Artificial embodiment displaces cortical neuromagnetic somatosensory responses.

Integrating artificial limbs as part of one's body involves complex neuroplastic changes resulting from various sensory inputs. While somatosensory feedback is crucial, plastic processes that enable embodiment remain unknown. We investigated this using somatosensory evoked fields (SEFs) in the primary somatosensory cortex (S1) following the Rubber Hand Illusion (RHI), known to quickly induce artificial limb embodiment. During electrical stimulation of the little finger and thumb, 19 adults underwent neuromagnetic recordings before and after the RHI. We found early SEF displacement, including an illusion-brain correlation between extent of embodiment and specific changes to the first cortical response at 20 ms in Area 3b, within S1. Furthermore, we observed a posteriorly directed displacement at 35 ms towards Area 1, known to be important for visual integration during touch perception. That this second displacement was unrelated to extent of embodiment implies a functional distinction between neuroplastic changes of these components and areas. The earlier shift in Area 3b may shape extent of limb ownership, while subsequent displacement into Area 1 may relate to early visual-tactile integration that initiates embodiment. Here we provide evidence for multiple neuroplastic processes in S1-lasting beyond the illusion-supporting integration of artificial limbs like prostheses within the body representation.

Tele-Impedance control of a virtual avatar based on EMG and M-IMU sensors: a proof-of-concept.

The broad spread of cooperative robots into many application domains has resulted in a demand for intuitive and effective solutions for teleoperated control. A relevant role in teleoperation has been assumed by impedance controllers, that allow the increase of stability and accuracy during interaction. This paper aims to test a teleoperation method based on an impedance controller, namely tele-impedance control, that is usable in unstructured environments since it relies only on wearable sensors. The proposed solution maps the joint stiffness and position of the human user, computed through six EMG and two M-IMU sensors, into the remote system to be teleoperated. We developed a 2-DoFs virtual task involving virtual physical interactions to compare the performance of our solution with the one of a traditional position-based controller. The study has been conducted on five healthy participants, who experienced both controllers in two different sessions. The tele-impedance approach has proved to be less physically demanding and more intuitive than the position-based one. Experimental data also allow us to investigate the strategy employed by the volunteers in the case of remote interactions, while using the two controllers. Of note, even though with the position controller the variation of subject impedance has no effect on the virtual arm, participants still tend to regulate both impedance and position of their own arm.

Experiencing an Elongated Limb in Virtual Reality Modifies the Tactile Distance Perception of the Corresponding Real Limb.

In measurement, a reference frame is needed to compare the measured object to something already known. This raises the neuroscientific question of which reference frame is used by humans when exploring the environment. Previous studies suggested that, in touch, the body employed as measuring tool also serves as reference frame. Indeed, an artificial modification of the perceived dimensions of the body changes the tactile perception of external object dimensions. However, it is unknown if such a change in tactile perception would occur when the body schema is modified through the illusion of owning a limb altered in size. Therefore, employing a virtual hand illusion paradigm with an elongated forearm of different lengths, we systematically tested the subjective perception of distance between two points [tactile distance perception (TDP) task] on the corresponding real forearm following the illusion. Thus, the TDP task is used as a proxy to gauge changes in the body schema. Embodiment of the virtual arm was found significantly greater after the synchronous visuotactile stimulation condition compared with the asynchronous one, and the forearm elongation significantly increased the TDP. However, we did not find any link between the visuotactile-induced ownership over the elongated arm and TDP variation, suggesting that vision plays the main role in the modification of the body schema. Additionally, significant effect of elongation found on TDP but not on proprioception suggests that these are affected differently by body schema modifications. These findings confirm the body schema malleability and its role as a reference frame in touch.

Intracortical and interhemispheric excitability changes in arm amputees: A TMS study.

OBJECTIVE: To evaluate cortical circuits and excitability of the motor cortex in the hemisphere contralateral to the affected (AH) and to the unaffected arm (UH), in upper limb amputees. METHODS: Motor evoked potentials (MEP) were recorded in 17 subjects who had upper limb amputation: 11 trans-radial (TR) and 6 trans-humeral (TH). Motor thresholds (MT), short interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI) in the available arm muscles of the stump were evaluated. RESULTS: There was no significant difference in MT between hemispheres. SICI was preserved in TR but not in TH group. Additionally, in the TR group, the MEP amplitudes in AH were higher than in UH. A significant IHI was observed in the whole sample but not in each hemisphere or patient group. CONCLUSIONS: In our population of TR amputees, we found increased corticospinal excitability in the AH with preserved intracortical inhibition. This finding was not observed in the TH population. SIGNIFICANCE: Understanding the changes in intracortical excitability in amputees may enhance knowledge of the functional reorganization of the brain in the post-amputation phase, bringing useful information for prosthetic rehabilitation.

