International Journal of Mental Health Nursing (2003) 12, 22–29

INTRODUCTION

This paper is consistent with that consensus statement onmanaging the risks of repeated transcranial magnetic–stimulation (rTMS) of the International Society forTranscranial Stimulation (ISTS), which is published on theISTS web page (http://www.ists.unibe.ch/). Relevantextracts include:

rTMS should only be administered under the supervisionof an appropriately trained and licensed physician. Thisdoes not mean that a physician must be physicallypresent…However, expert medical assistance should beimmediately available…Those who administer rTMSshould be trained as ‘first responders’ in order to renderappropriate care in the event of seizure.

rTMS is used in research in psychiatry and neurophys-

iology around the world. It has been accepted as a routinetreatment of depression in Canada and Israel. There havebeen five meta-analyses of the studies comparing rTMSand sham in the treatment of major depression (Burt et al.2002; Holtzheimer et al. 2001; Kozel & George 2002;Martin et al. 2002; McNamara et al. 2001). All have foundrTMS to have significantly greater antidepressant effectthan sham. With respect to the size of this antidepressanteffect, there have been four studies in which TMS has beencompared to ECT in major depression (Dannon et al. 2002;Grunhaus et al. 2000; Janicak et al. 2002; Pridmore et al.2000). All have found rTMS to be as effective or almost aseffective as ECT. rTMS may eventually have a place in thetreatment of a range of psychiatric disorders, but moreresearch is required. See George et al. (2002) for a review.

To this point in the development of this new field, spe-cialist medical officers with additional training have exclu-sively operated rTMS devices when applied for therapeuticpurposes. As knowledge and experience with rTMS grows,it is probable that professionals with other backgroundswill have the opportunity to assist in the application ofrTMS. The aim of this article is to present information thatwill be of benefit to those who operate rTMS devices underthe direction of a specialist medical officer.

rTMS opens a new and sophisticated chapter in medical

FEATURE ARTICLE

Information for assistants of repeated transcranialmagnetic stimulation

Correspondence: Saxby Pridmore, Department of PsychologicalMedicine, Royal Hobart Hospital, and Discipline of Psychiatry,University of Tasmania, GPO Box 1061 L, Hobart 7001, Tasmania,Australia. Email: s.pridmore@utas.edu.au

Saxby Pridmore, MD.Umeed Khan, MD.Moacyr A. Rosa, MD.Mark S. George, MD.Accepted January 2003.

Saxby Pridmore,1 Umeed Khan,2 Moacyr A. Rosa3 and Mark S. George4

1Department of Psychiatry, Royal Hobart Hospital and University of Tasmania, Hobart, Tasmania, Australia, 2Facultyof Medicine, International Islamic University of Malaysia, Kuantan, Malaysia, 3Psychiatric Hospital and Clinics,University of Sao Paulo, Sao Paulo, Brazil and 4Brain Stimulation Laboratory, Medical University of South Carolina,Charleston, South Carolina, USA

ABSTRACT: Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology being used inpsychiatric and neurological research in many centres around the world. rTMS has been accepted as a routinetreatment of depression in Canada and Israel. To this point, it has been exclusively conducted by medical officers.As knowledge and experience grows, it is probable that professionals with other backgrounds will have the oppor-tunity to play a role. The aim of this paper is to provide information that will be valuable to assistants.Electromagnetic principles are harnessed to deliver electric currents to localized regions of the cortex. rTMS doesnot involve anaesthesia or seizure. Side-effects appear to be few. Much remains uncertain, however, even includ-ing the most appropriate treatment parameters.

KEY WORDS: assistants in repeated transcranial magnetic stimulation, depression, repeated trans-cranial magnetic stimulation, training in repeated transcranial magnetic stimulation.

science. This article does not attempt complete coverage,and it does not prepare professionals to take completeresponsibility for rTMS service. It does not approach thesubject of diagnosis or the selection of the stimulationparameters (intensity, frequency, train length, rest period,number of trains, site) or coil type, these being theresponsibility of the specialist medical officer.

rTMS employs electromagnetic technology to applysmall electric currents to particular regions of the cortex.A coil is held by human hand (or a mechanical clamp)against the hair/scalp. The patient sits in a comfortablechair and remains fully awake (Fig. 1). Some patientsexperience an uncomfortable taping or pinching on thescalp, and mild headache occurs in a small proportion ofpatients.

ELECTROCONVULSIVE THERAPY

rTMS is both similar to and radically different from electro-convulsive therapy (ECT). The status of ECT as potentpsychiatric treatment is well established. It is the strongestantidepressant available, and it also has an important rolein the treatment of postnatal psychosis, catatonia andintractable mania, among other psychiatric conditions.

The essential feature of ECT is the passage of an elec-trical current through the brain. The skull is highly resis-tant to electricity. Accordingly, using electrodes attachedto the skin, electricity cannot be focused on particular brainstructures, and spreads throughout both hemispheres andother parts of the brain. A seizure is triggered. Musclerelaxants are required to modify the seizure, which in turnmeans that general anaesthesia must be administered.Even if muscle relaxants were not required, a generalanaesthetic would be humane, as the electrical stimulus ofECT would be otherwise painful.

ECT is frequently followed by a severe headache,muscle pains and temporary (usually) memory disorder.Occasionally, lips are bitten or teeth chipped. As a generalanaesthetic is necessary, the expenses of the services of ananaesthetist and nursing staff and recovery space areincurred.

rTMS also involves the passage of an electrical currentthrough the brain. However, by this method, the currentcan be focused and is very small in comparison. A seizuredoes not occur. While some patients (fewer than 20%)experience a mild headache on some treatment days, rTMSis relatively free of known side-effects.

It is not expected that rTMS will replace ECT, but itmay be a useful alternative in certain circumstances. ECThas been mentioned here to make the point that thepassage of electrical currents through the brain has beenan accepted therapeutic practice in clinical psychiatry formore than 60 years (Abrams 1997).

ELECTROMAGNETISM

When an electric current is passed along a coil a magneticfield is induced in the surrounding space. In 1831 MichaelFaraday found that when two coils are close together (butnot touching) and a current is passed through one, as thecurrent is turned on and off, a brief pulse of electricitypasses through the other. The magnetic field created bythe electrical current in the first coil extended into thesecond coil, and when this magnetic field commenced andceased, it created a small electrical current in the second.These two currents have been termed primary andsecondary. A second coil is not necessary, as a secondarycurrent can be induced in any conductor, including muscleand nerve cells, which is close to a coil through which aprimary current is pulsed.

We have all moved a needle or paper clip around on awooden tabletop with a magnet held underneath. Thisdemonstrates that magnetic fields, unlike electricity, pass

INFORMATION FOR ASSISTANTS IN TMS 23

FIG. 1: During repeated transcranial magnetic stimulation (rTMS)the patient is seated in a comfortable chair and remains conscious. A coilis applied to the hair/scalp. This picture is of the latest technology andshows the coil being positioned by both a mechanical gantry and hand.With this type of rTMS device some mechanical assistance is necessaryin the positioning of the coil, as this is a new generation coil, which is heavier than the circular or figure eight coils. Photo: X Li, A Walkerand M. S. George of Medical University of South Carolina. (Used withpermission.)

unimpeded, through non-conductors of electricity. This isof great importance, as it allows secondary currents to beexactly located in chosen regions of the cortex.

The magnetic field is proportional to the current passingthrough the primary coil, and the secondary current is pro-portional to the rate of change of the magnetic field. Thusboth the size of the primary current and the precision withwhich it can be turned on and off, influence the charac-teristics of the secondary current. Other influences includethe geometry and construction of the coil.

NEURONS AND DEPOLARIZATION

The neuron is designed to receive and transmit impulses(signals). Glial cells physically support and nurture theneurons. The most common type of neuron is composedof three main parts, the cell body, the dendrites and theaxon, the long string-like projection from the cell body. Forpresent purposes, attention will be limited to the axon.

Transmission of signals is possible because of the specialproperties of the membrane which encloses the neuron.In the resting neuron, the material inside the membraneis negatively charged in relation to the material outside.This difference is achieved by the special positioning ofcharged chemicals (ions).

In the resting state, there is a slight excess of negativeions inside the membrane and a slight excess of positiveions outside the membrane. The potential difference (anelectrical measure) between the inside and outside of thecell is about 70 mV (millivolts or thousandths of a volt).

This imbalance of ions is the result of several factorsthat work together. Most important are tiny sodium pumpsin the membrane that pump sodium ions (positivelycharged) through special channels, out of the cell. The cellmembrane also contains voltage activated ion channels.When the stimulus applied to the cell membrane is suffi-ciently strong, the potential difference between the insideand outside of the cell is reduced to below a threshold level.The local voltage activated ion channels then open,allowing sodium ions to flow into the cell. Consequently,there is complete, temporary, loss of potential differenceacross the membrane. These changes lead to similarchanges in adjacent areas. In this way an electrical impulse(action potential) progresses along the axon, away from thesite of the triggering stimulus.

When rTMS is applied, the induced electric field causesa flow of current and electric charges accumulate on mem-branes, resulting in depolarization. The site of depolari-zation varies because of the different geometrical factors.It is believed, however, that with the application of rTMS,depolarization most frequently occurs at bends in axons.

With currently available apparatus, used in the recom-mended manner, it appears that depolarization frequently

occurs at about the junction of the grey and white matter.At this point, axons with cell bodies in the grey matter bendas they descend into deeper portions of the brain. This isat about 2 cm below the coil, and the electric field at thispoint is about 70 V/m (Ruohonen & Ilmoniemi 2002).

NEUROPLASTICITY

The term neuroplasticity covers a range of processes bywhich neurons adapt or change in response to internal andexternal stimuli. These neuroplastic changes take the formof growth of dendritic and axonal branches, formation ofnew synapses, changes in the ‘strength’ (efficiency) ofparticular synapses, in the density of particular intracellularstructures such as Golgi apparatus and ion channels, inmetabolic pathways, and in the availability of particularneurotransmitters.

Neuroplastic change is the result of selective geneexpression (Hyman & Nestler 1993). It can be triggeredby a range of inputs, from learning experiences to psycho-tropic medication, and by electrically induced depolari-zation. It is probable that therapeutic effects are the resultof induced neuroplastic changes. The details of themechanisms remain uncertain, but much research isproceeding on this topic (Duman et al. 1999).

rTMS APPARATUS

The apparatus consists of a stimulator (usually mounted onwheels) about the size of a large briefcase (up to the sizeof three large briefcases, depending on the componentspurchased) and a coil, connected to the stimulator by athick, flexible, insulated conducting cable.

Along with many other components, stimulators containcapacitors, electrical devices that store charge, and athyrister, a special electronic switch through which thecapacitors are discharged, to pass through the coil. Thethyrister is a device which makes it possible to start andstop currents within microseconds.

Commercial devices capable of delivering one stimulusabout every 3 seconds have been available for over a decadeand are designed for use in research and clinical neuro-physiology. While it may be possible to use such a machinein one type of rTMS, it would be impossible to use a ‘singleshot’ machine for the more common therapeutic rTMSprocedures.

As rTMS calls for repeated stimulation, more than onecondenser is usually required. The number (up to four)and their construction characteristics are the main factordetermining the size of machines.

Coils are of two main types. The first coils to becomeavailable were of circular construction. Set in non-conducting material, they were one or more turns of

24 S. PRIDMORE ET AL.

copper, with a diameter of 8–10 cm. Most devices comewith a circular coil as a standard attachment. Counter tointuition, there is little if any electrical activity under thecentre of the coil. Instead, activity is strongest under theouter edge of the coil. The magnetic field thus resemblesa doughnut under the coil.

The circular coils used in the early studies of therapeuticrTMS were often placed over the vertex and large areas ofthe cortex were stimulated.

The most recent studies of rTMS have involved moreprecise stimulation, such as specific stimulation of the leftprefrontal cortex. This can be achieved with the largecircular coil by touching the outer edge of the coil on thedesignated site. This method is open to error and a figureeight coil probably provides more consistency of stimulation.

Figure eight coils are two circular coils, often about 7 cmin diameter, mounted close to each other, and arrangedsuch that their currents pass in opposite directions. Thus,the magnetic field intensity directly below the junction ismultiplied. The volume beneath the junction which isaffected is of the order of 3 cm long, by 2 cm wide, by2–3 cm deep (Bohning 2000). New generation ‘coils’,which may be more efficient and provide other patterns ofstimulation, are being developed (Fig. 1).

