Activation of a Rhythmic Lower Limb Movement Pattern during the Use of a Multimodal Brain-Computer Interface: A Case Study of a Clinically Complete Spinal Cord Injury.

Brain-computer interfaces (BCIs) that integrate virtual reality with tactile feedback are increasingly relevant for neurorehabilitation in spinal cord injury (SCI). In our previous case study employing a BCI-based virtual reality neurorehabilitation protocol, a patient with complete T4 SCI experienced reduced pain and emergence of non-spastic lower limb movements after 10 sessions. However, it is still unclear whether these effects can be sustained, enhanced, and replicated, as well as the neural mechanisms that underlie them. The present report outlines the outcomes of extending the previous protocol with 24 more sessions (14 months, in total). Clinical, behavioral, and neurophysiological data were analyzed. The protocol maintained or reduced pain levels, increased self-reported quality of life, and was frequently associated with the appearance of non-spastic lower limb movements when the patient was engaged and not experiencing stressful events. Neural activity analysis revealed that changes in pain were encoded in the theta frequency band by the left frontal electrode F3. Examination of the lower limbs revealed alternating movements resembling a gait pattern. These results suggest that sustained use of this BCI protocol leads to enhanced quality of life, reduced and stable pain levels, and may result in the emergence of rhythmic patterns of lower limb muscle activity reminiscent of gait.

Neurophysiological correlates of tactile width discrimination in humans.

Introduction: Tactile information processing requires the integration of sensory, motor, and cognitive information. Width discrimination has been extensively studied in rodents, but not in humans. Methods: Here, we describe Electroencephalography (EEG) signals in humans performing a tactile width discrimination task. The first goal of this study was to describe changes in neural activity occurring during the discrimination and the response periods. The second goal was to relate specific changes in neural activity to the performance in the task. Results: Comparison of changes in power between two different periods of the task, corresponding to the discrimination of the tactile stimulus and the motor response, revealed the engagement of an asymmetrical network associated with fronto-temporo-parieto-occipital electrodes and across multiple frequency bands. Analysis of ratios of higher [Ratio 1: (0.5-20 Hz)/(0.5-45 Hz)] or lower frequencies [Ratio 2: (0.5-4.5 Hz)/(0.5-9 Hz)], during the discrimination period revealed that activity recorded from frontal-parietal electrodes was correlated to tactile width discrimination performance between-subjects, independently of task difficulty. Meanwhile, the dynamics in parieto-occipital electrodes were correlated to the changes in performance within-subjects (i.e., between the first and the second blocks) independently of task difficulty. In addition, analysis of information transfer, using Granger causality, further demonstrated that improvements in performance between blocks were characterized by an overall reduction in information transfer to the ipsilateral parietal electrode (P4) and an increase in information transfer to the contralateral parietal electrode (P3). Discussion: The main finding of this study is that fronto-parietal electrodes encoded between-subjects' performances while parieto-occipital electrodes encoded within-subjects' performances, supporting the notion that tactile width discrimination processing is associated with a complex asymmetrical network involving fronto-parieto-occipital electrodes.

Embodiment Comfort Levels During Motor Imagery Training Combined With Immersive Virtual Reality in a Spinal Cord Injury Patient.

Brain-machine interfaces combining visual, auditory, and tactile feedback have been previously used to generate embodiment experiences during spinal cord injury (SCI) rehabilitation. It is not known if adding temperature to these modalities can result in discomfort with embodiment experiences. Here, comfort levels with the embodiment experiences were investigated in an intervention that required a chronic pain SCI patient to generate lower limb motor imagery commands in an immersive environment combining visual (virtual reality -VR), auditory, tactile, and thermal feedback. Assessments were made pre-/ post-, throughout the intervention (Weeks 0-5), and at 7 weeks follow up. Overall, high levels of embodiment in the adapted three-domain scale of embodiment were found throughout the sessions. No significant adverse effects of VR were reported. Although sessions induced only a modest reduction in pain levels, an overall reduction occurred in all pain scales (Faces, Intensity, and Verbal) at follow up. A high degree of comfort in the comfort scale for the thermal-tactile sleeve, in both the thermal and tactile feedback components of the sleeve was reported. This study supports the feasibility of combining multimodal stimulation involving visual (VR), auditory, tactile, and thermal feedback to generate embodiment experiences in neurorehabilitation programs.

