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The successful completion of complex tasks like hanging a picture or laparoscopic surgery requires coordinated motion of more than two limbs. User-controlled supernumerary robotic limbs (SL) have been proposed to bypass the need for coordination with a partner in such tasks. However, neither the capability to control multiple limbs alone relative to collaborative control with partners, nor how that capability varies across different tasks, is well understood. In this work, we present an investigation of tasks requiring three-hands where the foot was used as an additional source of motor commands. We considered: (1) how does simultaneous control of three hands compare to a cooperating dyad; (2) how this relative performance was altered by the existence of constraints emanating from real or virtual physical connections (mechanical constraints) or from cognitive limits (cognitive constraints). It was found that a cooperating dyad outperformed a single user in all scenarios in terms of task score, path efficiency and motion smoothness. However, while the participants were able to reach more targets with increasing mechanical constraints/decreasing number of simultaneous goals, the relative difference in performance between a dyad and a participant performing trimanual activities decreased, suggesting further potential for SLs in this class of scenario.

Tele-operational tasks often suffer from instability issues and limited reliability during unpredictable interactions. We propose a real-time control law reproducing the impedance and kinematic behaviour of a subject's arm (shoulder and elbow) on a remote avatar in a 2-DoF task. The human arm impedance and kinematics are estimated respectively from EMG and M-IMU data and then mapped into the avatar arm through an impedance control. Contrary to literature methods, our portable tele-impedance controller relies only on wearable sensors and enables an easy use in unstructured environments. The good performance (R

Objective: This article presents the development and validation of a new robotic system for Transcranial Magnetic Stimulation (TMS), characterized by a new control approach, and an ad-hoc calibration methodology, specifically devised for the TMS application. Methods: The robotic TMS platform is composed of a 7 dof manipulator, controlled by an impedance control, and a camera-based neuronavigation system. The proposed calibration method was optimized on the workspace useful for the specific TMS application (spherical shell around the subject's head), and tested on three different hand-eye and robot-world calibration algorithms. The platform functionality was tested on six healthy subjects during a real TMS procedure, over the left primary motor cortex. Results: employing our method significantly decreases ( $p ) the calibration error by 34% for the position and 19% for the orientation. The robotic TMS platform achieved greater orientation accuracy than the expert operators, significantly reducing orientation errors by 46% ( $p ). No significant differences were found in the position errors and in the amplitude of the motor evoked potentials (MEPs) between the robot-aided TMS and the expert operators. Conclusion: The proposed calibration represents a valid method to significantly reduce the calibration errors in robot-aided TMS applications. Results showed the efficacy of the proposed platform (including the control algorithm) in administering a real TMS procedure, achieving better coil positioning than expert operators, and similar results in terms of MEPs. Significance: This article spotlights how to improve the performance of a robotic TMS platform, providing a reproducible and low-cost alternative to the few devices commercially available.

We present a system to provide the user with real time proprioceptive feedback regarding the state of a supernumerary robotic limb (SRL). The system converted the robot kinematics into a vibration amplitude-frequency value, using a custom electronic board. Four eccentric-motors placed on the leg delivered the vibrotactile pattern to subjects. We measured the accuracy in real-time tracking of the robot end-effector position and the delay from the robot movement onset. We tested four subjects in a preliminary study, and we found an average Position Error and a Delay of 0.084 ± 0.010 m and 1.169 ± 0.408 s respectively, which validated the feasibility of the presented setup. Increasing the learning phase duration should further improve subject performance. Additionally, the present platform could easily be employed to test the efficacy of different feedbacks (such as joint angles and torques) for real time tracking of SRL.

Movement control process can be considered to take place on at least two different levels: a high, more cognitive level and a low, sensorimotor level. On a high level processing a motor command is planned accordingly to the desired goal and the sensory afference, mainly proprioception, is used to determine the necessary adjustments in order to minimize any discrepancy between predicted and executed action. On a lower level processing, the proprioceptive feedback later employed in high level regulations, is generated by Ia sensory fibers positioned in muscle main proprioceptors: muscle spindles. By entraining the activity of these spindle fibers through 80Hz vibration of triceps distal tendon, we show the intriguing possibility of inducing kinematics adjustments due to negative feedback corrections, during a lifting task.

Over a lifetime of experience, the representation of the body is built upon congruent integration of multiple elements constituting the sensorimotor loop. To investigate its robustness against the rupture of congruency between senses and with motor command, we selectively manipulated in healthy subjects the binds between sight, proprioception, and efferent motor command. Two experiments based on the Moving Hand Illusion were designed employing Tendon Vibration Illusion to modulate proprioception and generate illusory altered feedback of movement. In Experiment A, visuomotor congruency was modulated by introducing adelay between complex multifingered movements performed by arobotic hand and real movement of each participant's hand. In the presence of the motor command, visuomotor congruency enhanced ownership, agency, and skin conductance, while proprioceptive-motor congruency was not effective, confirming the prevalence of vision upon proprioception. In Experiment B, the impact of visuo-proprioceptive congruency was tested in the absence of motor command because the robotic hand moved autonomously. Intersensory congruency compensated for the absence of motor command only for ownership. Skin conductance in Exp Band Proprioceptive Drift in both experiments did not change. Results suggest that ownership and agency are independently processed, and presence of the efferent component modulates sensory feedbacks salience. The brain seems to require the integration of at least two streams of congruent information. Bodily awareness can be generated from sensory information alone, but to feel in charge of the body, senses must be double-checked with the prediction generated from efference copy, which is treated as an additional sensory modality.

A unique virtual reality platform for multisensory integration studies is presented. It allows to provide multimodal sensory stimuli (i.e. auditory, visual, tactile, etc.) ensuring temporal coherence, key factor in cross-modal integration. Four infrared cameras allow to real-time track the human motion and correspondingly control a virtual avatar. A user-friendly interface allows to manipulate a great variety of features (i.e. stimulus type, duration and distance from the participants’ body, as well as avatar gender, height, arm pose, perspective, etc.) and to real-time provide quantitative measures of all the parameters. The platform has been validated on two healthy participants testing a reaction time task which combines tactile and visual stimuli, for the investigation of peripersonal space. Results proved the effectiveness of the proposed platform, showing a significant correlation (p=0.013) between the participant’s hand distance from the visual stimulus and the reaction time to the tactile stimulus. More participants will be recruited to further investigate the other measures provided by the platform.

In this paper we compare three approaches to solve the hand-eye and robot-world calibration problem, for their application to a Transcranial Magnetic Stimulation (TMS) system. The selected approaches are: i) non-orthogonal approach (QR24); ii) stochastic global optimization (SGO); iii) quaternion-based (QUAT) method. Performance were evaluated in term of translation and rotation errors, and computational time. The experimental setup is composed of a 7 dof Panda robot (by Franka Emika GmbH) and a Polaris Vicra camera (by Northern Digital Inc) combined with the SofTaxic Optic software (by E.M.S. srl). The SGO method resulted to have the best performance, since it provides lowest errors and high stability over different datasets and number of calibration points. The only drawback is its computational time, which is higher than the other two, but this parameter is not relevant for TMS application. Over the different dataset used in our tests, the small workspace (sphere with radius of 0.05m) and a number of calibration points around 150 allow to achieve the best performance with the SGO method, with an average error of $0.83\pm 0.35mm$ for position and $0.22\pm 0.12deg$ for orientation.

The aim of this review is to collect and discuss the current best evidence published in literature about the effect of the Masai Barefoot Technology(MBT) shoes on gait and muscle activation and try to draw conclusions on the possible benefits. We searched Medline, CINAHL, Embase and the Cochrane Central Registry of Controlled Trials. The reference lists of the previously selected articles were then examined by hand. Only studies comparing biomechanical and clinical outcomes were selected. Review, anatomical studies, letter to editor and instructional course were excluded. Finally, all the resulting articles were reviewed and discussed by all the authors to further confirm their suitability for this review: in the end, 22 articles were included. A total of 532 patients presenting a mean age of 34.3 years were studied. All patients evaluated were healthy or amateur sports except in two studies where only obese subjects and knee osteoarthritis patients were involved. Seven studies evaluated only male subjects, whereas four studies evaluated only female. Twelve of twenty-two studies performed electromyographic analyses. Weight was reported in 19 studies, whereas body mass index were reported only in a five studies. All studies reported kinematic analysis of shoe effects and compared the relationship between muscle recruitment and electromyographic activity. Unstable footwears were shown to immediately alter the stability in gait during daily-life activities. The center of body pressure is moved posteriorly with a consequent posterior displacement of the upper part of body in order to regain an appropriate body balance, and these postural changes are associated with an overall increase in the activity of lumbar erector spine muscles, as well as certain lower limb muscles. Current literature provides enough cues to conclude for a beneficial role of MBT shoes in the postural and proprioceptive recovery, but from the same literature cannot be drown clear and appropriate guidance to determine more in detail their indication for specific pathological conditions or for particular phases of the musculoskeletal recovery process.

Parkinson's disease (PD) is a neurodegenerative brain disorder that slowly brings on the dopaminergic neurons death. The depletion of the dopaminergic signal causes the onset of motor symptoms such as tremor, bradykinesia and rigidity. Usually, neurologists regularly monitor motor symptoms and motor fluctuations using the MDS-UPDRS part III clinical scale. Nevertheless, to have a more objective and quantitative evaluation, it is possible to assess the cardinal motor symptoms of PD using wearable sensors and portable robotic devices. Unfortunately while there are several research papers on the use of these devices on PD patients, their use is not so common in clinical practice. In this work we recorded specific MDS-UPDRS motor tasks using magneto-inertial devices, worn by seven PD subjects and seven age-matched controls, in order to deeply analyze the kinematic and dynamic characteristics of goal-directed movements of upper limb, in addition to extract quantitative indices (peak velocity, smoothness, etc) useful for the assessment of motor symptoms. Using only gyroscope signals we looked at those parameters useful to assess bradykinesia. We observed parameters changes from OFF to ON phase congruent with the MDS-UPDRS changes, especially in the frequency domain. Our results suggest the prono-supination task is the more consistent to describe the bradykinesia symptom with the gyroscopes. Probably because of the amplitude of the movement performed. Moreover the peak power looks appropriate for bradykinesia symptom evaluation. We can conclude that, similar to the studies in which tremor symptom is evaluated, it is possible to monitor the bradykinesia using few wearable sensors and few simple parameters.

Background In recent years, many studies have evaluated the effects of noninvasive brain stimulation (NIBS) techniques for the treatment of several neurological and psychiatric disorders. Positive results led to approval of NIBS for some of these conditions by the Food and Drug Administration in the USA. The therapeutic effects of NIBS have been related to bi-directional changes in cortical excitability with the direction of change depending on the choice of stimulation protocol. Although after-effects are mostly short lived, complex neurobiological mechanisms related to changes in synaptic excitability bear the potential to further induce therapy-relevant lasting changes. Objective To review recent neurobiological findings obtained from in vitro and in vivo studies that highlight molecular and cellular mechanisms of short- and long-term changes of synaptic plasticity after NIBS. Findings Long-term potentiation (LTP) and depression (LTD) phenomena by itself are insufficient in explaining the early and long term changes taking place after short episodes of NIBS. Preliminary experimental studies indicate a complex scenario potentially relevant to the therapeutic effects of NIBS, including gene activation/regulation, de novo protein expression, morphological changes, changes in intrinsic firing properties and modified network properties resulting from changed inhibition, homeostatic processes and glial function. Conclusions This review brings into focus the neurobiological mechanisms underlying long-term after-effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) recently obtained from in vitro and in vivo studies, both in animals and humans.

In this paper we propose and validate a teleoperated control approach for an anthropomorphic redundant robotic manipulator, using magneto-inertial sensors (IMUs). The proposed method allows mapping the motion of the human arm (used as the master) on the robot end-effector (the slave). We record arm movements using IMU sensors, and calculate human forward kinematics to be mapped on robot movements. In order to solve robot kinematic redundancy, we implemented different algorithms for inverse kinematics that allows imposing anthropomorphism criteria on robot movements. The main objective is to let the user to control the robotic platform in an easy and intuitive manner by providing the control input freely moving his/her own arm and exploiting redundancy and anthropomorphism criteria in order to achieve human-like behaviour on the robot arm. Therefore, three inverse kinematics algorithms are implemented: Damped Least Squares (DLS), Elastic Potential (EP) and Augmented Jacobian (AJ). In order to evaluate the performance of the algorithms, four healthy subjects have been asked to control the motion of an anthropomorphic robot arm (i.e. the Kuka Light Weight Robot 4+) through four magneto-inertial sensors (i.e. Xsens Wireless Motion Tracking sensors - MTw) positioned on their arm. Anthropomorphism indices and position and orientation errors between the human hand pose and the robot end-effector pose were evaluated to assess the performance of our approach.

In healthy volunteers (HVs), we recently observed that the rules of the time-dependent paired-associative plasticity found in the sensorimotor system are valid also for the visual system. With the latter method, here, we have tested whether dysfunctioning associative plasticity might characterize the visual system in patients with episodic migraine without aura (MO), where abnormalities in both inhibitory and excitatory paired-associative sensorimotor plasticity have been observed between attacks (1). In 11 MO between attacks and in 14 HVs, we performed a visual paired associative stimulation (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with low-frequency TMS pulses over the occipital cortex at 2 interstimulus intervals in separate sessions by subtracting or adding 25 ms to the visual evoked potential (VEP) P100 latency. We recorded VEPs (600 sweeps) before, after, and 10-min later each vPAS session. VEPs were partitioned in 6 blocks of 100 sweeps. We analysed VEP N1-P1 first block amplitude and delayed habituation. While vPAS-25 significantly enhanced and vPAS + 25 reduced VEP amplitude habituation in HVs, they both did not significantly change VEP amplitude habituation in MO between attacks. We provide evidence for lack of excitability depressing and enhancing short-term associative plasticity mechanisms within the visual system in interictal migraine.

The development of a new generation of hand prostheses that can ideally approximate the human 'physiological' performance in terms of movement dexterity and sensory feedback for amputees still poses many open research challenges. The most promising approaches aim at establishing a direct connection with either the central or the peripheral human nervous system by means of invasive or non-invasive neural interfaces. This paper starts from the assumption that a major contribution to derive functional and technical specifications for such interfaces, and even for the whole prosthetic system, can stem from in-depth analysis of the nervous system reorganization following limb amputation. Neuroplasticity can be modulated by the use of hand prostheses both in the acute phase and in the long-term. We hereby critically review the literature concerning neuroplastic phenomena in amputees, in terms of changes at different CNS levels, particularly for their implications on the development of bidirectional neural interfaces for cybernetic hand prostheses. Our analysis of the literature demonstrates that: (1) the level of CNS reorganization could be used as a parameter of the effectiveness achieved by the prosthetic device and its interfaces, in restoring the hand physiological functionality, (2) the prosthetic system could be seen as a neurorehabilitation tool, as it could induce reduction in aberrant plasticity and promote 'good' plasticity and (3) new generations of 'natural' interfaces can be developed by fully exploiting neuroplastic phenomena to restore neural connections originally governing the lost limb and linking them to the prosthetic system.

Fiber Bragg Grating (FBG) technology is very attractive to develop sensors for the measurement of thermal and mechanical parameters in biological applications, particularly in presence of electromagnetic interferences. This work presents the design, working principle and experimental characterization of a force sensor based on two FBGs, with the feature of being compatible with Magnetic Resonance. Two prototypes based on different designs are considered and characterized: 1) the fiber with the FBGs is encapsulated in a polydimethylsiloxane (PDMS) sheet; 2) the fiber with the FBGs is free without the employment of any polymeric layer. Results show that the prototype which adopts the polymeric sheet has a wider range of measurement (4200 mN vs 250 mN) and good linearity; although it has lower sensitivity (≈0.1 nm-N1 vs 7 nm-N1). The sensor without polymeric layer is also characterized by employing a differential configuration which allows neglecting the influence of temperature. This solution improves the linearity of the sensor, on the other hand the sensitivity decreases. The resulting good metrological properties of the prototypes here tested make them attractive for the intended application and in general for force measurement during biomedical applications in presence of electromagnetic interferences. © 2014 IEEE.

Associative stimulation of peripheral afferents paired with low-frequency transcranial magnetic stimulation (LF-TMS) over the motor area (PAS) at an interstimulus interval (ISI) slightly shorter or longer than the time needed for the afferent inputs to reach the cerebral cortex, can decrease or increase the excitability of the motor system. None has proven whether the same time-dependent plasticity rules may also be valid for the visual system. In 12 healthy subjects, we performed a visual PAS (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with LF-TMS pulses over the occipital cortex at 4 ISIs in separate sessions chosen by subtracting or adding 25/50 ms to the visual evoked potential (VEP) P1 latency. We recorded VEPs (600 sweeps) before, after, and 10-min later each vPAS session. VEPs were partitioned in 6 blocks of 100 sweeps. We analyzed VEP N1-P1 first amplitude and delayed habituation. VEP amplitude of the first block was reduced immediately after PAS+25, while it remained unchanged after the other vPAS protocols. Delayed VEP habituation significantly increased after PAS−25, and decreased after PAS+25. Associative bidirectional synaptic plasticity is not confined to the corticomotor system, but can also be a feature of the visual system.

Previous studies suggested that both robotic rehabilitation and non-invasive brain stimulation could produce improvement in chronic stroke patients. It is still unknown whether their combination can produce synergistic effects. We designed a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial to assess the safety and efficacy of this combination. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement. The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke.

It has been proved that Transcranial DCS (tDCS) can modulate cortical excitability, enhancing or decreasing, respectively by anodal or cathodal polarity. The short-term and lasting alterations induced by tDCS are strictly related to the charge density, duration of stimulation and the depth of neuron below the skull. Epilepsy represents a pathophysiological model of unbalanced relation between cortical excitation and inhibition. In this line, tDCS can be exploited to counterbalance the neuronal hyper-excitation through electric neural modulation. This paper aims at providing the efficacy of cathodal tDCS in reducing seizures’ frequency in drug-resistant focal epilepsy. The study was single blind and sham-controlled and compared seizure rate in the 7 days before and after tDCS and after sham in a cross-over design. 9 patients affected by focal resistant epilepsy were enrolled. After tDCS 3 out 9 patients have not any change in seizure rate. 6 patients reduced their seizure frequency >50%. No significant modification were recorded after sham. This study represents the proof that cathodal tDCS may be efficient in reducing seizures’frequency in focal resistant epilepsy.

Purpose: Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. Methods: Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG–TMS experiment. Results: The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. Conclusions: The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi-hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition.

Objective Delta waves (DW) are present both during sleep and in wakefulness. In the first case, DW are considered effectors of synaptic plasticity, while in wakefulness, when they appear in the case of brain lesions, their functional meaning is not unanimously recognized. To throw light on the latter, we aimed to investigate the impact on DW exerted by the cortical plasticity-inducing protocol of intermittent theta burst stimulation (iTBS). Methods Twenty healthy subjects underwent iTBS (11 real iTBS and nine sham iTBS) on the left primary motor cortex with the aim of inducing long-term potentiation (LTP)-like phenomena. Five-minute resting open-eye 32-channel EEG , right opponens pollicis motor-evoked potentials (MEPs), and alertness behavioral scales were collected before and up to 30 min after the iTBS. Power spectral density (PSD), interhemispheric coherence between homologous sensorimotor regions, and intrahemispheric coherence were calculated for the frequency bands ranging from delta to beta. Results Real iTBS induced a significant increase of both MEP amplitude and DW PSD lasting up to 30 min after stimulation, while sham iTBS did not. The DW increase was evident over frontal areas ipsilateral and close to the stimulated cortex (electrode F3). Neither real nor sham iTBS induced significant modifications in the PSD of theta, alpha, and beta bands and in the interhemispheric coherence. Behavioral visuo-analogic scales score did not demonstrate changes in alertness after stimulations. No correlations were found between MEP amplitude and PSD changes in the delta band. Conclusions Our data showed that LTP induction in the motor cortex during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of DW over the ipsilateral frontal cortex. Significance The present results are strongly in favor of a prominent role of DW in the neural plasticity processes taking place during the awake state.

It has been proved that Transcranial DCS (tDCS) can modulate cortical excitability, enhancing or decreasing, respectively by anodal or cathodal polarity. The short-term and lasting alterations induced by tDCS are strictly related to the charge density, duration of stimulation and the depth of neuron below the skull. Epilepsy represents a pathophysiological model of unbalanced relation between cortical excitation and inhibition. In this line, tDCS can be exploited to counterbalance the neuronal hyper-excitation through electric neural modulation. This paper aims at providing the efficacy of cathodal tDCS in reducing seizures’ frequency in drug-resistant focal epilepsy. The study was single blind and sham-controlled and compared seizure rate in the 7 days before and after tDCS and after sham in a cross-over design. 9 patients affected by focal resistant epilepsy were enrolled. After tDCS 3 out 9 patients have not any change in seizure rate. 6 patients reduced their seizure frequency >50%. No significant modification were recorded after sham. This study represents the proof that cathodal tDCS may be efficient in reducing seizures’frequency in focal resistant epilepsy.

Purpose: This work investigates how a direct bidirectional connection between brain and hand prosthesis modifies the bi-hemispheric sensorimotor system devoted to the movement control of the lost limb. Hand prostheses are often unable to satisfy users' expectations, mostly due to the poor performance of their interfacing system. Neural Interfaces implanted inside nerves of the stump offer the advantage of using the bidirectional neural pathways 'naturally' dispatching signals to control proper hand actions and feed-back sensations. Learning to control a neurally-interfaced hand prosthesis and decode sensory information was previously observed to reduce the inter-hemispheric asymmetry of cortical motor maps and the clinical symptoms of phantom limb syndrome. Methods: Electroencephalographic (EEG) data was analysed using Functional Source Separation (FSS), a semi-blind method that incorporates prior knowledge about the signal of interest into data decomposition to give access to cortical patch activities. Results: Bi-hemispheric cortices showed normalization of their activity (topographical and spectral patterns) and of functional connectivity between homologous hand controlling areas, during the delivery of the motor command to the cybernetic prosthesis. Conclusions: The re-establishment of central-peripheral communication with the lost limb induced by a neurally-interfaced hand prosthesis produces beneficial plastic reorganization, not only restructuring contralateral directly-connected control areas, but also their functional balance within the bi-hemispheric system necessary for motor control.

The possibility of controlling dexterous hand prostheses by using a direct connection with the nervous system is particularly interesting for the significant improvement of the quality of life of patients, which can derive from this achievement. Among the various approaches, peripheral nerve based intrafascicular electrodes are excellent neural interface candidates, representing an excellent compromise between high selectivity and relatively low invasiveness. Moreover, this approach has undergone preliminary testing in human volunteers and has shown promise. In this paper, we investigate whether the use of intrafascicular electrodes can be used to decode multiple sensory and motor information channels with the aim to develop a finite state algorithm that may be employed to control neuroprostheses and neurocontrolled hand prostheses. The results achieved both in animal and human experiments show that the combination of multiple sites recordings and advanced signal processing techniques (such as wavelet denoising and spike sorting algorithms) can be used to identify both sensory stimuli (in animal models) and motor commands (in a human volunteer). These findings have interesting implications, which should be investigated in future experiments.

The foreign body reaction that the neural tissue develops around an implanted electrode contributes to insulate the probe and enhances the electrical and mechanical mismatch. It is a complex interaction among cells and soluble mediators and the knowledge of this phenomenon can benefits of formal and analytical methods that characterize the mathematical models. This work offers a lumped component model, described by ordinary differential equations, that taking into account the main geometrical (size, shape, insertion angle) and chemical (coating surface) properties of the implant predict the thickness of the fibrotic capsule in a time frame when the reaction stabilizes. This tool allows to evaluate different hypothetical solutions for accounting the tissue-electrode mismatch.

This paper reports the preliminary results of a research effort aiming at conceptualizing novel insect/machine hybrid controllers for autonomous exploratory vehicles. In particular, we investigate the possibility to include pre-developed animal intelligence capable of sensory-motor integration, decision-making and learning behaviors. In this context we present an in-depth review of insect neurophysiology focussing on mechanisms related to navigation. In addition we critically review current approaches towards hybridity and insect/machine interfaces. Finally, a novel insect/machine hybrid control architecture is proposed. It includes biological/artificial modules and deliberative/reactive behaviors.

Objective Delta waves are the most prominent electroencephalographic (EEG) feature of non-rapid eye movement sleep with cortical origin. Several human studies suggested they are sensor of synaptic weight and possible effectors of sleep-dependent synaptic plasticity. During wakefulness delta waves are almost absent in physiological conditions, but they come out when a subcortical brain lesion occurs. For these reasons delta waves during wakefulness are considered as a lesional sign but no definitive data about its functional significance were provided. Our aim was to verify whether delta waves can be a sign of plastic cortical modifications. Materials and methods 11 young healthy subjects (28 ± 3) were enrolled in the study. Intermittent theta burst stimulation (iTBS) was administered on left primary motor cortex to induce enduring cortical motor plasticity. High density scalp EEG (32 channels) was recorded all along the experiment. PSD for standard frequency bands (delta 1–3.5 Hz, theta 4–7.5 Hz, alpha 8–12 Hz, beta 13–22 Hz) was calculated in each longitudinal bipolar derivation. 5-min resting opened-eyes EEG was analyzed pre-iTBS (T0) and immediately after iTBS (T1), after 15 (T2) and 30 (T3) min. MEP amplitude and visual analogic scales about sleepiness, alertness, and the Stanford Sleepiness Scale were analyzed at the same time-points to explore motor plasticity induction and alertness status. Results iTBS induced a 9%-increase of MEP amplitude which remained stable until 30 min after stimulation (T1vsT0 p = 0.005; T2vsT1 p = 0.560; T3vsT2 p = 0.158). A selective increase (+87.5%) in delta band PSD was evident at T1 vs T0, remaining stable all along the experiment (T1vsT0 p = 0.019, T2vsT1 p = 0.724, T3vsT2 p = 1). Significant changes were bilaterally present only in fronto-central derivations ( p Discussion Our experiment firstly demonstrated a large and enduring increase in EEG delta activity in cortical areas undergoing plasticity induction during wakefulness. Present results may open new scenarios in interpreting scalp EEG slow waves after brain lesions not only as sign of lesion but also as sign of neuronal plastic rearrangement not with a negative value.

Aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject’s cortico-cortical excitability, connectivity and plasticity were directly tested via neuronavigated EEG–TMS. The statistical analysis demonstrated a significant modulation of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When looking at the individual latencies in that time range, significant differences between T0 and T1 condition at 30 ms, ms and 60 ms latencies were present. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity.

Humans increasingly often act through virtual and robotic avatars, which can feed back to their user only virtual sensory information. Since avatar is user’s embodiment and body image is mostly based on senses, how virtualization of sensory inputs affects avatar self-attribution is a key question for understanding nowadays human behavior. By manipulating visual and tactile inputs in a series of experiments fashioned after the rubber hand illusion, we assessed the relative weight of the virtualization of sight (Real, Robotic, Virtual) and of touch (Real, Virtual) on artificial hand embodiment. Virtualization decreased embodiment, but unexpectedly lowest embodiment was found when only one sense was virtual. Discordant levels of virtualization of sight and touch elicited revulsion, extending the concept of the uncanny valley to avatar embodiment. Besides timing, spatial constraints and realism of feedback, a matched degree of virtualization of seen and felt stimuli is a further constraint in building the representation of the body.

Inclusion of the prosthesis in the body schema lets the device felt by the user as an extension of the self and consequently improves its performance and acceptability. Two paradigmatic models that faced the issue of the illusory embodiment, the rubber hand illusion and the mirror box, revealed that such process goes in parallel with changes in the activity of cortical sensorimotor areas devoted to the limb and that a key factor is represented by the visual inflow that overrides the mismatching kinesthesia. In spite of that, vision alone is not able to trigger prosthesis embodiment in amputees everyday-life. In order to disentangle the contributes of visual and proprioceptive feedback in the induction of sensorimotor plasticity we develop the Illusion Box of Syndactyly that, through an ad hoc algorithm, produces an index-middle finger illusory fingers webbing. The algorithm works in realtime and, trough background difference, it segments the hands, recognizes the fingers and produces the virtual syndactyly. We perform preliminary tests on a healthy subject, suggesting that the setup is robust and efficient to induce the illusion.

A novel system to provide the user with proprioceptive feedback from a supernumerary robotic limb through vibrotactile stimulation is presented. The system is composed of a dedicated electronic board that converts the robot state, acquired through serial communication, into a vibration amplitude-frequency value and commands up to sixteen eccentric motors, placed on the user’s leg skin. The system is designed to allow the subject to have cues on the robot state even without visual feedback. Two different feedback encoding paradigms, one based on a kinematic approach and the other on a dynamic one, have been tested in three healthy subjects to validate the platform. In a planar task and with slow robot motions, conveying the robot state through the cartesian position (kinematic method) allows to achieve hugely better (d=4.278) performance than using joint torques (dynamic approach) or non-informative feedback.

The performance of motor neuroprostheses or robotic arm prostheses can be significantly improved by delivering sensory feed-back related to the ongoing motor task (e.g. the slippage of an object during grasping). Microfabricated neural electrodes implantable in peripheral nervous system seem a promising approach to this aim. New generation of thin-film intrafascicular electrodes longitudinally implantable in peripheral nerves (tf-LIFE4) has been developed and tested for afferent stimulation in human amputee case study.

The development of hybrid neuroprosthetic systems (HBSs) linking the human nervous system with artificial devices is an important area of research that is currently addressed by several groups to restore sensorimotor function in people affected by different disabilities. It is particularly important to establish a fast, intuitive, bidirectional flow of information between the nervous system of the user and the smart robotic device. Among the possible solutions to achieve this goal, interfaces with the peripheral nervous system and in particular intraneural electrodes can represent an interesting choice. In the present study, thin-film longitudinal intra-fascicular electrodes were implanted in the median and ulnar nerves of an amputee. The possibility of restoring the bidirectional link between the subject and the external world was investigated during a 4 week trial. The result showed that both the extraction of motor information and the restoration of sensory function are possible.

The aim of this work was to investigate the possibility to obtain stable bioactive coatings for polyimide/platinum neural interfaces based on thin film technology for applications into the peripheral nervous system (PNS). Laminin (LI), a glycoprotein of the extracellular matrix, which guides and promotes differentiation and growth of neurons, was selected to deposit bioactive coatings. Dip-coating was performed on dummy structures at different LI concentrations. Indirect methods allowed to identify and characterize laminin on coated samples. Mechanical stability was also confirmed by indirect evaluations. Pilot experiments with differentiated PC12 cells, by the addition of nerve growth factor (NGF), showed improved neurite outgrowth on the coated probes compared to bare polyimide samples.