The field declines dramatically the further away fromthe coil one goes. For example, the magnetic field on theopposite side of the head is near zero. The magnetic fieldnear the heart, when the coil is applied to the scalp, is alsominimal. Finally, the magnetic field to which the operatoris exposed is very small.

Naturally, great care should be used when positioningthe coil on the scalp during treatment. There are someother positioning issues. Placing the coil on a metal benchwill result in the coil jumping into the air if accidentallydischarged. Credit cards, computer discs or any other formof magnetic storage media can be erased if the coil is closeto them when an rTMS device is discharged. Although itis unlikely that a rTMS pulse could produce an arrhythmiadue to the short pulse width and limited depth ofpenetration, the coil should not be held on the chest overthe heart.

STIMULUS INTENSITY

To the present, the intensity of the stimulus employed inparticular sessions of therapeutic rTMS has used the motorthreshold (MT) as the basic measure. In recent researchthe lowest intensity of stimulus has been 80% MT and thehighest has been 110% MT.

To determine the MT, the coil is placed over the motorcortex and moved until the smallest possible impulseproduces either a small motor evoked potential (MEP)(usually 50 µV) (Rossini et al. 1994) or a visible movement

of the thumb, wrist or fingers (Pridmore et al. 1998) in atleast half of 10 stimulations. Whether electrophysiologicalor the visualization of movement method is used will dependon the accepted practice in the host hospital or clinic.

The MT will be determined as a particular level of themachine output. Each machine can provide a range ofstimulus intensities, and thus, there is a maximum or totalmachine output. The smallest percentage of the totalmachine output which causes depolarization is equal to100% MT. An example: if depolarization is detected at 60%of the total machine output, and the medical officer hasprescribed therapeutic rTMS at 90% MT, one needs to find90% of 60, that is, stimulate with 54% of the machine totaloutput.

Determining stimulus strength using the MT methodis far from satisfactory. It is used because the motor cortexis the only brain region which gives an easily detected signal(muscle twitch) when it has been stimulated. To thepresent, no established therapeutic rTMS involves stimu-lation of the motor cortex. Having used the motor thresh-old to determine the percentage of total machine outputwhich causes depolarization, the coil is then moved toanother area of the head. This is usually 5 cm forward, tothe scalp overlaying the prefrontal cortex, but it could beto the scalp overlying the temporal lobe, or some otherregion. The strength of the magnetic field decreases expo-nentially with distance from the coil, which means thedistance from the coil to the brain is a crucial factor. Thedistance from the scalp (coil) to the motor cortex may notbe the same as the distance from the scalp to other partsof the cortex, nor may other parts of the cortex have thesame sensitivity to electrical stimulation as the motorcortex. Thus, there are major flaws in using the MT as theindex of stimulus intensity. This is the best approximationavailable at the moment, but advances in the method ofdetermining the intensity of stimulation are expected.

SLOW AND FAST rTMS

By convention, ‘slow’ rTMS refers to stimulation at onecycle per second (1 Hertz or Hz) or less, and ‘fast’ rTMSrefers to stimulation at greater than 1 Hz. Evidence indi-cates that slow rTMS decreases (Chen et al. 1997) theexcitability, while fast rTMS increases (Pascual-Leone et al.1994) the excitability of the primary motor cortex. Whetherthese observations hold for all individuals and whether theyhold for cortex other than the motor cortex is yet to beconfirmed. Nevertheless, these observations have beenused in devising therapeutic approaches.

Imaging studies of various forms have frequently shownthat in major depressive episode, the left prefrontal cortexis less active than the right. Accordingly, with the aim ofincreasing the activity of the left prefrontal cortex, fast

INFORMATION FOR ASSISTANTS IN TMS 25

rTMS (George et al. 2000) has been applied to that region,with beneficial effects. Also, with the aim of bringing theactivity of the two hemispheres back into balance, slowrTMS (Klein et al. 1999) has been applied to the right pre-frontal cortex. Again, with beneficial effects.