Does Symptom Recognition Improve Self-Care in Patients with Heart Failure? A Pilot Study Randomised Controlled Trial.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognition of symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate the longitudinal effect of a nursing-led complex intervention on self-care management and quality-of-life changes in patients with heart failure and assessed by a pilot study performed on sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p < 0.001) and emergency admission (IRR 4.24; p < 0.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (ßSlope. Assignment_group = -0.881; p < 0.001) and in the quality of life (ßSlope. Assignment_group = 1.739; p < 0.001). This study supports that a nurse-led programme on symptom recognition and fluid restriction can positively impact self-care behaviours and quality of life in patients with heart failure. This randomised controlled trial was retrospectively registered (NCT04892004).

Translation and Cross-Cultural Adaptation of Quality of Life Scale in Patients with Onychomycosis.

(1) Background: Onychomycosis (OM) is a fungal nail infection, considered a risk factor for diabetic foot ulcers. It is associated with changes in quality of life, in terms of pain, self-confidence and self-esteem. The aim was to translate and adapt the OM quality of life questionnaire "OnyCOE-tTM-Quality Of Life Questionnaire Onychomycosis (Nail Fungal Condition)". (2) Methods: This study followed the guidelines proposed by Beaton et al. (2000), where two English to Portuguese translations were performed and, after an expert consensus, a common version was obtained. This was followed by two back-translations. The expert committee achieved semantic equivalence, idioms and concepts. The pre-test was applied to 49 people. The final version and processed data were sent to the authors. (3) Results: We adapted terms semantically, modified statements syntactically, altering items from interrogative to affirmative. (4) Conclusions: The translated version of the "Quality of life-Onychomycosis" questionnaire suggested that it can be used for further studies to test validity and reliability in this population.

Quality of life and therapeutic regimen management in onychomycosis patients and in vitro study of antiseptic solutions.

Onychomycosis or tinea unguium (EE12.1) and Onychomycosis due to non-dermatophyte moulds (1F2D.5) (OM) is a fungal infection of the nail plates with a high prevalence that often affects vulnerable people with co-existing health problems. Gold standard pharmacological treatments for onychomycosis have been associated with low success rates and increasing antifungal resistance, suggesting that treatment outcome is dependent on multiple variables. Here, the prevalence of OM and quality of life were characterized in two vulnerable populations-Hospital patients and Homeless people. Comparing both groups, the most prevalent fungal species were identified in Hospital patients. Then, the in vitro fungicidal properties of the antiseptics povidone-iodine, polyhexamethylene biguanide-betaine, octenidine dihydrochloride, and a super-oxidized solution against two ATCC strains (Candida albicans and Aspergillus niger) and three clinical fungal isolates from Hospital patients (Candida parapsilosis, Trichophyton interdigitale, and Trichophyton rubrum) were tested. OM prevalence was high in both patient groups studied, who also reported a reduction in quality of life and concerns about the state of their feet. In addition, Hospital patients had a non-negligent therapeutic regimen management style. Antiseptics tested in vitro revealed antifungal properties. As antiseptics are low-cost and easy to apply and have few iatrogenic effects, the demonstration of fungicidal properties of these solutions suggests that they may constitute potential supportive therapeutics for OM.

Symptom perception management education improves self-care in patients with heart failure.

