Improvement of gait and balance function in chronic post-stroke patients induced by Lower Extremity - Constraint Induced Movement Therapy: a randomized controlled clinical trial.

OBJECTIVE: To evaluate the effects of Lower Extremity - Constraint Induced Movement Therapy on gait function and balance in chronic hemiparetic patients. METHODS: Randomized, controlled, single-blinded study. We recruited chronic post stroke patients and allocated them to Lower Extremity - Constraint Induced Movement Tharapy (LE-CIMT) or Control Group. The LE-CIMT group received this protocol 2.5 hour/day for 15 followed days, including: 1) intensive supervised training, 2) use of shaping as a strategy for motor training, and 3) application of a transfer package. The control group received conventional physiotherapy for 2.5 hours/day for 15 followed days. Outcomes were assessed at baseline, after the interventions, and after 6 months, through 6-minute walk test and Mini-Balance Evaluation Systems Test; 10-meter walk test, Timed Up and Go, 3-D gait analysis, and Lower Extremity - Motor Activity Log. RESULTS: LE-CIMT was superior on the Assistance and confidence subscale of Lower Extremity - Motor Activity Log, Mini-BESTest and 6-minute walk test. The effect size for all outcomes was small when comparing both groups. LE-CIMT showed clinically significant differences in daily activities, balance, and gait capacity, with no clinically significant difference for spatiotemporal parameters. CONCLUSION: The LE-CIMT protocol had positive outcomes on balance, performance, and confidence perception.

Epileptic seizure suppression: A computational approach for identification and control using real data.

Epilepsy affects millions of people worldwide every year and remains an open subject for research. Current development on this field has focused on obtaining computational models to better understand its triggering mechanisms, attain realistic descriptions and study seizure suppression. Controllers have been successfully applied to mitigate epileptiform activity in dynamic models written in state-space notation, whose applicability is, however, restricted to signatures that are accurately described by them. Alternatively, autoregressive modeling (AR), a typical data-driven tool related to system identification (SI), can be directly applied to signals to generate more realistic models, and since it is inherently convertible into state-space representation, it can thus be used for the artificial reconstruction and attenuation of seizures as well. Considering this, the first objective of this work is to propose an SI approach using AR models to describe real epileptiform activity. The second objective is to provide a strategy for reconstructing and mitigating such activity artificially, considering non-hybrid and hybrid controllers - designed from ictal and interictal events, respectively. The results show that AR models of relatively low order represent epileptiform activities fairly well and both controllers are effective in attenuating the undesired activity while simultaneously driving the signal to an interictal condition. These findings may lead to customized models based on each signal, brain region or patient, from which it is possible to better define shape, frequency and duration of external stimuli that are necessary to attenuate seizures.

Stepwise options for preparing therapeutic plasma proteins from domestic plasma in low- and middle-income countries.

Industrial plasma fractionation, a complex and highly regulated technology, remains largely inaccessible to many low- and middle-income countries (LMICs). This, combined with the limited availability and high cost of plasma-derived medicinal products (PDMPs), creates deficiency of access to adequate treatment for patients in resource-limited countries, and leads to their suffering. Meanwhile, an increasing number of LMICs produce surplus plasma, as a by-product of red blood cell preparation from whole blood, that is discarded because of the lack of suitability for fractionation. This article reviews pragmatic technological options for processing plasma collected from LMICs into therapies and supports a realistic stepwise approach aligned with recent World Health Organization guidance and initiatives launched by the Working Party for Global Blood Safety of the International Society of Blood Transfusion. When industrial options based on contract or toll plasma fractionation programme and, even more, domestic fractionation facilities require larger volumes of quality plasma than is produced, alternative methods should be considered. In-bag minipool or small-scale production procedures implementable in blood establishments or national service centres are the only realistic options available to gradually reduce plasma wastage, provide safer treatments for patients currently treated with non-pathogen-reduced blood products and concurrently improve Good Manufacturing Practice (GMP) levels with minimum capital investment. As a next step, when the available volume of quality-assured plasma reaches the necessary thresholds, LMICs could consider engaging with an established fractionator in a fractionation agreement or a contract in support of a domestic fractionation facility to improve the domestic PDMP supply and patients' treatment.

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model.

Introduction: The paraventricular nucleus of the hypothalamus (PVN) contains premotor neurons involved in the control of sympathetic vasomotor activity. It is known that the stimulation of specific areas of the PVN can lead to distinct response patterns at different target territories. The underlying mechanisms, however, are still unclear. Recent evidence from sympathetic nerve recording suggests that relevant information is coded in the power distribution of the signal along the frequency range. In the present study, we addressed the hypothesis that the PVN is capable of organizing specific spectral patterns of sympathetic vasomotor activation to distinct territories in both normal and hypertensive animals. Methods: To test it, we investigated the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), before and after disinhibition of the PVN by bicuculline microinjection. Subjects were control and Goldblatt rats, a sympathetic overactivity-characterized model of neurogenic hypertension (2K1C). Additionally, considering the importance of angiotensin II type 1 receptors (AT1) in the sympathetic responses triggered by bicuculline in the PVN, we also investigated the impact of angiotensin AT1 receptors blockade in the spectral features of the rSNA and sSNA activity. Results: The results revealed that each nerve activity (renal and splanchnic) presents its own electrophysiological pattern of frequency-coded rhythm in each group (control, 2K1C, and 2K1C treated with AT1 antagonist losartan) in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the losartan 2K1C treated group showed no decrease in the hypertensive response triggered by bicuculline when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups (control and 2K1C), suggesting that the blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic responses nor the electrophysiological patterns in Goldblatt rats, but act on their spectral frequency distribution. Discussion: The results suggest that the differential responses evoked by the PVN were preferentially coded in frequency, but not in the global power of the vasomotor sympathetic responses, indicating that the PVN is able to independently control the frequency and the power of sympathetic discharges to different territories.

Human-machine interface for two-dimensional steering control with the auricular muscles.

Human-machine interfaces (HMIs) can be used to decode a user's motor intention to control an external device. People that suffer from motor disabilities, such as spinal cord injury, can benefit from the uses of these interfaces. While many solutions can be found in this direction, there is still room for improvement both from a decoding, hardware, and subject-motor learning perspective. Here we show, in a series of experiments with non-disabled participants, a novel decoding and training paradigm allowing naïve participants to use their auricular muscles (AM) to control two degrees of freedom with a virtual cursor. AMs are particularly interesting because they are vestigial muscles and are often preserved after neurological diseases. Our method relies on the use of surface electromyographic records and the use of contraction levels of both AMs to modulate the velocity and direction of a cursor in a two-dimensional paradigm. We used a locking mechanism to fix the current position of each axis separately to enable the user to stop the cursor at a certain location. A five-session training procedure (20-30 min per session) with a 2D center-out task was performed by five volunteers. All participants increased their success rate (Initial: 52.78 ± 5.56%; Final: 72.22 ± 6.67%; median ± median absolute deviation) and their trajectory performances throughout the training. We implemented a dual task with visual distractors to assess the mental challenge of controlling while executing another task; our results suggest that the participants could perform the task in cognitively demanding conditions (success rate of 66.67 ± 5.56%). Finally, using the Nasa Task Load Index questionnaire, we found that participants reported lower mental demand and effort in the last two sessions. To summarize, all subjects could learn to control the movement of a cursor with two degrees of freedom using their AM, with a low impact on the cognitive load. Our study is a first step in developing AM-based decoders for HMIs for people with motor disabilities, such as spinal cord injury.

Toward the Identification of Neurophysiological Biomarkers for Alzheimer's Disease in Down Syndrome: A Potential Role for Cross-Frequency Phase-Amplitude Coupling Analysis.

Cross-frequency coupling (CFC) mechanisms play a central role in brain activity. Pathophysiological mechanisms leading to many brain disorders, such as Alzheimer's disease (AD), may produce unique patterns of brain activity detectable by electroencephalography (EEG). Identifying biomarkers for AD diagnosis is also an ambition among research teams working in Down syndrome (DS), given the increased susceptibility of people with DS to develop early-onset AD (DS-AD). Here, we review accumulating evidence that altered theta-gamma phase-amplitude coupling (PAC) may be one of the earliest EEG signatures of AD, and therefore may serve as an adjuvant tool for detecting cognitive decline in DS-AD. We suggest that this field of research could potentially provide clues to the biophysical mechanisms underlying cognitive dysfunction in DS-AD and generate opportunities for identifying EEG-based biomarkers with diagnostic and prognostic utility in DS-AD.

Rehabilitation of People With Chronic Spinal Cord Injury Using a Laparoscopically Implanted Neurostimulator: Impact on Mobility and Urinary, Anorectal, and Sexual Functions.

OBJECTIVES: This study aimed to assess the impact of the laparoscopic implantation of neuromodulation electrodes (Possover-LION procedure) on mobility and on sexual, urinary, and anorectal functions of people with chronic spinal cord injury (SCI). MATERIAL AND METHODS: Longitudinal analysis of 30 patients with chronic SCI (21 ASIA impairment scale (AIS) A, eight AIS B, and one AIS C) submitted to the Possover-LION procedure for bilateral neuromodulation of femoral, sciatic, and pudendal nerves. Assessments were performed before the surgical procedure and at 3, 6, and 12 months postoperatively. The primary outcome was evolution in walking, measured by the Walking Index for Spinal Cord Injury score, preoperatively and at 12 months. Secondary outcomes were changes in overall mobility (Mobility Assessment Tool for Evaluation of Rehabilitation score), urinary function and quality of life (Qualiveen questionnaire), and bowel (time for bowel emptying proceedings and Wexner's Fecal Incontinence Severity Index [FISI]) and sexual functions (International Index of Erectile Function for men and Female Sexual Function Index for women). Surgical time, intraoperative bleeding, and perioperative complications were also recorded. RESULTS: Qualitatively, 18 of 25 (72%) patients with thoracic injury and 3 of 5 (60%) patients with cervical injury managed to establish a walker-assisted gait at one-year follow-up (p < 0.0001). A total of 11 (47.8%) have improved in their urinary incontinence (p < 0.0001), and seven (30.4%) improved their enuresis (p = 0.0156). The FISI improved from a median of 9 points preoperatively to 5.5 at 12 months (p = 0.0056). Of note, 20 of 28 (71.4%) patients reported an improvement on genital sensitivity at 12 months postoperatively (p < 0.0001), but this was not reflected in sexual quality-of-life questionnaires. CONCLUSIONS: Patients experienced improved mobility and genital sensitivity and a reduction in the number of urinary and fecal incontinence episodes. By demonstrating reproducible outcomes and safety, this study helps establish the Possover-LION procedure as an addition to the therapeutic armamentarium for the rehabilitation of patients with chronic SCI. CLINICAL TRIAL REGISTRATION: This study was registered at the WHO Clinical Trials Database through the Brazilian Registry of Clinical Trials-REBEC (Universal Tracking Number: U1111-1261-4428).

Rationale for supporting stepwise access to safe plasma proteins through local production in low- and middle-income countries: A commentary of an international workshop.

This document provides a commentary and further elaboration on the conclusions reached during a recent international workshop on plasma protein therapies organized by the Working Party for Global Safety of the International Society of Blood Transfusion (ISBT). The workshop addressed the profound deficiency in access to safe plasma protein therapies that persists in low- and middle-income countries (LMICs). We provide additional factual economic and technological information that highlights why local production of small-scale virus-inactivated concentrates of clotting factors and immune globulins from domestic recovered plasma through stepwise introduction of available validated technologies is a pragmatic approach to gradually improve the care of patients with bleeding disorders and immune deficiencies in LMIC while supporting progress toward fractionation of plasma. This strategy is in line with a recent WHO guidance. We stress that the active involvement of international blood donor and blood transfusion organizations, patient organizations, governments and industry will be essential in supporting stepwise and sustainable improvements in access to safe, effective, and quality assured plasma protein therapies.

Embodiment of a virtual prosthesis through training using an EMG-based human-machine interface: Case series.

Therapeutic strategies capable of inducing and enhancing prosthesis embodiment are a key point for better adaptation to and acceptance of prosthetic limbs. In this study, we developed a training protocol using an EMG-based human-machine interface (HMI) that was applied in the preprosthetic rehabilitation phase of people with amputation. This is a case series with the objective of evaluating the induction and enhancement of the embodiment of a virtual prosthesis. Six men and a woman with unilateral transfemoral traumatic amputation without previous use of prostheses participated in the study. Participants performed a training protocol with the EMG-based HMI, composed of six sessions held twice a week, each lasting 30 mins. This system consisted of myoelectric control of the movements of a virtual prosthesis immersed in a 3D virtual environment. Additionally, vibrotactile stimuli were provided on the participant's back corresponding to the movements performed. Embodiment was investigated from the following set of measurements: skin conductance response (affective measurement), crossmodal congruency effect (spatial perception measurement), ability to control the virtual prosthesis (motor measurement), and reports before and after the training. The increase in the skin conductance response in conditions where the virtual prosthesis was threatened, recalibration of the peripersonal space perception identified by the crossmodal congruency effect, ability to control the virtual prosthesis, and participant reports consistently showed the induction and enhancement of virtual prosthesis embodiment. Therefore, this protocol using EMG-based HMI was shown to be a viable option to achieve and enhance the embodiment of a virtual prosthetic limb.

