Transcranial magnetic stimulation (TMS) is a noninvasive method to excite neurons in the brain The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all. In vertebrates, the brain is located in the head, protected by the skull and close to the primary: weak electric currents The SI unit of electric current intensity is the ampere. Electric current is measured using an ammeter are induced in the tissue by rapidly changing magnetic fields A magnetic field is a vector field which surrounds magnets and electric currents, and is detected by the force it exerts on moving electric charges and on magnetic materials. When placed in a magnetic field, magnetic dipoles tend to align their axes parallel to the magnetic field. Magnetic fields also have their own energy with an energy density (electromagnetic induction Electromagnetic induction is the production of voltage across a conductor situated in a changing magnetic field or a conductor moving through a stationary magnetic field). This way, brain activity can be triggered with minimal discomfort, and the functionality of the circuitry and connectivity of the brain can be studied.

Repetitive transcranial magnetic stimulation is known as rTMS and can produce longer lasting changes. Numerous small-scale pilot studies have shown it could be a treatment tool for various neurological conditions (e.g. migraine Migraine is a neurological syndrome characterized by altered bodily perceptions, headaches, and nausea. Physiologically, the migraine headache is a neurological condition more common to women than to men. The word migraine was borrowed from Old French migraigne . The French term derived from a vulgar pronunciation of the Late Latin word hemicrania,, stroke A stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood supply) caused by thrombosis or embolism or due to a hemorrhage. As a result, the affected area of the brain is unable to function, leading to inability to move one or more limbs on one side of, Parkinson's disease Parkinson's disease is a chronic and progressive degenerative disease of the brain that impairs motor control, speech, and other functions. The disease is named after English physician James Parkinson, who gave a detailed description of it in an 1817 work titled, "An Essay on the Shaking Palsy", dystonia Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be inherited or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to drugs, particularly neuroleptics, tinnitus Tinnitus is the perception of sound within the human ear in the absence of corresponding external sound) and psychiatric conditions (e.g. major depression Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder in, auditory hallucinations A hallucination, in the broadest sense, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid, substantial, and located in external objective space. The latter).

Contents

Background

The principle of inductive brain stimulation with eddy currents An eddy current is an electrical phenomenon discovered by French physicist Léon Foucault in 1851. It is caused when a conductor is exposed to a changing magnetic field due to relative motion of the field source and conductor; or due to variations of the field with time. This can cause a circulating flow of electrons, or a current, within the body has been noted since the 19th century. The first successful TMS study was performed in 1985 by Anthony Barker et al.[1] in Sheffield Sheffield (pronounced /ˈʃɛfiːld/ ) is a city and metropolitan borough of South Yorkshire, England. It is so named because of its origins in a field on the River Sheaf that runs through the city, England England /ˈɪŋɡlənd/ is a country that is part of the United Kingdom. Its inhabitants account for more than 83% of the total UK population, while its mainland territory occupies most of the southern two-thirds of the island of Great Britain. England is bordered by Scotland to the north, Wales to the west and the North Sea, Irish Sea, Celtic Sea,. Its earliest application was in the demonstration of conduction of nerve impulses from the motor cortex Motor cortex is a term that describes regions of the cerebral cortex involved in the planning, control, and execution of voluntary motor functions to the spinal cord The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain. The brain and spinal cord together make up the central nervous system. Enclosed within, and protected by, the bony vertebral column, the spinal cord functions primarily in the transmission of neural signals between the brain and the. This had been done with transcranial electrical stimulation a few years earlier, but use of this technique was limited by severe discomfort. By stimulating different points of the cerebral cortex The cerebral cortex is a structure within the brain that plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It constitutes the outermost layer of the cerebrum. In preserved brains, it has a grey color, hence the name "grey matter". Grey matter is formed by neurons and their unmyelinated and recording responses, e.g., from muscles, one may obtain maps of functional brain areas. By measuring functional imaging (e.g. MRI Magnetic Resonance Imaging , or nuclear magnetic resonance imaging (NMRI), is primarily a medical imaging technique most commonly used in radiology to visualize the internal structure and function of the body. MRI provides much greater contrast between the different soft tissues of the body than computed tomography (CT) does, making it especially) or EEG Electroencephalography is the recording of electrical activity along the scalp produced by the firing of neurons within the brain. In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a short period of time, usually 20–40 minutes, as recorded from multiple electrodes placed on the scalp. In, information may be obtained about the cortex The cerebral cortex is a structure within the brain that plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It constitutes the outermost layer of the cerebrum. In preserved brains, it has a grey color, hence the name "grey matter". Grey matter is formed by neurons and their unmyelinated (its reaction to TMS) and about area-to-area connections.

TMS publications.

Pioneers in the use of TMS in neuroscience research include Anthony Barker, Vahe Amassian, John Rothwell of the Institute of Neurology, Queen Square, London, Mark S. George, MD of the Medical University of South Carolina, David H. Avery, MD of the University of Washington University of Washington, founded in 1861, is a public research university in Seattle, Washington, United States. UW is the largest university in the northwestern United States and one of the oldest public universities on the west coast. The university has three campuses, with its flagship campus in Seattle's University District and much smaller at Seattle, Charles M. Epstein of Emory University Emory University is a private research university in the metropolitan area of Atlanta in the Druid Hills CDP in unincorporated Dekalb County, Georgia. In addition to its two undergraduate divisions, Emory has nine graduate and professional schools, including schools of business, law, medicine, theology, nursing, and public health, as well as, Drs. Mark Hallett, Leonardo G. Cohen, and Eric Wassermann of the National Institutes of Health The National Institutes of Health is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical and health-related research. It consists of 27 separate institutes and centers plus the Office of the Director. Its science and engineering counterpart is, and Alvaro Pascual-Leone Alvaro Pascual-Leone is a Professor of Neurology at Harvard Medical School, with which he has been affiliated since 1997. He is the Director of the Berenson-Allen Center for Noninvasive Brain Stimulation and Program Director of the Harvard-Thorndike Clinical Research Center of the Beth Israel Deaconess Medical Center in Boston of Harvard Medical School Harvard Medical School is one of the graduate schools of Harvard University. It is currently ranked first among American medical schools by U.S. News and World Report. Currently, thousands of TMS stimulators are in use. More than 3000 scientific publications have been published describing scientific, diagnostic, and therapeutic trials.

Effects on the brain

The exact details of how TMS functions are still being explored. The effects of TMS can be divided into two types depending on the mode of stimulation:

As such, it is important to distinguish TMS from repetitive TMS (rTMS) as they are used in different ways for different purposes.

In research

One reason TMS is important in cognitive psychology The school of thought arising from this approach is known as cognitivism which is interested in how people mentally represent information processing. It had its foundations in the the work of Wilhelm Wundt, Gestalt psychology of Max Wertheimer, Wolfgang Köhler, and Kurt Koffka, and in the work of Jean Piaget, who provided a theory of stages//neuroscience Cognitive neuroscience is an academic field concerned with the scientific study of biological substrates underlying cognition, with a specific focus on the neural substrates of mental processes and their behavioral manifestations. It addresses the questions of how psychological/cognitive functions are produced by the neural circuitry. Cognitive is that it can demonstrate causality Causality is the process of making something happen. Often it denotes a necessary relationship between one event and another event (called effect) which is the direct consequence of the first. This two event type of causality is known as accidental causality. Another variety, essential causality, has one event seen in two ways. Aristotle's example. A noninvasive For centuries, physicians have employed many simple non-invasive methods based on physical parameters in order to assess body function in health and disease , such as pulse-taking, the auscultation of heart sounds and lung sounds (using the stethoscope), temperature examination (using thermometers), respiratory examination, peripheral vascular mapping technique such as fMRI Functional MRI or functional Magnetic Resonance Imaging is a type of specialized MRI scan. It measures the haemodynamic response related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of neuroimaging. Since the early 1990s, fMRI has come to dominate the brain mapping field allows researchers to see what regions of the brain are activated when a subject performs a certain task, but this is not proof that those regions are actually used for the task; it merely shows that a region is associated with a task. If activity in the associated region is suppressed (i.e. 'knocked out') with TMS stimulation and a subject then performs worse on a task, this is much stronger evidence that the region is used in performing the task.

For example: subjects asked to memorize and repeat a stream of numbers would be likely to show activation in the prefrontal cortex The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas (PFC) via fMRI, indicating the association of this brain region in short-term memory. If the researcher then interfered with the PFC via TMS, the subjects' ability to remember numbers might decline, and the researcher would have evidence that the PFC is used for short-term memory, because reducing subjects' PFC capability led to reduced short-term memory.

This ‘knock-out’ technique (also known as virtual lesioning) can be done in two ways:

In a 2008 article in the UK's “The Psychologist” Dr. Chris Chambers, Senior Research Fellow at the (School of Psychology, University of Cardiff and the Institute of Cognitive Neuroscience, University College London University College London is a university institution and constituent college of the University of London based primarily in London, England, United Kingdom. It was founded in 1826, as London University, and was the first university institution to be founded in London, the first British university to be established on an entirely secular basis,) focused on recent advances in the cognitive neuroscience of attention using TMS [5].

Risks

As it induces an electrical current in the human brain The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all. In vertebrates, the brain is located in the head, protected by the skull and close to the primary, TMS and rTMS can produce a seizure An epileptic seizure is a transient symptom of excessive or synchronous neuronal activity in the brain. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms . The medical syndrome of recurrent, unprovoked seizures is termed epilepsy, but seizures can occur in people who do not.[6][7] The risk is very low with TMS except in patients with epilepsy Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy, with almost 90% of these people being in developing countries. Epilepsy is more and patients on medications. The risk is significantly higher, but still very low, in rTMS especially when given at rates >5Hz at high intensity. The only other effects of TMS which are reported in most subjects are:

The long-term effects of TMS remain unknown,[6] although no effects on cognitive capacities (such as memory) have been reported yet.[7]

Clinical uses

The uses of TMS and rTMS can be divided into diagnostic and therapeutic uses.

Diagnosis

TMS is used currently clinically to measure activity and function of specific brain circuits in humans. The most robust and widely-accepted use is in measuring the connection between the primary motor cortex The primary motor cortex is a brain region that in humans is located in the posterior portion of the frontal lobe. It works in association with pre-motor areas to plan and execute movements. M1 contains large neurons known as Betz cells which send long axons down the spinal cord to synapse onto alpha motor neurons which connect to the muscles. Pre- and a muscle (i.e. MEP amplitude, MEP latency, central motor conduction time). This is most useful in stroke A stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood supply) caused by thrombosis or embolism or due to a hemorrhage. As a result, the affected area of the brain is unable to function, leading to inability to move one or more limbs on one side of, spinal cord The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain. The brain and spinal cord together make up the central nervous system. Enclosed within, and protected by, the bony vertebral column, the spinal cord functions primarily in the transmission of neural signals between the brain and the injury, multiple sclerosis and motor neuron disease. There are numerous other measures which have been shown to be abnormal in various diseases but few are validated or reproduced and more importantly, no one knows the significance of these measures. The most famous is short-interval intracortical inhibition (SICI) which measures the internal circuitry (intracortical circuits) of the motor cortex described by Kujirai et al. in 1993.[9]

Plasticity of the human brain can also be measured now with repetitive TMS (and variants of the technique, e.g. theta-burst stimulation, paired associative stimulation) and it has been suggested that this abnormality of plasticity is the primary abnormality in a number of conditions.

Therapy

A large number of studies with TMS and rTMS have been conducted for a variety of neurological and psychiatric conditions but few have been confirmed and most show very modest effects, if any. Multiple controlled studies support the use of this method in treatment-resistant depression; it has been approved for this indication in Europe, Canada, Australia, and the US.[10][11][12] Some conditions which have been reported to be responsive to TMS-based therapy are:

FDA approval

As of October 8, 2008, a TMS device, NeuroStar, manufactured by Neuronetics Inc. has been approved for use by the Food and Drug Administration (FDA) in the United States for use in adult patients with major depression who have previously tried medication and not improved satisfactorily.[16]

Several TMS/rTMS devices are approved by the FDA for stimulation of peripheral nerve and, therefore, can be used "off label" by individual physicians to treat brain disorders, essentially in any way they believe appropriate, analogous to the off label use of medications. However, most legitimate use of TMS in the USA and elsewhere is currently being done under research protocols approved by hospital ethics boards and, in the US, often under Investigational Device Exemption from the U.S. Food and Drug Administration (FDA). The requirement for FDA approval for research use of TMS is determined by the degree of risk as assessed by the investigators, the FDA, and the local ethics authority.

Technical information

TMS is simply the application of the principle of induction to get electrical current across the insulating tissues of the scalp and skull without discomfort. A coil of wire, encased in plastic, is held to the head. When the coil is energized by the rapid discharge of a large capacitor, a rapidly changing current flows in its windings. This produces a magnetic field oriented orthogonally to the plane of the coil. The magnetic field passes unimpeded through the skin and skull, inducing an oppositely directed current in the brain that flows tangentially with respect to skull. The current induced in the structure of the brain activates nearby nerve cells in much the same way as currents applied directly to the cortical surface. The path of this current is complex to model because the brain is a non-uniform conductor with an irregular shape. These magnetic fields do not directly affect the whole brain; they only reach about 2-3 centimeters into the brain directly beneath the treatment coil.[17] With stereotactic MRI-based control, the precision of targeting TMS can be approximated to a few millimeters (Hannula et al., Human Brain Mapping 2005).

Typical data: [18]

Coil types

TMS - Butterfly Coils

The design of transcranial magnetic stimulation coils used in either treatment or diagnostic/experimental studies may differ in a variety of ways. These differences should be considered in the interpretation of any study result, and the type of coil used should be specified in the study methods for any published reports.

The most important considerations include:

With regard to coil composition, the core material may be either a magnetically inert substrate (ie, the so-called ‘air-core’coil design), or possess a solid, ferromagnetically active material (ie, the so-called ‘solid-core’ design). Solid core coil design result in a more efficient transfer of electrical energy into a magnetic field, with a substantially reduced amount of energy dissipated as heat, and so can be operated under more aggressive duty cycles often mandated in therapeutic protocols, without treatment interruption due to heat accumulation, or the use of an accessory method of cooling the coil during operation. Varying the geometric shape of the coil itself may also result in variations in the focality, shape, and depth of cortical penetration of the magnetic field. Differences in the coil substance as well as the electronic operation of the power supply to the coil may also result in variations in the biophysical characteristics of the resulting magnetic pulse (eg, width or duration of the magnetic field pulse). All of these features should be considered when comparing results obtained from different studies, with respect to both safety and efficacy. [19][20]

A number of different types of coils exist, each of which produce different magnetic field patterns. Some examples:

See also

References

  1. ^ Barker AT, Jalinous R, Freeston IL. (May 1985). "Non-invasive magnetic stimulation of human motor cortex". The Lancet 1 (8437): 1106–1107. doi:10.1016/S0140-6736(85)92413-4. PMID 2860322.
  2. ^ Alvaro Pascual-Leone, Nick Davey, John Rothwell, Eric M. Wassermann, Besant K. Puri (January 2002). Handbook of Transcranial Magnetic Stimulation. Hodder Arnold. ISBN 0340720093.
  3. ^ Paul B. Fitzgerald, Sarah Fountain, Zafiris J. Daskalakis (December 2006). "A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition". Clinical Neurophysiology 117 (12): 2584–96. doi:10.1016/j.clinph.2006.06.712. PMID 16890483.
  4. ^ Strafella AP, Ko JH, Monchi O (July 2006). "Therapeutic application of transcranial magnetic stimulation in Parkinson's disease: the contribution of expectation.". Clinical Neurophysiology 31 (4): 1666–72. PMID 16545582.
  5. ^ Chambers, C., (2008), A stimulating take on attention, The Psychologist, Vol 21, Part 6, June 2008, 502–505
  6. ^ a b "Transcranial Magnetic Stimulation - Risks". Mayo Clinic. http://www.mayoclinic.com/health/transcranial-magnetic-stimulation/MY00185/DSECTION=risks. Retrieved on 15 December 2008.
  7. ^ a b c "Transcranial Magnetic Stimulation (TMS)". National Alliance on Mental Illness. http://www.nami.org/Content/ContentGroups/Helpline1/Transcranial_Magnetic_Stimulation_(rTMS).htm. Retrieved on 15 December 2008.
  8. ^ Roth BJ, Pascual-Leone A, Cohen LG, Hallett M (1992). "The heating of metal electrodes during rapid-rate magnetic stimulation: A possible safety hazard.". Electroenceph. clin. Neurophysiol. 85: 116-123.
  9. ^ Kujirai T, Caramia MD, Rothwell JC, et al. (November 1993). "Corticocortical inhibition in human motor cortex". J. Physiol. (Lond.) 471: 501–19. PMID 8120818. PMC: 1143973. http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=8120818.
  10. ^ Marangell LB, Martinez M, Jurdi RA, Zboyan H (September 2007). "Neurostimulation therapies in depression: A review of new modalities". Acta Psychiatrica Scandinavica 116 (3): 174–81. doi:10.1111/j.1600-0447.2007.01033.x. PMID 17655558.
  11. ^ Schutter DJ (April 2008). "Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: A meta-analysis". Psychological Medicine: 1–11. doi:10.1017/S0033291708003462. PMID 18447962.
  12. ^ DeNoon, Daniel J. (October 8, 2008). "FDA OKs TMS Depression Device: Brain-Stimulating Device Cleared for Depression Treatment After 1 Drug Failure". WebMD. WebMD. http://www.webmd.com/depression/news/20081008/fda-oks-tms-depression-device. Retrieved on 10 November 2008.
  13. ^ Naeser Aphasia Research
  14. ^ Kleinjung T, Vielsmeier V, Landgrebe M, Hajak G, Langguth B (2008). "Transcranial magnetic stimulation: a new diagnostic and therapeutic tool for tinnitus patients". Int Tinnitus J 14 (2): 112–8. PMID 19205161.
  15. ^ Press Releases
  16. ^ "FDA clears Neuronetics’ depression therapy". 2008-10-08. http://www.philly.com/inquirer/breaking/business_breaking/20081008_FDA_clears_Neuronetics_depression_therapy.html.
  17. ^ "TMS Center of New York"
  18. ^ "TMS terminology", BioMag Laboratory at Helsinki University Central Hospital
  19. ^ Riehl M (2008). "TMS Stimulator Design". in Wassermann EM, Epstein CM, Ziemann U, Walsh V, Paus T, Lisanby SH. Oxford Handbook of Transcranial Stimulation. Oxford: Oxford University Press. pp. 13–23. ISBN 0198568924.
  20. ^ Epstein CM (2008). "TMS Stimulation Coils". in Wassermann EM, Epstein CM, Ziemann U, Walsh V, Paus T, Lisanby SH. Oxford Handbook of Transcranial Stimulation. Oxford: Oxford University Press. pp. 25–32. ISBN 0198568924.
  21. ^ "Israeli scientists probe deeper to lift depression", Reuters.com
  22. ^ Roth BJ, Maccabee PJ, Eberle L, Amassian VE, Hallett M, Cadwell J, Anselmi GD, Tatarian GT (1994). "In-vitro evaluation of a four-leaf coil design for magnetic stimulation of peripheral nerve.". Electroenceph. clin. Neurophysiol. 93: 68-74.

Categories: Neurophysiology | Neuropsychology | Neurotechnology | Magnetic devices | Psychiatric treatments | Treatment of bipolar disorder

 

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