BACKGROUND: Patients with heart failure often have difficulty recognizing signs and symptoms of the disease, which delays seeking help, and therefore interferes with patient engagement and self-care management. Early detection of these symptoms could lead to care-seeking and avoid hospitalizations. OBJECTIVE: The purpose of this study was to design a complex intervention through a systematic literature review and qualitative study. METHODS: Our design followed the Medical Research Council's recommendations. To design a complex intervention, we combined a systematic literature review on education, symptom recognition, and self-care management in patients with heart failure, and semi-structured interviews with cardiology healthcare providers and patients with heart failure admitted to a cardiology ward. RESULTS: The systematic literature review identified 582 studies published between 2005 and 2014, of which four were included in the final review. These suggested that patient education focused on symptom recognition, combined with reinforcements, led to better self-care behaviors. Additionally, content analysis of semi-structured interviews revealed three themes: health management, behavior management, and support received. CONCLUSIONS: Combining the findings of the literature review and the themes that emerged from the semi-structured interviews, we proposed the development and implementation of a complex intervention on symptom perception and fluid management.

Differential width discrimination task for active and passive tactile discrimination in humans.

The neurophysiological basis of width discrimination has been extensively studied in rodents and has shown that active and passive tactile discrimination engage fundamentally different neural networks. Although previous studies have analyzed active and passive tactile processing in humans, little is known about the neurophysiological basis of width discrimination in humans. Here we present a width discrimination task for humans that reproduces the main features of the width discrimination task previously developed for rodents. The task required subjects to actively or passively sample two movable bars forming a "narrow" or "wide" aperture. Subjects were then required to press one of two buttons to indicate if the bar width was "narrow" or "wide". Behavioral testing showed that subjects were capable of discriminating between wide or narrow apertures up to distances of 0.1 cm. Electroencephalography (EEG) recordings further suggested distinct topographic maps for active and passive versions of the task during the period associated with the aperture discrimination. These results indicate that the Human Differential Width Discrimination Task is a valuable tool to describe the behavioral characteristics and neurophysiological basis of tactile processing.•Active and passive width discrimination has been extensively studied in rodents but not in humans.•Human subjects were capable of discriminating aperture widths of 0.1 cm.•Electroencephalography recordings showed that active and passive versions of the task were associated with different topographic maps.

Method for positioning and rehabilitation training with the ExoAtlet ® powered exoskeleton.

Exoskeletons for locomotion, support, or other uses are becoming more common. An increasing number of studies are demonstrating relevant results in rehabilitation. Here we describe the steps required to properly place and train patients in ExoAtlet ® powered exoskeletons (Moscow, Russia), for which there is currently limited information available. These steps combine actions related to the hardware, software, as well as safety, rehabilitation, and psycho-emotional state of the subject. Training starts with a general preparation of the environment, the equipment, and the patient. When the actual training program begins, the patient needs to gradually learn to perform the different actions that will be required to control the exoskeleton. Initially, training requires transferring weight between legs to guarantee adequate equilibrium control. Then, actions assisted by computer-controlled motors begin, namely: standing up, walking in place, moving small distances and sitting down. As the patient becomes comfortable with the exoskeleton and the cardiovascular system becomes adjusted to the upright position, training can then include walking over longer distances, inclined planes, opening doors, and climbing stairs.•Powered exoskeletons are becoming a common method in rehabilitation.•The use of ExoAtlet ® powered exoskeletons in clinical research requires manipulation of variables thought to promote rehabilitation, without compromising safety standards.•The phases of training are: transferring weight between legs, walk in place, and walk over longer distances.

Frequency-specific coupling in fronto-parieto-occipital cortical circuits underlie active tactile discrimination.

Processing of tactile sensory information in rodents is critically dependent on the communication between the primary somatosensory cortex (S1) and higher-order integrative cortical areas. Here, we have simultaneously characterized single-unit activity and local field potential (LFP) dynamics in the S1, primary visual cortex (V1), anterior cingulate cortex (ACC), posterior parietal cortex (PPC), while freely moving rats performed an active tactile discrimination task. Simultaneous single unit recordings from all these cortical regions revealed statistically significant neuronal firing rate modulations during all task phases (anticipatory, discrimination, response, and reward). Meanwhile, phase analysis of pairwise LFP recordings revealed the occurrence of long-range synchronization across the sampled fronto-parieto-occipital cortical areas during tactile sampling. Causal analysis of the same pairwise recorded LFPs demonstrated the occurrence of complex dynamic interactions between cortical areas throughout the fronto-parietal-occipital loop. These interactions changed significantly between cortical regions as a function of frequencies (i.e. beta, theta and gamma) and according to the different phases of the behavioral task. Overall, these findings indicate that active tactile discrimination by rats is characterized by much more widespread and dynamic complex interactions within the fronto-parieto-occipital cortex than previously anticipated.

Ceftriaxone modulates the acute corticosterone effects in local field potentials in the primary somatosensory cortex of anesthetized mice.

Stress responses are associated with elevations in corticosterone levels and, as a consequence, increases in glutamate in the central nervous system which can lead to neurological impairment. Ceftriaxone promotes glutamate transport and has been used to reduce glutamate toxicity, but so far it is not known whether ceftriaxone is able to reverse the effects of corticosterone administration. Here we describe the separate and combined effects of acute ceftriaxone and acute corticosterone administration in local field potentials (LFPs) recorded from the somatosensory cortex (S1) of anesthetized mice. For this, LFPs were recorded from groups of anesthetized mice injected with saline, corticosterone, ceftriaxone, or both. Comparison of global state maps, and their displacements, as measured by ratios of different frequency bands (Ratio 1: 0.5-20 Hz/0.5-45 Hz; and Ratio 2: 0.5-4.5 Hz/0.5-9 Hz) revealed distinct and opposite effects for corticosterone and for ceftriaxone. Corticosterone specifically increased the displacement in Ratio 2, while ceftriaxone decreased it; in addition, when both corticosterone and ceftriaxone were injected, Ratio 2 displacement values were again similar to those of the control group. The present results suggest that ceftriaxone and corticosterone modulate specific frequency bands in opposite directions and reveal a potential role for ceftriaxone in counteracting the effects of corticosterone.

A Closed Loop Brain-machine Interface for Epilepsy Control Using Dorsal Column Electrical Stimulation.

Although electrical neurostimulation has been proposed as an alternative treatment for drug-resistant cases of epilepsy, current procedures such as deep brain stimulation, vagus, and trigeminal nerve stimulation are effective only in a fraction of the patients. Here we demonstrate a closed loop brain-machine interface that delivers electrical stimulation to the dorsal column (DCS) of the spinal cord to suppress epileptic seizures. Rats were implanted with cortical recording microelectrodes and spinal cord stimulating electrodes, and then injected with pentylenetetrazole to induce seizures. Seizures were detected in real time from cortical local field potentials, after which DCS was applied. This method decreased seizure episode frequency by 44% and seizure duration by 38%. We argue that the therapeutic effect of DCS is related to modulation of cortical theta waves, and propose that this closed-loop interface has the potential to become an effective and semi-invasive treatment for refractory epilepsy and other neurological disorders.

Cortical and thalamic contributions to response dynamics across layers of the primary somatosensory cortex during tactile discrimination.

Tactile information processing in the rodent primary somatosensory cortex (S1) is layer specific and involves modulations from both thalamocortical and cortico-cortical loops. However, the extent to which these loops influence the dynamics of the primary somatosensory cortex while animals execute tactile discrimination remains largely unknown. Here, we describe neural dynamics of S1 layers across the multiple epochs defining a tactile discrimination task. We observed that neuronal ensembles within different layers of the S1 cortex exhibited significantly distinct neurophysiological properties, which constantly changed across the behavioral states that defined a tactile discrimination. Neural dynamics present in supragranular and granular layers generally matched the patterns observed in the ventral posterior medial nucleus of the thalamus (VPM), whereas the neural dynamics recorded from infragranular layers generally matched the patterns from the posterior nucleus of the thalamus (POM). Selective inactivation of contralateral S1 specifically switched infragranular neural dynamics from POM-like to those resembling VPM neurons. Meanwhile, ipsilateral M1 inactivation profoundly modulated the firing suppression observed in infragranular layers. This latter effect was counterbalanced by contralateral S1 block. Tactile stimulus encoding was layer specific and selectively affected by M1 or contralateral S1 inactivation. Lastly, causal information transfer occurred between all neurons in all S1 layers but was maximal from infragranular to the granular layer. These results suggest that tactile information processing in the S1 of awake behaving rodents is layer specific and state dependent and that its dynamics depend on the asynchronous convergence of modulations originating from ipsilateral M1 and contralateral S1.

Computing Arm Movements with a Monkey Brainet.

Traditionally, brain-machine interfaces (BMIs) extract motor commands from a single brain to control the movements of artificial devices. Here, we introduce a Brainet that utilizes very-large-scale brain activity (VLSBA) from two (B2) or three (B3) nonhuman primates to engage in a common motor behaviour. A B2 generated 2D movements of an avatar arm where each monkey contributed equally to X and Y coordinates; or one monkey fully controlled the X-coordinate and the other controlled the Y-coordinate. A B3 produced arm movements in 3D space, while each monkey generated movements in 2D subspaces (X-Y, Y-Z, or X-Z). With long-term training we observed increased coordination of behavior, increased correlations in neuronal activity between different brains, and modifications to neuronal representation of the motor plan. Overall, performance of the Brainet improved owing to collective monkey behaviour. These results suggest that primate brains can be integrated into a Brainet, which self-adapts to achieve a common motor goal.

Building an organic computing device with multiple interconnected brains.

Recently, we proposed that Brainets, i.e. networks formed by multiple animal brains, cooperating and exchanging information in real time through direct brain-to-brain interfaces, could provide the core of a new type of computing device: an organic computer. Here, we describe the first experimental demonstration of such a Brainet, built by interconnecting four adult rat brains. Brainets worked by concurrently recording the extracellular electrical activity generated by populations of cortical neurons distributed across multiple rats chronically implanted with multi-electrode arrays. Cortical neuronal activity was recorded and analyzed in real time, and then delivered to the somatosensory cortices of other animals that participated in the Brainet using intracortical microstimulation (ICMS). Using this approach, different Brainet architectures solved a number of useful computational problems, such as discrete classification, image processing, storage and retrieval of tactile information, and even weather forecasting. Brainets consistently performed at the same or higher levels than single rats in these tasks. Based on these findings, we propose that Brainets could be used to investigate animal social behaviors as well as a test bed for exploring the properties and potential applications of organic computers.

A brain-to-brain interface for real-time sharing of sensorimotor information.

A brain-to-brain interface (BTBI) enabled a real-time transfer of behaviorally meaningful sensorimotor information between the brains of two rats. In this BTBI, an "encoder" rat performed sensorimotor tasks that required it to select from two choices of tactile or visual stimuli. While the encoder rat performed the task, samples of its cortical activity were transmitted to matching cortical areas of a "decoder" rat using intracortical microstimulation (ICMS). The decoder rat learned to make similar behavioral selections, guided solely by the information provided by the encoder rat's brain. These results demonstrated that a complex system was formed by coupling the animals' brains, suggesting that BTBIs can enable dyads or networks of animal's brains to exchange, process, and store information and, hence, serve as the basis for studies of novel types of social interaction and for biological computing devices.

Simultaneous top-down modulation of the primary somatosensory cortex and thalamic nuclei during active tactile discrimination.

The rat somatosensory system contains multiple thalamocortical loops (TCLs) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial, and the posterior medial thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations before the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal's discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal's performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system.