Integration of proprioception in upper limb prostheses through non-invasive strategies: a review.

Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.

From rubber hands to neuroprosthetics: Neural correlates of embodiment.

Our interaction with the world rests on the knowledge that we are a body in space and time, which can interact with the environment. This awareness is usually referred to as sense of embodiment. For the good part of the past 30 years, the rubber hand illusion (RHI) has been a prime tool to study embodiment in healthy and people with a variety of clinical conditions. In this paper, we provide a critical overview of this research with a focus on the RHI paradigm as a tool to study prothesis embodiment in individuals with amputation. The RHI relies on well-documented multisensory integration mechanisms based on sensory precision, where parietal areas are involved in resolving the visuo-tactile conflict, and premotor areas in updating the conscious bodily representation. This mechanism may be transferable to prosthesis ownership in amputees. We discuss how these results might transfer to technological development of sensorised prostheses, which in turn might progress the acceptability by users.

Exploring crossmodal correspondences for future research in human movement augmentation.

"Crossmodal correspondences" are the consistent mappings between perceptual dimensions or stimuli from different sensory domains, which have been widely observed in the general population and investigated by experimental psychologists in recent years. At the same time, the emerging field of human movement augmentation (i.e., the enhancement of an individual's motor abilities by means of artificial devices) has been struggling with the question of how to relay supplementary information concerning the state of the artificial device and its interaction with the environment to the user, which may help the latter to control the device more effectively. To date, this challenge has not been explicitly addressed by capitalizing on our emerging knowledge concerning crossmodal correspondences, despite these being tightly related to multisensory integration. In this perspective paper, we introduce some of the latest research findings on the crossmodal correspondences and their potential role in human augmentation. We then consider three ways in which the former might impact the latter, and the feasibility of this process. First, crossmodal correspondences, given the documented effect on attentional processing, might facilitate the integration of device status information (e.g., concerning position) coming from different sensory modalities (e.g., haptic and visual), thus increasing their usefulness for motor control and embodiment. Second, by capitalizing on their widespread and seemingly spontaneous nature, crossmodal correspondences might be exploited to reduce the cognitive burden caused by additional sensory inputs and the time required for the human brain to adapt the representation of the body to the presence of the artificial device. Third, to accomplish the first two points, the benefits of crossmodal correspondences should be maintained even after sensory substitution, a strategy commonly used when implementing supplementary feedback.

Comparing end-effector position and joint angle feedback for online robotic limb tracking.

Somatosensation greatly increases the ability to control our natural body. This suggests that supplementing vision with haptic sensory feedback would also be helpful when a user aims at controlling a robotic arm proficiently. However, whether the position of the robot and its continuous update should be coded in a extrinsic or intrinsic reference frame is not known. Here we compared two different supplementary feedback contents concerning the status of a robotic limb in 2-DoFs configuration: one encoding the Cartesian coordinates of the end-effector of the robotic arm (i.e., Task-space feedback) and another and encoding the robot joints angles (i.e., Joint-space feedback). Feedback was delivered to blindfolded participants through vibrotactile stimulation applied on participants' leg. After a 1.5-hour training with both feedbacks, participants were significantly more accurate with Task compared to Joint-space feedback, as shown by lower position and aiming errors, albeit not faster (i.e., similar onset delay). However, learning index during training was significantly higher in Joint space feedback compared to Task-space feedback. These results suggest that Task-space feedback is probably more intuitive and more suited for activities which require short training sessions, while Joint space feedback showed potential for long-term improvement. We speculate that the latter, despite performing worse in the present work, might be ultimately more suited for applications requiring long training, such as the control of supernumerary robotic limbs for surgical robotics, heavy industrial manufacturing, or more generally, in the context of human movement augmentation.

Upper limb home-based robotic rehabilitation in chronic stroke patients: A pilot study.

Introduction: Robotic therapy allow to propose sessions of controlled and identical exercises, customizing settings, and characteristics on the individual patient. The effectiveness of robotic assisted therapy is still under study and the use of robots in clinical practice is still limited. Moreover, the possibility of treatment at home allows to reduce the economic costs and time to be borne by the patient and the caregiver and is a valid tool during periods of pandemic such as covid. The aim of this study is to assess whether a robotic home-based treatment rehabilitation using the iCONE robotic device has effects on a stroke population, despite the chronic condition of patients involved and the absence of a therapist next to the patient while performing the exercises. Materials and methods: All patients underwent an initial (T0) and final (T1) assessment with the iCONE robotic device and clinical scales. After T0 evaluation, the robot was delivered to the patient's home for 10 days of at-home treatment (5 days a week for 2 weeks). Results: Comparison between T0 and T1 evaluations revealed some significant improvements in robot-evaluated indices such as Independence and Size for the Circle Drawing exercise and Movement Duration for Point-to-Point exercise, but also in the MAS of the elbow. From the analysis of the acceptability questionnaire, a general appreciation of the robot emerged: patients spontaneously asked for the addition of further sessions and to continue therapy. Discussion: Telerehabilitation of patients suffering from a chronic stroke is an area that is still little explored. From our experience, this is one of the first studies to carry out a telerehabilitation with these characteristics. The use of robots can become a method to reduce the rehabilitation health costs, to ensure continuity of care, and to arrive in more distant places or where the availability of resources is limited. Conclusion: From the data obtained, this rehabilitation seems to be promising for this population. Moreover, promoting the recovery of the upper limb, iCONE can improve patient's quality of life. It would be interesting to conduct RCT studies to compare a conventional treatment in structure with a robotic telematics treatment.

Wrist redundancy management during pointing tasks remains stable over time and in presence of a visuomotor perturbation.

Pointing at a screen using wrist and forearm movements is a kinematically redundant task, and the Central Nervous System seems to manage this redundancy by using a simplifying strategy, named Donders' Law for the wrist. In this work we investigated (1) whether this simplifying approach is stable over time and (2) whether a visuomotor perturbation provided in the task space influences the strategy used to solve the redundancy problem. We conducted two experiments asking participants to perform the same pointing task in four different days (first experiment), and providing a visual perturbation, i.e. a visuomotor rotation to the controlled cursor (second experiment), while recording their wrist and forearm rotations. Results showed that the participant-specific wrist redundancy management (described by the Donders' surfaces) (1) neither changes over time (2) nor varies when a visuomotor perturbation is provided in the task space.

Reduced connectivity of primary auditory and motor cortices during exposure to auditory white noise.

Auditory white noise (WN) is widely used in daily life for inducing sleep, and in neuroscience to mask unwanted environmental noise and cues. However, WN was recently reported to influence corticospinal excitability and behavioral performance. Here, we expand previous preliminary findings on the influence of WN exposure on cortical functioning, and we hypothesize that it may modulate cortical connectivity. We tested our hypothesis by performing magnetoencephalography in 20 healthy subjects. WN reduces cortical connectivity of the primary auditory and motor regions with very distant cortical areas, showing a right lateralized connectivity reduction for primary motor cortex. The present results, together with previous finding concerning WN impact on corticospinal excitability and behavioral performance, further support the role of WN as a modulator of cortical function. This suggest avoiding its unrestricted use as a masking tool, while purposely designed and controlled WN application could be exploited to harness brain function and to treat neuropsychiatric conditions.

High-frequency oscillations-based precise temporal resolution of short latency afferent inhibition in the human brain.

OBJECTIVE: Sensorimotor integration is a crucial process for adaptive behaviour and can be explored non-invasively with a conditioned transcranial magnetic stimulation (TMS) paradigm - i.e. short-latency afferent inhibition (SAI). To gain insight into the sensorimotor integration phenomenon, we used two different approaches to combine peripheral and cortical stimulation in the SAI paradigm, measuring not only the latency of low frequency somatosensory evoked potentials (SEPs) but also the peaks of high frequency oscillations (HFOs) underlying SEPs. METHODS: The interstimulus intervals (ISIs) between the electrical stimulation of the median nerve and the motor cortex magnetic stimulation were determined relative to the latency of the earliest SEPs cortical potential (N20) or the HFOs peaks. In particular, the first and last negative and positive peaks of HFOs were extracted through a custom-made MATLAB script. RESULTS: Thirty-three healthy subjects participated in this study. We found out that muscle responses after TMS were suppressed when ISIs were comprised between -1 to +3 ms relative to the N20 peak and at all ISIs relative to HFOs peaks, except for the first negative peak. CONCLUSIONS: Coupling peripheral and cortical stimulation at early interstimulus intervals - before the SEPs N20 peak - may modulate muscle response. SIGNIFICANCE: Our findings confirm that afferent inhibition is produced both through a direct (thalamus-motor cortex) and indirect (thalamus-somatosensory-motor cortex) pathway.

Stimulation with acoustic white noise enhances motor excitability and sensorimotor integration.

Auditory white noise (WN) is widely used in neuroscience to mask unwanted environmental noise and cues, e.g. TMS clicks. However, to date there is no research on the influence of WN on corticospinal excitability and potentially associated sensorimotor integration itself. Here we tested the hypothesis, if WN induces M1 excitability changes and improves sensorimotor performance. M1 excitability (spTMS, SICI, ICF, I/O curve) and sensorimotor reaction-time performance were quantified before, during and after WN stimulation in a set of experiments performed in a cohort of 61 healthy subjects. WN enhanced M1 corticospinal excitability, not just during exposure, but also during silence periods intermingled with WN, and up to several minutes after the end of exposure. Two independent behavioural experiments highlighted that WN improved multimodal sensorimotor performance. The enduring excitability modulation combined with the effects on behaviour suggest that WN might induce neural plasticity. WN is thus a relevant modulator of corticospinal function; its neurobiological effects should not be neglected and could in fact be exploited in research applications.

Design of multi-pad electrotactile system envisioned as a feedback channel for supernumerary robotic limbs.

BACKGROUND: Providing real-time haptic feedback is an important, but still not sufficiently explored aspect of the use of supernumerary robotic limbs (SRLs). We present a multi-pad electrode for conveying multi-modal proprioceptive and sensory information from SRL to the user's thigh and propose a method for stimuli calibration. METHODS: Within two pilot tests, we investigated return electrode configuration and active electrode discrimination in three healthy subjects to select the appropriate electrode pad topology. Based on the obtained results and anthropometric data from the literature, the electrode was designed to have three branches of 10 pads and two additional pads that can be displaced over/under the electrode branches. The electrode was designed to be connected to the stimulator that allows full multiplexing so that specific branches can serve as a common return electrode. To define the procedure for application of this system, the sensation, localization, and discomfort thresholds applicable for the novel electrode were determined and analyzed in 10 subjects. RESULTS: The results showed no overlaps between the three thresholds for individual pads, with significantly different average values, suggesting that the selected electrode positioning and design provide a good active range of useful current amplitude. The results of the subsequent analysis suggested that the stimuli intensity level of 200% of the sensation threshold is the most probable value of the localization threshold. Furthermore, this level ensures a low chance (i.e., 0.7%) of reaching the discomfort. CONCLUSIONS: We believe that envisioned electrotactile system could serve as a high bandwidth feedback channel that can be easily set up to provide proprioceptive and sensory feedback from supernumerary limbs.

Embodying an artificial hand increases blood flow to the investigated limb [version 3; peer review: 2 approved].

Background: The autonomic nervous system is the main determinant of the blood flow directed towards a body part, and it is tightly connected to the representation of the body in the brain; would the experimental modulation of the sense of limb ownership affect its blood perfusion? Methods: In healthy participants, we employed the rubber hand illusion paradigm to modulate limb ownership while we monitored the brachial artery blood flow and resistance index within the investigated limb. Results: In all conditions with brush-stroking, we found an initial drop in the blood flow due to tactile stimulation. Subsequently, in the illusion condition (where both the rubber and real hand synchronous brush-stroking were present), the blood flow rose significantly faster and reached significantly higher values. Moreover, the increase in blood flow correlated with the extent of embodiment as measured by questionnaires and correlated negatively with the change of peripherical vascular resistance. Conclusions: These findings suggest that modulating the representation of a body part impacts its blood perfusion.

A Soft Zwitterionic Hydrogel as Potential Coating on a Polyimide Surface to Reduce Foreign Body Reaction to Intraneural Electrodes.

Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees. Nevertheless, in chronic implants, the progressive formation of a fibrotic capsule can gradually isolate the electrode surface from the surrounding tissue leading to loss of functionality. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR). The commonly used poly(ethylene glycol) (PEG)-based low-fouling coatings of implantable devices can be easily encapsulated and are susceptible to oxidative damage in long-term in vivo applications. Recently, sulfobetaine-based zwitterionic hydrogels have emerged as an important class of robust ultra-low fouling biomaterials, holding great potential to mitigate FBR. The aim of this proof-of-principle in vitro work was to assess whether the organic zwitterionic-poly(sulfobetaine methacrylate) [poly(SBMA)]-hydrogel could be a suitable coating for Polyimide (PI)-based intraneural electrodes to reduce FBR. We first synthesized and analyzed the hydrogel through a mechanical characterization (i.e., Young's modulus). Then, we demonstrated reduced adhesion and activation of fibrogenic and pro-inflammatory cells (i.e., human myofibroblasts and macrophages) on the hydrogel compared with PEG-coated and polystyrene surfaces using cell viability assays, confocal fluorescence microscopy and high-content analysis of oxidative stress production. Interestingly, we successfully coated PI surfaces with a thin film of the hydrogel through covalent bond and demonstrated its high hydrophilicity via water contact angle measurement. Importantly, we showed the long-term release of an anti-fibrotic drug (i.e., Everolimus) from the hydrogel. Because of the low stiffness, biocompatibility, high hydration and ultra-low fouling characteristics, our zwitterionic hydrogel could be envisioned as long-term diffusion-based delivery system for slow and controlled anti-inflammatory and anti-fibrotic drug release in vivo.

Principles of human movement augmentation and the challenges in making it a reality.

Augmenting the body with artificial limbs controlled concurrently to one's natural limbs has long appeared in science fiction, but recent technological and neuroscientific advances have begun to make this possible. By allowing individuals to achieve otherwise impossible actions, movement augmentation could revolutionize medical and industrial applications and profoundly change the way humans interact with the environment. Here, we construct a movement augmentation taxonomy through what is augmented and how it is achieved. With this framework, we analyze augmentation that extends the number of degrees-of-freedom, discuss critical features of effective augmentation such as physiological control signals, sensory feedback and learning as well as application scenarios, and propose a vision for the field.

Resting state network connectivity is attenuated by fMRI acoustic noise.

INTRODUCTION: During the past decades there has been an increasing interest in tracking brain network fluctuations in health and disease by means of resting state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI however does not provide the ideal environmental setting, as participants are continuously exposed to noise generated by MRI coils during acquisition of Echo Planar Imaging (EPI). We investigated the effect of EPI noise on resting state activity and connectivity using magnetoencephalography (MEG), by reproducing the acoustic characteristics of rs-fMRI environment during the recordings. As compared to fMRI, MEG has little sensitivity to brain activity generated in deep brain structures, but has the advantage to capture both the dynamic of cortical magnetic oscillations with high temporal resolution and the slow magnetic fluctuations highly correlated with BOLD signal. METHODS: Thirty healthy subjects were enrolled in a counterbalanced design study including three conditions: a) silent resting state (Silence), b) resting state upon EPI noise (fMRI), and c) resting state upon white noise (White). White noise was employed to test the specificity of fMRI noise effect. The amplitude envelope correlation (AEC) in alpha band measured the connectivity of seven Resting State Networks (RSN) of interest (default mode network, dorsal attention network, language, left and right auditory and left and right sensory-motor). Vigilance dynamic was estimated from power spectral activity. RESULTS: fMRI and White acoustic noise consistently reduced connectivity of cortical networks. The effects were widespread, but noise and network specificities were also present. For fMRI noise, decreased connectivity was found in the right auditory and sensory-motor networks. Progressive increase of slow theta-delta activity related to drowsiness was found in all conditions, but was significantly higher for fMRI . Theta-delta significantly and positively correlated with variations of cortical connectivity. DISCUSSION: rs-fMRI connectivity is biased by unavoidable environmental factors during scanning, which warrant more careful control and improved experimental designs. MEG is free from acoustic noise and allows a sensitive estimation of resting state connectivity in cortical areas. Although underutilized, MEG could overcome issues related to noise during fMRI, in particular when investigation of motor and auditory networks is needed.