G. Di Pino

Decoding Information From Neural Signals Recorded Using Intraneural Electrodes: Toward the Development of a Neurocontrolled Hand Prosthesis

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.

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. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subjects 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.

Intrafascicular thin-film multichannel electrodes for sensory feedback: Evidences on a human amputee

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.

On the control of a robot hand by extracting neural signals from the PNS: Preliminary results from a human implantation

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.

ODEs model of foreign body reaction around peripheral nerve implanted electrode

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.

Preliminary investigations on laminin coatings for flexible polyimide/platinum thin films for PNS applications

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.

Conceptualization of an insect/machine hybrid controller for space applications

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.

An MR-compatible force sensor based on FBG technology for biomedical application

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.

35. Association of robot-assisted rehabilitation and non-invasive brain stimulation to improve upper limb function in chronic stroke patients

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.

62. Efficacy of cathodal transcranial direct current stimulation in drug-resistant epilepsy: A proof of principle

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.