The Intersection Between the Oculomotor Nerve and the Internal Carotid Artery to Distinguish Extracavernous and Intracavernous Paraclinoid Aneurysms Using Anatomic Dissections-A New 3T Magnetic Resonance Imaging Protocol Confirmed by Three-Dimensionally Printed Biomodels.

OBJECTIVE: To evaluate the relationship between the oculomotor nerve (CNIII) and the internal carotid artery (ICA) as a new anatomic-radiologic landmark for distinguishing the exact location of a paraclinoid intracranial aneurysm (IA). METHODS: Microanatomic dissections were performed in 20 cavernous sinuses to evaluate the ICA paraclinoid region. Based on anatomic observations, a new magnetic resonance (MRI) protocol to classify paraclinoid aneurysms was proposed. MRI of 42 IAs from 34 patients was independently analyzed and classified as intracavernous, extracavernous, or transitional by 2 neuroradiologists. To validate the proposed MRI protocol, each IA was classified by a three-dimensionally (3D) printed biomodel and agreement with the radiologic classifications was evaluated. Of 42 IAs, 23 undergoing microsurgeries were also classified by direct visualization. RESULTS: We observed that the true cavernous sinus roof is defined by the carotid-oculomotor membrane, which has an intimate relationship with the intersection between the superior limit of the CNIII and the ICA. Based on this intersection, all 42 IAs were radiologically classified and agreement with the 3D printed biomodels was observed in 95% IAs. Concordance tests showed a statistically significant (P < 0.05) agreement between the classifications. All 23 IAs treated had the radiologic and 3D biomodel classification confirmed. CONCLUSIONS: The intersection between the ICA and the CNIII, which crosses it transversely in its entire diameter, is a reliable anatomic-radiologic landmark to correctly classify paraclinoid aneurysms. Through a new MRI protocol, it is possible to radiologically identify this intersection and to easily distinguish the intracavernous and extracavernous ICA paraclinoid aneurysms.

Self-organization of in vitro neuronal assemblies drives to complex network topology.

Activity-dependent self-organization plays an important role in the formation of specific and stereotyped connectivity patterns in neural circuits. By combining neuronal cultures, and tools with approaches from network neuroscience and information theory, we can study how complex network topology emerges from local neuronal interactions. We constructed effective connectivity networks using a transfer entropy analysis of spike trains recorded from rat embryo dissociated hippocampal neuron cultures between 6 and 35 days in vitro to investigate how the topology evolves during maturation. The methodology for constructing the networks considered the synapse delay and addressed the influence of firing rate and population bursts as well as spurious effects on the inference of connections. We found that the number of links in the networks grew over the course of development, shifting from a segregated to a more integrated architecture. As part of this progression, three significant aspects of complex network topology emerged. In agreement with previous in silico and in vitro studies, a small-world architecture was detected, largely due to strong clustering among neurons. Additionally, the networks developed in a modular topology, with most modules comprising nearby neurons. Finally, highly active neurons acquired topological characteristics that made them important nodes to the network and integrators of modules. These findings leverage new insights into how neuronal effective network topology relates to neuronal assembly self-organization mechanisms.

Chaotic and stochastic dynamics of epileptiform-like activities in sclerotic hippocampus resected from patients with pharmacoresistant epilepsy.

The types of epileptiform activity occurring in the sclerotic hippocampus with highest incidence are interictal-like events (II) and periodic ictal spiking (PIS). These activities are classified according to their event rates, but it is still unclear if these rate differences are consequences of underlying physiological mechanisms. Identifying new and more specific information related to these two activities may bring insights to a better understanding about the epileptogenic process and new diagnosis. We applied Poincaré map analysis and Recurrence Quantification Analysis (RQA) onto 35 in vitro electrophysiological signals recorded from slices of 12 hippocampal tissues surgically resected from patients with pharmacoresistant temporal lobe epilepsy. These analyzes showed that the II activity is related to chaotic dynamics, whereas the PIS activity is related to deterministic periodic dynamics. Additionally, it indicates that their different rates are consequence of different endogenous dynamics. Finally, by using two computational models we were able to simulate the transition between II and PIS activities. The RQA was applied to different periods of these simulations to compare the recurrences between artificial and real signals, showing that different ranges of regularity-chaoticity can be directly associated with the generation of PIS and II activities.

Estimating the Parameters of the Epileptor Model for Epileptic Seizure Suppression.

Epilepsy is one of the most common brain disorders worldwide, affecting millions of people every year. Given the partially successful existing treatments for epileptiform activity suppression, dynamic mathematical models have been proposed with the purpose of better understanding the factors that might trigger an epileptic seizure and how to mitigate it, among which Epileptor stands out, due to its relative simplicity and consistency with experimental observations. Recent studies using this model have provided evidence that establishing a feedback-based control approach is possible. However, for this strategy to work properly, Epileptor's parameters, which describe the dynamic characteristics of a seizure, must be known beforehand. Therefore, this work proposes a methodology for estimating such parameters based on a successive optimization technique. The results show that it is feasible to approximate their values as they converge to reference values based on different initial conditions, which are modeled by an uncertainty factor or noise addition. Also, interictal (healthy) and ictal (ongoing seizure) conditions, as well as time resolution, must be taken into account for an appropriate estimation. At last, integrating such a parameter estimation approach with observers and controllers for purposes of seizure suppression is carried out, which might provide an interesting alternative for seizure suppression in practice in the future.

Stepwise access to safe plasma proteins in resource-constrained countries: Local production and pathways to fractionation-Report of an International Society of Blood Transfusion Workshop.

BACKGROUND AND OBJECTIVES: Actions are needed to improve access to safe plasma-derived medicinal products (PDMPs) in low- and middle-income countries (LMICs). MATERIALS AND METHODS: The International Society of Blood Transfusion (ISBT) Working Party for Global Blood Safety organized an on-line workshop during 21-23 September 2021 to advance access to safe plasma proteins in resource-constrained countries, consistent with recent World Health Organization (WHO) guidance documents. RESULTS: The meeting drew attention to the considerable unmet needs for access to essential PDMPs in LMICs, in particular coagulation factors and immunoglobulins, and stepwise actions to address these deficits. First, improved access to safe plasma protein therapies requires blood component separation with prevention of wastage of recovered plasma. Quality and safety of collected blood and plasma must be assured so that plasma in excess of transfusion needs can be processed into safe plasma proteins. Second, local production of safe plasma proteins can be implemented using available technologies to locally obtain pathogen-reduced plasma and prepare pathogen-reduced cryoprecipitate and immunoglobulins from small plasma pools. Third, when a sufficient, stable volume of quality-assured plasma is available (approximately 50,000 L/year), contract or toll fractionation by a foreign plasma fractionator can expand the supply of PDMPs. Fourth, when the national infrastructure supports high-technology industrial production and stable volumes of quality plasma reach at least 200,000 L/year, technology transfer for domestic fractionation can be considered. CONCLUSION: Action is needed including commitments of the organizations that made the workshop possible (WHO, ISBT, World Federation of Haemophilia [WFH], Plasma Protein Therapeutics Association [PPTA], International Plasma Fractionation Association [IPFA], International Patient Organization of Primary Immunodeficiencies [IPOPI] and International Federation of Blood Donor Organizations [FIODS]).

Partial protective effects of cannabidiol against PTZ-induced acute seizures in female rats during the proestrus-estrus transition.

