Advances in the electrode microfabrication, biomimetic materials, power and data telemetry, and processing and modeling of neuronal signaling drive the development of neuroprosthetic devices for treatment of neurological disorders. This Research Topic features the original research aimed at development of neural interfaces from the early prototypes toward eventual clinical use. Main focus is on implantable devices directly interfaced to neurons inside the brain rather than noninvasive BMI/BCI techniques. A variety of applications is covered including restoring sensory functions (auditory and visual prostheses) and motor functions (functional electrical stimulation and spinal cord stimulation) and neuromodulation (in the deep brain, cortex, spinal cord, and peripheral nerves). Papers will be reviewed by members of the Alliance for Innovations in Neural Technology <a href="http://neurotechzone.com/alliance" class="paperTitle" target="_blank">http://neurotechzone.com/alliance</a>.

Medipace Inc

This research focuses on improving deep brain stimulating devices by using flexible implant materials and a fibrinous hydrogel coating to protect cells against shear forces. It also presents a set of generic tools to allow bi-directional and real-time interaction with neural modules, which is validated using a 60-channel extracellular multi-electrode recording and stimulation set-up. Additionally, a multi-electrode array was implanted in the spinal cord to record neural signals during behavior in rats. Frequency analysis and principal component analysis revealed multiple channels of neural activity that correlated to the behavior, suggesting potential applications in differentiating between behaviors. <ul> <li>Flexible implant materials and a fibrinous hydrogel coating to protect cells against shear forces.</li> <li>Generic tools to allow bi-directional and real-time interaction with neural modules.</li> <li>Multi-electrode array implanted in the spinal cord to record neural signals during behavior in rats.</li> <li>Frequency analysis and principal component analysis revealed multiple channels of neural activity.</li> <li>Potential applications in differentiating between behaviors.</li> </ul>

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Frontiers in Neuroscience

Neuroprosthetics

Frontiers in Neurology

Neuroprosthetic devices

Minimizing the foreign body response is seen as one critical research strategy for implants especially when designed for immune-privileged organs like the brain. The context of this work is to improve deep brain stimulating devices used in a consistently growing spectrum of psychomotor and psychiatric diseases mainly in form of stiff electrodes. Based on the compliance match hypothesis of biocompatibility we present another step forward using flexible implant materials covered with brain cell-mimicking layers. We covered two types of flexible polyimide films with glandular stem cells derived from pancreatic acini. Using real time-PCR and fluorescent immunocytochemistry we analyzed markers representing various cell types of all three germ layers and stemness. The results demonstrate an unchanged differentiation potential of the polyimide fixated cells as measured by mRNA and protein level. Additionally we developed a fibrinous hydrogel coating to protect them against shear forces upon eventual implantation. By repeating previous analysis and additional metabolism tests for all stages we corroborate the validity of this improvement. Consequently we assume that a stem cell-containing cover may provide a native, fully and actively integrating brain-mimicking interface to the neuropil.

Minimizing the foreign body response is seen as one critical research strategy for implants especially when designed for immune-privileged organs like the brain. The context of this work is to improve deep brain stimulating devices used in a consistently growing spectrum of psychomotor and psychiatric diseases mainly in form of stiff electrodes. Based on the compliance match hypothesis of biocompatibility we present another step forward using flexible implant materials covered with brain cell-mimicking layers. We covered two types of flexible polyimide films with glandular stem cells derived from pancreatic acini. Using real time-PCR and fluorescent immunocytochemistry we analyzed markers representing various cell types of all three germ layers and stemness. The results demonstrate an unchanged differentiation potential of the polyimide fixated cells as measured by mRNA and protein level. Additionally we developed a fibrinous hydrogel coating to protect them against shear forces upon eventual implantation. By repeating previous analysis and additional metabolism tests for all stages we corroborate the validity of this improvement. Consequently we assume that a stem cell-containing cover may provide a native, fully and actively integrating brain-mimicking interface to the neuropil.

Cellular Modulation of Polymeric Device Surfaces: Promise of Adult Stem Cells for Neuro-Prosthetics

Distinct modules of the neural circuitry interact with each other and (through the motor-sensory loop) with the environment, forming a complex dynamic system. Neuro-prosthetic devices seeking to modulate or restore CNS function need to interact with the information flow at the level of neural modules electrically, bi-directionally and in real-time. A set of freely available generic tools is presented that allow computationally demanding multi-channel short-latency bi-directional interactions to be realized in in vivo and in vitro preparations using standard PC data acquisition and processing hardware and software (Mathworks Matlab and Simulink). A commercially available 60-channel extracellular multi-electrode recording and stimulation set-up connected to an ex vivo developing cortical neuronal culture is used as a model system to validate the method. We demonstrate how complex high-bandwidth (>10 MBit/s) neural recording data can be analyzed in real-time while simultaneously generating specific complex electrical stimulation feedback with deterministically timed responses at sub-millisecond resolution.

Distinct modules of the neural circuitry interact with each other and (through the motor-sensory loop) with the environment, forming a complex dynamic system. Neuro-prosthetic devices seeking to modulate or restore CNS function need to interact with the information flow at the level of neural modules electrically, bi-directionally and in real-time. A set of freely available generic tools is presented that allow computationally demanding multi-channel short-latency bi-directional interactions to be realized in in vivo and in vitro preparations using standard PC data acquisition and processing hardware and software (Mathworks Matlab and Simulink). A commercially available 60-channel extracellular multi-electrode recording and stimulation set-up connected to an ex vivo developing cortical neuronal culture is used as a model system to validate the method. We demonstrate how complex high-bandwidth (&gt;10 MBit/s) neural recording data can be analyzed in real-time while simultaneously generating specific complex electrical stimulation feedback with deterministically timed responses at sub-millisecond resolution.

A generic framework for real-time multi-channel neuronal signal analysis, telemetry control and sub-millisecond latency feedback generation

A multi-electrode array (MEA) was implanted in the dorsolateral funiculus of the cervical spinal cord to record descending information during behavior in freely moving rats. Neural signals were characterized in terms of frequency and information content. Frequency analysis revealed components both at the range of local field potentials and multi-unit activity. Coherence between channels decreased steadily with inter-contact distance and frequency suggesting greater spatial selectivity for multi-unit activity compared to local field potentials. Principal component analysis (PCA) extracted multiple channels of neural activity with patterns that correlated to the behavior, indicating multiple dimensionality of the signals. Two different behaviors involving the forelimbs, face cleaning and food reaching, generated neural signals through distinctly different combination of neural channels, which suggested that these two behaviors could readily be differentiated from recordings. This preliminary data demonstrated that descending spinal cord signals recorded with MEAs can be used to extract multiple channels of command control information and potentially be utilized as a means of communication in high level spinal cord injury subjects.