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Neural engineering (also known as neuroengineering) is a discipline within
biomedical engineering Biomedical engineering (BME) or medical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes (e.g., diagnostic or therapeutic). BME is also traditionally logical sciences ...
that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs
Hetling, 2008
.


Overview

The field of neural engineering draws on the fields of
computational neuroscience Computational neuroscience (also known as theoretical neuroscience or mathematical neuroscience) is a branch of neuroscience which employs mathematical models, computer simulations, theoretical analysis and abstractions of the brain to u ...
, experimental neuroscience,
neurology Neurology (from el, wikt:νεῦρον, νεῦρον (neûron), "string, nerve" and the suffix wikt:-logia, -logia, "study of") is the branch of specialty (medicine), medicine dealing with the diagnosis and treatment of all categories of co ...
,
electrical engineering Electrical engineering is an engineering discipline concerned with the study, design, and application of equipment, devices, and systems which use electricity, electronics, and electromagnetism. It emerged as an identifiable occupation in the l ...
and
signal processing Signal processing is an electrical engineering subfield that focuses on analyzing, modifying and synthesizing ''signals'', such as audio signal processing, sound, image processing, images, and scientific measurements. Signal processing techniq ...
of living neural tissue, and encompasses elements from
robotics Robotics is an interdisciplinary branch of computer science and engineering. Robotics involves design, construction, operation, and use of robots. The goal of robotics is to design machines that can help and assist humans. Robotics integrat ...
,
cybernetics Cybernetics is a wide-ranging field concerned with circular causality, such as feedback, in regulatory and purposive systems. Cybernetics is named after an example of circular causal feedback, that of steering a ship, where the helmsperson m ...
,
computer engineering Computer engineering (CoE or CpE) is a branch of electrical engineering and computer science that integrates several fields of computer science and electronic engineering required to develop computer hardware and software. Computer engineers ...
, neural tissue engineering, materials science, and
nanotechnology Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal o ...
. Prominent goals in the field include restoration and augmentation of human function via direct interactions between the nervous system and artificial devices. Much current research is focused on understanding the coding and processing of information in the sensory and
motor An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power gen ...
systems, quantifying how this processing is altered in the
pathological Pathology is the study of the causal, causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when us ...
state, and how it can be manipulated through interactions with artificial devices including
brain–computer interface A brain–computer interface (BCI), sometimes called a brain–machine interface (BMI) or smartbrain, is a direct communication pathway between the brain, brain's electrical activity and an external device, most commonly a computer or robotic l ...
s and
neuroprosthetics Neuroprosthetics (also called neural prosthetics) is a discipline related to neuroscience and biomedical engineering concerned with developing neural prostheses. They are sometimes contrasted with a brain–computer interface, which connects the ...
. Other research concentrates more on investigation by experimentation, including the use of
neural implants Brain implants, often referred to as neural implants, are technological devices that connect directly to a biological subject's brain – usually placed on the surface of the brain, or attached to the brain's cortex. A common purpose of modern brai ...
connected with external technology. Neurohydrodynamics is a division of neural engineering that focuses on
hydrodynamics In physics and engineering, fluid dynamics is a subdiscipline of fluid mechanics that describes the flow of fluids—liquids and gases. It has several subdisciplines, including ''aerodynamics'' (the study of air and other gases in motion) and ...
of the neurological system.


History

As neural engineering is a relatively new field, information and research relating to it is comparatively limited, although this is changing rapidly. The first journals specifically devoted to neural engineering, ''The Journal of Neural Engineering'' and ''The Journal of NeuroEngineering and Rehabilitation'' both emerged in 2004. International conferences on neural engineering have been held by the IEEE since 2003, from 29 April until 2 May 2009 in Antalya, Turkey 4th Conference on Neural Engineering, the 5th International IEEE EMBS Conference on Neural Engineering in April/May 2011 in
Cancún Cancún ( ), often Cancun in English (without the accent; or ) is a city in southeast Mexico on the northeast coast of the Yucatán Peninsula in the Mexican state of Quintana Roo. It is a significant tourist destination in Mexico and the seat ...
,
Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...
, and the 6th conference in
San Diego San Diego ( , ; ) is a city on the Pacific Ocean coast of Southern California located immediately adjacent to the Mexico–United States border. With a 2020 population of 1,386,932, it is the List of United States cities by population, eigh ...
,
California California is a U.S. state, state in the Western United States, located along the West Coast of the United States, Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the List of states and territori ...
in November 2013. The 7th conference was held in April 2015 in
Montpellier Montpellier (, , ; oc, Montpelhièr ) is a city in southern France near the Mediterranean Sea. One of the largest urban centres in the region of Occitania (administrative region), Occitania, Montpellier is the prefecture of the Departments of ...
. The 8th conference was held in May 2017 in
Shanghai Shanghai (; , , Standard Mandarin pronunciation: ) is one of the four direct-administered municipalities of the People's Republic of China (PRC). The city is located on the southern estuary of the Yangtze River, with the Huangpu River flow ...
.


Fundamentals

The fundamentals behind neuroengineering involve the relationship of neurons, neural networks, and nervous system functions to quantifiable models to aid the development of devices that could interpret and control signals and produce purposeful responses.


Neuroscience

Messages that the body uses to influence thoughts, senses, movements, and survival are directed by nerve impulses transmitted across brain tissue and to the rest of the body.
Neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s are the basic functional unit of the nervous system and are highly specialized cells that are capable of sending these signals that operate high and low level functions needed for survival and quality of life. Neurons have special electro-chemical properties that allow them to process information and then transmit that information to other cells. Neuronal activity is dependent upon neural membrane potential and the changes that occur along and across it. A constant voltage, known as the
membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
, is normally maintained by certain concentrations of specific ions across neuronal membranes. Disruptions or variations in this voltage create an imbalance, or polarization, across the membrane.
Depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
of the membrane past its
threshold potential In electrophysiology, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. In neuroscience, threshold potentials are necessary to regulate and propagate signaling in both ...
generates an action potential, which is the main source of signal transmission, known as
neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
of the nervous system. An
action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
results in a cascade of ion flux down and across an axonal membrane, creating an effective voltage spike train or "electrical signal" which can transmit further electrical changes in other cells. Signals can be generated by electrical, chemical, magnetic, optical, and other forms of stimuli that influence the flow of charges, and thus voltage levels across neural membranes (He 2005).


Engineering

Engineers employ quantitative tools that can be used for understanding and interacting with complex neural systems. Methods of studying and generating chemical, electrical, magnetic, and optical signals responsible for extracellular field potentials and synaptic transmission in neural tissue aid researchers in the modulation of neural system activity (Babb et al. 2008). To understand properties of neural system activity, engineers use signal processing techniques and computational modeling (Eliasmith & Anderson 2003). To process these signals, neural engineers must translate the voltages across neural membranes into corresponding code, a process known as neural coding.
Neural coding Neural coding (or Neural representation) is a neuroscience field concerned with characterising the hypothetical relationship between the stimulus and the individual or ensemble neuronal responses and the relationship among the electrical activity o ...
studies on how the brain encodes simple commands in the form of central pattern generators (CPGs), movement vectors, the cerebellar internal model, and somatotopic maps to understand movement and sensory phenomena. Decoding of these signals in the realm of
neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
is the process by which neurons understand the voltages that have been transmitted to them. Transformations involve the mechanisms that signals of a certain form get interpreted and then translated into another form. Engineers look to mathematically model these transformations (Eliasmith & Anderson 2003). There are a variety of methods being used to record these voltage signals. These can be intracellular or extracellular. Extracellular methods involve single-unit recordings, extracellular field potentials, and amperometry; more recently,
multielectrode array Microelectrode arrays (MEAs) (also referred to as multielectrode arrays) are devices that contain multiple (tens to thousands) microelectrodes through which neural signals are obtained or delivered, essentially serving as neural interfaces that co ...
s have been used to record and mimic signals.


Scope


Neuromechanics

Neuromechanics is the coupling of neurobiology, biomechanics, sensation and perception, and robotics (Edwards 2010). Researchers are using advanced techniques and models to study the mechanical properties of neural tissues and their effects on the tissues' ability to withstand and generate force and movements as well as their vulnerability to traumatic loading (Laplaca & Prado 2010). This area of research focuses on translating the transformations of information among the neuromuscular and skeletal systems to develop functions and governing rules relating to operation and organization of these systems (Nishikawa et al. 2007). Neuromechanics can be simulated by connecting computational models of neural circuits to models of animal bodies situated in virtual physical worlds (Edwards 2010). Experimental analysis of biomechanics including the kinematics and dynamics of movements, the process and patterns of motor and sensory feedback during movement processes, and the circuit and synaptic organization of the brain responsible for motor control are all currently being researched to understand the complexity of animal movement. Dr. Michelle LaPlaca's lab at Georgia Institute of Technology is involved in the study of mechanical stretch of cell cultures, shear deformation of planar cell cultures, and shear deformation of 3D cell containing matrices. Understanding of these processes is followed by development of functioning models capable of characterizing these systems under closed loop conditions with specially defined parameters. The study of neuromechanics is aimed at improving treatments for physiological health problems which includes optimization of prostheses design, restoration of movement post injury, and design and control of mobile robots. By studying structures in 3D hydrogels, researchers can identify new models of nerve cell mechanoproperties. For example, LaPlaca et al. developed a new model showing that strain may play a role in cell culture (LaPlaca et al. 2005).


Neuromodulation

Neuromodulation Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second ...
aims to treat disease or injury by employing medical device technologies that would enhance or suppress activity of the nervous system with the delivery of pharmaceutical agents, electrical signals, or other forms of energy stimulus to re-establish balance in impaired regions of the brain. Researchers in this field face the challenge of linking advances in understanding neural signals to advancements in technologies delivering and analyzing these signals with increased sensitivity, biocompatibility, and viability in closed loops schemes in the brain such that new treatments and clinical applications can be created to treat those with neural damage of various kinds.Potter S. 2012. NeuroEngineering: Neuroscience - Applied. In TEDxGeorgiaTech: TEDx Neuromodulator devices can correct nervous system dysfunction related to Parkinson's disease, dystonia, tremor, Tourette's, chronic pain, OCD, severe depression, and eventually epilepsy. Neuromodulation is appealing as treatment for varying defects because it focuses in on treating highly specific regions of the brain only, contrasting that of systemic treatments that can have side effects on the body. Neuromodulator stimulators such as microelectrode arrays can stimulate and record brain function and with further improvements are meant to become adjustable and responsive delivery devices for drugs and other stimuli.


Neural regrowth and repair

Neural engineering and rehabilitation applies neuroscience and engineering to investigating peripheral and central nervous system function and to finding clinical solutions to problems created by brain damage or malfunction. Engineering applied to
neuroregeneration Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous syste ...
focuses on engineering devices and materials that facilitate the growth of neurons for specific applications such as the regeneration of peripheral nerve injury, the regeneration of the spinal cord tissue for spinal cord injury, and the regeneration of retinal tissue.
Genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including t ...
and
tissue engineering Tissue engineering is a biomedical engineering discipline that uses a combination of Cell (biology), cells, engineering, Materials science, materials methods, and suitable biochemistry, biochemical and physicochemical factors to restore, maintai ...
are areas developing scaffolds for spinal cord to regrow across thus helping neurological problems (Schmidt & Leach 2003).


Research and applications

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


Neural imaging

Neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incre ...
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 Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...
(fMRI),
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI),
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
(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 is used to map metabolic responses in specific regions of the brain to a given task or stimulus. PET, CT scanners, and
electroencephalography Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
(EEG) are currently being improved and used for similar purposes.


Neural networks

Scientists can use experimental observations of neuronal systems and theoretical and computational models of these systems to create
Neural network A neural network is a network or circuit of biological neurons, or, in a modern sense, an artificial neural network, composed of artificial neurons or nodes. Thus, a neural network is either a biological neural network, made up of biological ...
s 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 neurotechnological 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 network Artificial neural networks (ANNs), usually simply called neural networks (NNs) or neural nets, are computing systems inspired by the biological neural networks that constitute animal brains. An ANN is based on a collection of connected unit ...
s 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.


Neural interfaces

Neural interface In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
s are a major element used for studying neural systems and enhancing or replacing neuronal function with engineered devices. Engineers are challenged with developing electrodes that 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 recording The history of optical recording can be divided into a few number of distinct major contributions. The pioneers of optical recording worked mostly independently, and their solutions to the many technical challenges have very distinctive features, su ...
s and
optogenetics Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individu ...
, making certain brain cells sensitive to light in order to modulate their activity.
Fiber optics An optical fiber, or optical fibre in Commonwealth English, is a flexible, transparent fiber made by drawing glass (silica) or plastic to a diameter slightly thicker than that of a human hair. Optical fibers are used most often as a means to ...
can be implanted in the brain to stimulate or silence targeted neurons using light, as well as record photon activity—a
proxy Proxy may refer to: * Proxy or agent (law), a substitute authorized to act for another entity or a document which authorizes the agent so to act * Proxy (climate), a measured variable used to infer the value of a variable of interest in climate ...
of neural activity— instead of using electrodes.
Two-photon excitation microscopy Two-photon excitation microscopy (TPEF or 2PEF) is a fluorescence imaging technique that allows imaging of living tissue up to about one millimeter in thickness, with 0.64 μm lateral and 3.35 μm axial spatial resolution. Unlike traditional flu ...
can study living neuronal networks and the communicatory events among neurons.


Brain–computer interfaces

Brain–computer interface A brain–computer interface (BCI), sometimes called a brain–machine interface (BMI) or smartbrain, is a direct communication pathway between the brain, brain's electrical activity and an external device, most commonly a computer or robotic l ...
s 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 Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleu ...
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).


= Microelectrode arrays

=
Microelectrode array Microelectrode arrays (MEAs) (also referred to as multielectrode arrays) are devices that contain multiple (tens to thousands) microelectrodes through which neural signals are obtained or delivered, essentially serving as neural interfaces that co ...
s 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 Neuroprosthetics (also called neural prosthetics) is a discipline related to neuroscience and biomedical engineering concerned with developing neural prostheses. They are sometimes contrasted with a brain–computer interface, which connects the ...
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 A cochlear implant (CI) is a surgically implanted neuroprosthesis that provides a person who has moderate-to-profound sensorineural hearing loss with sound perception. With the help of therapy, cochlear implants may allow for improved speech und ...
which has restored hearing abilities to the deaf.
Visual prosthesis A visual prosthesis, often referred to as a bionic eye, is an experimental visual device intended to restore functional vision in those with partial or total blindness. Many devices have been developed, usually modeled on the cochlear implant or ...
for restoring visual capabilities of blind persons is still in more elementary stages of development.
Motor prosthesics An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power ...
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. Sensory prosthetics provide sensory feedback by transforming mechanical stimuli from the periphery into encoded information accessible by the nervous system. Electrodes placed on the skin can interpret signals and then control the prosthetic limb. These prosthetics have been very successful.
Functional electrical stimulation Functional electrical stimulation (FES) is a technique that uses low-energy electrical pulses to artificially generate body movements in individuals who have been paralyzed due to injury to the central nervous system. More specifically, FES can ...
(FES) is a system aimed at restoring motor processes such as standing, walking, and hand grasp.


Neurorobotics

Neurorobotics Neurorobotics is the combined study of neuroscience, robotics, and artificial intelligence. It is the science and technology of embodied autonomous neural systems. Neural systems include brain-inspired algorithms (e.g. connectionist networks), compu ...
is the study of how neural systems can be embodied and movements emulated in mechanical machines. Neurorobots are typically used to study
motor control Motor control is the regulation of movement in organisms that possess a nervous system. Motor control includes reflexes as well as directed movement. To control movement, the nervous system must integrate multimodal sensory information (both f ...
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 with idiopathic generalized epilepsy. The method was able to generate stimuli able to lessen the seizures.


Neural tissue regeneration

Neural tissue regeneration, or
neuroregeneration Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous syste ...
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 A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
and
spinal cord injuries A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...
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 Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogene ...
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 In ecology, allogenic succession is succession driven by the abiotic components of an ecosystem. In contrast, autogenic succession is driven by the biotic components of the ecosystem. An allogenic succession can be brought about in a number of ways ...
or
xenogenic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
tissues that must be combined with
immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified in ...
s. while others include small intestinal
submucosa The submucosa (or tela submucosa) is a thin layer of tissue (biology), tissue in various organ (anatomy), organs of the gastrointestinal tract, gastrointestinal, respiratory tract, respiratory, and genitourinary system, genitourinary tracts. It i ...
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 Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing de ...
(Schmidt & Leach 2003).
Methylcellulose Methyl cellulose (or methylcellulose) is a compound derived from cellulose. It is sold under a variety of trade names and is used as a thickener and emulsifier in various food and cosmetic products, and also as a bulk-forming laxative. Like cellu ...
-based constructs have been 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.


= Nerve guidance channels

= Nerve guidance channels,
Nerve guidance conduit A nerve guidance conduit (also referred to as an artificial nerve conduit or artificial nerve graft, as opposed to an autograft) is an artificial means of guiding axonal regrowth to facilitate nerve regeneration and is one of several clinical trea ...
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 Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous syst ...
.
Neurotrophic factor Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and cell differentiation, differentiation of both developing and mature neurons. Most ...
s can influence development, survival, outgrowth, and branching. Neurotrophins include
nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was on ...
(NGF),
brain derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canon ...
(BDNF),
neurotrophin-3 Neurotrophin-3 is a protein that in humans is encoded by the ''NTF3'' gene. The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activi ...
(NT-3) and neurotrophin-4/5 (NT-4/5). Other factors are
ciliary neurotrophic factor Ciliary neurotrophic factor is a protein that in humans is encoded by the ''CNTF'' gene. The protein encoded by this gene is a polypeptide hormone and neurotrophic factor whose actions have mainly been studied in the nervous system where it prom ...
(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 Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...
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 molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s such as
L1 family The L1 family is a family of cell adhesion molecules that includes four different L1-like proteins. They are members of the immunoglobulin superfamily ( IgSF CAM). The members of the L1-family in humans are called L1 or L1cam, CHL1 (close homo ...
,
NCAM Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. Although CD56 is often considered a marker of neural lineage commitment due to its discover ...
, and
N-cadherin Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in multipl ...
(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 Human enhancement (HE) can be described as the natural, artificial, or technological alteration of the human body in order to enhance physical or mental capabilities. Technologies Existing technologies Three forms of human enhancement curre ...
using engineering techniques is another possible application of neuroengineering. 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.


See also

*
Brain–computer interface A brain–computer interface (BCI), sometimes called a brain–machine interface (BMI) or smartbrain, is a direct communication pathway between the brain, brain's electrical activity and an external device, most commonly a computer or robotic l ...
*
Brain-reading Brain-reading or thought identification uses the responses of multiple voxels in the brain evoked by stimulus then detected by fMRI in order to decode the original stimulus. Advances in research have made this possible by using human neuroimaging ...
*
Cybernetics Cybernetics is a wide-ranging field concerned with circular causality, such as feedback, in regulatory and purposive systems. Cybernetics is named after an example of circular causal feedback, that of steering a ship, where the helmsperson m ...
*
Cyberware Cyberware is a relatively new and unknown field (a proto-science, or more adequately a "proto-technology"). In science fiction circles, however, it is commonly known to mean the hardware or machine parts implanted in the human body and acting as ...
*
Neuroprosthetics Neuroprosthetics (also called neural prosthetics) is a discipline related to neuroscience and biomedical engineering concerned with developing neural prostheses. They are sometimes contrasted with a brain–computer interface, which connects the ...
*
Neurosecurity Neurosecurity has been defined as "a version of Computer security, computer science security principles and methods applied to neural engineering", or more fully, as "the protection of the confidentiality, Data integrity, integrity, and availability ...
*
Neurotechnology Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity. Common design goals for neurotechnologies include using neural activity readings to control external devic ...
* Prosthetic neuronal memory silicon chips *
Sensory substitution Sensory substitution is a change of the characteristics of one sensory modality into stimuli of another sensory modality. A sensory substitution system consists of three parts: a sensor, a coupling system, and a stimulator. The sensor records stimu ...
*
Simulated reality The simulation theory is the hypothesis that reality could be simulated—for example by quantum computer simulation—to a degree indistinguishable from "true" reality. It could contain conscious minds that may or may not know that they live i ...


References

* * * * * Edwards DH. 2010. Neuromechanical simulation. Front Behav Neurosci 4 * Eliasmith C, Anderson CH. 2003. Neural engineering : computation, representation, and dynamics in neurobiological systems. Cambridge, Mass.: MIT Press. xii, 356 p. pp. * He B. 2005. Neural engineering. New York: Kluwer Academic/Plenum. xv, 488 p. pp. * * * * * * * * * * * Neural Engineering (Bioelectric Engineering) (2005) * Operative Neuromodulation: Volume 1: Functional Neuroprosthetic Surgery. An Introduction (2007) * Deep Brain Stimulation for Parkinson's Disease (2007) * Handbook of Stereotactic and Functional Neurosurgery (2003) * Neural Prostheses: Fundamental Studies (1990) * IEEE Handbook of Neural Engineering (2007) * Foundations on Cellular Neurophysiology (1995) *


External links


IEEE Transactions on Biomedical EngineeringIEEE Transactions on Neural Systems and Rehabilitation EngineeringThe Journal of Neural EngineeringJNER Journal of NeuroEngineering and RehabilitationJournal of Neurophysiology
{{Neuroscience