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Non-invasive neuroprosthetic (NP) technologies for movement compensation and rehabilitation remain with challenges for their clinical application. Two of those major challenges are selective activation of muscles and fatigue management. This review discusses how electrode arrays improve the efficiency and selectivity of functional electrical stimulation (FES) applied via transcutaneous electrodes. In this paper we review the principles and achievements during the last decade on techniques for artificial motor unit recruitment to improve the selective activation of muscles. We review the key factors affecting the outcome of muscle force production via multi-pad transcutaneous electrical stimulation and discuss how stimulation parameters can be set to optimize external activation of body segments. A detailed review of existing electrode array systems proposed by different research teams is also provided. Furthermore, a review of the targeted applications of existing electrode arrays for control of upper and lower limb NPs is provided. Eventually, last section demonstrates the potential of electrode arrays to overcome the major challenges of NPs for compensation and rehabilitation of patient-specific impairments. ; This work has been done with partial financial support of the Ministry of Science and Innovation, in the framework of national project HYPER(CSD 2009-00067- Hybrid Neuroprosthetic and Neurorobotic Devices for Functional Compensation and Rehabilitation of Motor Disorders) and European Union in the framework of TREMOR Project: "TREMOR: An ambulatory BCI-driven tremor suppression system based on functional electrical stimulation", ICT-2007-224051, and "NeuroTREMOR: A novel concept for support to diagnosis and remote management of tremor", ICT-2011.5.1-287739. ; Peer reviewed

Background: Brain machine interface (BMI) technology has demonstrated its efficacy for rehabilitation of paralyzed chronic stroke patients. The critical component in BMI-training consists of the associative connection (contingency) between the intention and the feedback provided. However, the relationship between the BMI design and its performance in stroke patients is still an open question. Methods: In this study we compare different methodologies to design a BMI for rehabilitation and evaluate their effects on movement intention decoding performance. We analyze the data of 37 chronic stroke patients who underwent 4 weeks of BMI intervention with different types of association between their brain activity and the proprioceptive feedback. We simulate the pseudo-online performance that a BMI would have under different conditions, varying: (1) the cortical source of activity (i.e., ipsilesional, contralesional, bihemispheric), (2) the type of spatial filter applied, (3) the EEG frequency band, (4) the type of classifier; and also evaluated the use of residual EMG activity to decode the movement intentions. Results: We observed a significant influence of the different BMI designs on the obtained performances. Our results revealed that using bihemispheric beta activity with a common average reference and an adaptive support vector machine led to the best classification results. Furthermore, the decoding results based on brain activity were significantly higher than those based on muscle activity. Conclusions: This paper underscores the relevance of the different parameters used to decode movement, using EEG in severely paralyzed stroke patients. We demonstrated significant differences in performance for the different designs, which supports further research that should elucidate if those approaches leading to higher accuracies also induce higher motor recovery in paralyzed stroke patients. ; This study was funded by the Baden-Württemberg Stiftung (GRUENS ROB-1), the Deutsche Forschungsgemeinschaft (DFG, Koselleck and Grant SP 1533/2– 1), the Bundesministerium für Bildung und Forschung BMBF: MOTORBIC (FKZ 13GW0053) and AMORSA (FKZ 16SV7754), the fortüne-Program of the University of Tübingen (2422-0-1 and 2452-0-0) and the Basque Government Science Program (EXOTEK: KK 2016/00083).

Our eyes never remain still. Even when we stare at a fixed point, small involuntary movements take place in our eyes in an imperceptible manner. Researchers agree on the presence of three main contributions to eye movements when we fix the gaze: microsaccades, drifts and tremor. These small movements carry the image across the retina stimulating the photoreceptors and thus avoiding fading. Nowadays it is commonly accepted that these movements can improve the discrimination performance of the retina. In this paper, several retina models with and without fixational eye movements were implemented by mean of RetinaStudio tool to test the feasibility of these models to be incorporated in future neuroprostheses. For this purpose each retina model has been stimulated with natural scene images in two experiments. Results are discussed from the point of view of a neuroprosthesis development. ; This work has been supported in part by the ONCE (National Organization of the Spanish Blind), by the Research Chair on Retinitis Pigmentosa Bidons Egara and by the Grant SAF2008-03694 from the Spanish Government.

