A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers.

Peripheral nerves are anisotropic and heterogeneous neural tissues. Their complex physiology restricts realistic in vitro models, and high resolution and selective probing of axonal activity. Here, we present a nerve-on-a-chip platform that enables rapid extracellular recording and axonal tracking of action potentials collected from tens of myelinated fibers.

Development and Characterization of PEDOT:PSS/Alginate Soft Microelectrodes for Application in Neuroprosthetics.

Reducing the mechanical mismatch between the stiffness of a neural implant and the softness of the neural tissue is still an open challenge in neuroprosthetics. The emergence of conductive hydrogels in the last few years has considerably widened the spectrum of possibilities to tackle this issue. Nevertheless, despite the advancements in this field, further improvements in the fabrication of conductive hydrogel-based electrodes are still required.

Multilayer 3D electrodes for neural implants.

Objective: In many applications, multielectrode arrays employed as neural implants require a high density and a high number of electrodes to precisely record and stimulate the activity of the nervous system while preserving the overall size of the array.

Approach: Here we present a multilayer and three-dimensional (3D) electrode array, together with its manufacturing method, enabling a higher electrode density and a more efficient signal transduction with the biological tissue.

Main Results: The 3D structure of the electrode array allows for a multilayer placement of the interconnects within a flexible substrate, it narrows the probe size per the same number of electrodes, and it maintains the electrode contacts at the same level within the tissue.

Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury.

The delivery of brain-controlled neuromodulation therapies during motor rehabilitation may augment recovery from neurological disorders. To test this hypothesis, we conceived a brain-controlled neuromodulation therapy that combines the technical and practical features necessary to be deployed daily during gait rehabilitation. Rats received a severe spinal cord contusion that led to leg paralysis.

Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke.

Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES.

Soft Hydrogel Zwitterionic Coatings Minimize Fibroblast and Macrophage Adhesion on Polyimide Substrates.

Minimizing the foreign body reaction to polyimide-based implanted devices plays a pivotal role in several biomedical applications. In this work, we propose materials exhibiting nonbiofouling properties and a Young's modulus reflecting that of soft human tissues. We describe the synthesis, characterization, and in vitro validation of poly(carboxybetaine) hydrogel coatings covalently attached to polyimide substrates via a photolabile 4-azidophenyl group, incorporated in poly(carboxybetaine) chains at two concentrations of 1.

Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees.

Objective: The aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording "phantom" somatosensory evoked potentials from the corresponding brain areas.

Methods: We implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials.

Bilateral Tactile Input Patterns Decoded at Comparable Levels But Different Time Scales in Neocortical Neurons.

The presence of contralateral tactile input can profoundly affect ipsilateral tactile perception, and unilateral stroke in somatosensory areas can result in bilateral tactile deficits, suggesting that bilateral tactile integration is an important part of brain function. Although previous studies have shown that bilateral tactile inputs exist and that there are neural interactions between inputs from the two sides, no previous study explored to what extent the local neuronal circuitry processing contains detailed information about the nature of the tactile input from the two sides. To address this question, we used a recently introduced approach to deliver a set of electrical, reproducible, tactile afferent, spatiotemporal activation patterns, which permits a high-resolution analysis of the neuronal decoding capacity, to the skin of the second forepaw digits of the anesthetized male rat.

Applying dimension reduction to EEG data by Principal Component Analysis reduces the quality of its subsequent Independent Component decomposition.

Independent Component Analysis (ICA) has proven to be an effective data driven method for analyzing EEG data, separating signals from temporally and functionally independent brain and non-brain source processes and thereby increasing their definition. Dimension reduction by Principal Component Analysis (PCA) has often been recommended before ICA decomposition of EEG data, both to minimize the amount of required data and computation time. Here we compared ICA decompositions of fourteen 72-channel single subject EEG data sets obtained (i) after applying preliminary dimension reduction by PCA, (ii) after applying no such dimension reduction, or else (iii) applying PCA only.

Gastrocnemius Myoelectric Control of a Robotic Hip Exoskeleton Can Reduce the User's Lower-Limb Muscle Activities at Push Off.

We present a novel assistive control strategy for a robotic hip exoskeleton for assisting hip flexion/extension, based on a proportional Electromyography (EMG) strategy. The novelty of the proposed controller relies on the use of the Gastrocnemius Medialis (GM) EMG signal instead of a hip flexor muscle, to control the hip flexion torque. This strategy has two main advantages: first, avoiding the placement of the EMG electrodes at the human-robot interface can reduce discomfort issues for the user and motion artifacts of the recorded signals; second, using a powerful signal for control, such as the GM, could improve the reliability of the control system.

Effective Synchronization of EEG and EMG for Mobile Brain/Body Imaging in Clinical Settings.

Mobile Brain/Body Imaging (MoBI) is rapidly gaining traction as a new imaging modality to study how cognitive processes support locomotion. Electroencephalogram (EEG) and electromyogram (EMG), due to their time resolution, non-invasiveness and portability are the techniques of choice for MoBI, but synchronization requirements among others restrict its use to high-end research facilities. Here we test the effectiveness of a technique that enables us to achieve MoBI-grade synchronization of EEG and EMG, even when other strategies (such as Lab Streaming Layer (LSL)) cannot be used e.

