Non-Invasive Recording of Ocular-Following Responses in Children: A Promising Tool for Stereo Deficiency Evaluation.

Background: The ability to merge the two retinal images to perceive depth (stereopsis) plays an important role in human vision. Its proper development requires binocular alignment and good visual acuity in both eyes during childhood. Because treatments are more effective when applied early, early diagnosis is important. Unfortunately, assessing stereo deficiencies in infants and young children remains challenging. Recently, it has been shown that ocular-following responses (OFRs; reflexive, short-latency eye movements induced by the sudden motion of a large textured pattern) are sensitive to changes in interocular correlation, making them potentially useful for stereo deficiency assessments. To test this hypothesis, we measured OFRs elicited by dichoptic stimulation in children with normal and compromised stereopsis (due to amblyopia). Methods: Two groups of six children (age- and sex-matched: 3M/3F aged 7-12 yo), one with compromised stereopsis and one with normal stereopsis, were included. OFRs were recorded using a custom high-resolution video eye-tracking system. The relative differences between eye displacement induced by correlated stimuli (up-correlated-down-correlated) and anticorrelated (up-anticorrelated-down-anticorrelated) were compared. Results: We found significant differences between OFRs induced by two dichoptic conditions (correlated and anticorrelated stimuli) in most children with normal stereopsis, whereas no differences were observed in children with compromised stereopsis, indicating a lack of disparity detectors. Conclusions: OFRs might thus be exploited as a diagnostic tool for the objective identification of stereo deficiencies in children. This might lead to improved early diagnosis and treatment outcomes for conditions like amblyopia and strabismus.

Neuromuscular assessment of force development, postural, and gait performance under cognitive-motor dual-tasking in healthy older adults and people with early Parkinson's disease: Study protocol for a cross-sectional Mobile Brain/Body Imaging (MoBI) study.

Background: Neuromuscular dysfunction is common in older adults and more pronounced in neurodegenerative diseases. In Parkinson's disease (PD), a complex set of factors often prevents the effective performance of activities of daily living that require intact and simultaneous performance of the motor and cognitive tasks. Methods: The cross-sectional study includes a multifactorial mixed-measure design. Between-subject factor grouping the sample will be Parkinson's Disease (early PD vs. healthy). The within-subject factors will be the task complexity (single- vs. dual-task) in each motor activity, i.e., overground walking, semi-tandem stance, and isometric knee extension, and a walking condition (wide vs. narrow lane) will be implemented for the overground walking activity only. To study dual-task (DT) effects, in each motor activity participants will be given a secondary cognitive task, i.e., a visual discrimination task for the overground walking, an attention task for the semi-tandem, and mental arithmetic for the isometric extension. Analyses of DT effects and underlying neuronal correlates will focus on both gait and cognitive performance where applicable. Based on an a priori sample size calculation, a total N = 42 older adults (55-75 years) will be recruited. Disease-specific changes such as laterality in motor unit behavior and cortical control of movement will be studied with high-density surface electromyography and electroencephalography during static and dynamic motor activities, together with whole-body kinematics. Discussion: This study will be one of the first to holistically address early PD neurophysiological and neuromuscular patterns in an ecologically valid environment under cognitive-motor DT conditions of different complexities. The outcomes of the study aim to identify the biomarker for early PD either at the electrophysiological, muscular or kinematic level or in the communication between these systems. Clinical Trial Registration: ClinicalTrials.Gov, NCT05477654. This study was approved by the Medical Ethical Committee (106/2021).

Sleep Spindle-Related EEG Connectivity in Children with Attention-Deficit/Hyperactivity Disorder: An Exploratory Study.

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder with known brain abnormalities but no biomarkers to support clinical diagnosis. Recently, EEG analysis methods such as functional connectivity have rekindled interest in using EEG for ADHD diagnosis. Most studies have focused on resting-state EEG, while connectivity during sleep and spindle activity has been underexplored. Here we present the results of a preliminary study exploring spindle-related connectivity as a possible biomarker for ADHD. We compared sensor-space connectivity parameters in eight children with ADHD and nine age/sex-matched healthy controls during sleep, before, during, and after spindle activity in various frequency bands. All connectivity parameters were significantly different between the two groups in the delta and gamma bands, and Principal Component Analysis (PCA) in the gamma band distinguished ADHD from healthy subjects. Cluster coefficient and path length values in the sigma band were also significantly different between epochs, indicating different spindle-related brain activity in ADHD.

Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI.

Cognitive impairment is one of the most prevalent symptoms of post Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) state, which is known as Long COVID. Advanced neuroimaging techniques may contribute to a better understanding of the pathophysiological brain changes and the underlying mechanisms in post-COVID-19 subjects. We aimed at investigating regional cerebral perfusion alterations in post-COVID-19 subjects who reported a subjective cognitive impairment after a mild SARS-CoV-2 infection, using a non-invasive Arterial Spin Labeling (ASL) MRI technique and analysis. Using MRI-ASL image processing, we investigated the brain perfusion alterations in 24 patients (53.0 ± 14.5 years, 15F/9M) with persistent cognitive complaints in the post COVID-19 period. Voxelwise and region-of-interest analyses were performed to identify statistically significant differences in cerebral blood flow (CBF) maps between post-COVID-19 patients, and age and sex matched healthy controls (54.8 ± 9.1 years, 13F/9M). The results showed a significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, as identified by a non-parametric permutation testing (p < 0.05, FWE-corrected with TFCE). The hypoperfusion areas identified in the right hemisphere regions were more extensive. These findings support the hypothesis of a large network dysfunction in post-COVID subjects with cognitive complaints. The non-invasive nature of the ASL-MRI method may play an important role in the monitoring and prognosis of post-COVID-19 subjects.

Stroop in motion: Neurodynamic modulation underlying interference control while sitting, standing, and walking.

There is conflicting evidence about how interference control in healthy adults is affected by walking as compared to standing or sitting. Although the Stroop paradigm is one of the best-studied paradigms to investigate interference control, the neurodynamics associated with the Stroop task during walking have never been studied. We investigated three Stroop tasks using variants with increasing interference levels - word-reading, ink-naming, and the switching of the two tasks, combined in a systematic dual-tasking fashion with three motor conditions - sitting, standing, and treadmill walking. Neurodynamics underlying interference control were recorded using the electroencephalogram. Worsened performance was observed for the incongruent compared to congruent trials and for the switching Stroop compared to the other two variants. The early frontocentral event-related potentials (ERPs) associated with executive functions (P2, N2) differentially signaled posture-related workloads, while the later stages of information processing indexed faster interference suppression and response selection in walking compared to static conditions. The early P2 and N2 components as well as frontocentral Theta and parietal Alpha power were sensitive to increasing workloads on the motor and cognitive systems. The distinction between the type of load (motor and cognitive) became evident only in the later posterior ERP components in which the amplitude non-uniformly reflected the relative attentional demand of a task. Our data suggest that walking might facilitate selective attention and interference control in healthy adults. Existing interpretations of ERP components recorded in stationary settings should be considered with care as they might not be directly transferable to mobile settings.

On the Influence of Aging on Classification Performance in the Visual EEG Oddball Paradigm Using Statistical and Temporal Features.

The utilization of a non-invasive electroencephalogram (EEG) as an input sensor is a common approach in the field of the brain-computer interfaces (BCI). However, the collected EEG data pose many challenges, one of which may be the age-related variability of event-related potentials (ERPs), which are often used as primary EEG BCI signal features. To assess the potential effects of aging, a sample of 27 young and 43 older healthy individuals participated in a visual oddball study, in which they passively viewed frequent stimuli among randomly occurring rare stimuli while being recorded with a 32-channel EEG set. Two types of EEG datasets were created to train the classifiers, one consisting of amplitude and spectral features in time and another with extracted time-independent statistical ERP features. Among the nine classifiers tested, linear classifiers performed best. Furthermore, we show that classification performance differs between dataset types. When temporal features were used, maximum individuals' performance scores were higher, had lower variance, and were less affected overall by within-class differences such as age. Finally, we found that the effect of aging on classification performance depends on the classifier and its internal feature ranking. Accordingly, performance will differ if the model favors features with large within-class differences. With this in mind, care must be taken in feature extraction and selection to find the correct features and consequently avoid potential age-related performance degradation in practice.

Ocular-following responses in school-age children.

Ocular following eye movements have provided insights into how the visual system of humans and monkeys processes motion. Recently, it has been shown that they also reliably reveal stereoanomalies, and, thus, might have clinical applications. Their translation from research to clinical setting has however been hindered by their small size, which makes them difficult to record, and by a lack of data about their properties in sizable populations. Notably, they have so far only been recorded in adults. We recorded ocular following responses (OFRs)-defined as the change in eye position in the 80-160 ms time window following the motion onset of a large textured stimulus-in 14 school-age children (6 to 13 years old, 9 males and 5 females), under recording conditions that closely mimic a clinical setting. The OFRs were acquired non-invasively by a custom developed high-resolution video-oculography system, described in this study. With the developed system we were able to non-invasively detect OFRs in all children in short recording sessions. Across subjects, we observed a large variability in the magnitude of the movements (by a factor of 4); OFR magnitude was however not correlated with age. A power analysis indicates that even considerably smaller movements could be detected. We conclude that the ocular following system is well developed by age six, and OFRs can be recorded non-invasively in young children in a clinical setting.

A data-driven machine learning approach for brain-computer interfaces targeting lower limb neuroprosthetics.

Prosthetic devices that replace a lost limb have become increasingly performant in recent years. Recent advances in both software and hardware allow for the decoding of electroencephalogram (EEG) signals to improve the control of active prostheses with brain-computer interfaces (BCI). Most BCI research is focused on the upper body. Although BCI research for the lower extremities has increased in recent years, there are still gaps in our knowledge of the neural patterns associated with lower limb movement. Therefore, the main objective of this study is to show the feasibility of decoding lower limb movements from EEG data recordings. The second aim is to investigate whether well-known neuroplastic adaptations in individuals with an amputation have an influence on decoding performance. To address this, we collected data from multiple individuals with lower limb amputation and a matched able-bodied control group. Using these data, we trained and evaluated common BCI methods that have already been proven effective for upper limb BCI. With an average test decoding accuracy of 84% for both groups, our results show that it is possible to discriminate different lower extremity movements using EEG data with good accuracy. There are no significant differences (p = 0.99) in the decoding performance of these movements between healthy subjects and subjects with lower extremity amputation. These results show the feasibility of using BCI for lower limb prosthesis control and indicate that decoding performance is not influenced by neuroplasticity-induced differences between the two groups.

Toward a diagnostic CART model for Ischemic heart disease and idiopathic dilated cardiomyopathy based on heart rate total variability.

Diagnosis of etiology in early-stage ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) patients may be challenging. We aimed at investigating, by means of classification and regression tree (CART) modeling, the predictive power of heart rate variability (HRV) features together with clinical parameters to support the diagnosis in the early stage of IHD and DCM. The study included 263 IHD and 181 DCM patients, as well as 689 healthy subjects. A 24 h Holter monitoring was used and linear and non-linear HRV parameters were extracted considering both normal and ectopic beats (heart rate total variability signal). We used a CART algorithm to produce classification models based on HRV together with relevant clinical (age, sex, and left ventricular ejection fraction, LVEF) features. Among HRV parameters, MeanRR, SDNN, pNN50, LF, LF/HF, LFn, FD, Beta exp were selected by the CART algorithm and included in the produced models. The model based on pNN50, FD, sex, age, and LVEF features presented the highest accuracy (73.3%). The proposed approach based on HRV parameters, age, sex, and LVEF features highlighted the possibility to produce clinically interpretable models capable to differentiate IHD, DCM, and healthy subjects with accuracy which is clinically relevant in first steps of the IHD and DCM diagnostic process.

Wake-up Stroke Outcome Prediction by Interpretable Decision Tree Model.

Outcome prediction in wake-up ischemic stroke (WUS) is important for guiding treatment strategies, in order to improve recovery and minimize disability. We aimed at producing an interpretable model to predict a good outcome (NIHSS 7-day<5) in thrombolysis treated WUS patients by using Classification and Regression Tree (CART) method. The study encompassed 104 WUS patients and we used a dataset consisting of demographic, clinical and neuroimaging features. The model was produced by CART with Gini split criterion and evaluated by using 5-fold cross-validation. The produced decision tree model was based on NIHSS at admission, ischemic core volume and age features. The predictive accuracy of model was 86.5% and the AUC-ROC was 0.88. In conclusion, in this preliminary study we identified interpretable model based on clinical and neuroimaging features to predict clinical outcome in thrombolysis treated wake-up stroke patients.

Influence of smoking and other cardiovascular risk factors on heart rate circadian rhythm in normotensive and hypertensive subjects.

Circadian heart rate (HR) is influenced by hypertension and other cardiovascular risk factors particularly smoking, obesity and dyslipidemia. Until now, to evaluate the HR changes due to presence of these risk factors, a single HR office measure or a mean evaluated on day time or night time or 24h was used. However, since HR shows a circadian behavior, a single value represents only a rough approximation of this behavior. In this study, we analyzed the influence of smoking, obesity and dyslipidemia on the circadian rhythm in normotensive and hypertensive subject groups presenting only one of these risk factors. The 24h HR recordings of 170 normotensive (83 without risk factors, 20 smokers, 44 with dyslipidemia, 23 obese) and 353 hypertensive (169 without risk factors, 32 smokers, 99 with dyslipidemia, 53 obese) subjects were acquired using a Holter Blood Pressure Monitor. Results highlighted a specific circadian behavior with three characteristic periods presenting different HR means and rates of HR change in the eight subject groups. The slopes could be used both to estimate the morning HR surge associated with acute cardiovascular effects in the awakening and to evaluate the decline during the night. Moreover, we suggest to use three HR mean values (one for each identified period of the day) rather than two HR values to better describe the circadian HR behavior. Furthermore, smoking increased and dyslipidemia decreased mean HR values from 10:00 to 04:00, both in normotensive and hypertensive subjects in comparison with subjects without risk factors. In this time interval, hypertensive obese subjects showed higher values while normotensive ones presented quite similar values than subjects without risk factors. During the awakening (05:00-10:00) the slopes were similar among all groups with no significant difference among the mean HR values.

Early EEG Alterations Correlate with CTP Hypoperfused Volumes and Neurological Deficit: A Wireless EEG Study in Hyper-Acute Ischemic Stroke.

Brain electrical activity in acute ischemic stroke is related to the hypoperfusion of cerebral tissue as manifestation of neurovascular coupling. EEG could be applicable for bedside functional monitoring in emergency settings. We aimed to investigate the relation between hyper-acute ischemic stroke EEG changes, measured with bedside wireless-EEG, and hypoperfused core-penumbra CT-perfusion (CTP) volumes. In addition, we investigated the association of EEG and CTP parameters with neurological deficit measured by NIHSS. We analyzed and processed EEG, CTP and clinical data of 31 anterior acute ischemic stroke patients registered within 4.5 h from symptom onset. Delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR) and relative delta power correlated directly (ρ = 0.72; 0.63; 0.65, respectively), while alpha correlated inversely (ρ = - 0.66) with total hypoperfused volume. DAR, DTBAR and relative delta and alpha parameters also correlated with ischemic core volume (ρ = 0.55; 0.50; 0.59; - 0.51, respectively). The same EEG parameters and CTP volumes showed significant relation with NIHSS at admission. The multivariate stepwise regression showed that DAR was the strongest predictor of NIHSS at admission (p < 0.001). The results of this study showed that hyper-acute alterations of EEG parameters are highly related to the extent of hypoperfused tissue highlighting the value of quantitative EEG as a possible complementary tool in the evaluation of stroke severity and its potential role in acute ischemic stroke monitoring.

Hyper-acute EEG alterations predict functional and morphological outcomes in thrombolysis-treated ischemic stroke: a wireless EEG study.

Owing to the large inter-subject variability, early post-stroke prognosis is challenging, and objective biomarkers that can provide further prognostic information are still needed. The relation between quantitative EEG parameters in pre-thrombolysis hyper-acute phase and outcomes has still to be investigated. Hence, possible correlations between early EEG biomarkers, measured on bedside wireless EEG, and short-term/long-term functional and morphological outcomes were investigated in thrombolysis-treated strokes. EEG with a wireless device was performed in 20 patients with hyper-acute (< 4.5 h from onset) anterior ischemic stroke before reperfusion treatment. The correlations between outcome parameters (i.e., 7-day/12-month National Institutes of Health Stroke Scale NIHSS, 12-month modified Rankin Scale mRS, final infarct volume) and the pre-treatment EEG parameters were studied. Relative delta power and alpha power, delta/alpha (DAR), and (delta+theta)/(alpha+beta) (DTABR) ratios significantly correlated with NIHSS 7-day (rho = 0.80, - 0.81, 0.76, 0.75, respectively) and NIHSS 12-month (0.73, - 0.78, 0.74, 0.73, respectively), as well as with final infarct volume (0.75, - 0.70, 0.78, 0.62, respectively). A good outcome in terms of mRS ≤ 2 at 12 months was associated with DAR parameter (p = 0.008). The neurophysiological biomarkers obtained by non-invasive and portable technique as wireless EEG in the early pre-treatment phase may contribute as objective parameters to the short/long-term outcome prediction pivotal to better establish the treatment strategies.Graphical abstract Block diagram of study protocol and main findings. Assessment at admission including wireless EEG acquisition in emergency setting (< 4.5 from stroke onset), extracted EEG features before reperfusion thrombolytic treatment. The main findings in our study sample are summarized in two different exemplificative stroke patients with different pre-thrombolysis alterations of EEG parameters resulting in different final infarct volume extensions and short/long-term clinical outcomes (NIHSS, mRS).

Effect of power feature covariance shift on BCI spatial-filtering techniques: A comparative study.

BACKGROUND AND OBJECTIVE: The input data distributions of EEG-based BCI systems can change during intra-session transitions due to nonstationarity caused by features covariate shifts, thus compromising BCI performance. We aimed to identify the most robust spatial filtering approach, among most used methods, testing them on calibration dataset, and test dataset recorded 30 min afterwards. In addition, we also investigated if their performance improved after application of Stationary Subspace Analysis (SSA). METHODS: We have recorded, in 17 healthy subjects, the calibration set at the beginning of the upper limb motor imagery BCI experiment and testing set separately 30 min afterwards. Both the calibration and test data were pre-processed and the BCI models were produced by using several spatial filtering approaches on the calibration set. Those models were subsequently evaluated on a test set. The differences between the accuracy estimated by cross-validation on the calibration dataset and the accuracy on the test dataset were investigated. The same procedure was performed with, and without SSA pre-processing step. RESULTS: A significant reduction in accuracy on the test dataset was observed for CSP, SPoC and SpecRCSP approaches. For SLap and SpecCSP only a slight decreasing trend was observed, while FBCSP and FBCSPT largely maintained moderately high median accuracy >70%. In the case of application of SSA pre-processing, the differences between accuracy observed on calibration and test dataset were reduced. In addition, accuracy values both on calibration and test set were slightly higher in case of SSA pre-processing and also in this case FBCSP and FBCSPT presented slightly better performance compared to other methods. CONCLUSION: The intrinsic signal nonstationarity characteristics, caused by covariance shifts of power features, reduced the accuracy of BCI model, therefore, suggesting that this evaluation framework should be considered for testing and simulating real life performance. FBCSP and FBSCPT approaches showed to be more robust to feature covariance shift. SSA can improve the models performance and reduce accuracy decline from calibration to test set.

BCIAUT-P300: A Multi-Session and Multi-Subject Benchmark Dataset on Autism for P300-Based Brain-Computer-Interfaces.

There is a lack of multi-session P300 datasets for Brain-Computer Interfaces (BCI). Publicly available datasets are usually limited by small number of participants with few BCI sessions. In this sense, the lack of large, comprehensive datasets with various individuals and multiple sessions has limited advances in the development of more effective data processing and analysis methods for BCI systems. This is particularly evident to explore the feasibility of deep learning methods that require large datasets. Here we present the BCIAUT-P300 dataset, containing 15 autism spectrum disorder individuals undergoing 7 sessions of P300-based BCI joint-attention training, for a total of 105 sessions. The dataset was used for the 2019 IFMBE Scientific Challenge organized during MEDICON 2019 where, in two phases, teams from all over the world tried to achieve the best possible object-detection accuracy based on the P300 signals. This paper presents the characteristics of the dataset and the approaches followed by the 9 finalist teams during the competition. The winner obtained an average accuracy of 92.3% with a convolutional neural network based on EEGNet. The dataset is now publicly released and stands as a benchmark for future P300-based BCI algorithms based on multiple session data.

A CT perfusion based model predicts outcome in wake-up stroke patients treated with recombinant tissue plasminogen activator.

OBJECTIVE: Advanced neuroimaging has proved to be pivotal in the management of acute ischemic stroke. The use of CT perfusion (CTP) core and penumbra parameters to predict the outcome in wake-up stroke (WUS) patients in everyday clinical scenarios has not yet been investigated. The aim of our study was to investigate the predictive power of CTP parameters on functional and morphological outcomes in WUS patients treated with recombinant tissue plasminogen activator (rTPA). APPROACH: We analyzed clinical data and processed CTP images of 83 consecutive WUS patients treated with rTPA. The predictive power of whole-brain CTP features and of the clinical stroke-related parameters to predict the National Institutes of Health Stroke Scale (NIHSS) score at the seventh day and ischemic lesion volume outcome was investigated by means of multivariate regression analysis as well as least absolute shrinkage and selection operator (LASSO) modeling. MAIN RESULTS: Multivariate analysis showed that CTP core volume (ß = 0.403, p = 0.000), NIHSS at admission (ß = 0.323, p = 0.005) and Alberta Stroke Program Early CT (ASPECT) score (ß = -0.224, p = 0.012) predict NIHSS at 7 days, while total hypoperfused volume (ß = 0.542, p = 0.000) and core volume on CTP (ß =0.441, p = 0.000) predict infarct lesion volume at follow-up CT. The LASSO modeling approach confirmed the significant predictive power of CTP core volume, total hypoperfused CTP volume, NIHSS at baseline and ASPECT score, producing a sparse model with adequate reliability (the root mean square error on a previously unseen testing dataset was 3.68). SIGNIFICANCE: Our findings highlight the importance of CT multimodal imaging features for decision-making and prediction in the hyperacute phase of WUS. The predictive model supports the hypothesis that an irreversible necrotic core rather than the extent of the penumbra is the main prognostic factor in WUS patients treated with rTPA.