Mapping of the central sulcus using non-invasive ultra-high-density brain recordings.

Brain mapping is vital in understanding the brain's functional organization. Electroencephalography (EEG) is one of the most widely used brain mapping approaches, primarily because it is non-invasive, inexpensive, straightforward, and effective. Increasing the electrode density in EEG systems provides more neural information and can thereby enable more detailed and nuanced mapping procedures. Here, we show that the central sulcus can be clearly delineated using a novel ultra-high-density EEG system (uHD EEG) and somatosensory evoked potentials (SSEPs). This uHD EEG records from 256 channels with an inter-electrode distance of 8.6 mm and an electrode diameter of 5.9 mm. Reconstructed head models were generated from T1-weighted MRI scans, and electrode positions were co-registered to these models to create topographical plots of brain activity. EEG data were first analyzed with peak detection methods and then classified using unsupervised spectral clustering. Our topography plots of the spatial distribution from the SSEPs clearly delineate a division between channels above the somatosensory and motor cortex, thereby localizing the central sulcus. Individual EEG channels could be correctly classified as anterior or posterior to the central sulcus with 95.2% accuracy, which is comparable to accuracies from invasive intracranial recordings. Our findings demonstrate that uHD EEG can resolve the electrophysiological signatures of functional representation in the brain at a level previously only seen from surgically implanted electrodes. This novel approach could benefit numerous applications, including research, neurosurgical mapping, clinical monitoring, detection of conscious function, brain-computer interfacing (BCI), rehabilitation, and mental health.

Upper extremity training followed by lower extremity training with a brain-computer interface rehabilitation system.

Introduction: Brain-computer interfaces (BCIs) based on functional electrical stimulation have been used for upper extremity motor rehabilitation after stroke. However, little is known about their efficacy for multiple BCI treatments. In this study, 19 stroke patients participated in 25 upper extremity followed by 25 lower extremity BCI training sessions. Methods: Patients' functional state was assessed using two sets of clinical scales for the two BCI treatments. The Upper Extremity Fugl-Meyer Assessment (FMA-UE) and the 10-Meter Walk Test (10MWT) were the primary outcome measures for the upper and lower extremity BCI treatments, respectively. Results: Patients' motor function as assessed by the FMA-UE improved by an average of 4.2 points (p < 0.001) following upper extremity BCI treatment. In addition, improvements in activities of daily living and clinically relevant improvements in hand and finger spasticity were observed. Patients showed further improvements after the lower extremity BCI treatment, with walking speed as measured by the 10MWT increasing by 0.15 m/s (p = 0.001), reflecting a substantial meaningful change. Furthermore, a clinically relevant improvement in ankle spasticity and balance and mobility were observed. Discussion: The results of the current study provide evidence that both upper and lower extremity BCI treatments, as well as their combination, are effective in facilitating functional improvements after stroke. In addition, and most importantly improvements did not stop after the first 25 upper extremity BCI sessions.

Electrophysiological Characterization of Subclinical and Overt Hypertrophic Cardiomyopathy by Magnetic Resonance Imaging-Guided Electrocardiography.

BACKGROUND: Ventricular arrhythmia in hypertrophic cardiomyopathy (HCM) relates to adverse structural change and genetic status. Cardiovascular magnetic resonance (CMR)-guided electrocardiographic imaging (ECGI) noninvasively maps cardiac structural and electrophysiological (EP) properties. OBJECTIVES: The purpose of this study was to establish whether in subclinical HCM (genotype [G]+ left ventricular hypertrophy [LVH]-), ECGI detects early EP abnormality, and in overt HCM, whether the EP substrate relates to genetic status (G+/G-LVH+) and structural phenotype. METHODS: This was a prospective 211-participant CMR-ECGI multicenter study of 70 G+LVH-, 104 LVH+ (51 G+/53 G-), and 37 healthy volunteers (HVs). Local activation time (AT), corrected repolarization time, corrected activation-recovery interval, spatial gradients (GAT/GRTc), and signal fractionation were derived from 1,000 epicardial sites per participant. Maximal wall thickness and scar burden were derived from CMR. A support vector machine was built to discriminate G+LVH- from HV and low-risk HCM from those with intermediate/high-risk score or nonsustained ventricular tachycardia. RESULTS: Compared with HV, subclinical HCM showed mean AT prolongation (P = 0.008) even with normal 12-lead electrocardiograms (ECGs) (P = 0.009), and repolarization was more spatially heterogenous (GRTc: P = 0.005) (23% had normal ECGs). Corrected activation-recovery interval was prolonged in overt vs subclinical HCM (P < 0.001). Mean AT was associated with maximal wall thickness; spatial conduction heterogeneity (GAT) and fractionation were associated with scar (all P < 0.05), and G+LVH+ had more fractionation than G-LVH+ (P = 0.002). The support vector machine discriminated subclinical HCM from HV (10-fold cross-validation accuracy 80% [95% CI: 73%-85%]) and identified patients at higher risk of sudden cardiac death (accuracy 82% [95% CI: 78%-86%]). CONCLUSIONS: In the absence of LVH or 12-lead ECG abnormalities, HCM sarcomere gene mutation carriers express an aberrant EP phenotype detected by ECGI. In overt HCM, abnormalities occur more severely with adverse structural change and positive genetic status.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states.

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (<0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.

Real-time estimation of EEG-based engagement in different tasks.

Objective.Recent trends in brain-computer interface (BCI) research concern the passive monitoring of brain activity, which aim to monitor a wide variety of cognitive states. Engagement is such a cognitive state, which is of interest in contexts such as learning, entertainment or rehabilitation. This study proposes a novel approach for real-time estimation of engagement during different tasks using electroencephalography (EEG).Approach.Twenty-three healthy subjects participated in the BCI experiment. A modified version of the d2 test was used to elicit engagement. Within-subject classification models which discriminate between engaging and resting states were trained based on EEG recorded during a d2 test based paradigm. The EEG was recorded using eight electrodes and the classification model was based on filter-bank common spatial patterns and a linear discriminant analysis. The classification models were evaluated in cross-task applications, namely when playing Tetris at different speeds (i.e. slow, medium, fast) and when watching two videos (i.e. advertisement and landscape video). Additionally, subjects' perceived engagement was quantified using a questionnaire.Main results.The models achieved a classification accuracy of 90% on average when tested on an independent d2 test paradigm recording. Subjects' perceived and estimated engagement were found to be greater during the advertisement compared to the landscape video (p= 0.025 andp<0.001, respectively); greater during medium and fast compared to slow Tetris speed (p<0.001, respectively); not different between medium and fast Tetris speeds. Additionally, a common linear relationship was observed for perceived and estimated engagement (rrm= 0.44,p<0.001). Finally, theta and alpha band powers were investigated, which respectively increased and decreased during more engaging states.Significance.This study proposes a task-specific EEG engagement estimation model with cross-task capabilities, offering a framework for real-world applications.

A Few-Shot Transfer Learning Approach for Motion Intention Decoding from Electroencephalographic Signals.

In this study, a few-shot transfer learning approach was introduced to decode movement intention from electroencephalographic (EEG) signals, allowing to recognize new tasks with minimal adaptation. To this end, a dataset of EEG signals recorded during the preparation of complex sub-movements was created from a publicly available data collection. The dataset was divided into two parts: the source domain dataset (including 5 classes) and the support (target domain) dataset, (including 2 classes) with no overlap between the two datasets in terms of classes. The proposed methodology consists in projecting EEG signals into the space-frequency-time domain, in processing such projections (rearranged in channels × frequency frames) by means of a custom EEG-based deep neural network (denoted as EEGframeNET5), and then adapting the system to recognize new tasks through a few-shot transfer learning approach. The proposed method achieved an average accuracy of 72.45 ± 4.19% in the 5-way classification of samples from the source domain dataset, outperforming comparable studies in the literature. In the second phase of the study, a few-shot transfer learning approach was proposed to adapt the neural system and make it able to recognize new tasks in the support dataset. The results demonstrated the system's ability to adapt and recognize new tasks with an average accuracy of 80 ± 0.12% in discriminating hand opening/closing preparation and outperforming reported results in the literature. This study suggests the effectiveness of EEG in capturing information related to the motor preparation of complex movements, potentially paving the way for BCI systems based on motion planning decoding. The proposed methodology could be straightforwardly extended to advanced EEG signal processing in other scenarios, such as motor imagery or neural disorder classification.

