A Computational Framework for Electrical Stimulation of Vestibular Nerve.

The vestibular organs are very important to generate reflexes critical for stabilizing gaze and body posture. Vestibular diseases significantly reduce the quality of life of people who are affected by them. Some research groups have recently started developing vestibular neuroprostheses to mitigate these symptoms.

A three-dimensional self-opening intraneural peripheral interface (SELINE).

Objective: In this study we present the development and testing in a rat model of the self-opening neural interface (SELINE), a novel flexible peripheral neural interface.

Approach: This polyimide-based electrode has a three-dimensional structure that provides an anchorage system to the nerve and confers stability after implant. This geometry has been achieved by means of the plastic deformation of polyimide.

Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.

The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections.

Modular organization of reaching and grasping movements investigated using EEG microstates.

How movements are generated and controlled by the central nervous system (CNS) is still not well understood. In this work, we tested the hypothesis of a modular organization of the brain activity during the execution of voluntary movements. In particular, we extracted meta-stable topographies as a measure for global brain state, so-called microstates, from electroencephalography (EEG) data during pure planar reaching movements as well as reaching and grasping of different objects, and we compared them with those extracted during resting-state.

NGF-loaded PLGA microparticles for advanced multifunctional regenerative electrodes.

Nerve guide conduits are currently the elective device for peripheral nerve reconstruction applications, as nerve autograft often is hampered by procedure invasiveness and limited nerve availability. Many technological improvements have been approached to enhance nerve regeneration driven by these devices, whose main drawbacks are often disordered sprouting and ineffective axon guidance. Among the adopted solutions to overcome these problems, embedding of extracellular matrix (ECM) proteins and neurotrophic factors (NF) in nerve conduits has been a promising one.

Detecting slipping-like perturbations by using adaptive oscillators.

This study introduces a novel algorithm to detect unexpected slipping-like perturbations based on the comparison between actual leg joint angles and those predicted by a pool of adaptive oscillators. The approach grounds on the hypothesis that during postural transitions, the difference between these datasets diverges and can early signal that the dynamic balance is challenged. To test this hypothesis, leg joint angles of twelve healthy young participants were recorded while undergoing four different perturbations delivered during steady locomotion.

Quantitative kinematic characterization of reaching impairments in mice after a stroke.

Background And Objective: Kinematic analysis of reaching movements is increasingly used to evaluate upper extremity function after cerebrovascular insults in humans and has also been applied to rodent models. Such analyses can require time-consuming frame-by-frame inspections and are affected by the experimenter's bias. In this study, we introduce a semi-automated algorithm for tracking forepaw movements in mice.

Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats.

RELICA: a method for estimating the reliability of independent components.

Independent Component Analysis (ICA) is a widely applied data-driven method for parsing brain and non-brain EEG source signals, mixed by volume conduction to the scalp electrodes, into a set of maximally temporally and often functionally independent components (ICs). Many ICs may be identified with a precise physiological or non-physiological origin. However, this process is hindered by partial instability in ICA results that can arise from noise in the data.

Development, manufacturing and application of double-sided flexible implantable microelectrodes.

Many neuroprosthetic applications require the use of very small, flexible multi-channel microelectrodes (e.g. polyimide-based film-like electrodes) to fit anatomical constraints.

A real-time research platform to study vestibular implants with gyroscopic inputs in vestibular deficient subjects.

Researchers have succeeded in partly restoring damaged vestibular functionality in several animal models. Recently, acute interventions have also been demonstrated in human patients. Our previous work on a vestibular implant for humans used predefined stimulation patterns; here we present a research tool that facilitates motion-modulated stimulation.

Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis.

The vestibular system plays a crucial role in the multisensory control of balance. When vestibular function is lost, essential tasks such as postural control, gaze stabilization, and spatial orientation are limited and the quality of life of patients is significantly impaired. Currently, there is no effective treatment for bilateral vestibular deficits.

Why effectiveness of robot-mediated neurorehabilitation does not necessarily influence its adoption.

This paper discusses the reasons why evidence of clinical effectiveness is not enough to facilitate adequate adoption of robotic technologies for upper-limb neurorehabilitation. The paper also provides a short review of the state of the art technologies. In particular, the paper highlights the barriers to the adoption of these technologies by the markets in which they are, or should be, deployed.

Pre-impact fall detection: optimal sensor positioning based on a machine learning paradigm.

The aim of this study was to identify the best subset of body segments that provides for a rapid and reliable detection of the transition from steady walking to a slipping event. Fifteen healthy young subjects managed unexpected perturbations during walking. Whole-body 3D kinematics was recorded and a machine learning algorithm was developed to detect perturbation events.

The effect of arm weight support on upper limb muscle synergies during reaching movements.

Background: Compensating for the effect of gravity by providing arm-weight support (WS) is a technique often utilized in the rehabilitation of patients with neurological conditions such as stroke to facilitate the performance of arm movements during therapy. Although it has been shown that, in healthy subjects as well as in stroke survivors, the use of arm WS during the performance of reaching movements leads to a general reduction, as expected, in the level of activation of upper limb muscles, the effects of different levels of WS on the characteristics of the kinematics of motion and of the activity of upper limb muscles have not been thoroughly investigated before.

Methods: In this study, we systematically assessed the characteristics of the kinematics of motion and of the activity of 14 upper limb muscles in a group of 9 healthy subjects who performed 3-D arm reaching movements while provided with different levels of arm WS.

Restoring natural sensory feedback in real-time bidirectional hand prostheses.

Hand loss is a highly disabling event that markedly affects the quality of life. To achieve a close to natural replacement for the lost hand, the user should be provided with the rich sensations that we naturally perceive when grasping or manipulating an object. Ideal bidirectional hand prostheses should involve both a reliable decoding of the user's intentions and the delivery of nearly "natural" sensory feedback through remnant afferent pathways, simultaneously and in real time.

Robot-assisted gait training improves motor performances and modifies Motor Unit firing in poststroke patients.

Background: Robotics and related technologies are realizing their promise to improve the delivery of rehabilitation therapy but the mechanism by which they enhance recovery is still unknown. The electromechanical-driven gait orthosis Lokomat has demonstrated its utility for gait rehabilitation after stroke.

Aim: To test the efficacy of Lokomat in gait retraining and to investigate the neurophysiological mechanisms underlying the recovery process.

A computational model for epidural electrical stimulation of spinal sensorimotor circuits.

Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES.

A robotic system for quantitative assessment and poststroke training of forelimb retraction in mice.

Background: Neurorehabilitation protocols based on the use of robotic devices have recently shown to provide promising clinical results. However, their efficacy is still limited because of the poor comprehension of the mechanisms at the basis of functional enhancements.

Objective: To increase basic understanding of robot-mediated neurorehabilitation by performing experiments on a rodent model of stroke.

Personalized neuroprosthetics.

Decades of technological developments have populated the field of neuroprosthetics with myriad replacement strategies, neuromodulation therapies, and rehabilitation procedures to improve the quality of life for individuals with neuromotor disorders. Despite the few but impressive clinical successes, and multiple breakthroughs in animal models, neuroprosthetic technologies remain mainly confined to sophisticated laboratory environments. We summarize the core principles and latest achievements in neuroprosthetics, but also address the challenges that lie along the path toward clinical fruition.

Selecting the best number of synergies in gait: preliminary results on young and elderly people.

Matrix factorization algorithms are increasingly used to extract meaningful information from multivariate EMG datasets. However a key issue is the selection of the number of synergies (i.e.

Does an intraneural interface short-term implant for robotic hand control modulate sensorimotor cortical integration? An EEG-TMS co-registration study on a human amputee.

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.

Corticospinal neuroprostheses to restore locomotion after spinal cord injury.

In this conceptual review, we highlight our strategy for, and progress in the development of corticospinal neuroprostheses for restoring locomotor functions and promoting neural repair after thoracic spinal cord injury in experimental animal models. We specifically focus on recent developments in recording and stimulating neural interfaces, decoding algorithms, extraction of real-time feedback information, and closed-loop control systems. Each of these complex neurotechnologies plays a significant role for the design of corticospinal neuroprostheses.

Effects of early and intensive neuro-rehabilitative treatment on muscle synergies in acute post-stroke patients: a pilot study.

Background: After a stroke, patients show significant modifications of neural control of movement, such as abnormal muscle co-activation, and reduced selectivity and modulation of muscle activity. Nonetheless, results reported in literature do not allow to unequivocally explain whether and, in case, how a cerebrovascular accident affects muscle synergies underlying the control of the upper limb. These discrepancies suggest that a complete understanding of the modular re-organization of muscle activity due to a stroke is still lacking.

Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.

Background: Recently, the effects of nanogratings have been investigated on PC12 with respect to cell polarity, neuronal differentiation, migration, maturation of focal adhesions and alignment of neurites.

Methodology/principal Findings: A synergistic procedure was used to study the mechanism of alignment of PC12 neurites with respect to the main direction of nanogratings. Finite Element simulations were used to qualitatively assess the distribution of stresses at the interface between non-spread growth cones and filopodia, and to study their dependence on filopodial length and orientation.