Frontmatter -- CONTENTS -- Introduction -- INTRACEREBRAL STEM CELL TRANSPLANTATION -- Brain, Mind and Regenerative Medicine: Ethical Uncertainties and the Paradox of their Technical Fix -- Can Intracerebral Interventions Change our Self? - Neuroethical Implications of Ontological Assumptions -- Parfit's Concept of Personal Identity and its Implications for Intercerebral Stem Cell Transplants -- Changes in Personality: Possible Hazards Arising from Stem Cell Grafts - An Ethical and Philosophical Approach -- Establishing Regenerative Medicine for the Human Brain: Ethical Aspects of Intracerebral Stem Cell Transplantation -- Experimenting Innovative Cell Therapies for Parkinson's Disease: A View from Ethics -- Coping and Expectations of Patients with Amyotrophic Lateral Sclerosis -- DEEP BRAIN STIMULATION -- Deep Brain Stimulation in Psychiatric Disorders -- The Essential Tension: On Ethical and Historical Conundrums in the Trajectories of Deep Brain Stimulation -- Changes in Personality: Possible Hazards Arising from Chronic Implantation of Electrostimulation Devices such as Deep Brain Stimulation Systems (DBS) or Advanced Electronic Neuroprostheses -- Personality Changes through Deep Brain Stimulation of the Subthalamic Nucleus in Parkinsonian Patients - An Ethical Discussion -- Manipulating the Brain - An Ethical Challenge? Lessons from Deep Brain Stimulation in Movement Disorders -- Questions on Deep Brain Stimulation on Children and Juveniles with Neuropsychiatric Disorders with Extremely Adverse Course -- Traditional vs. Modern Neuroenhancement: Notes from a Medico-ethical and Societal Perspective -- CONTRIBUTORS

Abstract
Deep brain stimulation (DBS) is a powerful tool for the treatment of circuitopathy-related neurological and psychiatric diseases and disorders such as Parkinson's disease and obsessive-compulsive disorder, as well as a critical research tool for perturbing neural circuits and exploring neuroprostheses. Electrically mediated DBS, however, is limited by the spread of stimulus currents into tissue unrelated to disease course and treatment, potentially causing undesirable patient side effects. In this work, we utilize infrared neural stimulation (INS), an optical neuromodulation technique that uses near to midinfrared light to drive graded excitatory and inhibitory responses in nerves and neurons, to facilitate an optical and spatially constrained DBS paradigm. INS has been shown to provide spatially constrained responses in cortical neurons and, unlike other optical techniques, does not require genetic modification of the neural target. We show that INS produces graded, biophysically relevant single-unit responses with robust information transfer in rat thalamocortical circuits. Importantly, we show that cortical spread of activation from thalamic INS produces more spatially constrained response profiles than conventional electrical stimulation. Owing to observed spatial precision of INS, we used deep reinforcement learning (RL) for closed-loop control of thalamocortical circuits, creating real-time representations of stimulus-response dynamics while driving cortical neurons to precise firing patterns. Our data suggest that INS can serve as a targeted and dynamic stimulation paradigm for both open and closed-loop DBS.

Utilising science and technology to maximize human performance is often an essential feature of military activity. This can often be focused on mission success rather than just the welfare of the individuals involved. This tension has the potential to threaten the autonomy of soldiers and military physicians around the taking or administering of enhancement neurotechnologies (e.g., pills, neural implants, and neuroprostheses). The Hybrid Framework was proposed by academic researchers working in the U.S. context and comprises "rules" for military neuroenhancement (e.g., ensuring transparency and maintaining dignity of the warfighter). Integrating traditional bioethical perspectives with the unique requirements of the military environment, it has been referenced by military/government agencies tasked with writing official ethical frameworks. Our two-part investigation explored the ethical dimensions of military neuroenhancements with military officers – those most likely to be making decisions in this area in the future. In three workshops, structured around the Hybrid Framework, we explored what they thought about the ethical issues of enhancement neurotechnologies. From these findings, we conducted a survey (N = 332) to probe the extent of rule endorsement. Results show high levels of endorsement for a warfighter's decision-making autonomy, but lower support for the view that enhanced warfighters would pose a danger to society after service. By examining the endorsement of concrete decision-making guidelines, we provide an overview of how military officers might, in practice, resolve tensions between competing values or higher-level principles. Our results suggest that the military context demands a recontextualisation of the relationship between military and civilian ethics.

Utilising science and technology to maximize human performance is often an essential feature of military activity. This can often be focused on mission success rather than just the welfare of the individuals involved. This tension has the potential to threaten the autonomy of soldiers and military physicians around the taking or administering of enhancement neurotechnologies (e.g., pills, neural implants, and neuroprostheses). The Hybrid Framework was proposed by academic researchers working in the U.S. context and comprises "rules" for military neuroenhancement (e.g., ensuring transparency and maintaining dignity of the warfighter). Integrating traditional bioethical perspectives with the unique requirements of the military environment, it has been referenced by military/government agencies tasked with writing official ethical frameworks. Our two-part investigation explored the ethical dimensions of military neuroenhancements with military officers – those most likely to be making decisions in this area in the future. In three workshops, structured around the Hybrid Framework, we explored what they thought about the ethical issues of enhancement neurotechnologies. From these findings, we conducted a survey (N = 332) to probe the extent of rule endorsement. Results show high levels of endorsement for a warfighter's decision-making autonomy, but lower support for the view that enhanced warfighters would pose a danger to society after service. By examining the endorsement of concrete decision-making guidelines, we provide an overview of how military officers might, in practice, resolve tensions between competing values or higher-level principles. Our results suggest that the military context demands a recontextualisation of the relationship between military and civilian ethics.

Utilising science and technology to maximize human performance is often an essential feature of military activity. This can often be focused on mission success rather than just the welfare of the individuals involved. This tension has the potential to threaten the autonomy of soldiers and military physicians around the taking or administering of enhancement neurotechnologies (e.g., pills, neural implants, and neuroprostheses). The Hybrid Framework was proposed by academic researchers working in the U.S. context and comprises "rules" for military neuroenhancement (e.g., ensuring transparency and maintaining dignity of the warfighter). Integrating traditional bioethical perspectives with the unique requirements of the military environment, it has been referenced by military/government agencies tasked with writing official ethical frameworks. Our two-part investigation explored the ethical dimensions of military neuroenhancements with military officers – those most likely to be making decisions in this area in the future. In three workshops, structured around the Hybrid Framework, we explored what they thought about the ethical issues of enhancement neurotechnologies. From these findings, we conducted a survey (N = 332) to probe the extent of rule endorsement. Results show high levels of endorsement for a warfighter's decision-making autonomy, but lower support for the view that enhanced warfighters would pose a danger to society after service. By examining the endorsement of concrete decision-making guidelines, we provide an overview of how military officers might, in practice, resolve tensions between competing values or higher-level principles. Our results suggest that the military context demands a recontextualisation of the relationship between military and civilian ethics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12152-022-09490-2.

Neuroprostheses aimed to restore lost functions after a limb amputation are based on the interaction with the nervous system by means of neural interfaces. Among the different designs, intraneural electrodes implanted in peripheral nerves represent a good strategy to stimulate nerve fibers to send sensory feedback and to record nerve signals to control the prosthetic limb. However, intraneural electrodes, as any device implanted in the body, induce a foreign body reaction (FBR) that results in the tissue encapsulation of the device. The FBR causes a progressive decline of the electrode functionality over time due to the physical separation between the electrode active sites and the axons to the interface. Modulation of the inflammatory response has arisen as a good strategy to reduce the FBR and maintain electrode functionality. In this paper, transversal intraneural multi-channel electrodes (TIMEs) were implanted in the rat sciatic nerve and tested for three months to evaluate stimulation and recording capabilities under chronic administration of dexamethasone. Dexamethasone treatment significantly reduced the threshold for evoking muscle responses during the follow-up compared to saline-treated animals, without affecting the selectivity of stimulation. However, dexamethasone treatment did not improve the signal-to-noise ratio of the recorded neural signals. Dexamethasone treatment allowed to maintain more working active sites along time than saline treatment. Thus, systemic administration of dexamethasone appears as a useful treatment in chronically implanted animals with neural electrodes as it increases the number of functioning contacts of the implanted TIME and reduces the intensity needed to stimulate the nerve. ; This research was supported by the European Union FPTICT projects NEBIAS (contract number FP7-611687), EPIONE (FP7-602547), FEDER and by the European Union's Horizon 2020 Graphene Flagship Core Project 2 (grant agreement 785219) and FLAG-ERA JTC 2017 project GRAFIN, by TERCEL (RD12/0019/0011) and CIBERNED (CB06/05/1105) funds from the Instituto de Salud Carlos III of Spain, and by Fundación Ramón Areces (CIVP18A3897). The ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant SEV-2013-0295), and by the CERCA Programme/Generalitat de Catalunya. ; Peer reviewed

It is possible to develop implantable microstimulators whose actuation principle is based on rectification of high frequency (HF) current bursts supplied through skin electrodes. This has been demonstrated previously by means of devices consisting of a single diode. However, previous single diode devices caused DC currents which made them impractical for clinical applications. Here flexible thread-like stimulation implants which perform charge balance are demonstrated in vivo. Approach. The implants weight 40.5 mg and they consist of a 3 cm long tubular silicone body with a diameter of 1 mm, two electrodes at opposite ends and, within the central section of the body, an electronic circuit made up of a diode, two capacitors and a resistor. In the present study, each implant was percutaneously introduced through a 14G catheter into either the gastrocnemius muscle or the cranial tibial muscle of a rabbit hind limb. Then stimulation was performed by delivering HF bursts (amplitude < 60 V, frequency 1 MHz, burst repetition frequency from 10 Hz to 200 Hz, duration = 200 μs) through a pair of textile electrodes strapped around the hind limb and either isometric plantarflexion or dorsiflexion forces were recorded. Stimulation was also assayed 1, 2 and 4 weeks after implantation. Main results. The implants produced bursts of rectified current whose mean value was of a few mA and were capable of causing local neuromuscular stimulation. The implants were well tolerated during the 4 weeks. Significance. Existing power supply methods, and in particular inductive links, comprise stiff and bulky parts. This hinders the development of minimally invasive implantable devices for neuroprostheses based on electrical stimulation. The proposed methodology is intended for relieving such bottleneck. In terms of mass, thinness and flexibility, the demonstrated implants appear to be unprecedented among the intramuscular stimulation implants ever assayed in vertebrates. ; AI's research was supported by a Ramón y Cajal fellowship from the Spanish government and a Marie Curie grant (IRG 256376) from the European Commission. LB's research is supported by a scholarship from the UPF. QC's research is supported by a scholarship from the Spanish Ministry of Education.

Objective. Brain–computer-interfaces (BCIs) have been proposed not only as assistive technologies but also as rehabilitation tools for lost functions. However, due to the stochastic nature, poor spatial resolution and signal to noise ratio from electroencephalography (EEG), multidimensional decoding has been the main obstacle to implement non-invasive BCIs in real-live rehabilitation scenarios. This study explores the classification of several functional reaching movements from the same limb using EEG oscillations in order to create a more versatile BCI for rehabilitation. Approach. Nine healthy participants performed four 3D center-out reaching tasks in four different sessions while wearing a passive robotic exoskeleton at their right upper limb. Kinematics data were acquired from the robotic exoskeleton. Multiclass extensions of Filter Bank Common Spatial Patterns (FBCSP) and a linear discriminant analysis (LDA) classifier were used to classify the EEG activity into four forward reaching movements (from a starting position towards four target positions), a backward movement (from any of the targets to the starting position and rest). Recalibrating the classifier using data from previous or the same session was also investigated and compared. Main results. Average EEG decoding accuracy were significantly above chance with 67%, 62.75%, and 50.3% when decoding three, four and six tasks from the same limb, respectively. Furthermore, classification accuracy could be increased when using data from the beginning of each session as training data to recalibrate the classifier. Significance. Our results demonstrate that classification from several functional movements performed by the same limb is possible with acceptable accuracy using EEG oscillations, especially if data from the same session are used to recalibrate the classifier. Therefore, an ecologically valid decoding could be used to control assistive or rehabilitation mutli-degrees of freedom (DoF) robotic devices using EEG data. These results have important implications towards assistive and rehabilitative neuroprostheses control in paralyzed patients. ; This study was funded by the Baden-Württemberg Stiftung (GRUENS), the Deutsche Forschungsgemeinschaft (DFG, Koselleck and SP-1533/2-1), Bundes Ministerium für Bildung und Forschung BMBF MOTORBIC (FKZ 13GW0053), the fortune-Program of the University of Tübingen (2422-0-0), and AMORSA (FKZ 16SV7754). A Sarasola-Sanz's work is supported by the La Caixa-DAAD scholarship, and N IrastorzaLanda's work by the Basque Government and IKERBASQUE, Basque Foundation for Science.