Recording physiological and pathological cortical activity and exogenous electric fields using graphene microtransistor arrays in vitro.

Graphene-based solution-gated field-effect transistors (gSGFETs) allow the quantification of the brain's full-band signal. Extracellular alternating current (AC) signals include local field potentials (LFP, population activity within a reach of hundreds of micrometers), multiunit activity (MUA), and ultimately single units. Direct current (DC) potentials are slow brain signals with a frequency under 0.1 Hz, and commonly filtered out by conventional AC amplifiers. This component conveys information about what has been referred to as "infraslow" activity. We used gSGFET arrays to record full-band patterns from both physiological and pathological activity generated by the cerebral cortex. To this end, we used an in vitro preparation of cerebral cortex that generates spontaneous rhythmic activity, such as that occurring in slow wave sleep. This examination extended to experimentally induced pathological activities, including epileptiform discharges and cortical spreading depression. Validation of recordings obtained via gSGFETs, including both AC and DC components, was accomplished by cross-referencing with well-established technologies, thereby quantifying these components across different activity patterns. We then explored an additional gSGFET potential application, which is the measure of externally induced electric fields such as those used in therapeutic neuromodulation in humans. Finally, we tested the gSGFETs in human cortical slices obtained intrasurgically. In conclusion, this study offers a comprehensive characterization of gSGFETs for brain recordings, with a focus on potential clinical applications of this emerging technology.

Technical development and feasibility of a reusable vest to integrate cardiovascular magnetic resonance with electrocardiographic imaging.

BACKGROUND: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. METHODS: CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. RESULTS: 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [rs] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (rs between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). CONCLUSION: Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insights into arrhythmogenesis and potentially pave the way for more personalised risk stratification. CLINICAL TRIAL REGISTRATION: Title: Multimorbidity Life-Course Approach to Myocardial Health-A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD) (MyoFit46). National Clinical Trials (NCT) number: NCT05455125. URL: https://clinicaltrials.gov/ct2/show/NCT05455125?term=MyoFit&draw=2&rank=1.

Brain-computer interface treatment for gait rehabilitation in stroke patients.

The use of Brain-Computer Interfaces (BCI) as rehabilitation tools for chronically ill neurological patients has become more widespread. BCIs combined with other techniques allow the user to restore neurological function by inducing neuroplasticity through real-time detection of motor-imagery (MI) as patients perform therapy tasks. Twenty-five stroke patients with gait disability were recruited for this study. Participants performed 25 sessions with the MI-BCI and assessment visits to track functional changes during the therapy. The results of this study demonstrated a clinically significant increase in walking speed of 0.19 m/s, 95%CI [0.13-0.25], p < 0.001. Patients also reduced spasticity and improved their range of motion and muscle contraction. The BCI treatment was effective in promoting long-lasting functional improvements in the gait speed of chronic stroke survivors. Patients have more movements in the lower limb; therefore, they can walk better and safer. This functional improvement can be explained by improved neuroplasticity in the central nervous system.

Characterization of High-Gamma Activity in Electrocorticographic Signals.

Introduction: Electrocorticographic (ECoG) high-gamma activity (HGA) is a widely recognized and robust neural correlate of cognition and behavior. However, fundamental signal properties of HGA, such as the high-gamma frequency band or temporal dynamics of HGA, have never been systematically characterized. As a result, HGA estimators are often poorly adjusted, such that they miss valuable physiological information. Methods: To address these issues, we conducted a thorough qualitative and quantitative characterization of HGA in ECoG signals. Our study is based on ECoG signals recorded from 18 epilepsy patients while performing motor control, listening, and visual perception tasks. In this study, we first categorize HGA into HGA types based on the cognitive/behavioral task. For each HGA type, we then systematically quantify three fundamental signal properties of HGA: the high-gamma frequency band, the HGA bandwidth, and the temporal dynamics of HGA. Results: The high-gamma frequency band strongly varies across subjects and across cognitive/behavioral tasks. In addition, HGA time courses have lowpass character, with transients limited to 10 Hz. The task-related rise time and duration of these HGA time courses depend on the individual subject and cognitive/behavioral task. Task-related HGA amplitudes are comparable across the investigated tasks. Discussion: This study is of high practical relevance because it provides a systematic basis for optimizing experiment design, ECoG acquisition and processing, and HGA estimation. Our results reveal previously unknown characteristics of HGA, the physiological principles of which need to be investigated in further studies.

Effect of Lower Limb Exoskeleton on the Modulation of Neural Activity and Gait Classification.

Neurorehabilitation with robotic devices requires a paradigm shift to enhance human-robot interaction. The coupling of robot assisted gait training (RAGT) with a brain-machine interface (BMI) represents an important step in this direction but requires better elucidation of the effect of RAGT on the user's neural modulation. Here, we investigated how different exoskeleton walking modes modify brain and muscular activity during exoskeleton assisted gait. We recorded electroencephalographic (EEG) and electromyographic (EMG) activity from ten healthy volunteers walking with an exoskeleton with three modes of user assistance (i.e., transparent, adaptive and full assistance) and during free overground gait. Results identified that exoskeleton walking (irrespective of the exoskeleton mode) induces a stronger modulation of central mid-line mu (8-13 Hz) and low-beta (14-20 Hz) rhythms compared to free overground walking. These modifications are accompanied by a significant re-organization of the EMG patterns in exoskeleton walking. On the other hand, we observed no significant differences in neural activity during exoskeleton walking with the different assistance levels. We subsequently implemented four gait classifiers based on deep neural networks trained on the EEG data during the different walking conditions. Our hypothesis was that exoskeleton modes could impact the creation of a BMI-driven RAGT. We demonstrated that all classifiers achieved an average accuracy of 84.13±3.49% in classifying swing and stance phases on their respective datasets. In addition, we demonstrated that the classifier trained on the transparent mode exoskeleton data can classify gait phases during adaptive and full modes with an accuracy of 78.3±4.8% , while the classifier trained on free overground walking data fails to classify the gait during exoskeleton walking (accuracy of 59.4±11.8% ). These findings provide important insights into the effect of robotic training on neural activity and contribute to the advancement of BMI technology for improving robotic gait rehabilitation therapy.

Individual finger movement decoding using a novel ultra-high-density electroencephalography-based brain-computer interface system.

Brain-Computer Interface (BCI) technology enables users to operate external devices without physical movement. Electroencephalography (EEG) based BCI systems are being actively studied due to their high temporal resolution, convenient usage, and portability. However, fewer studies have been conducted to investigate the impact of high spatial resolution of EEG on decoding precise body motions, such as finger movements, which are essential in activities of daily living. Low spatial sensor resolution, as found in common EEG systems, can be improved by omitting the conventional standard of EEG electrode distribution (the international 10-20 system) and ordinary mounting structures (e.g., flexible caps). In this study, we used newly proposed flexible electrode grids attached directly to the scalp, which provided ultra-high-density EEG (uHD EEG). We explored the performance of the novel system by decoding individual finger movements using a total of 256 channels distributed over the contralateral sensorimotor cortex. Dense distribution and small-sized electrodes result in an inter-electrode distance of 8.6 mm (uHD EEG), while that of conventional EEG is 60 to 65 mm on average. Five healthy subjects participated in the experiment, performed single finger extensions according to a visual cue, and received avatar feedback. This study exploits mu (8-12 Hz) and beta (13-25 Hz) band power features for classification and topography plots. 3D ERD/S activation plots for each frequency band were generated using the MNI-152 template head. A linear support vector machine (SVM) was used for pairwise finger classification. The topography plots showed regular and focal post-cue activation, especially in subjects with optimal signal quality. The average classification accuracy over subjects was 64.8 (6.3)%, with the middle versus ring finger resulting in the highest average accuracy of 70.6 (9.4)%. Further studies are required using the uHD EEG system with real-time feedback and motor imagery tasks to enhance classification performance and establish the basis for BCI finger movement control of external devices.

Corrigendum: EEG biomarkers related with the functional state of stroke patients.

[This corrects the article DOI: 10.3389/fnins.2020.00582.].

How brain-computer interface technology may improve the diagnosis of the disorders of consciousness: A comparative study.