Approximately 70% of women with epilepsy experience additional challenges in seizure exacerbation due to hormonal changes, particularly during fluctuations of estrogen-progesterone levels in the menstrual cycle, which is known as catamenial epilepsy. In animal models of epilepsy, a sustained increase in seizure frequency has been observed in female rats during the proestrus-estrus transition when estrogen levels are high and progesterone levels are low resembling catamenial epilepsy. Cannabidiol (CBD) has been proposed to have anticonvulsant and anti-inflammatory effects, able to decrease seizure duration and increase seizure threshold in rats with epilepsy. However, most studies have used males to investigate the pharmacological effects of CBD on seizures, and the neuroprotective effects of CBD against seizures exacerbated by hormonal fluctuations in females are still little explored. Given this scenario, the aim of the present study was to investigate whether CBD would protect against acute seizures induced by pentylenetetrazole (PTZ) in female rats during a pro-convulsant hormonal phase. Therefore, CBD (50 mg/kg) or saline was administered during the proestrus-estrus transition phase, 1 h prior to induction of seizures with PTZ (60 mg/kg), and the following parameters were recorded: duration, latency to first seizure, as well as percentage of convulsing animals (incidence), mortality, and severity of seizures. Brains were processed for immunohistochemistry for microglial cells (Iba-1), and blood was collected for the analysis of cytokines (IL-1ß, IL-6, IL-10, and TNF-α). Cannabidiol pre-treated rats showed a significant reduction in duration and severity of seizures, and IL-1ß levels, although the latency, incidence of seizures, and mortality rate remained unchanged as well the quantification of microglia in the selected areas. Therefore, acute administration of CBD in a single dose prior to seizure induction showed a partial neuroprotective effect against seizure severity and inflammation, suggesting that female rats in the proconvulsant phase of proestrus-estrus have a low seizure threshold and are more resistant to the anticonvulsant effects of CBD. It appears that other doses or administration windows of CBD may be required to achieve a full protective effect against seizures, suggesting that CBD could be used as an adjunctive therapy during fluctuations of estrogen-progesterone levels. In this sense, considering the hormonal fluctuation as a seizure-potentiating factor, our study contributes to understand the anticonvulsant activity of CBD in females in a pro-convulsant hormonal phase, similar to catamenial seizures in humans.

The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies.

Background: Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility. Methods: We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, ex vivo studies, in vitro studies, studies in humans, or in silico studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis. Results: Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, n = 6 and intensity of motor signals, n = 3) and electrophysiological analysis (spikes/min, n = 4, and amplitude, n = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was -130.98 [95% CI: -203.47, -58.49] (seconds) and the intensity of motor signals was -0.40 [95% CI: -1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with -26.96 [95% CI: -39.56, -14.36], and for spike amplitude (µV) with -282.64 [95% CI: -466.81, -98.47]. Discussion: Limitations of evidence. A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. Interpretation. Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (µV)] induced by the administration of different chemoconvulsants. Systematic Review Registration: PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.

Cardiac and Autonomic Dysfunctions Assessed Through Recurrence Quantitative Analysis of Electrocardiogram Signals and an Application to the 6-Hydroxydopamine Parkinson's Disease Animal Model.

A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as Standard Deviation of n-n intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. In this proof-of-concept study we propose the use of Poincaré mapping and Recurrence Quantification Analysis (RQA) to identify and characterize stochasticity and chaoticity dynamics in ECG recordings. By applying these non-linear techniques in the ECG signals recorded from a set of Parkinson's disease (PD) animal model 6-hydroxydopamine (6-OHDA), we showed that they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results suggest that PD animal models present more "rigid heart rate" associated with "trembling ECG" and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating the main ECG features of atrial fibrillation and QT-long syndrome.

Burster Reconstruction Considering Unmeasurable Variables in the Epileptor Model.

Epilepsy is one of the most common brain disorders worldwide, affecting millions of people every year. Although significant effort has been put into better understanding it and mitigating its effects, the conventional treatments are not fully effective. Advances in computational neuroscience, using mathematical dynamic models that represent brain activities at different scales, have enabled addressing epilepsy from a more theoretical standpoint. In particular, the recently proposed Epileptor model stands out among these models, because it represents well the main features of seizures, and the results from its simulations have been consistent with experimental observations. In addition, there has been an increasing interest in designing control techniques for Epileptor that might lead to possible realistic feedback controllers in the future. However, such approaches rely on knowing all of the states of the model, which is not the case in practice. The work explored in this letter aims to develop a state observer to estimate Epileptor's unmeasurable variables, as well as reconstruct the respective so-called bursters. Furthermore, an alternative modeling is presented for enhancing the convergence speed of an observer. The results show that the proposed approach is efficient under two main conditions: when the brain is undergoing a seizure and when a transition from the healthy to the epileptiform activity occurs.