Silvia Bossi

Interfacing with the nervous system to restore functional motor activity is a promising therapy to augment the classical surgical approaches to treating peripheral nerve injuries. Despite the advances in electrode microelectronics engineering, the challenge of extracting information from injured nerves to help restore motor function remains unsolved. Here we used waveform feature extraction and clustering techniques to identify a discrete set of events in intraneural recordings of the median nerve in a non-human primate (NHP) during grasping tasks. This analysis allowed the classification of the different phases of hand grasping. The waveform features were found to be significantly different for each phase of grasping. Since these waveforms can be seen as the minimal signal components that result from the activation of a group of nerve fibers, we denominated them miniature compound nerve action potentials (mCNAPs). The correlation between mCNAPs and the different stages of movement can be utilized in the near future to design high-performance neuroprosthetic therapies.

Restoration of motor function in cases of peripheral nerve injury is a challenging problem. Although peripheral nerves do regenerate, the time required for peripheral nerves to regenerate often causes atrophy to occur in the muscles before they can be re-innervated. This paper presents a solution through proximal recording of nerve signals and distal muscle stimulation. A fully implantable hardware architecture is described that can be operated by means of inductive power and MICS band data transmission schemes. Preliminary experiments and validation studies are reported with non-human primates based on recordings in the median nerve, stimulation of hand muscles, and task decoding and classification. This approach shows promise in creating a neural prosthesis capable of restoring hand movements in patients with upper limb peripheral nerve injuries.

Neuroprosthetic devices that interface with the nervous system to restore functional motor activity offer a viable alternative to nerve regeneration, especially in proximal nerve injuries like brachial plexus injuries where muscle atrophy may set in before nerve re-innervation occurs. Prior studies have used control signals from muscle or cortical activity. However, nerve signals are preferred in many cases since they permit more natural and precise control when compared to muscle activity, and can be accessed with much lower risk than cortical activity. Identification of nerve signals that control the appropriate muscles is essential for the development of such a `bionic link'. Here we examine the correlation between muscle and nerve signals responsible for hand grasping in the M. fascicularis. Simultaneous recordings were performed using a 4-channel thin-film longitudinal intra-fascicular electrode (tf-LIFE) and 9 bipolar endomysial muscle electrodes while the animal performed grasping movements. We were able to identify a high degree of correlation (r > 0.6) between nerve signals from the median nerve and movement-dependent muscle activity from the flexor muscles of the forearm, with a delay that corresponded to 25 m/s nerve conduction velocity. The phase of the flexion could be identified using a wavelet approximation of the ENG. This result confirms this approach for a future neu-roprosthetic device for the treatment of peripheral nerve injuries.

Thin-film longitudinal intrafascicular electrodes (tf-LIFE) are widely used for peripheral nerve recordings. tf-LIFEs are also promising electrodes for neural signal acquisition in future peripheral nerve prostheses. However, common mode signal interference, and electrical artifacts originating from long wire leads and wire movement are known problems encountered when using such electrodes, which lead to degradation in the recording quality. Here, we report an active tf-LIFE electrode implemented by integrating a neural amplifier chip die in close proximity to a tf-LIFE electrode. Consuming only 1mW and measuring 37 mm×7.2 mm×2.4 mm, this active tf-LIFE electrode creates a reliable connection and considerably shortens the distance between the electrode site and neural amplifier. This active electrode has demonstrated repeatable in-vivo recordings of compound action potentials from the rat sciatic nerve. Our results show that this electrode is suitable for repeated in-vivo recordings of compound action potentials from nerves in applications such as peripheral and visceral nerve interfaces that require low-noise stable nerve recordings.

Questo Libro Bianco sulla Robotica, che l’ENEA ha iniziato a realizzare nel 2012, e ancora lontano dalla conclusione e dallo scopo originale di raffigurare un quadro, ragionevolmente completo, della ricerca sulla robotica in Italia. Viaggio dopo viaggio, visita dopo visita, le informazioni ed i suggerimenti forniti dai ricercatori sono aumentate fino a costituire un dossier fin troppo ricco e senza che la fine del lavoro fosse prossima. Cio ha costretto il gruppo che l’ENEA aveva costituito a tale scopo a prendere una decisione dolorosa, ma ancora piu ambiziosa: abbandonare l’idea iniziale di realizzare un singolo volume con un panorama esaustivo della ricerca nazionale nel settore, e di redigere invece un testo che, seppure incompleto, sia comunque valido in termini di informazione nel momento in cui viene stampato; un testo da migliorare di anno in anno con il contributo di tutti i ricercatori. L’obiettivo finale e quello di rappresentare un quadro in questo campo di ricerca al fi...