Peptide-based coatings for flexible implantable neural interfaces.

In the last decade, the use of flexible biosensors for neuroprosthetic and translational applications has widely increased. Among them, the polyimide (PI)-based thin-film electrodes got a large popularity. However, the usability of these devices is still hampered by a non-optimal tissue-device interface that usually compromises the long-term quality of neural signals.

Closed-loop control of trunk posture improves locomotion through the regulation of leg proprioceptive feedback after spinal cord injury.

After spinal cord injury (SCI), sensory feedback circuits critically contribute to leg motor execution. Compelled by the importance to engage these circuits during gait rehabilitation, assistive robotics and training protocols have primarily focused on guiding leg movements to reinforce sensory feedback. Despite the importance of trunk postural dynamics on gait and balance, trunk assistance has comparatively received little attention.

Combining robotic training and inactivation of the healthy hemisphere restores pre-stroke motor patterns in mice.

Focal cortical stroke often leads to persistent motor deficits, prompting the need for more effective interventions. The efficacy of rehabilitation can be increased by 'plasticity-stimulating' treatments that enhance experience-dependent modifications in spared areas. Transcallosal pathways represent a promising therapeutic target, but their role in post-stroke recovery remains controversial.

Segregation of motor and sensory axons regenerating through bicompartmental tubes by combining extracellular matrix components with neurotrophic factors.

Segregation of regenerating motor and sensory axons may be a good strategy to improve selective functionality of regenerative interfaces to provide closed-loop commands. Provided that extracellular matrix components and neurotrophic factors exert guidance effects on different neuronal populations, we assessed in vivo the potential of separating sensory and motor axons regenerating in a bicompartmental Y-type tube, with each branch prefilled with an adequate combination of extracellular matrix and neurotrophic factors. The severed rat sciatic nerve was repaired using a bicompartmental tube filled with a collagen matrix enriched with fibronectin (FN) and brain-derived neurotrophic factor (BDNF) encapsulated in poly-lactic co-glycolic acid microspheres (FN + MP.

EEG topographies provide subject-specific correlates of motor control.

Electroencephalography (EEG) of brain activity can be represented in terms of dynamically changing topographies (microstates). Notably, spontaneous brain activity recorded at rest can be characterized by four distinctive topographies. Despite their well-established role during resting state, their implication in the generation of motor behavior is debated.

Unidirectional brain to muscle connectivity reveals motor cortex control of leg muscles during stereotyped walking.

Unlabelled: In lower mammals, locomotion seems to be mainly regulated by subcortical and spinal networks. On the contrary, recent evidence suggests that in humans the motor cortex is also significantly engaged during complex locomotion tasks. However, a detailed understanding of cortical contribution to locomotion is still lacking especially during stereotyped activities.

Aging does not affect the intralimb coordination elicited by slip-like perturbation of different intensities.

This study was aimed at verifying whether aging modifies intralimb coordination strategy during corrective responses elicited by unexpected slip-like perturbations delivered during steady walking on a treadmill. To this end, 10 young and 10 elderly subjects were asked to manage unexpected slippages of different intensities. We analyzed the planar covariation law of the lower limb segments, using the principal component analysis, to verify whether elevation angles of older subjects covaried along a plan before and after the perturbation.

Spatiotemporal Dynamics of the Cortical Responses Induced by a Prolonged Tactile Stimulation of the Human Fingertips.

The sense of touch is fundamental for daily behavior. The aim of this work is to understand the neural network responsible for touch processing during a prolonged tactile stimulation, delivered by means of a mechatronic platform by passively sliding a ridged surface under the subject's fingertip while recording the electroencephalogram (EEG). We then analyzed: (i) the temporal features of the Somatosensory Evoked Potentials and their topographical distribution bilaterally across the cortex; (ii) the associated temporal modulation of the EEG frequency bands.

An ecologically-controlled exoskeleton can improve balance recovery after slippage.

The evolution to bipedalism forced humans to develop suitable strategies for dynamically controlling their balance, ensuring stability, and preventing falling. The natural aging process and traumatic events such as lower-limb loss can alter the human ability to control stability significantly increasing the risk of fall and reducing the overall autonomy. Accordingly, there is an urgent need, from both end-users and society, for novel solutions that can counteract the lack of balance, thus preventing falls among older and fragile citizens.

Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons.

Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes.

Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes.

Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months.

Reducing GABA-mediated inhibition improves forelimb motor function after focal cortical stroke in mice.

A deeper understanding of post-stroke plasticity is critical to devise more effective pharmacological and rehabilitative treatments. The GABAergic system is one of the key modulators of neuronal plasticity, and plays an important role in the control of "critical periods" during brain development. Here, we report a key role for GABAergic inhibition in functional restoration following ischemia in the adult mouse forelimb motor cortex.

A Murine Model of Robotic Training to Evaluate Skeletal Muscle Recovery after Injury.

Purpose: In vivo studies have suggested that motor exercise can improve muscle regeneration after injury. Nevertheless, preclinical investigations still lack reliable tools to monitor motor performance over time and to deliver optimal training protocols to maximize force recovery. Here, we evaluated the utility of a murine robotic platform (i) to detect early impairment and longitudinal recovery after acute skeletal muscle injury and (ii) to administer varying intensity training protocols to enhance forelimb motor performance.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking.