, intrinsically related with the ventilatory process, but not commonly recorded in the clinical practice. Despite the usefulness of recording signals from multiple sources, few medical devices include the possibility of synchronizing its data with other provided by different biomedical equipment and some may use inaccurate sampling frequencies. Even thought a variant or inaccurate sampling rate does not affect the monitoring of critical patients, it restricts the study of simultaneous related events useful in research of respiratory system activity. In this article a device for temporal synchronization of signals recorded from multiple biomedical devices is described as well as its application in the study of patients undergoing mechanical ventilation with research purposes.

Computational tool for modeling and simulation of mechanically ventilated patients.

The mechanical ventilator settings in patients with respiratory diseases like chronic obstructive pulmonary disease (COPD) during episodes of acute respiratory failure (ARF) is not a simple task that in most cases is successful based on the experience of physicians. This paper describes an interactive tool based in mathematical models, developed to make easier the study of the interaction between a mechanical ventilator and a patient. It describes all stages of system development, including simulated ventilatory modes, the pathologies of interest and interaction between the user and the system through a graphical interface developed in Matlab and Simulink. The developed computational tool allows the study of most widely used ventilatory modes and its advantages in the treatment of different kind of patients. The graphical interface displays all variables and parameters in the common way of last generation mechanical ventilators do and it is totally interactive, making possible its use by clinical personal, hiding the complexity of implemented mathematical models to the user. The evaluation in different clinical simulated scenes adjusts properly with recent findings in mechanical ventilation scientific literature.