Making Sense of Vagus Nerve Stimulation for Stroke.

Implantable vagus nerve stimulation, paired with high-dose occupational therapy, has been shown to be effective in improving upper limb function among patients with stroke and received regulatory approval from the US Food and Drug Administration and the Centers for Medicare & Medicaid Services. Combining nonsurgical and surgical approaches of vagus nerve stimulation in recent meta-analyses has resulted in misleading reports on the efficacy of each type of stimulation among patients with stroke. This article aims to clarify the confusion surrounding implantable vagus nerve stimulation as a poststroke treatment option, highlighting the importance of distinguishing between transcutaneous auricular vagus nerve stimulation and implantable vagus nerve stimulation.

The NuroSleeve, a user-centered 3D printed hybrid orthosis for individuals with upper extremity impairment.

Background: Active upper extremity (UE) assistive devices have the potential to restore independent functional movement in individuals with UE impairment due to neuromuscular diseases or injury-induced chronic weakness. Academically fabricated UE assistive devices are not usually optimized for activities of daily living (ADLs), whereas commercially available alternatives tend to lack flexibility in control and activation methods. Both options are typically difficult to don and doff and may be uncomfortable for extensive daily use due to their lack of personalization.

Neuromotor prosthetic to treat stroke-related paresis: N-of-1 trial.

Background: Functional recovery of arm movement typically plateaus following a stroke, leaving chronic motor deficits. Brain-computer interfaces (BCI) may be a potential treatment for post-stroke deficits.

Methods: In this n-of-1 trial (NCT03913286), a person with chronic subcortical stroke with upper-limb motor impairment used a powered elbow-wrist-hand orthosis that opened and closed the affected hand using cortical activity, recorded from a percutaneous BCI comprised of four microelectrode arrays implanted in the ipsilesional precentral gyrus, based on decoding of spiking patterns and high frequency field potentials generated by imagined hand movements.

The role of electrical stimulation for rehabilitation and regeneration after spinal cord injury.

Electrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications.

An artificial nervous system to treat chronic stroke.

Despite remarkable advances in the treatment of numerous medical conditions, neurological disease and injury remains an outstanding challenge and cause of disability worldwide. The decreased regenerative capacity and extreme complexity and heterogeneity of nervous tissue, in particular the brain, and the fact that the brain remains the least understood organ, have hampered our ability to provide definitive treatments for prevalent conditions such as stroke. Stroke is the second-leading cause of death worldwide, and the nervous system is intimately involved in other prevalent conditions including ischemic heart disease, diabetes mellitus, and hypertension.

Development of optically controlled "living electrodes" with long-projecting axon tracts for a synaptic brain-machine interface.

For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable "living electrodes," living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity.

Contribution of left supramarginal and angular gyri to episodic memory encoding: An intracranial EEG study.

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs).

Innervation: the missing link for biofabricated tissues and organs.

Innervation plays a pivotal role as a driver of tissue and organ development as well as a means for their functional control and modulation. Therefore, innervation should be carefully considered throughout the process of biofabrication of engineered tissues and organs. Unfortunately, innervation has generally been overlooked in most non-neural tissue engineering applications, in part due to the intrinsic complexity of building organs containing heterogeneous native cell types and structures.

Emerging regenerative medicine and tissue engineering strategies for Parkinson's disease.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, affecting 1-2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway.

Bioactive Neuroelectronic Interfaces.

Within the neural engineering field, next-generation implantable neuroelectronic interfaces are being developed using biologically-inspired and/or biologically-derived materials to improve upon the stability and functional lifetime of current interfaces. These technologies use biomaterials, bioactive molecules, living cells, or some combination of these, to promote host neuronal survival, reduce the foreign body response, and improve chronic device-tissue integration. This article provides a general overview of the different strategies, milestones, and evolution of bioactive neural interfaces including electrode material properties, biological coatings, and "decoration" with living cells.

Assessing functional connectivity across 3D tissue engineered axonal tracts using calcium fluorescence imaging.

Objective: Micro-tissue engineered neural networks (micro-TENNs) are anatomically-inspired constructs designed to structurally and functionally emulate white matter pathways in the brain. These 3D neural networks feature long axonal tracts spanning discrete neuronal populations contained within a tubular hydrogel, and are being developed to reconstruct damaged axonal pathways in the brain as well as to serve as physiologically-relevant in vitro experimental platforms. The goal of the current study was to characterize the functional properties of these neuronal and axonal networks.

Engineered Axonal Tracts as "Living Electrodes" for Synaptic-Based Modulation of Neural Circuitry.

Brain-computer interface and neuromodulation strategies relying on penetrating non-organic electrodes/optrodes are limited by an inflammatory foreign body response that ultimately diminishes performance. A novel "biohybrid" strategy is advanced, whereby living neurons, biomaterials, and microelectrode/optical technology are used together to provide a biologically-based vehicle to probe and modulate nervous-system activity. Microtissue engineering techniques are employed to create axon-based "living electrodes", which are columnar microstructures comprised of neuronal population(s) projecting long axonal tracts within the lumen of a hydrogel designed to chaperone delivery into the brain.

Connecting the Brain to Itself through an Emulation.

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as culture preparations or ectopic construct organoids.

The Evolution of Neuroprosthetic Interfaces.

The ideal neuroprosthetic interface permits high-quality neural recording and stimulation of the nervous system while reliably providing clinical benefits over chronic periods. Although current technologies have made notable strides in this direction, significant improvements must be made to better achieve these design goals and satisfy clinical needs. This article provides an overview of the state of neuroprosthetic interfaces, starting with the design and placement of these interfaces before exploring the stimulation and recording platforms yielded from contemporary research.

Neural Substrate Expansion for the Restoration of Brain Function.

Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity.

Bottlenecks to clinical translation of direct brain-computer interfaces.

Despite several decades of research into novel brain-implantable devices to treat a range of diseases, only two-cochlear implants for sensorineural hearing loss and deep brain stimulation for movement disorders-have yielded any appreciable clinical benefit. Obstacles to translation include technical factors (e.g.

Power shifts track serial position and modulate encoding in human episodic memory.

The first events in a series exert a powerful influence on cognition and behavior in both humans and animals. This is known as the law of primacy. Here, we analyze the neural correlates of primacy in humans by analyzing electrocorticographic recordings in 84 neurosurgical patients as they studied and subsequently recalled lists of common words.

Brain-machine interfaces: electrophysiological challenges and limitations.

Brain-machine interfaces (BMI) seek to directly communicate with the human nervous system in order to diagnose and treat intrinsic neurological disorders. While the first generation of these devices has realized significant clinical successes, they often rely on gross electrical stimulation using empirically derived parameters through open-loop mechanisms of action that are not yet fully understood. Their limitations reflect the inherent challenge in developing the next generation of these devices.

Techniques and devices to restore cognition.

Executive planning, the ability to direct and sustain attention, language and several types of memory may be compromised by conditions such as stroke, traumatic brain injury, cancer, autism, cerebral palsy and Alzheimer's disease. No medical devices are currently available to help restore these cognitive functions. Recent findings about the neurophysiology of these conditions in humans coupled with progress in engineering devices to treat refractory neurological conditions imply that the time has arrived to consider the design and evaluation of a new class of devices.

A microscale photovoltaic neurostimulator for fiber optic delivery of functional electrical stimulation.

Recent advances in functional electrical stimulation (FES) show significant promise for restoring voluntary movement in patients with paralysis or other severe motor impairments. Current approaches for implantable FES systems involve multisite stimulation, posing research issues related to their physical size, power and signal delivery, surgical and safety challenges. To explore a different means for delivering the stimulus to a distant muscle nerve site, we have elicited in vitro FES response using a high efficiency microcrystal photovoltaic device as a neurostimulator, integrated with a biocompatible glass optical fiber which forms a lossless, interference-free lightwave conduit for signal and energy transport.

Decoding movement intent from human premotor cortex neurons for neural prosthetic applications.

Primary motor cortex (M1), a key region for voluntary motor control, has been considered a first choice as the source of neural signals to control prosthetic devices for humans with paralysis. Less is known about the potential for other areas of frontal cortex as prosthesis signal sources. The frontal cortex is widely engaged in voluntary behavior.

Neuronal ensemble control of prosthetic devices by a human with tetraplegia.

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks.