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Research and applications::Neural engineering

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Neural::neural    Brain::tissue    System::systems    Nerve::these    Devices::signals    Leach::schmidt

Research and applications Research is focused on neural engineering utilizes devices to study how the nervous system functions and malfunctions. (Schmidt & Leach 2003)

Neural imaging

Neuroimaging techniques are used to investigate the activity of neural networks, as well as the structure and function of the brain. Neuroimaging technologies include functional magnetic resonance imaging (fMRI), magnetic resonance imaging (MRI), positron emission tomography (PET) and computed axial tomography (CAT) scans. Functional neuroimaging studies are interested in which areas of the brain perform specific tasks. fMRI measures hemodynamic activity that is closely linked to neural activity. It probes the brain by tuning the brain scanner to a certain wavelength to see which part of the brain are activated doing different tasks by seeing what lights up doing different things. PET, CT scanners, and electroencephalography (EEG) are currently being improved and used for similar purposes(Potter 2012).

Neural networks

Scientists can use experimental observations of neuronal systems and theoretical and computational models of these systems to create Neural networks with the hopes of modeling neural systems in as realistic a manner as possible. Neural networks can be used for analyses to help design further neurotechnology devices. Specifically, researchers handle analytical or finite element modeling to determine nervous system control of movements and apply these techniques to help patients with brain injuries or disorders. Artificial neural networks can be built from theoretical and computational models and implemented on computers from theoretically devices equations or experimental results of observed behavior of neuronal systems. Models might represent ion concentration dynamics, channel kinetics, synaptic transmission, single neuron computation, oxygen metabolism, or application of dynamic system theory. (LaPlaca et al. 2005) Liquid-Based template assembly was used to engineer 3D neural networks from neuron-seeded microcarrier beads.<ref>Chen, P., Luo, Z., G├╝ven, S., Tasoglu, S., Ganesan, A. V., Weng, A. and Demirci, U. (2014), Microscale Assembly Directed by Liquid-Based Template. Adv. Mater.. doi: 10.1002/adma.201402079 http://onlinelibrary.wiley.com/doi/10.1002/adma.201402079/abstract</ref>

Neural interfaces

Neural interfaces are a major element used for studying neural systems and enhancing or replacing neuronal function with engineered devices. Engineers are challenged with developing electrodes than can selectively record from associated electronic circuits to collect information about the nervous system activity and to stimulate specified regions of neural tissue to restore function or sensation of that tissue.(Cullen et al. 2011) The materials used for these devices must match the mechanical properties of neural tissue in which they are placed and the damage must be assessed. Neural interfacing involves temporary regeneration of biomaterial scaffolds or chronic electrodes and must manage the body's response to foreign materials. Microelectrode arrays are recent advances that can be used to study neural networks(Cullen & Pfister 2011). Optical neural interfaces involve optical recordings and optogenetics stimulation that makes brain cells light sensitive. Fiber optics can be implanted in the brain to stimulate and record this photon activity instead of electrodes. Two-photon excitation microscopy can study living neuronal networks and the communicatory events among neurons (Potter 2012).

Brain computer interfaces

Brain computer interfaces seek to directly communicate with human nervous system to monitor and stimulate neural circuits as well as diagnose and treat intrinsic neurological dysfunction. Deep brain stimulation is a significant advance in this field that is especially effective in treating movement disorders such as Parkinson's disease with high frequency stimulation of neural tissue to suppress tremors(Lega et al. 2011).

Microsystems

Neural microsystems can be developed to interpret and deliver electrical, chemical, magnetic, and optical signals to neural tissue. They can detect variations in membrane potential and measure electrical properties such as spike population, amplitude, or rate by using electrodes, or by assessment of chemical concentrations, fluorescence light intensity, or magnetic field potential. The goal of these systems is to deliver signals that would influence neuronal tissue potential and thus stimulate the brain tissue to evoke a desired response(He 2005). {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

Microelectrode arrays

Microelectrode arrays are specific tools used to detect the sharp changes in voltage in the extracellular environments that occur from propagation of an action potential down an axon. Dr. Mark Allen and Dr. LaPlaca have microfabricated 3D electrodes out of cytocompatible materials such as SU-8 and SLA polymers which have led to the development of in vitro and in vivo microelectrode systems with the characteristics of high compliance and flexibility to minimize tissue disruption.

Neural prostheses

Neuroprosthetics are devices capable of supplementing or replacing missing functions of the nervous system by stimulating the nervous system and recording its activity. Electrodes that measure firing of nerves can integrate with prosthetic devices and signal them to perform the function intended by the transmitted signal. Sensory prostheses use artificial sensors to replace neural input that might be missing from biological sources(He 2005). Engineers researching these devices are charged with providing a chronic, safe, artificial interface with neuronal tissue. Perhaps the most successful of these sensory prostheses is the cochlear implant which has restored hearing abilities to the deaf. Visual prosthesis for restoring visual capabilities of blind persons is still in more elementary stages of development. Motor prosthesics are devices involved with electrical stimulation of biological neural muscular system that can substitute for control mechanisms of the brain or spinal cord. Smart prostheses can be designed to replace missing limbs controlled by neural signals by transplanting nerves from the stump of an amputee to muscles. Electrodes placed on the skin can interpret signals and then control the prosthetic limb. These prosthetics have been very successful. Functional electrical stimulation (FES) is a system aimed at restoring motor processes such as standing, walking, and hand grasp(Potter 2012).

Neurorobotics

Neurorobotics is the study of how neural systems can be embodied and movements emulated in mechanical machines. Neurorobots are typically used to study motor control and locomotion, learning and memory selection, and value systems and action selection. By studying neurorobots in real-world environments, they are more easily observed and assessed to describe heuristics of robot function in terms of its embedded neural systems and the reactions of these systems to its environment(Krichmar 2008). For instance, making use of a computational model of epilectic spike-wave dynamics, it has been already proven the effectiveness of a method to simulate seizure abatement through a pseudospectral protocol. The computational model emulates the brain connectivity by using a magnetic imaging resonance from a patient suffering of idiopathic generalized epilepsy. The method was able to generate stimuli able to lessen the seizures.

Neural tissue regeneration

Neural tissue regeneration, or neuroregeneration looks to restore function to those neurons that have been damaged in small injuries and larger injuries like those caused by traumatic brain injury. Functional restoration of damaged nerves involves re-establishment of a continuous pathway for regenerating axons to the site of innervation. Researchers like Dr. LaPlaca at Georgia Institute of Technology are looking to help find treatment for repair and regeneration after traumatic brain injury and spinal cord injuries by applying tissue engineering strategies . Dr. LaPlaca is looking into methods combining neural stem cells with an extracellular matrix protein based scaffold for minimally invasive delivery into the irregular shaped lesions that form after a traumatic insult. By studying the neural stem cells in vitro and exploring alternative cell sources, engineering novel biopolymers that could be utilized in a scaffold, and investigating cell or tissue engineered construct transplants in vivo in models of traumatic brain and spinal cord injury, Dr. LaPlaca's lab aims to identify optimal strategies for nerve regeneration post injury.

Current approaches to clinical treatment

End to end surgical suture of damaged nerve ends can repair small gaps with autologous nerve grafts. For larger injuries, an autologous nerve graft that has been harvested from another site in the body might be used, though this process is time consuming, costly and requires two surgeries. (Schmidt & Leach 2003) Clinical treatment for CNS is minimally available and focuses mostly on reducing collateral damage caused by bone fragments near the site of injury or inflammation. After swelling surrounding injury lessens, patients undergo rehabilitation so that remaining nerves can be trained to compensate for the lack of nerve function in injured nerves. No treatment currently exists to restore nerve function of CNS nerves that have been damaged(Schmidt & Leach 2003).

Engineering strategies for repair

Engineering strategies for the repair of spinal cord injury are focused on creating a friendly environment for nerve regeneration. Only PNS nerve damage has been clinically possible so far, but advances in research of genetic techniques and biomaterials demonstrate the potential for SC nerves to regenerate in permissible environments.

Grafts

Advantages of autologous tissue grafts are that they come from natural materials which have a high likelihood of biocompatibility while providing structural support to nerves that encourage cell adhesion and migration. (Schmidt & Leach 2003) Nonautologous tissue, acellular grafts, and extracellular matrix based materials are all options that may also provide ideal scaffolding for nerve regeneration. Some come from allogenic or xenogenic tissues that must be combined with immunosuppressants. while others include small intestinal submucosa and amniotic tissue grafts.(Schmidt & Leach 2003) Synthetic materials are attractive options because their physical and chemical properties can typically be controlled. A challenge that remains with synthetic materials is biocompatibility. (Schmidt & Leach 2003) Methylcellulose based constructs have be shown to be a biocompatible option serving this purpose.(Tate et al. 2001) AxoGen uses a cell graft technology AVANCE to mimic a human nerve. It has been shown to achieve meaningful recovery in 87 percent of patients with peripheral nerve injuries(2012b).

Nerve guidance channels

Nerve guidance channels, Nerve guidance conduit are innovative strategies focusing on larger defects that provide a conduit for sprouting axons directing growth and reducing growth inhibition from scar tissue. Nerve guidance channels must be readily formed into a conduit with the desired dimensions, sterilizable, tear resistant, and easy to handle and suture. (Schmidt & Leach 2003) Ideally they would degrade over time with nerve regeneration, be pliable, semipermeable, maintain their shape, and have a smooth inner wall that mimics that of a real nerve. (Schmidt & Leach 2003)

Biomolecular therapies

Highly controlled delivery systems are needed to promote neural regeneration. Neurotrophic factors can influence development, survival, outgrowth, and branching. Neurotrophins include nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5(NT-4/5). Other factors are ciliary neurotrophic factor (CNTF), glial cell line-derived growth factor (GDNF) and acidic and basic fibroblast growth factor (aFGF, bFGF) that promote a range of neural responses.(Schmidt & Leach 2003) Fibronectin has also been shown to support nerve regeneration following TBI in rats. (Tate et al. 2002) Other therapies are looking into regeneration of nerves by upregulating regeneration associated genes (RAGs), neuronal cytoskeletal components, and antiapoptosis factors. RAGs include GAP-43 and Cap-23, adhesion molecules such as L1 family, NCAM, and N-cadherin.(Schmidt & Leach 2003) There is also the potential for blocking inhibitory biomolecules in the CNS due to glial scarring. Some currently being studied are treatments with chondroitinase ABC and blocking NgR, ADP-ribose.(Schmidt & Leach 2003)

Delivery techniques

Delivery devices must be biocompatible and stable in vivo. Some examples include osmotic pumps, silicone reservoirs, polymer matrices, and microspheres. Gene therapy techniques have also been studied to provide long-term production of growth factors and could be delivered with viral or non-viral vectors such as lipoplexes. Cells are also effective delivery vehicles for ECM components, neurotrophic factors and cell adhesion molecules. Olfactory ensheathing cells (OECs) and stem cells as well as genetically modified cells have been used as transplants to support nerve regeneration. (LaPlaca et al. 2005, Schmidt & Leach 2003, Tate et al. 2002)

Advanced therapies

Advanced therapies combine complex guidance channels and multiple stimuli that focus on internal structures that mimic the nerve architecture containing internal matrices of longitudinally aligned fibers or channels. Fabrication of these structures can use a number of technologies: magnetic polymer fiber alignment, injection molding, phase separation, solid free-form fabrication, and ink jet polymer printing(Schmidt & Leach 2003).

Neural enhancement

Augmentation of human neural systems, or human enhancement using engineering techniques is another inevitable application of neuroengineering believed to develop within the next few decades. Deep brain stimulation has already been shown to enhance memory recall as noted by patients currently using this treatment for neurological disorders. Brain stimulation techniques are postulated to be able to sculpt emotions and personalities as well as enhance motivation, reduce inhibitions, etc. as requested by the individual. Ethical issues with this sort of human augmentation are a new set of questions that neural engineers have to grapple with as these studies develop(Potter 2012).


Neural engineering sections
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