It is unlikely that the simple rule of slow rTMS to theright and fast rTMS to the left, for the treatment of majordepressive episode, will survive. The human organism andmajor depression are complex issues and research willalmost certainly reveal a host of as yet unrecognized vari-ables which will need to be considered in the future rTMStherapy of depression. Nevertheless, it does appear thatfor a particular individual certain frequency stimulationwill decrease, while faster frequency stimulation willincrease, neural activity. It is unclear, at this stage, how thebest possible frequencies will be selected, but some formof imaging will probably be utilized to understand theoverall rules of the rTMS use parameters. It is unclearwhether this will need to be done on an individual basis,or whether general rules will suffice.

SIDE-EFFECTS

The problem is that one can never say that a side-effectwill never occur. Just because a side-effect has not beennoticed up to a certain point does not mean that it will nothappen when the next patient is treated. For example,asprin was considered completely safe in children fordecades before rare side-effects were detected. Underthese circumstances, the decision whether to treat is onlytaken after balancing the likely benefit of treatment andthe likelihood of serious side-effects.

Single pulses of TMS are considered to be relatively(Mills 1999; Wassermann 2002) and probably completelysafe.

Therapeutic rTMS, being repeated stimulation, andespecially when fast and at high intensity, has been a matterof concern. There was an early report of permanent hearingthreshold shift in animals, due to the acoustic artifact ofrTMS (Counter et al. 1990), however, no such deficits havebeen found in humans (Pascual-Leone et al. 1992).Another early report described microvacuolar changes inthe cortical neuropil of rodents exposed to over 100 high-intensity stimuli (Matsumiya et al. 1992). Attempts to repli-cate these changes were unsuccessful, however, and norelevant histopathology was found in brain tissue from twohuman subjects who had received over 2000 stimuli priorto anterotemporal epilepsy surgery (Gates et al. 1992).

Headache localized to the site of stimulation is notuncommon, occurring in up to 20% of patients. This is dueto stimulation of scalp nerves and muscles and usuallyresolves spontaneously. There is no evidence the rTMS cancause or trigger migraine or other serious headache.

The most worrying issue has been the possibility of trig-gering seizures. An international workshop on the risk andsafety of rTMS was held in 1996. Details were heard ofseven seizures which were thought to have resulted fromrTMS (Wassermann 1998). The workshop produced treat-ment parameter guidelines. Since then, only one relevantcase has been described (Conca et al. 2000). This was asuspected episode of complex partial seizure that followeda session of rTMS treatment. The amount of rTMS beingperformed around the world is uncertain, but the pub-lished studies detail some hundreds of patients who have,over a course of therapy, received at least 8–10 000 pulsesof fast rTMS. The incidence of seizure with rTMS, sincethe adoption of the 1996 safety guidelines, appears to beless than the incidence of seizures with many medications.

Adverse cognitive effects have not been found witheither 1 Hz or 20 Hz stimulation (Little et al. 2000; Speeret al. 2001). A neuroprotective effect of rTMS has beendemonstrated in rodents (Post & Keck 2001). After morethan a decade, no significant long-term adverse effects ofrTMS have been detected, and while still theoreticallypossible, they are clearly less likely than with pharma-cological agents. Nevertheless, caution continues to berecommended (Wassermann 2000).

CONTRAINDICATIONS TO rTMS

There are few absolute contraindications to rTMS treat-ment. A personal or strong family history of epilepsy isgenerally regarded to be a contraindication of fast rTMS.This also applies to slow rTMS, but with the reservationthat slow rTMS may prove useful in intractable epilepsy(Tergau et al. 1999).

Patients with serious medical conditions or excessiveuse of alcohol may be excluded from rTMS therapy, if it isconsidered they have a lowered seizure threshold.

Pregnancy is also generally considered to be a con-traindication to rTMS. This is a theoretical concern anddoubtless rTMS is best avoided during pregnancy. Therisks to a fetus from rTMS to the brain of a mother areprobably less than those from medication (Nahas et al.1999).

Intracranial metal objects are generally considered tobe a contraindication to rTMS. The theoretical risks arethat these may move or be heated. These risks appear tobe small, and there are no reports of brain damage result-ing from the influence of rTMS on intracranial metalobjects.

SEIZURE MANAGEMENT

While unlikely, a seizure remains a possibility. The patientmust be closely observed during rTMS for twitching or any

26 S. PRIDMORE ET AL.

sign of impending seizure and treatment is to be immedi-ately ceased if signs are suspected. The patient is to beclosely observed and the supervising medical officer is tobe summoned.

It is strongly recommended that rTMS be provided bya person with knowledge of seizure management, and onlyin a place where medical assistance can be quicklyprovided.

Seizure management protocols differ in minor detailsfrom one site to another. It is universally important to getthe patient into a semiprone lying position and to clear theairway. Check the pulse. Respiratory movements will belimited during the seizure.

Next, assistance should be summoned. If the seizurecontinues, intravenous diazepam may be appropriate, butpatients without a history of epilepsy, rarely experienceprotracted seizures. The resuscitation team will assist withfurther acute management.

A postictal EEG and CT should be considered, if for noother reason, then for medicolegal purposes. Admission tohospital should be an option but is not mandatory. Thepatient should not leave the facility until the cognitive stateis normal, and should not drive that day.

The patient should be seen by the medical officer on theday of the seizure and on the following day, and debriefingshould be considered. The patient should not receivefurther rTMS. The medical officer should give a full accountto the patient’s general practitioner, who should alsoexamine the patient before full return to normal activities.

USE PARAMETERS

In therapeutic rTMS, the parameters are chosen with atleast three factors in mind: the desire for a therapeuticeffect, the comfort of the patient, and the risk of seizure.High intensity and fast frequency increase patient dis-comfort and risk of seizure. Studies have shown that fastfrequency stimulation has an antidepressant effect whenapplied to the left prefrontal cortex, and it is reasonable toexpect that high intensity stimulation will have a strongerantidepressant effect. Twenty Hz and 10 Hz are commonlyused (Pascual-Leone et al. 1996; Pridmore et al. 2000),however, some evidence suggests that 5 Hz may be just aseffective (George et al. 2000).

When using fast frequency rTMS, to reduce the risk ofseizure, short trains of stimuli (1–10 seconds) are admin-istered, following which is a rest period in the order of halfa minute. Guidelines indicate the maximum length of train,for a given frequency and intensity of stimulation(Wassermann 1998).

Twenty to 30 trains are given per day, in one sitting ofabout 10–20-min. Treatment is provided five times perweek, for 2–4 weeks.

FORMAL TRAINING AND CERTIFICATION

Formal training and certification would be desirable forboth those prescribing and those assisting with the pro-vision of rTMS. As this is such a new field, however, theprocesses are not yet established. The specialist medicalpractitioners currently involved in rTMS obtain experienceby visiting existing centres. This article is presented as anearly contribution to training.

QUANTIFICATION

This paper outlines principles. The following quantifi-cation may be of interest to those with the appropriate tech-nical background (Bohning 2000).1 The peak voltages and current in the coil are of the

order of 2000 V and 10 000 A, respectively.2 The pulses of electricity are extremely short, approxi-

mately 250 microseconds, or 1/4000 second.3 The peak magnetic field, close to the coil, is of the order

of 1.5–2.5 T. This is similar to the constant magneticfield in a magnetic resonance imaging scanner, andabout 40 000 times greater than the earth’s magneticfield.

4 The electric field and the current density generatedwithin the patient, close to the coil, is estimated to beof the order of 150 V/m and 150 A/m, respectively.

5 The resting membrane potential of a neuron is approx-imately –70 mV, and when depolarized to approxi-mately –40 mV, an action potential is triggered.

FINAL COMMENT

rTMS is an exciting new technology which is being activelyresearched and has an antidepressant effect. To thepresent, rTMS has been exclusively conducted by special-ist medical officers with additional training. As knowledgeand experience with rTMS grows, it is probable that pro-fessionals with other backgrounds will have the oppor-tunity to assist in therapeutic rTMS. The aim of this articleis to provide information which will be valuable toassistants.

Therapeutic rTMS should be performed only on theprescription of a specialist medical officer with additionaltraining. In such circumstances, the medical officer bearsultimate responsibility. Nevertheless, an assistant wouldneed to be vigilant and would bear some responsibility fornegligence or careless actions.

REFERENCES

Abrams, R. (1997). Electroconvulsive Therapy, 3rd edn. NewYork: Oxford University Press.

INFORMATION FOR ASSISTANTS IN TMS 27

Bohning, D. (2000). Introduction and overview of TMS physics.In M. George & R. Belmaker (Eds), Transcranial MagneticStimulation in Neuropsychiatry (pp. 13–44). Washington:American Psychiatric Press.

Burt, T., Lisanby, S. & Sackheim, H. (2002). Neuropsychiatricapplications of transcranial magnetic stimulation: a metaanalysis. International Journal of Neuropsychopharmacology,5, 73–103.

Chen, R., Classen, J., Gerloff, C., Celnik, P., Wassermann, E. &Cohen, L. (1997). Depression of motor cortex excitability bylow-frequency transcranial magnetic stimulation. Neurology,48, 1398–1403.

Conca, A., Konig, P. & Housman, A. (2000). Transcranialmagnetic stimulation induces ‘pseudoabsence seizure’. ActaPsychiatrica Scandinavica, 101, 246–248.

Counter, S., Borg, E., Lofquist, L. & Brismar, T. (1990). Hearingloss from the acoustic artifact of the coil used in extracranialmagnetic stimulation. Neurology, 40, 1159–1162.

Dannon, P., Dolberg, O., Schreiber, S. & Grunhaus, L. (2002).Three and six-month outcome following courses of eitherECT or TMS in a population of severely depressed individ-uals – preliminary report. Biological Psychiatry, 51, 687–690.

Duman, R., Malberg, J. & Thome, J. (1999). Neural plasticity tostress and antidepressant treatment. Biological Psychiatry,46, 1181–1191.

Gates, J., Dhuna, A. & Pascual-Leone, A. (1992). Lack of patho-logic changes in human temporal lobes after transcranialmagnetic stimulation. Epilepsia, 33, 504–508.

George, M. S., Nahas, Z., Kozol, F et al. (2002). Mechanisms andstate of the art of transcranial magnetic stimulation. TheJournal of ECT, 18, 170–181.

George, M. S., Nahas, Z., Molloy, M. et al. (2000). A Controlledtrial of daily left prefrontal cortex TMS for treating depres-sion. Biological Psychiatry, 48, 962–970.

Grunhaus, L., Dannon, P. & Schreiber, S. (2000). Repetitivetranscranial magnetic stimulation is as effective as electro-convulsive therapy in the treatment of nondelusional majordepression: an open study. Biological Psychiatry, 47, 314–324.

Holtzheimer, P., Russo, J. & Avery, D. (2001). A meta-analysis ofrepetitive transcranial magnetic stimulation in the treatmentof depression. Psychopharmacological Bulletin, 35, 149–169.

Hyman, S. & Nestler, E. (1993). The molecular foundations ofpsychiatry. Washington: American Psychiatric Press.

Janicak, P., Dowd, S., Martis, B. et al. (2002). Repetitive tran-scranial magnetic stimulation versus electroconvulsivetherapy for major depression: preliminary results of a ran-domised trial. Biological Psychiatry, 51, 659–667.

Klein, E., Kreinin, I., Chistyakov, A. et al. (1999). Therapeuticefficiency of right prefrontal slow repetitive transcranialmagnetic stimulation in major depression: a double blind con-trolled trial. Archives of General Psychiatry, 56, 315–320.

Kozel, F. & George, M. (2002). Meta-analysis of the left prefrontal repetitive transcranial magnetic stimulation (TMS)to treat depression. Journal of Psychiatric Practice, 8,275–278.

Little, J., Kimbrell, T., Wassermann, E. et al. (2000). Cognitiveeffects of 1 and 20 Hz repetitive transcranial magnetic

stimulation in depression: preliminary report. Neuro-psychiatry, Neuropsychology and Behavioral Neurology, 13,119–124.

Martin, J., Barbanoj, M. & Schlaepfer, T. (2002). Transcranialmagnetic stimulation for treating depression (CochraneReview). In: The Cochrane Library. Oxford: Update Software.

Matsumiya, Y., Yamamoto, T., Yarita, M., Miyauchi, S. & Kling, J.(1992). Physical and physiological specification of magneticpulse stimuli that produce cortical damage in rats. Journal ofClinical Neurophysiology, 9, 278–287.

McNamara, B., Ray, J., Arthurs, O. & Boniface, S. (2001).Transcranial magnetic stimulation of depression and otherpsychiatric disorders. Psychological Medicine, 31, 1141–1146.

Mills, K. (1999). Magnetic stimulation of the human nervoussystem. Oxford: Oxford University Press.

Nahas, Z., Bohning, D., Molloy, M., Oustz, J., Risch, S. & George,M. S. (1999). Safety and feasibility of repetitive transcranialmagnetic stimulation in the treatment of anxious depressionin pregnancy. Journal of Clinical Psychiatry, 60, 50–52.

Pascual-Leone, A., Cohen, L., Wassermann, E., Vallas-Sole, J.,Brasil-Neto, J. & Hallet, M. (1992). Lack of evidence ofauditory dysfunction due to transcranial magnetic stimulation.Neurology, 42, 647–651.

Pascual-Leone, A., Rubio, B., Pallardo, F. & Catala, M. (1996).Rapid-rate transcranial magnetic stimulation of left dorsolat-eral prefrontal cortex in drug resistant depression. Lancet,348, 233–237.

Pascual-Leone, A., Valls-Sole, J., Wassermann, E. & Hallett, M.(1994). Responses to rapid-rate transcranial magnetic stimu-lation of the human motor cortex. Brain, 117, 847–858.

Post, A. & Keck, M. (2001). Transcranial magnetic stimulation asa therapeutic tool in psychiatry: what do we know about theneurobiological mechanisms? Journal of PsychiatricResearch, 35, 193–215.

Pridmore, S., Bruno, R., Turnier-Shea, Y., Reid, P. & Rybak, M.(2000). Comparison of unlimited numbers of rapid trans-cranial magnetic stimulation (rTMS) and ECT treatmentsessions in major depressive episode. International Journal ofNeuropsychopharmacology, 3, 129–134.

Pridmore, S., Fernandes Filoh, J., Nahas, Z. & George, M. S.(1998). Motor threshold in transcranial magnetic stimulation:a comparison of a neurophysiological method and a visuali-zation of movement method. Journal of ECT, 14, 25–27.

Rossini, P., Barker, A., Berardelli, A. et al. (1994). Non-invasiveelectrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routineclinical application. Report of an IFCN committee.Electroencephalography and Clinical Neurophysiology, 91,79–92.

Ruohonen, J. & Ilmoniemi, R. (2002). Physical principles for trans-cranial magnetic stimulation. In A. Pascual-Leone, N. Davey,J. Rothwell, E. Wassermann & B. Puri (Eds). Handbook ofTranscranial Magnetic Stimulation (pp. 17–29). London:Arnold.

Speer, A., Repella, J., Figueras, S. et al. (2001). Lack of adversecognitive effects of 1 Hz and 20 Hz repetitive transcranialmagnetic stimulation at 100% of motor threshold over left pre-frontal cortex in depression. Journal of ECT, 17, 259–263.

28 S. PRIDMORE ET AL.

INFORMATION FOR ASSISTANTS IN TMS 29

Tergau, F., Naumann, U., Paulus, W. & Steinhoff, B. (1999). Low-frequency repetitive transcranial magnetic stimulationimproves intractable epilepsy. Lancet, 353, 2209.

Wassermann, E. (1998). Risk and safety of repetitive transcranialmagnetic stimulation: report and suggested guidelines fromthe International Workshop on the Safety of RepetitiveTranscranial Magnetic Stimulation, June 5–7, 1996. Electro-encephalography and Clinical Neurophysiology, 108, 1–16.

Wassermann, E. (2000). Side effects of repetitive transcranialmagnetic stimulation. Depress and Anxiety, 12, 124–129.

Wassermann, E. (2002). Introduction. In A. Pascual-Leone, N.Davey, J. Rothwell, E. Wassermann & B. Puri (Eds),Handbook of Transcranial Magnetic Stimulation (p. 2).London: Arnold.