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.

Serious Game Design and Clinical Improvement in Physical Rehabilitation: Systematic Review.

BACKGROUND: Serious video games have now been used and assessed in clinical protocols, with several studies reporting patient improvement and engagement with this type of therapy. Even though some literature reviews have approached this topic from a game perspective and presented a broad overview of the types of video games that have been used in this context, there is still a need to better understand how different game characteristics and development strategies might impact and relate to clinical outcomes. OBJECTIVE: This review assessed the relationship between the characteristics of serious games (SGs) and their relationship with the clinical outcomes of studies that use this type of therapy in motor impairment rehabilitation of patients with stroke, multiple sclerosis, or cerebral palsy. The purpose was to take a closer look at video game design features described in the literature (game genre [GG], game nature [GN], and game development strategy [GDS]) and assess how they may contribute toward improving health outcomes. Additionally, this review attempted to bring together medical and game development perspectives to facilitate communication between clinicians and game developers, therefore easing the process of choosing the video games to be used for physical rehabilitation. METHODS: We analyzed the main features of SG design to obtain significant clinical outcomes when applied to physical rehabilitation of patients recovering from motor impairments resulting from stroke, multiple sclerosis, and cerebral palsy. We implemented a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) database-adjusted electronic search strategy for the PubMed, IEEE Xplore, and Cochrane databases. RESULTS: We screened 623 related papers from 2010-2021 and identified 12 that presented results compatible with our inclusion criteria. A total of 512 participants with stroke (8 studies, 417 participants), cerebral palsy (1 study, 8 participants), and multiple sclerosis (2 studies, 46 participants) were included; 1 study targeting the elderly (41 participants) was also included. All studies assessed motor, sensory, and functional functions, while some also measured general health outcomes. Interventions with games were used for upper-limb motor rehabilitation. Of the 12 studies, 8 presented significant improvements in at least one clinical measurement, of which 6 presented games from the casual GG, 1 combined the casual, simulation, and exergaming GGs, and 2 combined the sports and simulation GGs. CONCLUSIONS: Of the possible combinations of game design features (GG, GN, and GDS) described, custom-made casual games that resort to the first-person perspective, do not feature a visible player character, are played in single-player mode, and use nonimmersive virtual reality attain the best results in terms of positive clinical outcomes. In addition, the use of custom-made games versus commercial off-the-shelf games tends to give better clinical results, although the latter are perceived as more motivating and engaging.

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.

Fibrinogen-coated droplets of olive oil for delivery of docetaxel to a fibrin(ogen)-rich ascites form of a murine mammary tumor.

Micronized droplets of olive oil loaded with docetaxel and coated with functional fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)-rich ascites form of the TA3/St mammary tumor. When compared with docetaxel administered intraperitoneally as its commercial formulation (i.e., Taxotere), docetaxel-loaded oil droplets coated with murine fibrinogen prolonged the median survival time of tumor-bearing mice from 14.5 to 29.5 days. Drug-free oil droplets provided no therapeutic benefit. Significantly more docetaxel was associated with tumor cells 24 and 48 hours after administration of the drug in fibrinogen-coated oil droplets than after its administration as Taxotere. Consistent with a role for thrombin in the retention of fibrinogen-coated oil droplets within the tumor microenvironment, hirudin significantly reduced the association of tumor cells with docetaxel delivered in fibrinogen-coated oil droplets and, at the same time, reduced the therapeutic efficacy of the droplets to that of Taxotere. Importantly, fibrinogen-coated oil droplets formed rosettes with tumor cells in vivo, a process prevented by hirudin. Although mice treated with oil droplets developed antifibrinogen antibodies, those antibodies seemed to be inconsequential. Taken together, our results and observations indicate fibrinogen-coated oil droplets markedly improve the therapeutic efficacy of docetaxel for the treatment of a mammary tumor grown in ascites form, a consequence of thrombin-mediated retention of the drug-loaded droplets within the tumor microenvironment.