Objective: Clinical assessment of consciousness relies on behavioural assessments, which have several limitations. Hence, disorder of consciousness (DOC) patients are often misdiagnosed. In this work, we aimed to compare the repetitive assessment of consciousness performed with a clinical behavioural and a Brain-Computer Interface (BCI) approach. Materials and methods: For 7 weeks, sixteen DOC patients participated in weekly evaluations using both the Coma Recovery Scale-Revised (CRS-R) and a vibrotactile P300 BCI paradigm. To use the BCI, patients had to perform an active mental task that required detecting specific stimuli while ignoring other stimuli. We analysed the reliability and the efficacy in the detection of command following resulting from the two methodologies. Results: Over repetitive administrations, the BCI paradigm detected command following before the CRS-R in seven patients. Four clinically unresponsive patients consistently showed command following during the BCI assessments. Conclusion: Brain-Computer Interface active paradigms might contribute to the evaluation of the level of consciousness, increasing the diagnostic precision of the clinical bedside approach. Significance: The integration of different diagnostic methods leads to a better knowledge and care for the DOC.

Optimizing Motor Imagery Parameters for Robotic Arm Control by Brain-Computer Interface.

Brain-Computer Interface (BCI) technology has been shown to provide new communication possibilities, conveying brain information externally. BCI-based robot control has started to play an important role, especially in medically assistive robots but not only there. For example, a BCI-controlled robotic arm can provide patients diagnosed with neurodegenerative diseases such as Locked-in syndrome (LIS), Amyotrophic lateral sclerosis (ALS), and others with the ability to manipulate different objects. This study presents the optimization of the configuration parameters of a three-class Motor Imagery (MI) -based BCI for controlling a six Degrees of Freedom (DOF) robotic arm in a plane. Electroencephalography (EEG) signals are recorded from 64 positions on the scalp according to the International 10-10 System. In terms of the resulting classification of error rates, we investigated twelve time windows for the spatial filter and classifier calculation and three time windows for the variance smoothing time. The lowest error rates were achieved when using a 3 s time window for creating the spatial filters and classifier, for a variance time window of 1.5 s.

Study protocol: MyoFit46-the cardiac sub-study of the MRC National Survey of Health and Development.

BACKGROUND: The life course accumulation of overt and subclinical myocardial dysfunction contributes to older age mortality, frailty, disability and loss of independence. The Medical Research Council National Survey of Health and Development (NSHD) is the world's longest running continued surveillance birth cohort providing a unique opportunity to understand life course determinants of myocardial dysfunction as part of MyoFit46-the cardiac sub-study of the NSHD. METHODS: We aim to recruit 550 NSHD participants of approximately 75 years+ to undertake high-density surface electrocardiographic imaging (ECGI) and stress perfusion cardiovascular magnetic resonance (CMR). Through comprehensive myocardial tissue characterization and 4-dimensional flow we hope to better understand the burden of clinical and subclinical cardiovascular disease. Supercomputers will be used to combine the multi-scale ECGI and CMR datasets per participant. Rarely available, prospectively collected whole-of-life data on exposures, traditional risk factors and multimorbidity will be studied to identify risk trajectories, critical change periods, mediators and cumulative impacts on the myocardium. DISCUSSION: By combining well curated, prospectively acquired longitudinal data of the NSHD with novel CMR-ECGI data and sharing these results and associated pipelines with the CMR community, MyoFit46 seeks to transform our understanding of how early, mid and later-life risk factor trajectories interact to determine the state of cardiovascular health in older age. TRIAL REGISTRATION: Prospectively registered on ClinicalTrials.gov with trial ID: 19/LO/1774 Multimorbidity Life-Course Approach to Myocardial Health- A Cardiac Sub-Study of the MCRC National Survey of Health and Development (NSHD).

Brain-Computer Interfaces in Acute and Subacute Disorders of Consciousness.

SUMMARY: Disorders of consciousness include coma, unresponsive wakefulness syndrome (also known as vegetative state), and minimally conscious state. Neurobehavioral scales such as coma recovery scale-revised are the gold standard for disorder of consciousness assessment. Brain-computer interfaces have been emerging as an alternative tool for these patients. The application of brain-computer interfaces in disorders of consciousness can be divided into four fields: assessment, communication, prediction, and rehabilitation. The operational theoretical model of consciousness that brain-computer interfaces explore was reviewed in this article, with a focus on studies with acute and subacute patients. We then proposed a clinically friendly guideline, which could contribute to the implementation of brain-computer interfaces in neurorehabilitation settings. Finally, we discussed limitations and future directions, including major challenges and possible solutions.