John Wikswo | |
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Born | |
Scientific career | |
Fields | Biological Physics |
Institutions | Vanderbilt University |
John Peter Wikswo, Jr. (born October 6, 1949) is a biological physicist at Vanderbilt University. He was born in Lynchburg, Virginia, United States.
Wikswo is noted for his work on biomagnetism and cardiac electrophysiology.
In the 1970s, Wikswo was a graduate student at Stanford University, where he worked under physicist William M. Fairbank, studying magnetocardiography.
In 1977 he became an assistant professor in the Department of Physics and Astronomy at Vanderbilt University, where he set up a laboratory to study living state physics. In 1980, he made the first measurement of the magnetic field of an isolated nerve, by threading the a frog sciatic nerve through a wire-wound, ferrite-core toroid and detecting the induced current using a SQUID magnetometer. [1] At the same time, Wikswo and Ken Swinney calculated the magnetic field of a nerve axon. [2] This work was followed a few years later by the first detailed comparison of the measured and calculated magnetic field produced by a single nerve axon. [3]
In a related line of study, Wikswo collaborated with Vanderbilt Professor John Barach to analyze the information content of biomagnetic versus bioelectric signals. [4] [5] [6]
One of Wikswo's most important contributions to science is his work in cardiac electrophysiology. In 1987 he began collaborating with doctors at the Vanderbilt Medical School, including Dan Roden, to study electrical propagation in the dog heart. [7] These studies led to the discovery of the virtual cathode effect in cardiac tissue: during electrical stimulation, the action potential wave front originated farther from the electrode in the direction perpendicular to the myocardial fibers than in the direction parallel to them. [8]
In parallel with these experimental studies, Wikswo analyzed the virtual cathode effect theoretically using the bidomain model, a mathematical model of the electrical properties of cardiac tissue that takes into account the anisotropic properties of both the intracellular and extracellular spaces. He first used the bidomain model to interpret biomagnetic measurements from strands of cardiac tissue. [9] Wikswo realized that the property of unequal anisotropy ratios in cardiac tissue (the ratio of electrical conductivity in the directions parallel and perpendicular to the myocardial fibers is different in the intracellular and extracellular spaces) has important implications for the magnetic field associated with a propagating action potential wave front in the heart. With Nestor Sepulveda, Wikswo use the finite element method to calculate the distinctive fourfold symmetric magnetic field pattern produced by an outwardly propagating wave front. [10]
Unequal anisotropy ratios has even an even greater impact during electrical stimulation of the heart. Again using the finite element model, Wikswo, Roth and Sepulveda predicted the transmembrane potential distribution around a unipolar electrode passing current into a passive, two-dimensional sheet of cardiac tissue. [11] They found that the region of depolarization under a cathode extends farther in the direction perpendicular to the fibers than parallel to the fibers, a shape that Wikswo named the dog-bone. This prediction immediately explained the virtual cathode effect found experimentally in the dog heart; they were observing the dog-bone shaped virtual cathode. Later simulations using an active, time-dependent bidomain model confirmed this conclusion. [12]
The calculation of the transmembrane potential by a unipolar electrode resulted in another prediction: regions of hyperpolarization adjacent to the cathode in the direction parallel to the myocardial fibers. Reversal of the stimulus polarization provided a mechanism for anodal stimulation of cardiac tissue. In order to test this prediction experimentally, Wikswo mastered the technique of optical mapping using voltage sensitive dyes, allowing the measurement of transmembrane potential using optical methods. With Marc Lin, Wikswo made high resolution measurements of excitation following stimulation through a unipolar electrode in a rabbit heart, and confirmed four mechanisms of electrical stimulation—cathode make, cathode break, anode make, and anode break—that had been predicted by bidomain calculations. [13] (Cathode and anode refer to the polarity of the stimulus, and make and break indicate if the excitation occurred following the start or end of the stimulus pulse.) Later experiments using this technique led to the prediction of a new type of cardiac arrhythmia, which Wikswo named quatrefoil reentry. [14]
In the 1990s, Wikswo began developing high spatial resolution SQUID magnetometers for mapping the magnetic field, to use in both biomagnetic studies and in non-destructive testing. [15] [16] [17] As is characteristic of Wikswo's work, he simultaneously developed theoretical methods to image a two-dimensional current density distribution from magnetic field measurements. [18]
In the first two decades of the 21st century, Wikswo's research has emphasized the development and application of micro- and nano-scale devices for instrumenting and controlling single cells. [19] In 2001 he founded the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) to foster and enhance interdisciplinary research in the biophysical sciences and bioengineering at Vanderbilt. Wikswo refocused his research on systems biology, building microfabricated devices for measuring cellular properties and developing mathematical models of cellular signaling. He has designed organ-on-a-chip devices containing small populations of cells to fill the gaps between cell cultures and animals models, for use in pharmacology and toxicology. This work led to a second R&D 100 Award for the MultiWell MicroFormulator, which delivers and removes cell culture media to each of the 96 wells of a microwell plate for toxicology research.
He also serves on the scientific advisory boards of Hypres Inc. and CardioMag Imaging Inc. [20]
Year | Award |
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1980–1982 | Alfred P. Sloan Research Fellow |
1984 | IR-100 Award for Neuromagnetic Current Probe |
1989 | Fellow, American Physical Society |
1999 | Fellow, American Institute for Medical and Biological Engineering |
2001 | Fellow, American Heart Association |
2005 | Fellow, Biomedical Engineering Society |
2006 | Fellow, Heart Rhythm Society |
2008 | Fellow, IEEE |
2017 | R&D 100 Award for the MultiWell MicroFormulator |
An anode usually is an electrode of a polarized electrical device through which conventional current enters the device. This contrasts with a cathode, which is usually an electrode of the device through which conventional current leaves the device. A common mnemonic is ACID, for "anode current into device". The direction of conventional current in a circuit is opposite to the direction of electron flow, so electrons flow from the anode of a galvanic cell, into an outside or external circuit connected to the cell. For example, the end of a household battery marked with a "+" is the cathode.
Magnetoencephalography (MEG) is a functional neuroimaging technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain, using very sensitive magnetometers. Arrays of SQUIDs are currently the most common magnetometer, while the SERF magnetometer is being investigated for future machines. Applications of MEG include basic research into perceptual and cognitive brain processes, localizing regions affected by pathology before surgical removal, determining the function of various parts of the brain, and neurofeedback. This can be applied in a clinical setting to find locations of abnormalities as well as in an experimental setting to simply measure brain activity.
The sucrose gap technique is used to create a conduction block in nerve or muscle fibers. A high concentration of sucrose is applied to the extracellular space, which prevents the correct opening and closing of sodium and potassium channels, increasing resistance between two groups of cells. It was originally developed by Robert Stämpfli for recording action potentials in nerve fibers, and is particularly useful for measuring irreversible or highly variable pharmacological modifications of channel properties since untreated regions of membrane can be pulled into the node between the sucrose regions.
Bioelectromagnetics, also known as bioelectromagnetism, is the study of the interaction between electromagnetic fields and biological entities. Areas of study include electromagnetic fields produced by living cells, tissues or organisms, the effects of man-made sources of electromagnetic fields like mobile phones, and the application of electromagnetic radiation toward therapies for the treatment of various conditions.
Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. This type of neurotherapy was originally developed to help patients with brain injuries or neuropsychiatric conditions such as major depressive disorder. It can be contrasted with cranial electrotherapy stimulation, which generally uses alternating current the same way, as well as transcranial magnetic stimulation.
Biomagnetism is the phenomenon of magnetic fields produced by living organisms; it is a subset of bioelectromagnetism. In contrast, organisms' use of magnetism in navigation is magnetoception and the study of the magnetic fields' effects on organisms is magnetobiology.
The squid giant synapse is a chemical synapse found in squid. It is the largest known chemical junction in nature.
Magnetic Field Imaging (MFI) is a non-invasive and side-effect-free cardiac diagnostic method. In more recent technology, magnetocardiography (MCG) has become the clinically predominant application for recording the heart's magnetic signals. that detects and records the electromagnetic signals that are associated with the heartbeat using a multi-channel magnetic sensor array. The electric signals are known from the ECG. In the 1990s and beyond, more recent technology has supplanted the MFI, particularly MCG (xref. Cardiomag Imaging, Inc.). Through clinical research in Europe, Asia, and the U.S. (see publications in footnotes), MCG has been proven to have practical application for diagnosis of cardiac disease, and has become the clinically predominant application for recording the heart's magnetic signals. In comparison to MCG, MFI, among others, records the whole relevant area above the chest of the person.
In neurophysiology, several mathematical models of the action potential have been developed, which fall into two basic types. The first type seeks to model the experimental data quantitatively, i.e., to reproduce the measurements of current and voltage exactly. The renowned Hodgkin–Huxley model of the axon from the Loligo squid exemplifies such models. Although qualitatively correct, the H-H model does not describe every type of excitable membrane accurately, since it considers only two ions, each with only one type of voltage-sensitive channel. However, other ions such as calcium may be important and there is a great diversity of channels for all ions. As an example, the cardiac action potential illustrates how differently shaped action potentials can be generated on membranes with voltage-sensitive calcium channels and different types of sodium/potassium channels. The second type of mathematical model is a simplification of the first type; the goal is not to reproduce the experimental data, but to understand qualitatively the role of action potentials in neural circuits. For such a purpose, detailed physiological models may be unnecessarily complicated and may obscure the "forest for the trees". The FitzHugh–Nagumo model is typical of this class, which is often studied for its entrainment behavior. Entrainment is commonly observed in nature, for example in the synchronized lighting of fireflies, which is coordinated by a burst of action potentials; entrainment can also be observed in individual neurons. Both types of models may be used to understand the behavior of small biological neural networks, such as the central pattern generators responsible for some automatic reflex actions. Such networks can generate a complex temporal pattern of action potentials that is used to coordinate muscular contractions, such as those involved in breathing or fast swimming to escape a predator.
A model lipid bilayer is any bilayer assembled in vitro, as opposed to the bilayer of natural cell membranes or covering various sub-cellular structures like the nucleus. They are used to study the fundamental properties of biological membranes in a simplified and well-controlled environment, and increasingly in bottom-up synthetic biology for the construction of artificial cells. A model bilayer can be made with either synthetic or natural lipids. The simplest model systems contain only a single pure synthetic lipid. More physiologically relevant model bilayers can be made with mixtures of several synthetic or natural lipids.
The bidomain model is a mathematical model to define the electrical activity of the heart. It consists in a continuum (volume-average) approach in which the cardiac microstructure is defined in terms of muscle fibers grouped in sheets, creating a complex three-dimensional structure with anisotropical properties. Then, to define the electrical activity, two interpenetrating domains are considered, which are the intracellular and extracellular domains, representing respectively the space inside the cells and the region between them.
Quatrefoil reentry is a type of cardiac arrhythmia that consists of two adjacent figure-of-eight reentrant circuits.
Robert Plonsey was the Pfizer-Pratt University Professor Emeritus of Biomedical Engineering at Duke University. He is noted for his work on bioelectricity.
Neurostimulation is the purposeful modulation of the nervous system's activity using invasive or non-invasive means. Neurostimulation usually refers to the electromagnetic approaches to neuromodulation.
Magnetomyography (MMG) is a technique for mapping muscle activity by recording magnetic fields produced by electrical currents occurring naturally in the muscles, using arrays of SQUIDs. It has a better capability than electromyography for detecting slow or direct currents. The magnitude of the MMG signal is in the scale of pico (10−12) to femto (10−15) Tesla (T). Miniaturizing MMG offers a prospect to modernize the bulky SQUID to wearable miniaturized magnetic sensors.
A peripheral nerve interface is the bridge between the peripheral nervous system and a computer interface which serves as a bi‐directional information transducer recording and sending signals between the human body and a machine processor. Interfaces to the nervous system usually take the form of electrodes for stimulation and recording, though chemical stimulation and sensing are possible. Research in this area is focused on developing peripheral nerve interfaces for the restoration of function following disease or injury to minimize associated losses. Peripheral nerve interfaces also enable electrical stimulation and recording of the peripheral nervous system to study the form and function of the peripheral nervous system. For example, recent animal studies have demonstrated high accuracy in tracking physiological meaningful measures, like joint angle. Many researchers also focus in the area of neuroprosthesis, linking the human nervous system to bionics in order to mimic natural sensorimotor control and function. Successful implantation of peripheral nerve interfaces depend on a number of factors which include appropriate indication, perioperative testing, differentiated planning, and functional training. Typically microelectrode devices are implanted adjacent to, around or within the nerve trunk to establish contact with the peripheral nervous system. Different approaches may be used depending on the type of signal desired and attainable.
John Harris Miller Jr. is an American physicist with important contributions to the fields of physics, biophysics, Impedance spectroscopy, and material science, mainly known for his role in Charge density wave, research work on Cuprates and Impedance spectroscopy of living organisms. He is particularly known for an effect "Collective Quantum Tunneling of CDW Electrons" and for a well-known paper on the topic written by him and his colleagues, as published in Physical Review Letters. He was a noteworthy student of the twice Nobel laureate physicist John Bardeen who mentioned him at several places in his biography "True Genius: The Life and Science of John Bardeen".
John Walter Woodbury (1923–2017) was an American electrophysiologist and author of the first textbook explanation of the Hodgkin-Huxley_model studies of the action potential. He applied physical and mathematical techniques to experimentally elucidate the nature of electrical excitability in cells. He was also involved in the experimental and theoretical investigations of the mechanisms of ion penetration through the ion channels in muscle membranes, the regulation of cellular acid-base balance and the control of epileptic seizures by repetitive Vagus nerve stimulation.
Donald Choy Chang is a founding professor of the Hong Kong University of Science and Technology (HKUST). He was also the founding President of the Biophysical Society of Hong Kong. He is currently Professor Emeritus and adjunct professor in HKUST. Chang has wide research interests. He works in the fields of nuclear magnetic resonance, biophysics and quantum physics. He was elected a fellow of the American Physical Society in 2023.
Brian M. Salzberg is an American neuroscientist, biophysicist and professor. He is Professor of Neuroscience and of Physiology at the Perelman School of Medicine, University of Pennsylvania.
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