Regional specialization of movement encoding across the primate sensorimotor cortex.

The process by which the cerebral cortex generates movements to achieve different tasks remains poorly understood. Here, we leveraged the rich repertoire of well-controlled primate locomotor behaviors to study how task-specific movements are encoded across the dorsal premotor cortex (PMd), primary motor cortex (M1), and primary somatosensory cortex (S1) under naturalistic conditions. Neural population activity was confined within low-dimensional manifolds and partitioned into task-dependent and task-independent subspaces.

High-resolution prosthetic hearing with a soft auditory brainstem implant in macaques.

Individuals with compromised cochlear nerves are ineligible for cochlear implants and instead rely on auditory brainstem implants (ABIs). Most users of ABIs experience sound awareness, which aids in lip reading, yet not speech intelligibility. Here we engineered a dual-site (brainstem and cortex) implantable system, scaled to macaque anatomy, for the analysis of auditory perception evoked by electrical stimulation of the cochlear nucleus.

A soft, scalable and adaptable multi-contact cuff electrode for targeted peripheral nerve modulation.

Background: Cuff electrodes target various nerves throughout the body, providing neuromodulation therapies for motor, sensory, or autonomic disorders. However, when using standard, thick silicone cuffs, fabricated in discrete circular sizes, complications may arise, namely cuff displacement or nerve compression, due to a poor adaptability to variable nerve shapes and sizes encountered in vivo. Improvements in cuff design, materials, closing mechanism and surgical approach are necessary to overcome these issues.

A low-profile electromechanical packaging system for soft-to-flexible bioelectronic interfaces.

Interfacing the human body with the next generation of electronics requires technological advancement in designing and producing bioelectronic circuits. These circuits must integrate electrical functionality while simultaneously addressing limitations in mechanical compliance and dynamics, biocompatibility, and consistent, scalable manufacturing. The combination of mechanically disparate materials ranging from elastomers to inorganic crystalline semiconductors calls for modular designs with reliable and scalable electromechanical connectors.

Deployment of an electrocorticography system with a soft robotic actuator.

Electrocorticography (ECoG) is a minimally invasive approach frequently used clinically to map epileptogenic regions of the brain and facilitate lesion resection surgery and increasingly explored in brain-machine interface applications. Current devices display limitations that require trade-offs among cortical surface coverage, spatial electrode resolution, aesthetic, and risk consequences and often limit the use of the mapping technology to the operating room. In this work, we report on a scalable technique for the fabrication of large-area soft robotic electrode arrays and their deployment on the cortex through a square-centimeter burr hole using a pressure-driven actuation mechanism called eversion.

Subdural Soft Electrocorticography (ECoG) Array Implantation and Long-Term Cortical Recording in Minipigs.

Neurological impairments and diseases can be diagnosed or treated using electrocorticography (ECoG) arrays. In drug-resistant epilepsy, these help delineate the epileptic region to resect. In long-term applications such as brain-computer interfaces, these epicortical electrodes are used to record the movement intention of the brain, to control the robotic limbs of paralyzed patients.

Epidural electrical stimulation of the cervical dorsal roots restores voluntary upper limb control in paralyzed monkeys.

Regaining arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control has limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury, using spinal cord stimulation.

Chronic recording of cortical activity underlying vocalization in awake minipigs.

Background: Investigating brain dynamics underlying vocal production in animals is a powerful way to inform on the neural bases of human speech. In particular, brain networks underlying vocal production in non-human primates show striking similarities with the human speech production network. However, despite increasing findings also in birds and more recently in rodents, the extent to which the primate vocal cortical network model generalizes to other non-primate mammals remains unclear.

Intrafascicular peripheral nerve stimulation produces fine functional hand movements in primates.

Restoring dexterous hand control is critical for people with paralysis. Approaches based on surface or intramuscular stimulation provide limited finger control, generate insufficient force to recover functional movements, and require numerous electrodes. Here, we show that intrafascicular peripheral electrodes could produce functional grasps and sustained forces in three monkeys.

Viscoelastic surface electrode arrays to interface with viscoelastic tissues.

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials.

MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams.

Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival, impairs neurological recovery, increases the risk of cardiovascular disease, and reduces quality of life. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury, and restored walking after paralysis.

Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord.

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear.

Guidelines to Study and Develop Soft Electrode Systems for Neural Stimulation.

Electrical stimulation of nervous structures is a widely used experimental and clinical method to probe neural circuits, perform diagnostics, or treat neurological disorders. The recent introduction of soft materials to design electrodes that conform to and mimic neural tissue led to neural interfaces with improved functionality and biointegration. The shift from stiff to soft electrode materials requires adaptation of the models and characterization methods to understand and predict electrode performance.

Soft Printable Electrode Coating for Neural Interfaces.

The mechanical mismatch between implantable interfaces and neural tissues may be reduced by employing soft polymeric materials. Here, we report on a simple strategy to prepare and pattern a soft electrode coating of neural interfacing devices based on a screen-printable conducting hydrogel. The coating formulation, based on polyacrylamide and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, is suitable to additive manufacturing and exhibits excellent adhesion to polydimethylsiloxane, an elastomer commonly used as a substrate in soft neural interfaces.

Soft, Implantable Bioelectronic Interfaces for Translational Research.

The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab-based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e-dura.

Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants.

Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users.

Conformable Hybrid Systems for Implantable Bioelectronic Interfaces.

Conformable bioelectronic systems are promising tools that may aid the understanding of diseases, alleviate pathological symptoms such as chronic pain, heart arrhythmia, and dysfunctions, and assist in reversing conditions such as deafness, blindness, and paralysis. Combining reduced invasiveness with advanced electronic functions, hybrid bioelectronic systems have evolved tremendously in the last decade, pushed by progress in materials science, micro- and nanofabrication, system assembly and packaging, and biomedical engineering. Hybrid integration refers here to a technological approach to embed within mechanically compliant carrier substrates electronic components and circuits prepared with traditional electronic materials.

Long-term functionality of a soft electrode array for epidural spinal cord stimulation in a minipig model.

Long-term biointegration of man-made neural interfaces is influenced by the mechanical properties of the implant materials. Substantial experimental work currently aims at replacing conventional hard implant materials with soft alternatives that can favour a lower immune response. Here we assess the performance of a soft electrode array implanted in the spinal epidural space of a minipig model for a period of 6 months.

Implantable microcoils for intracortical magnetic stimulation.

Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome.