TMS Therapy Detailed Timeline

Analgesia using electricity is not new. The first use was "electrical" Malapterurus. On 5th Dynasty Egyptian tombs, 2750 BC, Nile catfish decorations appear. Ancient Egyptians used Malapterurus electric charge (electric eel) to cure certain types of pain.

Greek literature reports torpedo ray. Aristotle (384-322) wrote, "Torpedo fish can produce numbness even in humans." Actually, the word "torpedo" comes from the Latin "torpere," meaning numb.

Pliny the Elder treats burns using pulverized magnetic stones - (23-79 AD) Pliny Encyclopedia volume 37

Roman physician Scribonius Largus (1-50 AD) used torpedo fish (electric eels) caught in the Mediterranean Sea to treat headaches by touching the affected area with the animal for Emperors Tiberius, Caligula and Claudius. First recorded instance of electrical stimulation as medical treatment.

Galen of Pergamon (129-216 AD) studied live and dead electrical fish. He reported that eating the fish was no pain relief, but applying a live fish that gave an electrical shock was an effective analgesic. For 1500 years, Galen's work influenced medicine. Recently, "electric" fish were found to produce 40-50 volt discharges.

Indian physician Ibn-Sidah is said to have used electric catfish applied on the forehead of epileptic patients to relieve their seizures.

Paracelsus (1493-1541), Swiss-German doctor and astrologer, defines magnetic therapy as the "Prince of Medicine" and describes magnetic field treatments at Basel University

In his book "De Magnet" Sir William Gilbert (1554-1603) coined the phrase "electromagnetism" to describe correlations between magnetic forces and electrical forces: he used stones to apply magnetotherapy to his patients, with good success.

Stimulation experiment of Jan Swammerdam in 1664. Touching the motoric nerve of a frog muscle (b) in a glass vessel (a) with silver wire (c) and a copper loop (d) produces stimulation of the nerve, which elicits a muscular contraction; however, it is uncertain as to whether the stimulation was produced as a result of electricity from the two dissimilar metals or from the mechanical pinching. See also text. (Swammerdam, 1738.).

Otto von Guericke constructed the first electric machine which included a sphere of Sulphur with an iron axle. When rotating and rubbing the sphere it generated static electricity. (Guericke, 1672).

In an article entitled "A brief review of the use of electricity in psychiatry with special reference to John Wesley (1704-1791), he reported that by the later 1880s electrotherapy had Over 3,000 patients were treated in this dispensary during the following decade.

The Jesuit priest and astronomer at the University of Vienna, Father Maximilian Höll (1720-1793), illustrated his theories and practical experience to friend and physicist Franz Anton Mesmer (1720-1793). Mesmer started applying magnets to patients with hysteria and psychosomatic disorders, achieving some successes without scientific facts or clinical validation.

Italian physician Luigi Galvani (1737-1798), one of the early pioneers of bioelectricity, he is known for his extraordinary work on the nature and effects of electricity in an animal tissue, which later led to voltaic pile invention.

The discovery that electricity applied to frog legs caused muscle twitching led to discussions about whether "animal electricity" differed from electricity. Eventually, the scientific community discovered that while electricity can stimulate the nervous system and muscle tissue, the tissue itself produces electricity. This marked the beginnings of contemporary neuroscience.

Alessandro Volta (1745-1821) invents voltaic pile-able to power DC circuits.

Aldini treated patients with personality disorders and reported complete rehabilitation following transcranial electrical current. Aldini's work laid the ground for the development of various forms of electrotherapy used heavily later in the 19th century. Deep brain stimulation, currently used to relieve patients with motor or behavioral disorders, owes much to Aldini and galvanism.

Faraday saw the "lines of force" thus revealed as tension lines in the medium, i.e. air, surrounding the magnet, and soon discovered the law determining the production of electrical currents by magnets: the magnitude of a current depended on the number of lines of force cut by the conductor in unit time. He immediately realized that continuous current could be produced by rotating a copper disk between the poles of a powerful magnet. The outside of the disk would cut more lines than inside, creating a continuous current in the circuit connecting the rim to the center. This is the first dynamo. It was also the direct ancestor of electric motors, since it was only necessary to reverse the situation, to feed the disk with electric current, to rotate it.

Hitzig, in collaboration with Fritsch, concluded that electrical stimulation of certain areas of the cerebral cortex in the dog resulted in the movement of the contralateral limbs and that removal of these areas resulted in the weakness of the same limbs. Their revolutionary investigations, allegedly conducted in Hitzig's bedroom, were the beginning of cerebral cortex electrophysiology and the experimental approach to localizing function in it.

Ferrier electrically stimulated the brains of many species and mapped areas of the cortex, writing “The discovery of new methods of investigation opens up new fields of inquiry, and leads to the discovery of new truths. The discovery of the electrical excitability of the brain by Fritsch and Hitzig has given a fresh impetus to researches on the functions of the brain, and throws new light on many obscure points in cerebral physiology and pathology.”.

The French scientist Jacques-Arsène d'Arsonval (1851-1940) reported on the first human application of TMS already in 1896. He was able to induce phosphenes (flickering-light sensation, not elicited by visual perception), vertigo and syncope in subjects whose head was placed in a large electromagnetic coil (Geddes 1991)

Cerletti and Lucio Bini first used ECT on a person in April 1938, with diagnosed schizophrenic illusions, hallucinations, and confusion. The study showed that electrical shock therapy could improve the condition of patients diagnosed with certain diseases and bring the patient back to normal mind.

Kolin demonstrated for the first time that an alternating magnetic field is able to stimulate a sciatic frog nerve and could induce contractions of the gastronomic muscle.

Bickford was able to induce muscle twitching in humans by applying a pulsed magnetic field to ulnar, peroneal and sciatic nerves using harmonic magnetic fields.

Anthony Barker and his colleagues, Reza Jalinous and Ian Freeston, study the use of magnetic fields to alter electrical signals in the brain and introduce the first TMS device and perform the first successful TMS as a non-invasive treatment that stimulates accurate brain regions without electrical stimulation or pain. This paved the way for later therapy in a range of therapeutic and diagnostic procedures, including treatment for depression.

Barker and his colleagues release a set of TMS safety guidelines.

The decade sees thousands of clinical trials and numerous studies all proving the effectiveness and safety of TMS in stimulating the brain, especially the cerebral and prefrontal cortex, and indicating that TMS is safe and effective in treating major depression.

Health Canada approves the use of TMS therapy as a depression treatment in Canada.

FDA approves the use of TMS as therapy for the treatment of major depression.

A clinical trial by the National Institutes of Health (NIH) indicates TMS therapy is an effective form of treatment for depression.

A number of U.S. health insurance companies begin to cover TMS as a treatment for depression.

TMS therapy is widely used as a safe and effective treatment of major depression, especially in cases where drugs prove ineffective.


A physician and pharmacologist. He also commended the emperor to his Latin medical writings and, in appreciation of this patronage, Largus addressed and dedicated to him the Compositions, a collection of drug compounds or recipes, written in the Preface when he was abroad, with only a few books at his disposal.

Treatment of burns using pulverized magnetic stones - Pliny the Elder (23-79 AD) Encyclopedia volume 37

Galen of Pergamon (129-216 BC) studied live and dead electrical fish. He reported that eating the fish was no pain relief, but applying a live fish that gave an electrical shock was an effective analgesic. For 1500 years, Galen's work influenced medicine. Recently, "electric" fish were found to produce 40-50 volt discharges.

Indian physician Ibn-Sidah is said to have used electric catfish applied on the forehead of epileptic patients to relieve their seizures.

Paracelsus (1493-1541), Swiss-German doctor and astrologer, defines magnetic therapy as the "Prince of Medicine" and describes magnetic field treatments at Basel University

William Gilbert founded the magnetism science study and together with Galileo is considered a founding father of experimental science. A powerful advocate of the scientific experiment's power, he discovered that our planet has two magnetic poles; correctly defining these poles and establishing that the earth acts like a giant magnet. He correctly deduced that magnetism is caused by an organized form of the material of the magnet in everyday magnets. He created the world's first electroscope for electric charge detection, and coined the Latin word electricitas, which soon became English word electricity. Gilbert was a semi-scientist. By profession, he was an eminent medicine doctor, eventually becoming Queen Elizabeth and King James president of London's College of Physicians and personal physician. He spent much of his own wealth funding his scientific experiments.

An English clergyman who helped pioneer the use of electrical shock to treat illness. In 1760 he published The Desideratum: Or, Electricity made Plain and Useful by a Lover of Humanity and Common Sense based on his use of electricity in free clinics for the poor in Bristol and London a decade earlier.

Franz Mesmer is one of the very few people whose names have become a verb in daily use-mesmerize. Friends with some of history's most memorable characters, including Wolfgang Amadeus Mozart and Marie Antoinette. A qualified doctor, Mesmer believed he had discovered a remarkable new phenomenon called animal magnetism, which he used to cure diseases. In fact, Mesmer was a pseudoscientist. His treatments worked because of the power of suggestion, which was later recognized as a genuine phenomenon of hypnosis (or mesmerism). It enabled Mesmer to successfully treat people with psychosomatic diseases, rooted in mind.

Luigi Galvani was an Italian physician. One of the early pioneers of bioelectricity, he is known for his extraordinary work on the nature and effects of electricity in an animal tissue, which later led to voltaic pile invention.

Alessandro Volta was a pioneering physicist, chemist and electrical scientist. Best known for inventing the battery, he was also the first to isolate methane. Discovered air-mixed methane could explode with electric spark. Discovered "contact electricity" from various metal contacts. Recognized two electrical conduction types. Wrote first series electromotive. Discovered capacitor potential is directly proportional to electrical charge. Recognizing his contributions to science, the electrical potential unit is called the volt.

His scientific work was primarily concerned with galvanism, anatomy and its medical applications, the construction and illumination of lighthouses, and experiments to preserve human life and material objects from fire destruction. Besides his native Italian, he wrote French and English. Recognizing his merits, Austria's emperor made him an Iron Crown knight and a Milan State councilor where he died. He left a considerable sum to found Bologna's natural science school for artisans.

He discovered a number of new organic compounds, including benzene, and was the first to liquefy a "permanent" gas (i.e. one believed to be unable to liquefy). His major contribution, however, was electricity and magnetism. He was the first to produce a magnetic field electric current, invented the first electric motor and dynamo, demonstrated the relationship between electricity and chemical bonding, discovered the effect of magnetism on light, and discovered and named diamagnetism, the peculiar behavior of certain substances in strong magnetic fields. He provided the experimental and much theoretical foundation on which James Clerk Maxwell erected classical theory of electromagnetic fields.

Considered one of the most important figures of German anthropology, an excellent research work on various ethnographic studies in South Africa was developed. The highlight of his contribution to physiological science was studying the effects of electrical stimulation on cerebral cortex next to Hitzig. Fritsch's anthropology and physiology beginnings occurred in his college years, during which he toured several German universities, Berlin, Breslau and Heidelberg, expanding his knowledge of both disciplines. Before returning to Germany, Fritsch had managed to store an excellent file with detailed descriptions of African ethnic customs.

From a distinguished Jewish family, Hitzig first studied law, but soon moved to medical school in Berlin and to Würzburg for a while. He was fortunate to be taught by du Bois-Reymond, Virchow, Moritz Romberg, and Otto Westphal. As a result of an outstanding contribution to knowledge of the function of the cerebral cortex, Hitzig acquired an international reputation, and in 1875 he was offered directorship of the Berghölzli mental asylum near Zurich and professorship at the University of Zurich. From Zurich, Hitzig went to Halle University as psychiatric professor and mental asylum director at Nietleben. Hitzig's influence over the growing psychology field of the nineteenth century was extensive. As a specialty, he also influenced psychiatry development, maintaining that psychiatrists must also be fully qualified physicians.

Ferrier electrically stimulated the brains of many species and mapped areas of the cortex, writing “The discovery of new methods of investigation opens up new fields of inquiry, and leads to the discovery of new truths. The discovery of the electrical excitability of the brain by Fritsch and Hitzig has given a fresh impetus to researches on the functions of the brain, and throws new light on many obscure points in cerebral physiology and pathology.”.

From France's ancient nobility, Jaques-Arsène d'Arsonval studied classics until he graduated in 1869 and then decided to study medicine at Limoges. He arrived in Paris after the Franco-Prussian War of 1870 and met the famous physiologist Claude Bernard (1813-1878). Paul Bert, physiologist, politician and diplomat, considered the founder of modern aerospace medicine, was appointed Minister of Public Education and enabled D'Arsonval to set up a biophysics laboratory until 1910, when he moved to the new public-funded laboratory in Nogent-sur-Marne. Influenced by Bernard, d'Arsonval abandoned his medical career for research. His first projects as Bernard's assistant were on animal heat and body temperature, finding extracts from guinea pigs had antiseptic properties. D'Arsonval literally founded physiotherapy paramedics.

Ugo Cerletti specialized in neurology and neuropsychiatry, studied with Pierre Marie (1853-1940), Ernest Dupré (1862-1921), Munich with Emil Kraepelin (1856-1926), Alois Alzheimer (1864-1915), and Heidelberg with Franz Nissl (1860-191919). Subsequently, Cerletti was appointed head of the Neurobiological Institute at Milan's Mental Institute and received a lecture post in Bari in 1924. In 1928 he succeeded Enrico Morselli (1852-1929) in chairing the Department of Mental and Neurological Diseases at the University of Rome, where he developed electroconvulsive shock to treat several kinds of mental disorder, a discovery that made him world-famous.

Ragnar Arthur Granit was a Swedish-speaking Finnish and later Swedish scientist who was awarded the Nobel Prize in Physiology or Medicine in 1967 along with Haldan Keffer Hartline and George Wald "for their discoveries concerning the primary physiological and chemical visual processes in the eye"

After nearly a half-century of stagnant research in electrophysiology, the research group Kolin et al. releases a study that clearly demonstrates for the first time that time-varying magnetic fields can be used to initiate muscle contraction.


The study targeted two different brain regions with two male rhesus macaques of different ages and found that macaques with tDCS learned much more effectively to forage. Results were presented in line with the specific proposed action mechanism of modulating neuron spiking timing as they measured local field potential (LFP) and associated power and consistency changes with accelerated learning in some frequency bands. The main difference is that they measured using thin electrodes embedded in brain tissue rather than on scalp surfaces. It's not a complete testing model of how tDCS can enhance learning, but it looks like progress.

Bioelectromagnetism is a discipline that examines the electric, electromagnetic, and magnetic phenomena which arise in biological tissues.

Using microelectrode recordings to hear neurons talking to their neighbors, these conversations are a type of code that makes brain hardware visible. If the visual input statistics are known, part of this code can be understood; computational methods can determine the relationship between these statistics and neural activity. One of the research goals is to develop a quantitative understanding of how these aspects of neural activity relate to memory, perception, and behavior. They're especially interested in how subjects scan their surroundings using eye movements.

Variability and Predictors of Response to Continuous Theta Burst Stimulation: A TMS-EEG Study. a repetitive transcranial magnetic stimulation paradigm reported to decrease the excitability of the stimulated cortical area and which is thought to reflect a form of inhibitory synaptic plasticity

a newer form of TMS. Here, the magnetic pulses are applied in a certain pattern, called bursts. Research studies with TBS have been shown to produce similar if not greater effects on brain activity compared to standard repetitive transcranial magnetic stimulation (rTMS)

a type of invasive electrocorticography to locate the function of specific brain regions by directly stimulating the cerebral cortex. It remains one of the earliest methods of brain analysis, allowing researchers to study the relationship between cortical and systemic structure. Cortical stimulation mapping remains the preferred method for pre-operative mapping of motor cortex and language areas for several clinical and therapeutic applications to prevent unnecessary functional damage. There are also clinical applications to map cortical stimulation like epilepsy.

a form of neurostimulation via small, pulsed, alternating current. CES is used to treat various conditions like anxiety, depression, and insomnia. CES has been suggested as a possible treatment for headaches, fibromyalgia, smoking cessation, and opiate withdrawal, but there is little evidence of effectiveness for many of these conditions and evidence of use in acute depression is not sufficient to justify it.

Electric eels leap from water to electrify threats directly, including humans. Even small eels give their target substantial power. Currents far exceed nociceptor thresholds in various species.

It has always been noted for its impressive ability to shock and subdue its prey. It has recently become clear that electric eels also use a clever trick to deliver an intense, Taser-like jolt to potential predators: they leap from water to target endangering animals, including humans, above water. Now, a researcher measured (and experienced) how strong that jolt can be.

The Part Played by Electric Fish In The Early History Of Bioelectricity And Electrotherapy

New research, which includes the first draft assembly of an electric fish's complete genome, South American electric eel, identifies the genetic factors that animals used to create an organ that can deliver a jolt several times more powerful than standard household current.

Natural electrical phenomena fascinated humans since ancient times. The electrical discharges produced by torpedo fish were highly appreciated by ancient doctors like Hippocrates, Scribonius Largus and Galen and were prescribed for headache, gout and prolapsed anus. Torpedo's electrical properties were attributed to occult powers in the medieval period, while Renaissance physicists and scientists studied the anatomy and mechanical nature of the provoked shock paving the way for the discovery of the electrical nature of torpedo activity and the evolution of electrotherapy.

Also known as focal brain stimulation (FBS), A form of electrotherapy and technique used in research and clinical neurobiology to stimulate a neuronal or neural network in the brain by directly or indirectly exciting its cell membrane with electrical current.

Eduard Hitzig and Gustav Fritsch performed dog experiments to produce movement through electrical stimulation of specific cerebral cortex parts. Contemporaries saw the experiment as a milestone in the controversial issue of cerebral localization of functions, although this experiment came as a surprise to the community of experimental physiologists who had rejected localization several decades after the physiologist Pierre Flourens ' antiphrenological work.

Using electricity for analgesia is not new. First use of such treatment was "electric" fish. Nile catfish decorations on 5th Dynasty Egyptian tombs, 2750 BC. Greek literature reports torpedo rays. Aristotle wrote, "Torpedo fish can produce numbness, even in humans." The word "torpedo" comes from the Latin "torpere" meaning numb.

Formerly known as electroshock therapy, is a psychiatric treatment that electrically induces seizures in patients to relieve mental disorders. ECT procedures first conducted in 1938, replaced less safe and effective forms of biological treatments. ECT is often used with informed consent to respond safely and effectively to major depressive disorder, mania, and catatonia. Since 1976, the U.S. Food and Drug Administration (FDA) has placed ECT machines in Class III.

Electroconvulsive therapy (ECT) is a general anesthesia procedure in which small electrical currents pass through the brain, deliberately triggering a brief seizure. ECT seems to cause brain chemistry changes that can quickly reverse symptoms of certain mental health conditions.

Also known as pulsed electromagnetic field therapy (PEMFT), and tumor treatment fields (TTF) uses electromagnetic fields. While PEMF therapy is claimed to offer some benefit in fracture treatment, the mechanism of osteogenesis is unclear and evidence is inconclusive and insufficient to inform current clinical practice. Despite this, several such stimulators were cleared by the FDA by 2007.

Excellent reviews of history of magnetic stimulation are given by Anthony Barker (J Clin Neurophysiol. 8:26-37, 1991) and by Leslie Geddes (J Clin Neurophysiol. 8:3-9, 1991).

Magnetic stimulation is a way to stimulate excitable tissue from a variable external magnetic field. Electrical and magnetic methods stimulate the membrane with electrical current by detecting bioelectric activity of the excitable tissue. The first does so directly, but the second does so by the electrical current induced by a time-varying magnetic field in the volume conductor.

Biological tissue's electrical activity is the origin of the biomagnetic field generating an electrical volume conductor that induces a biomagnetic field. Not limited to producing bioelectric and biomagnetic fields from the same bioelectric sources, this correlation phenomenon also occurs in tissue stimulation.

In 1870 Gustav Fritsch and Edvard Hitzig showed that electrical stimulation of the cerebral cortex of a dog produced movements. This was a crucial event in the development of modern neuroscience because it was the first good experimental evidence for a) cerebral cortex involvement in motor function, b) the electrical excitability of the cortex, c) topographic representation in the brain, and d) localization of function in different regions of the cerebral cortex. This paper discusses their experiment and some developments in the previous two centuries that led to it including the ideas of Thomas Willis and Emanuel Swedenborg, the widespread interest in electricity and the localizations of function of Franz Joseph Gall, John Hughlings Jackson, and Paul Broca. We also consider the subsequent study of the motor cortex by David Ferrier and others.

The following dates and events were gathered from several sources. These events are certainly not all of the important events to take place in neuroscience... just some of the ones that I have selected. - Eric H. Chudler, Ph.D.

Cerebellar TMS is a new experimental field. The cerebellum is a high potential target for neuromodulation of neurological and psychiatric disorders due to its high superficial layer neuron density, electrical properties and its involvement in numerous circuits involving motor, cognitive and emotional functions.

Letter to the Editor: Brief history of transcranial direct current stimulation (tDCS): from electric fishes to microcontrollers

TDCS is investigated to modulate neuronal function, including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back over 200 years, since the 1960s, clinical trials with current controlled stimulation were published intermittently. TDCS ' modern era only began after 1998

Like tDCS neuromodulation, except tACS oscillates at a frequency chosen to interact with natural cortical oscillations in the brain. A large electrode is placed over a stimulating area of interest, while a reference electrode is placed at a neutral location. Exogenous oscillation can synchronize with brain endogenous frequency when applying a single consonant. Cortical oscillations may desynchronize when pulsing multiple oscillations. The effects of tACS depend on the frequency, amplitude and phase applied.

Transcranial Direct Current Stimulation (tDCS) has roots in history that go further back in time than most of us realize; to truly understand the rich history of tDCS, here is a compiled timeline of significant developments in tDCS technology.

Contrast with cranial electrotherapy stimulation, which similarly uses alternating current. Originally developed for brain injuries or psychiatric conditions, such as major depressive disorder. TDCS has potential to treat depression.

Believe it or not.. The first clinical application of electrical stimulation involved utilizing electricity derived from electric torpedo fish, catfish, and eels!

Transcranial electrical stimulation is a promising tool in rehabilitation, based on the growing evidence that delivery of current to specific brain regions can promote desirable plastic changes

In 2008, Göttingen University's Terney et al was the first group to apply tRNS to humans. They showed that motor cortex excitability (i.e. increased motor amplitude evoked potential) increased in healthy subjects for up to 60 minutes after 10 minutes of stimulation by using an alternative current with random amplitude and frequency. While tRNS showed positive effects in various studies, this technique's optimal parameters and potential clinical effects remain unclear.