Positive Energy Districts and Neighborhoods (PEDs) are seen as a promising pathway towards sustainable urban areas. Several cities have already taken up such PED-related developments. To support such approaches, European countries joined forces to achieve 100 PEDs until 2025 through a comprehensive research and innovation program. A solid understanding and consideration of cities’ strategies, experiences and project features serve as the basis for developing and designing the PED program. JPI Urban Europe has been collecting information on projects towards sustainable urbanization and the energy transition across Europe. The collected cases are summarized in a PED Booklet whose update was recently published on the JPI Urban Europe website. Results presented in this paper provide insights from the analysis of 61 projects in Europe and offer recommendations for future PED developments.

As artificial prostheses become more refined, they are most often used as a therapeutic option for hand amputation. Differently from extra- or intraneural interfaces, regenerative nerve electrodes are designed to enable electrical interface with regrowing axonal bundles of injured nerves, aiming to achieve high selectivity for recording and stimulation. However, most of the developed designs pose an obstacle to the regrowth mechanisms due to low transparency and cause an impairment of the nerve regeneration. Here we present the double-aisle electrode, a new type of highly transparent, non-obstructive regenerative electrode. Using a double-side thin-film polyimide planar multi-contact electrode, two nerve fascicles can regenerate without physical impairment through two electrically-isolated aisles. We show that this electrode can be used to selectively record and stimulate fascicles, acutely as well as chronically, and allows regeneration in nerve gaps of several millimeters without impairment. This multi-aisle regenerative electrode may be suitable for neuroprosthetic applications, such as prostheses for the restoration of hand function after amputation or severe nerve injuries.

Micro-electrocorticography (μECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely behaving rodents challenging. We report a novel high-density 60-electrode system for μECoG recording in freely moving rats. Multiplexed headstages overcome the problem of wiring complexity by combining signals from many electrodes to a smaller number of connections. We have developed a low-cost, multiplexed recording system with 60 contacts at 406 μm spacing. We characterized the quality of the electrode signals using multiple metrics that tracked spatial variation, evoked-response detectability, and decoding value. Performance of the system was validated both in anesthetized animals and freely moving awake animals. We recorded μECoG signals over the primary auditory cortex, measuring responses to acous...

ABSTRACT Ultrathin stable transparent conductive nickel films were deposited on quartz substrates by radio frequency sputtering at room temperature. Such films showed visible transmittance up to 80% and conductivity up to 1.8 × 104 S/cm, further increased to 2,3 × 105 S/cm by incorporation of a micrometric silver grid. Atomic force microscopy and scanning electron microscopy revealed quite compact, smooth and low surface roughness films. Excellent film stability, ease, fast and low cost process fabrication make these films highly competitive compared to indium tin oxide alternative transparent conductors. Films were characterized regarding their morphological, optical and electrical properties.

ABSTRACT In this paper a thin film intrafascicular interface has been modeled during the insertion procedure inside peripheral nerves using a theoretical approach and a FEM analysis. In particular, the aim was to investigate the effects of several characteristics of the intraneural interfaces (e.g., the interface width and Kevlar filament diameter) on the maximal Von Mises stress reached during implantation. The results were used to gather new guidelines to develop more reliable thin film interfaces with maximal success rate during the implantation phase.

ABSTRACT Despite recognized as one key component for establishing a functional electrical connection with nerves, neural invasive peripheral interfaces are still not optimal for long-term applications in humans. An improvement in the field of biocompatible and nontoxic materials is necessary to overcome the issues of interface/tissue mismatch and physiological reactions. The present work aimed to study, implement and characterize a novel approach to modify the surface of neural mi-crolectrodes basedon polyimide thin films. The purpose was to improve biocompatibility and to promote neuronal migration, growth and differentiation by increasing the surface roughness and endowing the surface with structure-reactivity for thiol-containing amino acids or peptides. L-Cysteine-Rhodamine B, used as a model biomolecule, was successfully grafted on samples surface via the introduction of cross-linkable vinyl groups on polyimide foils. Preliminary in vitro biological analysis allowed to evaluate the tendency of PC12 cells to adhere and to proliferate.

The development of interfaces linking the human nervous system with artificial devices is an important area of research and several groups are now addressing it. Interfaces represent the key enabling technology for the development of devices usable for the restoration of motor and sensory function in subjects affected by neurological disorders, injuries or amputations. For example, current hand prostheses use electromyographic (EMG) signals to extract volitional commands but this limits the possibility of controlling several degrees of freedom and of delivering sensory feedback. To achieve these goals, implantable neural interfaces are required. Among the candidate interfaces with the peripheral nervous system intra-neural electrodes seem to be an interesting solution due to their bandwidth and ability to access volition and deliver sensory feedback. However, several drawbacks have to be addressed in order to increase their usability. In this paper, experiments to address many of th...

ABSTRACT This article illustrates the development and preliminary results of SELINE, a self-opening neural interface. The advantages of this innovative neural interface are: higher selectivity due to its three-dimensional structure and efficient anchorage system to the nervous tissue. The device is made of polyimide that is a lightweight, flexible and biocompatible polymer. The electrode has been microfabricated using lithographic techniques; electrical and mechanical tests have been performed to evaluate the integrity of the device. Successful results have been obtained in the development of the electrode with excellent mechanical and electrical properties.

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.

The development of interfaces linking the human nervous system with artificial devices is an important area of research. Several groups are working on the development of devices able to restore sensory-motor function in subjects affected by neurological disorders, injuries or amputations. Neural electrodes implanted in peripheral nervous system, and in particular intrafascicular electrodes, seem to be a promising approach for the control of hand prosthesis thanks to the possibility to selectively access motor and sensory fibers for decoding motor commands and delivering sensory feedback. In this paper, activities on the use of PNS interfaces for the control of hand prosthesis are presented. In particular, the design and feasibility study of a self-opening neural interface is presented together with the decoding of ENG signals in one amputee to control a dexterous hand prosthesis.

In this paper a self-opening intrafascicular neural interface (SELINE) has been modeled using both a theoretical approach and a Finite Element (FE) analysis. This innovative self opening interface has several potential advantages such as: higher selectivity due to its three-dimensional structure and efficient anchorage system. Mechanical, structural and micro-technological issues have been considered to obtain an effective design of the electrode, as a feasibility study of the self-opening approach. A simple framework has been provided to model the insertion and partial retraction into peripheral nerves, resulting in the opening of wings. This integrated approach results in a rational procedure to optimize kinematics, geometry, and structural properties of peripheral interfaces. The design and feasibility study carried out in this work can potentially assure a correct behavior and dimensioning of the neural interface: in this way anomalous breakage should be avoided while mechanical and geometrical biocompatibility should increase.

In this paper, a new approach aimed at improving the performance of intraneural longitudinal interfaces (tf-LIFEs) with the peripheral nervous system (PNS) is presented. Our goal is to develop a movable interface by embedding microactuators into the flexible tf-LIFEs structure. In this way, the optimal position of the electrical contacts can be searched inside the PNS and lost connections with neural cells could be replaced. For this purpose a thin film of shape memory alloy (tf-SMA) was selected. A multisegmented SMA was realized and embedded between two polyimide thin films in order to simulate the tf-LIFE structure. Thermal evaluation, fabrication procedure, the first characterization and preliminary experimental results of the new movable interface are described in the manuscript. A total controllable stroke of about 10 microm was obtained for the presented prototype.

Important advancements have been recently achieved in the field of neural interfaces to restore lost sensory and motor functions. The aim of this letter was to develop an innovative approach to increase the selectivity and the lifetime of polyimide-based intrafascicular electrodes. The main idea was to obtain a neural interface that is able to restore a good signal quality by improving the electrical connection between the active sites and the surrounding axons. The high flexibility of polyimide-based neural interfaces allows to embed microactuators in the interface core and achieve desired microdisplacements of the active sites. Nearly equiatomic nickel-titanium alloy was selected as a microactuator because of its shape memory effect. A single TiNi thin film was obtained by dc magnetron sputtering, and was segmented into four distinct sectors. This solution allowed the independent actuation of the different active sites (multiactuation). A corrugated profile was impressed to the new actuated intraneural (ACTIN) interface. The active sites were positioned in correspondence to the peaks of the corrugation, thus maximizing the effects of the single actuations. The technological results, the electrical properties, the thermal behavior, and eventually, the actuation performances of the current ACTIN prototype are shown and discussed. The actuation cycle was thermally compatible for biomedical applications. Promising results were obtained from the current ACTIN prototype with an average controlled movement of 7 microm of the peaks.