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Repetitive Transcranial Magnetic Stimulation (rTMS / TMS); a research bibliography

Research appears to be escalating into the neurological and psychological effects of repetitive transcranial magnetic stimulation (rTMS/TMS) that apply relatively strong pulsed electromagnetic fields to the brain and neuroendocrine system at or beyond motor threshold (where eyelids flutter during the pulse).

This type of therapy called repetitive transcranial magnetic stimulation (rTMS) or transcranial magnetic stimulation (TMS – or – sometimes called slow-TMS if 1 Hz or less – i.e. 1 pulse per second or less-) or fast at greater 3 Hz is gaining a strong reputation for being extremely safe and providing measurable and perceptible benefits in users.

During the last 15 years, Professor Photios Anninos from Greece and neurologist Reuven Sandyk M.D. have been fabulously successful treating the neurological disorders Parkinson’s and Alzheimer’s using very weak AC magnetic fields transcranially. 

We have found that pulsed DC electromagnetic fields have comparable effect but when used during the night produce a wide spectrum of synergistic effects.  It is being discovered by researchers around the world that a host of beneficial biological effects appear to be triggered even where neurological and endocrine malfunction is a root cause of disease. We say that EarthPulse™ elevates mood at far less amplitude than used in rTMS.

effects of TMS therapy on brain health

In a new study in 2019, 16 people—ages 64 to 80 with normal age-related memory problems—shows it’s possible to alter memory ability in older adults using this Transcranial Magnetic Stimulation. This study was conducted by the well-known TMS researcher, Dr. Voss, Associate Professor of Medical Social SciencesNeurology – Ken and Ruth Davee Department and Psychiatry and Behavioral Sciences.

Though most therapeutic studies show TMS/rTMS provides safe, therapeutic effects warranting an explosion of research, widespread use of TMS/rTMS is strictly for diagnostic purposes. We have omitted most of these diagnostic studies from this resource.

In January ’07 the FDA Advisory rejected rTMS use for depression even though it does no harm and usually produces results. Although it is approved in both the US and Canada for treatment resistant (drug resistant) depression.

Peer reviewed journal abstracts in libraries by the National Institutes of Health (NIH) indicate rTMS / TMS as beneficial and without perceptible expected or unexpected adverse reactions in epilepsy, Parkinson’s disease, MS, Alzheimer’s, migraine headache, cluster headache, severe PMS, depression, ADD/ADHD and others.

Several hundred pulsed electromagnetic field therapy citations contained in our research bibliographies are linked directly to PubMed a service of the U.S. National Library of Medicine and the U.S. National Institutes of Health.

These studies are offered for your education only and are not intended as promotional material for EarthPulse™ Technologies, LLC.

rTMS Boosts Cognitive Function in Schizophrenia Plus Depression
Nikita Maslenikov, MD, Moscow Research Institute of Psychiatry, Russia.
32nd European College of Neuropsychopharmacology (ECNP) Congress: Abstract P.838. Presented September 8, 2019.
MedScape Article

To read the original source, use the search on Pubmed

Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline.
Nilakantan AS, Mesulam MM, Weintraub S, Karp EL, VanHaerents S, Voss JL.
Neurology. 2019 May 14;92(20):e2349-e2354. doi: 10.1212/WNL.0000000000007502. Epub 2019 Apr 17.
PMID: 30996057

Frequency-specific noninvasive modulation of memory retrieval and its relationship with hippocampal network connectivity.
Hermiller MS, VanHaerents S, Raij T, Voss JL.
Hippocampus. 2018 Nov 17. doi: 10.1002/hipo.23054.
PMID: 30447076

Hemisphere-specific effects of prefrontal theta-burst stimulation on visual recognition memory accuracy and awareness.
Carbajal I, O’Neil JT, Palumbo RT, Voss JL, Ryals AJ.
Brain Behav. 2019 Apr;9(4):e01228. doi: 10.1002/brb3.1228. Epub 2019 Mar 14.
PMID: 30873758

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions.
Chris B, Brem AK, Arns M, Brunoni AR, Filipčić I, Ana GÁ, Langguth B, Padberg F, Poulet E, Rachid F, Sack AT, Vanderhasselt MA, Bennabi D.
Curr Opin Psychiatry. 2019 May 27. doi: 10.1097/YCO.0000000000000533.
PMID: 31145145

High-Frequency Repetitive Transcranial Magnetic Stimulation Applied to the Parietal Cortex for Low-Functioning Children With Autism Spectrum Disorder: A Case Series.
Yang Y, Wang H, Xue Q, Huang Z, Wang Y.
Front Psychiatry. 2019 May 9;10:293. doi: 10.3389/fpsyt.2019.00293. eCollection 2019.
PMID: 31143132

State-Dependent Effects of Ventromedial Prefrontal Cortex Continuous Thetaburst Stimulation on Cocaine Cue Reactivity in Chronic Cocaine Users.
Kearney-Ramos TE, Dowdle LT, Mithoefer OJ, Devries W, George MS, Hanlon CA.
Front Psychiatry. 2019 May 8;10:317. doi: 10.3389/fpsyt.2019.00317. eCollection 2019.
PMID: 31133897

Sessions of prolonged continuous theta burst stimulation or high-frequency 10 Hz stimulation to left dorsolateral prefrontal cortex for three days decreased pain sensitivity by modulation of the efficacy of conditioned pain modulation.
De Martino E, Fernandes AM, Galhardoni R, De Oliveira Souza C, Ciampi De Andrade D, Graven-Nielsen T.
J Pain. 2019 May 24. pii: S1526-5900(19)30413-4. doi: 10.1016/j.jpain.2019.05.010. [Epub ahead of print]
PMID: 31132509

A systematic review of the safety and effectiveness of repetitive transcranial magnetic stimulation in the treatment of peripartum depression.
Cole J, Bright K, Gagnon L, McGirr A.
J Psychiatr Res. 2019 May 16;115:142-150. doi: 10.1016/j.jpsychires.2019.05.015. [Epub ahead of print] Review.
PMID: 31129438

Update on current and emerging therapies for dystonia.
Lizarraga KJ, Al-Shorafat D, Fox S.
Neurodegener Dis Manag. 2019 May 22. doi: 10.2217/nmt-2018-0047. [Epub ahead of print]
PMID: 31117876

Repetitive transcranial magnetic stimulation as treatment for neuropathic pain in patients with spinal cord injury.
Walter A, Denier N, Hund M, Suenderhauf C.
J Neurosurg Sci. 2019 May 15. doi: 10.23736/S0390-5616.19.04716-7. [Epub ahead of print]
PMID: 31111722

Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial.
Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J.
Am J Psychiatry. 2019 May 21:appiajp201918101180. doi: 10.1176/appi.ajp.2019.18101180. [Epub ahead of print]
PMID: 31109199

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics.
Lerner AJ, Wassermann EM, Tamir DI.
Clin Neurophysiol. 2019 Apr 6. pii: S1388-2457(19)30110-5. doi: 10.1016/j.clinph.2019.03.016. [Epub ahead of print]
PMID: 31104898

MEG recordings of patients with cerebral palsy before and after the application of pico-Tesla weak magnetic fields.
Anninos P, Kotini A, Adamopoulos A, Tsagas N.
J Integr Neurosci. 2019 Mar 30;18(1):17-21. doi: 10.31083/j.jin.2019.01.104.
PMID: 31091844

[Procognitive effects of transcranial magnetic stimulation in the light of neurocognitive deficit in schizophrenia].
Popov MM, Pluzhnikov IV, Kaleda VG.
Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(3):120-126. doi: 10.17116/jnevro2019119031120. Russian.
PMID: 31089106

Noninvasive Brain Stimulation for Rehabilitation of Paediatric Motor Disorders Following Brain Injury: Systematic Review of Randomized Controlled Trials.
Elbanna ST, Elshennawy S, Ayad MN.
Arch Phys Med Rehabil. 2019 May 9. pii: S0003-9993(19)30302-8. doi: 10.1016/j.apmr.2019.04.009. [Epub ahead of print] Review.
PMID: 31078616

The Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Advancing Parkinson’s Disease With Dysphagia: Double Blind Randomized Clinical Trial.
Khedr EM, Mohamed KO, Soliman RK, Hassan AMM, Rothwell JC.
Neurorehabil Neural Repair. 2019 May 10:1545968319847968. doi: 10.1177/1545968319847968. [Epub ahead of print]
PMID: 31072214

J Psychiatr Res. 2007 Oct;41(7):606-15. Epub 2006 Apr 4.
Metabolic alterations in the dorsolateral prefrontal cortex after treatment with high-frequency repetitive transcranial magnetic stimulation in patients with unipolar major depression.
Department of Psychiatry, Charite – Universitatsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, D-14050 Berlin, Germany.

J Psychiatr Res. 2007 Aug;41(5):395-403. Epub 2006 Mar 22.
Disturbed Sleep is predictor for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS).
Department of Psychiatry and Psychotherapy, Charite – Universitatsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.

Psychiatry Res. 2007 Mar 30;150(2):181-6. Epub 2007 Feb 14.
Long-lasting effects of high frequency repetitive transcranial magnetic stimulation in major depressed patients.
Casa di Cura “Villa S. Chiara”, Verona, Italy.

Clin Neurophysiol. 2006 Jul;117(7):1536-44. Epub 2006 Jun 5.
Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy
Andre-Obadia N, Peyron R, Mertens P, Mauguiere F, Laurent B, Garcia-Larrea L.
University Hospital Lyon Sud, Lyon, France; INSERM EMI 342; UCLB1 Lyon & UJM, Saint-Etienne, France.
OBJECTIVE: To assess, using a double-blind procedure, the pain-relieving effects of rTMS against placebo, and their predictive value regarding the efficacy of implanted motor cortex stimulation (MCS). METHODS: Three randomised, double-blinded, 25min sessions of focal rTMS (1Hz, 20Hz and sham) were performed in 12 patients, at 2 weeks intervals. Effects on pain were estimated from daily scores across 5 days before, and 6 days after each session. Analgesic effects were correlated with those of subsequent implanted motor cortex stimulation (MCS). RESULTS: Immediately after the stimulating session, pain scores were similarly decreased by all rTMS modalities.

Clin Neurophysiol. 2006 Jun 20; [Epub ahead of print]
Motor cortical excitability studied with repetitive transcranial magnetic stimulation in patients with Huntington’s disease.
Lorenzano C, Dinapoli L, Gilio F, Suppa A, Bagnato S, Curra A, Inghilleri M, Berardelli A.
Department of Neurological Sciences, University of Rome ‘La Sapienza’, Rome, Italy.

Pain. 2006 May;122(1-2):22-7. Epub 2006 Feb 21.
Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex.
Hirayama A, Saitoh Y, Kishima H, Shimokawa T, Oshino S, Hirata M, Kato A, Yoshimine T.
Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation-guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10-s 5-Hz TMS pulses, with 50-s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF-MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p<0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p<0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.Psychother Psychosom.

Exp Brain Res. 2006 May 9; [Epub ahead of print]
The effects of repetitive transcranial magnetic stimulation on cortical inhibition in healthy human subjects.
Daskalakis ZJ, Moller B, Christensen BK, Fitzgerald PB, Gunraj C, Chen R.
Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.

Clin Neurophysiol. 2006 Jan;117(1):103-9. Epub 2005 Dec 20.
Altered response to rTMS in patients with Alzheimer’s disease.
Inghilleri M, Conte A, Frasca V, Scaldaferri N, Gilio F, Santini M, Fabbrini G, Prencipe M, Berardelli A.
Department of Neurological Sciences, University of Rome La Sapienza, Viale dell’Universita, 30, 00185 Rome, Italy.

Stroke. 2005 Dec;36(12):2681-6. Epub 2005 Oct 27.
Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke.
Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K.
Department of Rehabilitation Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-0814, Japan.
BACKGROUND AND PURPOSE: A recent report has demonstrated that the contralesional primary motor cortex (M1) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition (TCI) in stroke patients. We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation (rTMS) caused an improved motor performance of the affected hand in stroke patients by releasing the TCI.CONCLUSIONS: We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected hand in stroke patients; this suggests a new neurorehabilitative strategy for stroke patients.

J Neurophysiol. 2005 Sep;94(3):1668-75. Epub 2005 May 4.
Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition.
Pal PK, Hanajima R, Gunraj CA, Li JY, Wagle-Shukla A, Morgante F, Chen R.
Divsion of Neurology and Krembil Neuroscience Centre, Toronto Western Research Institute, University Health Network, University of Toronto, Ontario, Canada.

Mov Disord. 2005 Sep;20(9):1178-84.
Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson’s disease and concurrent depression.
Boggio PS, Fregni F, Bermpohl F, Mansur CG, Rosa M, Rumi DO, Barbosa ER, Odebrecht Rosa M, Pascual-Leone A, Rigonatti SP, Marcolin MA, Araujo Silva MT.
Department of Experimental Psychology, Institute of Psychology, University of Sao Paulo, Sao Paulo, SP, Brazil.

We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.

Neurol Neurochir Pol. 2005 Sep-Oct;39(5):389-96.
[The diagnostic and therapeutic application of transcranial magnetic stimulation] [Article in Polish]
Derejko M, Niewiadomska M, Rakowicz M. Zaklad
Neurofizjologii Klinicznej, Instytut Psychiatrii i Neurologii, ul. Sobieskiego 9, 02-957 Warszawa.

The functional abnormalities of the central motor structures and its contribution of rigidity, tremor and bradykinesia in Parkinson’s disease seem mainly due to the degeneration of the nigro-striatal pathway. Recent reviews on the basic mechanisms of TMS in Parkinson’s disease show reduced inhibitory motor network at the cortical and spinal level. The observed changes are thought to be in relation with a dysfunction of subcortico-cortical and subcortico-spinal pathways. Observations made using TMS give new pathophysiological insights in functioning of the central motor structures in Parkinson’s disease and started new form of TMS – repetitive TMS (rTMS) as a treatment of the Parkinson’s disease motor signs. A few studies using rTMS with repetition rate of 0.2, 1, and 5 Hz showed improvement of motor signs in the Parkinson’s disease patients. Although these results support the beneficial effects of rTMS on Parkinson symptoms, long-term studies with large numbers of subjects should be conducted to assess the efficacy of the rTMS on Parkinson’s disease in future.

J Clin Psychiatry. 2005 Jul;66(7):930-7.
Add-on rTMS for medication-resistant depression: a randomized, double-blind, sham-controlled trial in Chinese patients.
Su TP, Huang CC, Wei IH.
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for improving depression by delivering magnetic stimulation to the brain. However, the apparent effects of rTMS on depression have been varied in different studies. The aims of this study were to determine whether left dorsolateral prefrontal cortex rTMS can alleviate medication-resistant depression in Chinese patients and to investigate what demographic variables or clinical features may predict better response.
METHOD: We designed a 2-week randomized, double-blind, sham-controlled study of add-on rTMS. A total of 30 medication-resistant patients with DSM-IV major depressive disorder or bipolar disorder, depressed episode completed 10 sessions of active or sham rTMS-10 patients at each of 2 frequencies, faster (20 Hz) or slower (5 Hz) at 100% motor threshold, and 10 patients at sham stimulation.
RESULTS: Patients at both stimulation frequencies demonstrated a superior reduction of depression severity compared to sham stimulation (active = 55.7% vs. sham = 16.3%). The response rate for active rTMS was 60%, in contrast to 10% for the sham treatment. No difference in clinical response was observed between 5 Hz and 20 Hz active rTMS.

Int J Neuropsychopharmacol. 2005 Jun;8(2):223-33. Epub 2004 Nov 30.
Antidepressant effects of different schedules of repetitive transcranial magnetic stimulation vs. clomipramine in patients with major depression: relationship to changes in cortical excitability.
Chistyakov AV, Kaplan B, Rubichek O, Kreinin I, Koren D, Feinsod M, Klein E.
Laboratory of Clinical Neurosciences, Department of Neurosurgery, Rambam Medical Center, B. Rappaport Faculty of Medicine, The Technion, Israel Institute of Technology, Haifa, Israel

J Neurol Neurosurg Psychiatry. 2005 Jun;76(6):833-8.
Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain.
Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Department of Neurology, Assiut University Hospital, Assiut, Egypt

J Neurol Sci. 2005 Mar 15;229-230:157-61. Epub 2004 Dec 16.
Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients.
Rektorova I, Megova S, Bares M, Rektor I.
First Department of Neurology, Masaryk University, Teaching Hospital sv. Anna, Pekarska 53, 656 91, Brno, Czech Republic.
AIMS: Examine whether one session of high frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) would induce any measurable cognitive changes in patients with cerebrovascular disease and mild cognitive deficits.
CONCLUSION: Our pilot study results showed that one session of the high frequency rTMS applied over the left DLPFC was safe in patients with cerebrovascular disease and mild executive deficits, and may induce measurable positive effects on executive functioning.

Clin Neurophysiol. 2005 Mar;116(3):605-13. Epub 2004 Nov 5.
Comparison between short train, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex.
Arai N, Okabe S, Furubayashi T, Terao Y, Yuasa K, Ugawa Y.
Department of Neurology, Division of Neuroscience, Graduate School of Medicine University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
OBJECTIVE: To compare motor evoked potentials (MEPs) elicited by short train, monophasic, repetitive transcranial magnetic stimulations (rTMS) with those by short train, biphasic rTMS. RESULTS: 2 or 3Hz stimulation with either monophasic or biphasic pulses evoked MEPs that gradually increased in amplitude with the later MEPs being significantly larger than the earlier ones. Monophasic rTMS showed much more facilitation than biphasic stimulation, particularly at 3Hz. Stimulation at the foramen magnum level at 3Hz elicited fairly constant MEPs.
CONCLUSIONS: The enhancement of cortical MEPs with no changes of responses to foramen magnum level stimulation suggests that the facilitation occurred at the motor cortex. We hypothesize that monophasic TMS has a stronger short-term effect during repetitive stimulation than biphasic TMS because monophasic pulses preferentially activate one population of neurons oriented in the same direction so that their effects readily summate. Biphasic pulses in contrast may activate several different populations of neurons (both facilitatory and inhibitory) so that summation of the effects is not so clear as with monophasic pulses.
SIGNIFICANCE: This means that when using rTMS as a therapeutic tool or in research fields, the difference in waveforms of magnetic pulses (monophasic or biphasic) may affect the results.

2003 Sep-Oct;72(5):286-8.
Transcranial magnetic stimulation in the reversal of motor conversion disorder.
Schonfeldt-Lecuona C, Connemann BJ, Spitzer M, Herwig U.
Department of Psychiatry, University of Ulm, Germany.
BACKGROUND: We tested the therapeutic potential of high-frequency repetitive transcranial magnetic stimulation (rTMS) in a 20-year-old patient suffering from a conversion paralysis of the right arm.
METHOD: rTMS was applied to the contralateral motor cortex. Stimulations were performed on working days at a frequency of 15 Hz.
RESULTS: Within 12 weeks, motor function, hyposensibility and muscle bulk were completely restored.
CONCLUSIONS: In addition to possible psychological effects, rTMS may have had a causal therapeutic effect by strengthening corticocortical connections and thereby priming voluntary movements. Further controlled studies are needed.

Arq Neuropsiquiatr. 2003 Mar;61(1):146-52. Epub 2003 Apr 16.
[Transcranial magnetic stimulation] [Article in Portuguese]
Conforto AB, Marie SK, Cohen LG, Scaff M.
Divisao de Clinica Neurologica, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.

Exp Brain Res. 2003 Jul 17 [Epub ahead of print].
Investigating human motor control by transcranial magnetic stimulation.
Petersen NT, Pyndt HS, Nielsen JB.
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
In this review we discuss the contribution of transcranial magnetic stimulation (TMS) to the understanding of human motor control. Compound motor-evoked potentials (MEPs) may provide valuable information about corticospinal transmission, especially in patients with neurological disorders, but generally do not allow conclusions regarding the details of corticospinal function to be made. Techniques such as poststimulus time histograms (PSTHs) of the discharge of single, voluntarily activated motor units and conditioning of H reflexes provide a more optimal way of evaluating transmission in specific excitatory and inhibitory pathways. Through application of such techniques, several important issues have been clarified. TMS has provided the first real evidence that direct monosynaptic connections from the motor cortex to spinal motoneurons exist in man, and it has been revealed that the distribution of these projections roughly follows the same proximal-distal gradient as in other primates. However, pronounced differences also exist. In particular, the tibialis anterior muscle appears to receive as significant a monosynaptic corticospinal drive as muscles in the hand. The reason for this may be the importance of this muscle in controlling the foot trajectory in the swing phase of walking. Conditioning of H reflexes by TMS has provided evidence of changes in cortical excitability prior to and during various movements. These experiments have generally confirmed information obtained from chronic recording of the activity of corticospinal cells in primates, but information about the corticospinal contribution to movements for which information from other primates is sparse or lacking has also been obtained. One example is walking, where TMS experiments have revealed that the corticospinal tract makes an important contribution to the ongoing EMG activity during treadmill walking. TMS experiments have also documented the convergence of descending corticospinal projections and peripheral afferents on spinal interneurons. Current investigations of the functional significance of this convergence also rely on TMS experiments. The general conclusion from this review is that TMS is a powerful technique in the analysis of motor control, but that care is necessary when interpreting the data. Combining TMS with other techniques such as PSTH and H reflex testing amplifies greatly the power of the technique.
PMID: 12879177

CNS Spectr. 2003 Jul;8(7):529-36.
Mechanisms and the current state of deep brain stimulation in neuropsychiatry.
Lisanby SH, Morales O, Payne N, Kwon E, Fitzsimons L, Luber B, Nobler MS, Sackeim HA.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.
New findings regarding the mechanisms of action of electroconvulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel electrode placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures (eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cog
PMID: 12894034

CNS Spectr. 2003 Jul;8(7):522-6.
Mechanisms and the current state of deep brain stimulation in neuropsychiatry.
Greenberg BD, Rezai AR.
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, Rhode Island, USA.
Deep brain stimulation (DBS) is established as a therapy for movement disorders, and it is an investigational treatment in other neurologic conditions. DBS precisely targets neuroanatomical targets deep within the brain that are proposed to be centrally involved in the pathophysiology of some neuropsychiatric illnesses. DBS is nonablative, offering the advantages of reversibility and adjustability. This might permit therapeutic effectiveness to be enhanced or side effects to be minimized. Preclinical and clinical studies have shown effects of DBS locally, at the stimulation target, and at a distance, via actions on fibers of passage or across synapses. Although its mechanisms of action are not fully elucidated, several effects have been proposed to underlie the therapeutic effects of DBS in movement disorders, and potentially in other conditions as well. The mechanisms of action of DBS are the focus of active investigation in a number of clinical and preclinical laboratories. As in severe movement disorders,
PMID: 12894033

CNS Spectr. 2003 Jul;8(7):488.
Progress in therapeutic brain stimulation in neuropsychiatry.
Schlaepfer TE.
Department of Psychiatry,Johns Hopkins University,Baltimore, USA.
PMID: 12894028

Cogn Behav Neurol. 2003 Jun;16(2):118-27.
Relative effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy on mood and memory: a neurocognitive risk-benefit analysis.
O’Connor M, Brenninkmeyer C, Morgan A, Bloomingdale K, Thall M, Vasile R, Leone AP.
Harvard Medical School, Boston, Massachusetts, USA.
OBJECTIVE: Two procedures for treating major depressive disorder were compared with regard to their respective effects on mood and cognition.
BACKGROUND: Fourteen patients underwent treatment with electroconvulsive therapy and 14 underwent treatment with repetitive transcranial magnetic stimulation. Patients were tested on three occasions: before initiation of treatment, at the end of treatment, and 2 weeks after the end of treatment.
METHODS: Electroconvulsive therapy was applied unilaterally approximately three times per week for 2 to 4 weeks. Repetitive transcranial magnetic stimulation was applied in sessions of 1600 stimuli at 10 Hertz and 90% of motor threshold intensity to the left dorsolateral prefrontal cortex daily (Monday through Friday) for 2 consecutive weeks.
RESULTS: Results indicate that electroconvulsive therapy had a more positive effect on mood than did a 2-week trial of repetitive transcranial magnetic stimulation. With regard to cognitive outcome measures, electroconvulsive therapy exerted a deleterious but transient effect on various components of memory that were no longer detected 2 weeks after the end of treatment; however, there was evidence of persistent retrograde amnesia after treatment with electroconvulsive therapy. As a group, repetitive transcranial magnetic stimulation patients experienced only a modest reduction in depression severity but there was no evidence of anterograde or retrograde memory deficits in the aftermath of treatment with repetitive transcranial magnetic stimulation.
CONCLUSIONS: Findings suggest that electroconvulsive therapy is associated with transient negative cognitive side effects, most of which dissipate in the days after treatment. Deficits of this sort are not apparent after treatment with a 2-week course of repetitive transcranial magnetic stimulation.
PMID: 12799598

Cogn Behav Neurol. 2003 Jun;16(2):128-35.
Prefrontal cortex transcranial magnetic stimulation does not change local diffusion: a magnetic resonance imaging study in patients with depression.
Li X, Nahas Z, Lomarev M, Denslow S, Shastri A, Bohning DE, George MS.
Brain Stimulation Laboratory, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
OBJECTIVE: To determine whether transcranial magnetic stimulation over the left dorsolateral prefrontal cortex produces pathologic changes or leakage of the blood-brain barrier in patients with depression by using apparent diffusion coefficient magnetic resonance imaging. BACKGROUND: Transcranial magnetic stimulation is a new technology for noninvasively stimulating the brain. It appears to be a relatively safe technique, with some important exceptions. Its neurobiologic mechanisms of action are poorly understood. One theory to explain its apparent antidepressant effects involves a potential change in local blood-brain barrier settings, allowing passage of peripheral substances directly into brain parenchyma. Knowing whether transcranial magnetic stimulation changes local brain diffusion is important as well from a safety perspective. To test whether transcranial magnetic stimulation changes local brain diffusion, we used apparent diffusion coefficient magnetic resonance imaging in depressed patients undergoing interleaved transcranial magnetic stimulation/functional magnetic resonance imaging over the left prefrontal cortex. METHODS: Within a 1.5 Tesla magnetic resonance imaging scanner, 14 depressed patients were stimulated with a figure-eight transcranial magnetic stimulation coil over the left prefrontal cortex. Apparent diffusion coefficient magnetic resonance imaging was acquired before, and immediately after, 1 Hertz transcranial magnetic stimulation (147 stimuli) intermittently delivered at a motor threshold of more than 7.35 minutes. Phase maps of the transcranial magnetic stimulation magnetic fields were used to guide region-of-interest placement. RESULTS: No significant qualitative apparent diffusion coefficient differences were observed before and after 1 Hertz transcranial magnetic stimulation underneath the coil. CONCLUSIONS: One Hertz transcranial magnetic stimulation over the left dorsolateral prefrontal cortex as applied in this study did not result in pathologic changes or leakage of the blood-brain barrier in patients with depression. If prefrontal transcranial magnetic stimulation at these usage parameters changes local diffusion, it is not an obvious or large effect.
PMID: 12799599

Electromyogr Clin Neurophysiol. 2003 Jun;43(4):235-40.
Hemiparkinson-hemiatrophy syndrome: a transcranial magnetic stimulation study.
Nardone R, Lochner P, Tezzon F.
Department of Neurology, F. Tappeiner Hospital, Merano, BZ.
We described the clinical and neuroradiological findings together with a transcranial magnetic stimulation study in two patient with hemiparkinson-hemiatrophy syndrome (HP-HA). In both patients the neuroradiological findings (MRI) and the central motor conduction were normal whereas the functional imaging studies (SPECT) showed asymmetrical perfusion in the basal ganglia; the intracortical inhibition at short interstimulus intervals and the silent period duration in the motor cortex contralateral to hemiparkinsonism were significantly increased only in one of the patient which has a poor response to L-Dopa therapy. These studies suggest that intracortical or thalamo-cortical neuronal inhibition may be increased in HP-HA. The etiopathogenetic considerations, the diagnostic criteria and the prognostic value of our finding to evaluate the clinical evolution of parkinsonism are discussed in the context of current models of basal ganglia-thalamo-cortical connectivity. Transcranial magnetic stimulation will provide valuable information for the differential diagnosis of the parkinsonian disorders and may predict the efficacy of L-Dopa therapy.
PMID: 12836589

9: Eur J Neurosci. 2003 Jun;17(11):2462-8.
Metabolic changes after repetitive transcranial magnetic stimulation (rTMS) of the left prefrontal cortex: a sham-controlled proton magnetic resonance spectroscopy (1H MRS) study of healthy brain.
Michael N, Gosling M, Reutemann M, Kersting A, Heindel W, Arolt V, Pfleiderer B.
Department of Psychiatry, University of Munster, FRG, Germany.
Rapid transcranial magnetic stimulation is being increasingly used in the treatment of psychiatric disorders, especially major depression. However, its mechanisms of action are still unclear. The aim of this study was to assess metabolic changes by proton magnetic resonance spectroscopy following high-frequency rapid transcranial magnetic stimulation (20 Hz), both immediately after a single session and 24 h after a series of five consecutive sessions. Twelve healthy volunteers were enrolled in a prospective single-blind, randomized study [sham (n = 5) vs. real (n = 7)]. Three brain regions were investigated (right, left dorsolateral prefrontal cortex, left anterior cingulate cortex). A single as well as a series of consecutive rapid transcranial magnetic stimulations affected cortical glutamate/glutamine levels. These effects were present not only close to the stimulation site (left dorsolateral prefrontal cortex), but also in remote (right dorsolateral prefrontal cortex, left cingulate cortex) brain regions. Remarkably, the observed changes in glutamate/glutamine levels were dependent on the pre-transcranial magnetic stimulation glutamate/glutamine concentration, i.e. the lower the pre-stimulation glutamate/glutamine level, the higher the glutamate/glutamine increase observed after short- or long-term stimulation (5 days). In general, the treatment was well tolerated and no serious side-effects were reported. Neither transient mood changes nor significant differences in the outcome of a series of neuropsychological test batteries after real or sham transcranial magnetic stimulation occurred in our experiment. In summary, these data indicate that rapid transcranial magnetic stimulation may act via stimulation of glutamatergic prefrontal neurons.
PMID: 12814378

10: Ann N Y Acad Sci. 2003 May;993:1-13; discussion 48-53.
Neuroprotection trek–the next generation: neuromodulation I. Techniques–deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.
Andrews RJ.
NASA Ames Research Center, Moffett Field, California, USA.
Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson’s disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.
PMID: 12853290

11: J Rehabil Med. 2003 May;(41 Suppl):20-6.
Transcranial magnetic stimulation to assess cortical plasticity: a critical perspective for stroke rehabilitation.
Butler AJ, Wolf SL.
Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Transcranial magnetic stimulation has gained increasing visibility as an evaluative and interventional tool during the past 15 years. Within the context of rehabilitation, transcranial magnetic stimulation has been applied to differentiate excitatory and inhibitory mechanisms and to assess cortical reorganization following specific interventions. This article reviews some of the more salient features of transcranial magnetic stimulation applications relevant to stroke rehabilitation, highlighting the strengths and weaknesses in this approach. Data derived from such studies may be profoundly over-interpreted. Information is provided showing the importance of utilizing fundamental principles of electrode placement and kinesiological electromyography to more accurately reflect and interpret data emerging from transcranial magnetic stimulation mapping studies, particularly as they apply to the interpretation of cortical reorganization following application of neurorehabilitative procedures.
PMID: 12817653

12: Clin Neurophysiol. 2003 Apr;114(4):600-4.
Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.
Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus W.
Department of Clinical Neurophysiology, University of Goettingen, Robert Koch Str. 40, 37075, Goettingen, Germany. <>
OBJECTIVE: To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. METHODS: Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. RESULTS: Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. CONCLUSIONS: Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.
PMID: 12686268

13: J Physiol. 2003 Mar 1;547(Pt 2):485-96. Epub 2003 Jan 17.
Ketamine increases human motor cortex excitability to transcranial magnetic stimulation.
Di Lazzaro V, Oliviero A, Profice P, Pennisi MA, Pilato F, Zito G, Dileone M, Nicoletti R, Pasqualetti P, Tonali PA.
Institute of Neurology, Universita Cattolica, Largo A. Gemelli 8, 00168 Rome, Italy.
Subanaesthetic doses of the N-methyl-D-aspartate (NMDA) antagonist ketamine have been shown to determine a dual modulating effect on glutamatergic transmission in experimental animals, blocking NMDA receptor activity and enhancing non-NMDA transmission through an increase in the release of endogenous glutamate. Little is known about the effects of ketamine on the excitability of the human central nervous system. The effects of subanaesthetic, graded incremental doses of ketamine (0.01, 0.02 and 0.04 mg kg-1 min-1, I.V.) on the excitability of cortical networks of the human motor cortex were examined with a range of transcranial magnetic and electric stimulation protocols in seven normal subjects. Administration of ketamine at increasing doses produced a progressive reduction in the mean resting motor threshold (RMT) (F(3, 18) = 22.33, P < 0.001) and active motor threshold (AMT) (F(3, 18) = 12.17, P < 0.001). Before ketamine administration, mean RMT +/- S.D. was 49 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 42.6 +/- 2.6 % (P < 0.001). Before ketamine administration, AMT +/- S.D. was 38 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 33 +/- 4.4 % (P < 0.002). Ketamine also led to an increase in the amplitude of EMG responses evoked by magnetic stimulation at rest; this increase was a function of ketamine dosage (F(3, 18) = 5.29, P = 0.009). In contrast to responses evoked by magnetic stimulation, responses evoked by electric stimulation were not modified by ketamine. The differential effect of ketamine on responses evoked by magnetic and electric stimulation demonstrates that subanaesthetic doses of ketamine enhance the recruitment of excitatory cortical networks in motor cortex. Transcranial magnetic stimulation produces a high-frequency repetitive discharge of pyramidal neurones and for this reason probably depends mostly on short-lasting AMPA transmission. An increase in this transmission might facilitate the repetitive discharge of pyramidal cells after transcranial magnetic stimulation which, in turn, results in larger motor responses and lower thresholds. We suggest that the enhancement of human motor cortex excitability to transcranial magnetic stimulation is the effect of an increase in glutamatergic transmission at non-NMDA receptors similar to that described in experimental studies.
PMID: 12562932

14: J Clin Neurophysiol. 2003 Feb;20(1):59-64.
Intracortical inhibition and facilitation of the response of the diaphragm to transcranial magnetic stimulation.
Demoule A, Verin E, Ross E, Moxham J, Derenne JP, Polkey MI, Similowski T.
Laboratoire de Physiopathologie Respiratoire et Unite de Reanimation, Service de Pneumologie, Groupe Hospitalier Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, France.
Respiratory muscles respond to a subcortical automatic command and to a neocortical voluntary command. In diseases such as stroke or motor neurone disease, an abnormal diaphragmatic response to single transcranial magnetic stimuli can identify a central source for respiratory disorders, but this is not likely to be the case in disorders affecting intracortical inhibitory and facilitatory mechanisms. This study describes the response of the diaphragm to paired transcranial magnetic stimulation. Thirteen normal subjects were studied (age range, 22 to 43 years; 7 men; phrenic conduction, <6.8 msec; latency of diaphragmatic motor evoked potential, <20.5 msec). Motor evoked potentials in response to paired stimulation were obtained in eight subjects only, with the motor threshold in the remaining five subjects too high to absorb the loss of power inherent in the double-stimulation montage. Interstimulus intervals less than 5 msec resulted in a statistically significant inhibition (p < 0.01 for interstimulus intervals of 1 and 3 ms), whereas intervals longer than 6 msec were facilitatory (maximal, 15 msec). The diaphragmatic pattern matched that of the biceps brachii. The authors conclude that it is possible to study intracortical inhibition and facilitation of diaphragmatic control, although not in all subjects. Technical improvement should alleviate current limitations and make paired transcranial magnetic stimulation a tool to study respiratory muscle abnormalities in settings in which intracortical interactions are important, such as movement disorders.
PMID: 12684560

15: Neuropsychopharmacology. 2003 Feb;28(2):201-5.
Efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of affective disorders.
Schlaepfer TE, Kosel M, Nemeroff CB.
Department of Psychiatry, University Hospital, Bern, Switzerland.
Transcranial magnetic stimulation (TMS) is a relatively noninvasive technique to interfere with the function of small cortical areas through currents induced by alternating magnetic fields emanating from a handheld coil placed directly above the targeted area. This technique has clear effects on a whole range of measures of brain function and has become an important research tool in neuropsychiatry. More recently, TMS has been studied in psychiatry mainly to assess its putative therapeutic effects in treatment refractory major depression. Most studies indicate that both low-frequency TMS and higher (20 Hz) frequency repetitive TMS may have some antidepressant properties. However, definite therapeutic effects of clinical significance still remain to be demonstrated.
PMID: 12589372

16: Neuroreport. 2002 Dec 3;13(17):2229-33.
Pulse configuration-dependent effects of repetitive transcranial magnetic stimulation on visual perception.
Antal A, Kincses TZ, Nitsche MA, Bartfai O, Demmer I, Sommer M, Paulus W.
Department of Clinical Neurophysiology, Georg-August University of Gottingen, Robert Koch Strasse 40, 37070 Gottingen, Germany.
Transcranial magnetic stimulation (TMS) is a noninvasive technique for direct stimulation of the neocortex. In the last two decades it is successfully applied in the study of motor and sensory physiology. TMS uses the indirect induction of electrical fields in the brain generated by intense changes of magnetic fields applied to the scalp. It encompasses two widely used waveform configurations: mono-phasic magnetic pulses induce a single current in the brain while biphasic pulses induce at least two currents of inverse direction. As has been shown for the motor cortex, efficacy of repetitive transcranial magnetic stimulation (rTMS) may depend on pulse configuration. In order to clarify this question with regard to visual perception, static contrast sensitivities (sCS) were evaluated before, during, immediately after and 10 minutes after monophasic and biphasic low frequency (1 Hz) rTMS applied to the occipital cortex of 15 healthy subjects. The intensity of stimulation was the phosphene threshold of each individual subject. Using 4 c/d spatial frequency, significant sCS loss was found during and immediately after 10 min of monophasic stimulation, while biphasic stimulation resulted in no significant effect. Ten minutes after the end of stimulation, the sCS values were at baseline level again. However, reversed current flow direction resulted in an increased efficacy of biphasic and decreased efficacy of monophasic stimulation. Our results are in agreement with previous findings showing that primary visual functions, such as contrast detection, can be transiently altered by low frequency transcranial magnetic stimulation. However the effect of modulation significantly depends on the current waveform and direction.
PMID: 12488802

17: Biol Psychiatry. 2002 Dec 1;52(11):1057-65.
Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis.
Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB, Toschi N, Fuchs E, Keck ME.
The German Primate Center, Division of Neurobiology, Gottingen, Germany.
BACKGROUND: Repetitive transcranial magnetic stimulation is increasingly used as a therapeutic tool in psychiatry and has been demonstrated to attenuate the activity of the stress hormone system. Stress-induced structural remodeling in the adult hippocampus may provide a cellular basis for understanding the impairment of neural plasticity in depressive illness. Accordingly, reversal of structural remodeling might be a desirable goal for antidepressant therapy. The present study investigated the effect of chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation treatment on stress hormone regulation and hippocampal neurogenesis. METHODS: Adult male rats were submitted to daily psychosocial stress and repetitive transcranial magnetic stimulation (20 Hz) for 18 days. Cell proliferation in the dentate gyrus was quantified by using BrdU immunohistochemistry, and both the proliferation rate of progenitors and the survival rate of BrdU-labeled cells were evaluated. To characterize the activity of the hypothalamic-pituitary-adrenocortical system, plasma corticotropin and corticosterone concentrations were measured. RESULTS: Chronic psychosocial stress resulted in a significant increase of stress hormone levels and potently suppressed the proliferation rate and survival of the newly generated hippocampal granule cells. Concomitant repetitive transcranial magnetic stimulation treatment normalized the stress-induced elevation of stress hormones; however, despite the normalized activity of the hypothalamic-pituitary-adrenocortical system, the decrement of hippocampal cell proliferation was only mildly attenuated by repetitive transcranial magnetic stimulation, while the survival rate of BrdU-labeled cells was further suppressed by the treatment. CONCLUSIONS: These results support the notion that attenuation of the hypothalamic-pituitary-adrenocortical system is an important mechanism underlying the clinically observed antidepressant effect of repetitive transcranial magnetic stimulation, whereas this experimental design did not reveal beneficial effects of repetitive transcranial magnetic stimulation on adult hippocampal neurogenesis.
PMID: 12460689

18: J ECT. 2002 Dec;18(4):170-81.
Mechanisms and state of the art of transcranial magnetic stimulation.
George MS, Nahas Z, Kozel FA, Li X, Denslow S, Yamanaka K, Mishory A, Foust MJ, Bohning DE.
Psychiatry Departmemt, Center for Advanced Imaging Research, Medical University of South Carolina, Charleston, SC 29425, USA.
In 1985, Barker et al. built a transcranial magnetic stimulation (TMS) device with enough power to stimulate dorsal roots in the spine. They quickly realized that this machine could likely also noninvasively stimulate the superficial cortex in humans. They waited a while before using their device over a human head, fearing that the TMS pulse might magnetically “erase the hard-drive” of the human brain. Almost 10 years later, in 1994, an editorial in this journal concerned whether TMS might evolve into a potential antidepressant treatment. In the intervening years, there has been an explosion of basic and clinical research with and about TMS. Studies are now uncovering the mechanisms by which TMS affects the brain. It does not “erase the hard-drive” of the brain, and it has many demonstrated research and clinical uses. This article reviews the major recent advances with this interesting noninvasive technique for stimulating the brain, critically reviewing the data on whether TMS has anticonvulsant effects or modulates cortical-limbic loops.
PMID: 12468991

19: Brain. 2002 Oct;125(Pt 10):2238-47.
Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.
Liebetanz D, Nitsche MA, Tergau F, Paulus W.
Department of Clinical Neurophysiology, Georg-August University Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.
Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.
PMID: 12244081

20: J Clin Neurophysiol. 2002 Aug;19(4):294-306.
Transcranial magnetic stimulation and epilepsy.
Macdonell RA, Curatolo JM, Berkovic SF.
Department of Neurology, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Transcranial magnetic stimulation has been used to study generalized and focal epilepsies for more than a decade. The technique appears safe and has yielded important information about the mechanisms underlying epilepsy. Transcranial magnetic stimulation findings differ depending on the epilepsy syndrome, lending support to the concept that there are distinct pathophysiologies underlying each condition. In most studies of generalized epilepsies, transcranial magnetic stimulation has indicated a state of relative hyperexcitability of excitatory cortical interneurons and possibly inhibitory interneurons as well, which can be reversed through the actions of anticonvulsant medications. Transcranial magnetic stimulation studies in patients with a seizure focus in the motor cortex indicate increased cortical excitability and reduced inhibition, but in patients with seizure foci located elsewhere the findings are similar to those in generalized epilepsies. Transcranial magnetic stimulation has also been used to study the mode of action of anticonvulsants and may prove to be a useful means of testing the potential for new drugs to act as anticonvulsants. Repetitive transcranial magnetic stimulation may prove to have a therapeutic role by producing long-lasting cortical inhibition after a train of impulses.
PMID: 12436086

21: Neuroreport. 2002 May 7;13(6):809-11.
Neuronal tissue polarization induced by repetitive transcranial magnetic stimulation?
Sommer M, Lang N, Tergau F, Paulus W.
Department of Clinical Neurophysiology, University of Gottingen, Robert-Koch-Str. 40, 37075 Gottingen, Germany.
In a blinded cross-over design, 10 healthy controls received 900 monophasic and biphasic repetitive transcranial magnetic stimuli over the primary motor cortex. Stimulation frequency was 1 Hz, and stimulation intensity 90% of the individual resting motor threshold. Suprathreshold stimuli applied at 0.1 Hz before and after repetitive stimulation controlled for changes in corticospinal excitability. We found a lasting corticospinal inhibition that was significantly more pronounced after monophasic than after biphasic repetitive transcranial magnetic stimulation (motor evoked potential amplitude reduced by 35 +/- 20% vs 12 +/- 37%, mean+/- s.d.). We propose that the current flow in the coil plays a significant role in optimising after effects, and asymmetric current flow may be particularly efficient in building up tissue polarization.
PMID: 11997692

22: Nervenarzt. 2002 Apr;73(4):332-5.
[Modulation of cortical excitability by transcranial direct current stimulation]
[Article in German]
Nitsche MA, Liebetanz D, Tergau F, Paulus W.
Abteilung Klinische Neurophysiolgie, Georg-August-Universitat Gottingen.
Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients’ cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed.
PMID: 12040980

23: Percept Mot Skills. 2002 Apr;94(2):575-94.
Effects of transcranial magnetic stimulation to the reciprocal Ia inhibitory interneurones in the human wrist.
Kato T, Kasai T, Maehara T.
Graduate School for International Development and Cooperation, Hiroshima University, Higashi-Hiroshima, Japan.
In humans, which neural volleys strongly activate the reciprocal Ia inhibitory interneurones have not been clarified via the corticospinal tract or from the muscle spindles. We examined the inhibition from the corticospinal tract and antagonist group Ia fibres to alpha motoneurone pools using the combined method of transcranial magnetic stimulation (TMS) and the standard H-reflex technique. The test stimulus for the forearm H-reflex and the conditioning stimulus to antagonist muscle afferents were applied to the median and radial nerves, respectively. The transcranial magnetic stimulation was applied noninvasively over the left motor cortex. The radial nerve conditioning strongly suppressed the H-reflex rather than the transcranial magnetic stimulation. Transcranial magnetic stimulation-induced inhibition was disinhibited by the conditioning stimulus applied to the median nerve. To estimate the subliminal inhibition produced by the transcranial magnetic stimulation, we used the following method: the radial nerve conditioning was altered among several different intensities, while transcranial magnetic stimulation intensity was fixed at that for which transcranial magnetic stimulation-induced inhibition was observable. A minor subliminal inhibition was observed. These results suggest that the corticospinal excitatory inputs to reciprocal Ia inhibitory interneurones in the human wrist are very weak relative to those of the originating group I muscle afferents.
PMID: 12027355

24: Biol Psychiatry. 2002 Mar 15;51(6):474-9.
Effects of different frequencies of transcranial magnetic stimulation (TMS) on the forced swim test model of depression in rats.
Sachdev PS, McBride R, Loo C, Mitchell PM, Malhi GS, Croker V.
School of Psychiatry, University of New South Wales, and Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
BACKGROUND: Repetitive transcranial magnetic stimulation has been demonstrated in humans as well as in animal models to have an antidepressant effect, but the optimal frequency of stimulation is not known. We examined this question in a rat model of depression. METHODS: Young male Sprague-Dawley rats were allocated to two placebo (restraint and sham transcranial magnetic stimulation), one active control (imipramine), and four transcranial magnetic stimulation groups at 1, 5, 15 and 25 Hz and 1000 stimuli each. The Porsolt Swim Test was performed on day 1 (experiment 1). In an extension (experiment 2), the treatments were repeated on days 2 through 5, and the Swim Test repeated on days 3, 5, and 7. RESULTS: After one treatment session, all transcranial magnetic stimulation groups had significantly reduced immobility times compared with sham stimulation (p =.000), but the higher frequencies (15 and 25 Hz) did not differ significantly from lower (1 and 5 Hz) frequencies. After three sessions, all transcranial magnetic stimulation groups were different from placebo, and the rapid transcranial magnetic stimulation groups had lower immobility times than the slow transcranial magnetic stimulation groups (p =.035). After five sessions, only 15- and 25-Hz groups were different from control, and on day 7, only the 25-Hz group had reduced immobility. There was an overall difference between fast and slow transcranial magnetic stimulation (p =.010), and 1 Hz was different from the other three transcranial magnetic stimulation conditions (p =.016). CONCLUSIONS: Repetitive transcranial magnetic stimulation reduces immobility time in the Forced Swim Test model of depression, suggesting an antidepressant effect, which is evident at a range (1-25 Hz) of frequencies. With repeated administration, the findings suggest that the antidepressant effect of the higher frequencies, as for imipramine, is likely to be sustained, although the model used for this (i.e., repeating the Swim Test) requires further validation.
PMID: 11922882

25: Actas Esp Psiquiatr. 2002 Mar-Apr;30(2):120-8.
[Transcranial magnetic stimulation. Clinical trials in psychiatry: therapeutical use]
[Article in Spanish]
Delgado Baquero Y, Crespo Hervas D, Cisneros S, Lopez-Ibor Alino JJ.
INSALUD Area 4, Miraflores de la Sierra, 28792 Madrid, Spain.
Transcranial magnetic stimulation is the noninvasive application of localized pulsed magnetic field to the surface of the skull, to cause a depolarization of neurons in the underlying cerebral cortex (Daryl E., Bohning PH.D.). Based on Reciprocal Induction (Faraday, 1831), and the Ampere Maxwell Law, according to which electric energy is associated with magnetic energy and vice versa, transcranial magnetic stimulation has been used during the last fifteen years in the diagnosis of Central Nervous System dysfunctions, its safeness and good tolerance having been proven.Since 1876, when Darsonval discovered that the use of a similar apparatus caused vertigo, phosphenes and fainting, thousands of transcranial magnetic stimulation studies have been carried out in the fields of Neurology and Psychiatry. The present is a review of clinical studies carried out in Psychiatry, specifically related to Mood Disorders, Obsessive-Compulsive Disorder and Post traumatic-Stress Syndrome.
PMID: 12028945

26: Biol Psychiatry. 2002 Mar 1;51(5):417-21.
Transcranial magnetic stimulation (TMS) effects on testosterone, prolactin, and corticosterone in adult male rats.
Hedges DW, Salyer DL, Higginbotham BJ, Lund TD, Hellewell JL, Ferguson D, Lephart ED.
Department of Psychology and the Neuroscience Center, Brigham Young University, Provo, Utah 84602, USA.
BACKGROUND: Transcranial magnetic stimulation is a relatively new technique for inducing small, localized, and reversible changes in living brain tissue. Although transcranial magnetic stimulation generally results in no immediate changes in plasma corticosterone, prolactin, and testosterone, it normalizes the dexamethasone suppression test in some depressed subjects and has been shown to attenuate stress-induced increases in adrenocorticotropic hormone in rats. METHODS: In this study, serum corticosterone and testosterone concentrations were assayed in male rats immediately and 3, 6, 9, 12, 24, and 48 hours following a single transcranial magnetic stimulation or sham application. Serum prolactin concentrations were determined immediately and 2 hours following a one-time application of either transcranial magnetic stimulation or sham. RESULTS: Transcranial magnetic stimulation animals displayed significantly lower corticosterone concentrations at 6 and 24 hours following a single application compared with sham-control values. Transcranial magnetic stimulation also resulted in lower corticosterone concentrations numerically but not statistically in transcranial magnetic stimulation animals immediately after application (p =.089). No significant differences were found between groups for serum prolactin or testosterone levels at any given collection time point. CONCLUSIONS: These findings 1) suggest that transcranial magnetic stimulation alters the hypothalamic-pituitary-adrenal stress axis and 2) provide time-course data for the implications of the hormonal mechanism that may be involved in the actions of transcranial magnetic stimulation.
PMID: 11904136

27: Eksp Klin Gastroenterol. 2002;(6):68-74, 114.
[Intraoperative monitoring of transcranial hemodynamics in gerontological patients under general anesthesia in abdominal surgeries]
[Article in Russian]
Fedorovskii NM, Kosachenko NM, Korsunskii SB.
Moscow I.M. Sechenov Medical Academy, Moscow State Clinical Hospital No. 50.
The efficiency of up-to-date medical technologies is closely related to the development of methods and tools of objective control over the patients’ state in the process of treatment. The problem of continuous control over diagnostic information occupies a special place in the medicine of critical states, since the monitoring of the patient’s current state can be of vital importance. The development of tools for the monitoring of the patients’ state is based on the recording of physiological data and their further evaluation with the purpose of determination of indices characterizing the operation of the most important systems of the organism.
PMID: 12685018

28: Semin Clin Neuropsychiatry. 2002 Jan;7(1):42-53.
Neuroimaging in neuropsychiatry.
Gordon E.
Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia.
Advances in physics, computing, and signal processing have provided a range of computerized brain imaging technologies that facilitate examination of the brain as a dynamical system. This article provides a review of brain imaging advances and their application in neuropsychiatry. The review encompasses (1) a description of the imaging technologies used in neuropsychiatry; (2) an outline of their temporospatial complementarity; (3) application to clinical applications; and (4) suggested future directions including an “integrative neuroscience” approach to neuropsychiatry (in which theoretical models, data and information concerning mechanisms are integrated). In the absence of a unified theory of the brain, an integrated approach is presented as one means of exploring converging brain-imaging evidence in relation to neuropsychiatric disorders. Copyright 2002 by W.B. Saunders Company
PMID: 11782890

29: Clin Neurophysiol. 2001 Dec;112(12):2312-9.
Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation.
Guggisberg AG, Dubach P, Hess CW, Wuthrich C, Mathis J.
Department of Neurology, University Hospital, Inselspital, 3010, Bern, Switzerland.
BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.
PMID: 11738204

30: J Child Neurol. 2001 Dec;16(12):891-4.
Subjective reactions of children to single-pulse transcranial magnetic stimulation.
Garvey MA, Kaczynski KJ, Becker DA, Bartko JJ.
Pediatric Movement Disorders Unit, Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1255, USA.
Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children’s subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings.
PMID: 11785502 ]

31: Psychiatry Res. 2001 Nov 30;108(2):123-31.
The navigation of transcranial magnetic stimulation.
Herwig U, Schonfeldt-Lecuona C, Wunderlich AP, von Tiesenhausen C, Thielscher A, Walter H, Spitzer M.
Department of Psychiatry, University of Ulm, Leimgrubenweg 12, D-89070 Ulm, Germany.
Transcranial magnetic stimulation (TMS) is a new method for investigating cortical information processing and for investigating therapeutic applications in psychiatry and neurology. A common problem of most studies in this field regards the localization of the magnetic coil with respect to the cortex. This article reviews the currently used methods and proposes a neuronavigational approach. The method of neuronavigated TMS is described and discussed in detail. It is used to guide the magnetic coil on an individual basis to a structurally or functionally predetermined cortical area while monitoring the location of the coil in relation to the subject’s head in real time. Possible applications of TMS in combination with functional neuroimaging in clinical research within a cognitive neuroscience framework are discussed. Future applications of TMS should take individual anatomy into account, and neuronavigation provides the means to do so.
PMID: 11738546 [PubMed – indexed for MEDLINE]

32: Clin Neurophysiol. 2001 Nov;112(11):2015-21.
The influence of current direction on phosphene thresholds evoked by transcranial magnetic stimulation.
Kammer T, Beck S, Erb M, Grodd W.
Department of Neurobiology, Max-Planck-Institute for Biological Cybernetics, Spemannstrasse 38, D-72076, Tubingen, Germany.
OBJECTIVES: To quantify phosphene thresholds evoked by transcranial magnetic stimulation (TMS) in the occipital cortex as a function of induced current direction. METHODS: Phosphene thresholds were determined in 6 subjects. We compared two stimulator types (Medtronic-Dantec and Magstim) with monophasic pulses using the standard figure-of-eight coils and systematically varied hemisphere (left and right) and induced current direction (latero-medial and medio-lateral). Each measurement was made 3 times, with a new stimulation site chosen for each repetition. Only those stimulation sites were investigated where phosphenes were restricted to one visual hemifield. Coil positions were stereotactically registered. Functional magnetic resonance imaging (fMRI) of retinotopic areas was performed in 5 subjects to individually characterize the borders of visual areas; TMS stimulation sites were coregistered with respect to visual areas. RESULTS: Despite large interindividual variance we found a consistent pattern of phosphene thresholds. They were significantly lower if the direction of the induced current was oriented from lateral to medial in the occipital lobe rather than vice versa. No difference with respect to the hemisphere was found. Threshold values normalized to the square root of the stored energy in the stimulators were lower with the Medtronic-Dantec device than with the Magstim device. fMRI revealed that stimulation sites generating unilateral phosphenes were situated at V2 and V3. Variability of phosphene thresholds was low within a cortical patch of 2x2cm(2). Stimulation over V1 yields phosphenes in both visual fields. CONCLUSIONS: The excitability of visual cortical areas depends on the direction of the induced current with a preference for latero-medial currents. Although the coil positions used in this study were centered over visual areas V2 and V3, we cannot rule out the possibility that subcortical structures or V1 could actually be the main generator for phosphenes.
PMID: 11682339

33: Exp Brain Res. 2001 Nov;141(1):128-32.
Transcranial magnetic stimulation. Which part of the current waveform causes the stimulation?
Corthout E, Barker AT, Cowey A.
Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK.
To investigate the mechanism of transcranial magnetic stimulation (TMS), we compared the directional effects of two stimulators (Magstim 200 and Magstim Super Rapid). First, stimulating visual cortex and facial nerve with occipital mid-line TMS, we found that, for a particular coil orientation, these two stimulators affected a particular neural structure in opposite hemispheres and that, to affect a particular neural structure in a particular hemisphere, these two stimulators required opposite coil orientations. Second, stimulating a membrane-simulating circuit, we found that, for a particular coil orientation, these two stimulators resulted in a peak induced current of the same polarity but in a peak induced charge accumulation of opposite polarity. We suggest that the critical parameter in TMS is the amplitude of the induced charge accumulation rather than the amplitude of the induced current. Accordingly, TMS would be elicited just before the end of the first (Magstim 200) and second (Magstim Super Rapid) phase of the induced current rather than just after the start of the first phase of the induced current.
PMID: 11685417

34: Scand J Psychol. 2001 Jul;42(3):297-305.
Transcranial magnetic stimulation as a tool for cognitive studies.
Bailey CJ, Karhu J, Ilmoniemi RJ.
BioMag Laboratory, Medical Engineering Centre, Helsinki University Central Hospital, Finland.
Transcranial Magnetic Stimulation (TMS) is a tool for the non-invasive stimulation of the human brain. It allows the activation of arbitrary sites of the superficial cortex and, combined with other brain-imaging techniques such as EEG, PET, and fMRI, it can be used to evaluate cortical excitability and connectivity. This is of major importance in, for example, the study of cognitive processes such as language, learning, memory and self-representation, which are thought to be represented in multiple brain areas. The mechanisms of action of TMS are known on a basic level, but its effect on the activation state of brain tissue is still poorly understood. Clinical applications of TMS have also been proposed and guidelines for its safe use drafted.
PMID: 11501743

35: Fukushima J Med Sci. 2001 Jun;47(1):21-32.
Spinal evoked potentials following transcranial magnetic stimulation.
Nemoto J, Sasaki T, Kikuchi Y, Konno Y, Sakuma J, Kodama N.
Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima City, Japan.
Motor evoked potentials by magnetic stimulation is less invasive and causes no pain as opposed to high current electric stimulation. However, the distribution of the magnetic field generated by the round coil has not been fully studied. In this report, we mapped the extent of the magnetic induction flux density, and then the evoked potentials from the spinal cord were investigated by transcranial magnetic stimulation. We also examined the origin of the evoked potentials obtained by the magnetic stimulation. The following results were obtained. The magnetic induction flux density was at its maximum at the edge of the coil. The potentials consisted of a first negative wave and subsequent multiphasic waves. The first negative wave was similar to a response of the subcorticospinal tract in the lower brain stem, while the subsequent multiphasic waves were similar to those of the pyramidal tract. Although magnetic stimulation has certain advantages over electric stimulation, several problems remain to be solved for the monitoring of motor functions in the clinical settings.
PMID: 11764415

36: Biol Psychiatry. 2001 Mar 1;49(5):468-70.
Transcranial magnetic stimulation-induced switch into mania: a report of two cases.
Dolberg OT, Schreiber S, Grunhaus L.
Department of Psychiatry C, Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel.
BACKGROUND: Transcranial magnetic stimulation is a novel, experimental procedure in the treatment of psychiatric disorders, most notably mood disorders. Transcranial magnetic stimulation is currently being widely studied in other applications, and its efficacies and potential side effects are being investigated. METHODS: Transcranial magnetic stimulation was administered five times a week for 4 weeks. RESULTS: In this report, a manic episode followed treatment with transcranial magnetic stimulation in two patients. CONCLUSIONS: Clinicians should be aware that, like with other antidepressive treatments, a switch into mania might complicate treatment with transcranial magnetic stimulation in bipolar patients.
PMID: 11274660

37: Clin Neurophysiol. 2001 Feb;112(2):250-8.
Motor thresholds in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types.
Kammer T, Beck S, Thielscher A, Laubis-Herrmann U, Topka H.
Department of Neurobiology, Max-Planck-Institut for Biological Cybernetics, Spemannstrasse 38, D-72076, Tubingen, Germany.
OBJECTIVES: To evaluate the stimulation effectiveness of different magnetic stimulator devices with respect to pulse waveform and current direction in the motor cortex. METHODS: In 8 normal subjects we determined motor thresholds of transcranial magnetic stimulation in a small hand muscle. We used focal figure-of-eight coils of 3 common stimulators (Dantec Magpro, Magstim 200 and Magstim Rapid) and systematically varied current direction (postero-anterior versus antero-posterior, perpendicular to the central sulcus) as well as pulse waveform (monophasic versus biphasic). The coil position was kept constant with a stereotactic positioning device. RESULTS: Motor thresholds varied consistently with changing stimulus parameters, despite substantial interindividual variability. By normalizing the values with respect to the square root of the energy of the capacitors in the different stimulators, we found a homogeneous pattern of threshold variations. The normalized Magstim threshold values were consistently higher than the normalized Dantec thresholds by a factor of 1.3. For both stimulator types the monophasic pulse was more effective if the current passed the motor cortex in a postero-anterior direction rather than antero-posterior. In contrast, the biphasic pulse was weaker with the first upstroke in the postero-anterior direction. We calculated mean factors for transforming the intensity values of a particular configuration into that of another configuration by normalizing the different threshold values of each individual subject to his lowest threshold value. CONCLUSIONS: Our transformation factors allow us to compare stimulation intensities from studies using different devices and pulse forms. The effectiveness of stimulation as a function of waveform and current direction follows the same pattern as in a peripheral nerve preparation (J Physiol (Lond) 513 (1998) 571).
PMID: 11165526 [PubMed – indexed for MEDLINE]

38: Neurosci Lett. 2000 Dec 15;296(1):61-3.
Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human.
Rosenkranz K, Nitsche MA, Tergau F, Paulus W.
Department of Clinical Neurophysiology, University of Goettingen, Robert-Koch-Strasse 40, 37075, Gottingen, Germany.
Training of a thumb movement in the opposite direction of a twitch in response to transcranial magnetic stimulation (TMS) induces a transient directional change of post-training TMS-evoked movements towards the trained direction. Functional synaptic mechanisms seem to underlie this rapid training-induced plasticity. Transcranial direct current stimulation (tDCS) induces outlasting changes of cerebral excitability, thus presenting as promising tool for neuroplasticity research. We studied the influence of tDCS, applied over the motorcortex during training, on angular deviation of post-training to pre-training TMS-evoked thumb movements. With tDCS of anodal and cathodal polarity the training-induced directional change of thumb movements was significantly reduced during a 10 min post-training interval, indicating an interference of tDCS with mechanisms of rapid training-induced plasticity.
PMID: 11099834

39: Nat Rev Neurosci. 2000 Oct;1(1):73-9.
Transcranial magnetic stimulation and cognitive neuroscience.
Walsh V, Cowey A.
Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK.
Transcranial magnetic stimulation has been used to investigate almost all areas of cognitive neuroscience. This article discusses the most important (and least understood) considerations regarding the use of transcranial magnetic stimulation for cognitive neuroscience and outlines advances in the use of this technique for the replication and extension of findings from neuropsychology. We also take a more speculative look forward to the emerging development of strategies for combining transcranial magnetic stimulation with other brain imaging technologies and methods in the cognitive neurosciences.
Publication Types:
* Review
* Review Literature
PMID: 11252771 [PubMed – indexed for MEDLINE]

40: J Physiol. 2000 Sep 15;527 Pt 3:633-9.
Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.
Nitsche MA, Paulus W.
Department of Clinical Neurophysiology, University of Goettingen, Robert Koch Strasse 40, 37075 Goettingen, Germany.
In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.
PMID: 10990547

41: Int J Neuropsychopharmacol. 2000 Sep;3(3):259-273.
Transcranial magnetic stimulation: applications in basic neuroscience and neuropsychopharmacology.
Lisanby SH, Luber B, Perera T, Sackeim HA.
Introduced 15 years ago, transcranial magnetic stimulation (TMS) is a non-invasive means of stimulating the cortex that has proved to be a unique tool for probing brain-behaviour relationships. While a therapeutic role for TMS in neuropsychiatry is uncertain, the utility of TMS in studying brain function has been demonstrated in diverse neuroscience applications. We review studies in animals on the mechanisms of action of TMS, and present a summary of the applications of TMS in basic neuroscience. TMS is still a relatively young technique, and unanswered questions remain regarding its acute and chronic impact on neural excitability and various aspects of brain function. Nonetheless, recent work with TMS has demonstrated its unique role in complementing other tools for studying brain function. As a brain intervention tool, TMS holds the promise of moving beyond correlative studies to help define the functional role of cortical regions in selected cognitive and affective processes.
PMID: 11343603

42: Fortschr Neurol Psychiatr. 2000 Jul;68(7):289-300.
[The study of central nervous information processing with transcranial magnetic stimulation]
[Article in German]
Herwig U, Schonfeldt-Lecuona C.
Abt. Psychiatrie III, Universitatsklinik Ulm.
In cognitive neuroscience different methods are used to study central nervous information processing. Transcranial magnetic stimulation (TMS) is a non-invasive, well tolerated technique to interfere with cortical neuronal activity with high temporal and fair spatial resolution. In the past 10 years the use of TMS expanded from its application as a diagnostic routine procedure in neurology to the study of various cognitive functions. In this paper the physical and technical aspects of TMS and studies on the effects of single pulse versus repetitive TMS in the motor cortex are reviewed. Then, research on visual perception and attention is presented and studies on higher cognitive functions, such as speech, memory, and emotions are discussed.
PMID: 10945155

43: Laryngoscope. 2000 Jul;110(7):1105-11.
Transcranial magnetic stimulation in acute facial nerve injury.
Har-El G, McPhee JR.
Department of Otolaryngology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
OBJECTIVE/HYPOTHESIS: Available electrodiagnostic tests that are used to evaluate facial nerve injury examine the nerve distal to the stylomastoid foramen; because most facial nerve injuries are within the temporal bone, the tests cannot evaluate the nerve at or across the injury site. The interpretation of these tests depends on the predictability (or unpredictability) of distal degenerative process. Transcranial magnetic stimulation may be able to stimulate the nerve proximal to the injury site. The hypothesis of the present study is that in cases of mild traumatic facial nerve injury where axonal integrity is maintained, proximal stimulation of the nerve using higher than normal stimulus intensities to “overcome” the block at the injury site result in recordable facial nerve activity. STUDY DESIGN: A prospective controlled animal study comparing response to transcranial magnetic stimulation of the facial nerve in the following groups: mild injury, severe injury/transection, and control. METHODS: We studied 44 facial nerves in 22 cats. Fifteen nerves were subjected to mild trauma. Five nerves were severely crushed, 2 nerves were completely transected, and 22 nerves were not traumatized. All nerves were examined with the transcranial magnetic stimulation system before the trauma, immediately after the trauma, and at 3, 8, and 12 weeks after trauma. RESULTS: All nerves in the mild and severe trauma groups showed complete clinical paralysis immediately after trauma. The nerves in the mild trauma group showed significant increase in threshold as well as significant increase in latency for recordable facial muscle response to transcranial magnetic stimulation. Thresholds and latencies decreased gradually within 3 to 12 weeks and returned almost to preinjury levels. This paralleled the return of clinical facial muscle movement. In the severe trauma/transection group, the nerves had no facial muscle response to transcranial magnetic stimulation after trauma. Neither facial muscle response to transcranial magnetic stimulation nor facial muscle movements recovered. CONCLUSIONS: In cats transcranial magnetic stimulation can assess the integrity of the facial nerve after trauma and predict its potential for regeneration. This technique can excite the nerve proximal to the injury site and may play a role in the clinical evaluation of the acute traumatic facial nerve paralysis. It can be used immediately after trauma, because it does not depend on wallerian degeneration to occur.
PMID: 10892678

44: Neurol Res. 2000 Jul;22(5):501-4.
Long latency response of the mentalis muscle following transcranial magnetic stimulation with a circular coil in normal subjects.
Ishikawa M, Takase M, Alberti O, Bertalanffy H.
Department of Neurosurgery, Philipps University Hospital, Marburg, Germany.
Short latency response (SLR), middle latency response and long latency response (LLR) are elicited in facial muscles by transcranial magnetic stimulation. Although it has been said that the LLRs are elicited by the trigeminal nerve stimulation, a trigeminofacial reflex is recorded easily in normal subjects by the electrical stimulation in orbicularis oculi muscles as a blind reflex, but a trigeminal-facial reflex recorded in orbicularis oris, namely a snout reflex, is more difficult to record in normal subjects. The aim of this study is to demonstrate the LLR of lower facial muscles (mentalis muscle) by the transcranial magnetic stimulation, using a circular coil. The transcranial magnetic stimulations were performed over parieto-occipital scalp with frequencies of random and 0.3 Hz in 11 normal subjects and the responses in the mentalis muscle were recorded. The LLR of the mentalis muscle was recorded in all 11 subjects following SLRs. The latency, duration and LLR/SLR ratio were 37.4 msec, 20.3 msec and 9.1%, respectively. The waveform of the LLR varied trial to trial showing habituation with a stimulation of 0.3 Hz. At this time the LLR of the masseter muscle was not recorded following this transmagnetic stimulation. It was suggested that the LLR of the mentalis muscle is recorded by the transcranial magnetic stimulation of the trigeminal nerve with a circular coil. The ease and reliability of their recording make it possible to apply this LLR clinically as well as a blink reflex.
PMID: 10935224

45: Exp Brain Res. 2000 Jun;132(3):384-9.
The excitability of human cortical inhibitory circuits responsible for the muscle silent period after transcranial brain stimulation.
Bertasi V, Bertolasi L, Frasson E, Priori A.
Dipartimento di Scienze Neurologiche e della Visione, Universita di Verona, Italy.
The silent period after transcranial magnetic brain stimulation mainly reflects the activity of inhibitory circuits in the human motor cortex. To assess the excitability of the cortical inhibitory mechanisms responsible for the silent period after transcranial stimulation, we studied, in 15 healthy human subjects, the recovery cycle of the silent period evoked by transcranial and mixed nerve stimulation delivered with a paired stimulation technique. The recovery cycle is defined as the time course of the changes in the size or duration of a conditioned test response when pairs of stimuli (conditioning and test) are used at different conditioning-test intervals. The recovery cycle of the duration of the silent period in the first dorsal interosseous (FDI) muscle during maximum voluntary contraction after transcranial magnetic stimulation was studied by delivering paired magnetic shocks (a conditioning shock and a test shock) at 120% motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The recovery cycle of the silent period in the FDI muscle during maximum voluntary contraction after nerve stimulation was evaluated by paired, supramaximum bipolar electrical stimulation of the ulnar nerve at the wrist (conditioning-test intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the silent period after transcranial magnetic stimulation delivered through the large round coil showed two phases of facilitation (lengthening of the silent period), one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an interposed phase of inhibition (shortening of the silent period) at 80-160 ms. The conditioning magnetic shock left the size of the test motor-evoked potentials statistically unchanged during maximum voluntary contraction. Paired transcranial stimulation with a figure-of-eight coil increased the duration of the test silent period only at short conditioning-test intervals. Conditioning nerve stimulation left the silent period produced by test nerve stimulation unchanged. In conclusion, after a single transcranial magnetic shock, inhibitory circuits in the human motor cortex undergo distinctive short-term changes in their excitability, probably involving different mechanisms.
PMID: 10883387

46: Ugeskr Laeger. 2000 Apr 17;162(16):2310-3.
[Repetitive transcranial magnetic stimulation. A method in the treatment of depressions]
[Article in Danish]
Hansen PE.
Arhus Universitetshospital, Psykiatrisk Hospital i Arhus, Forskningsafdeling for Affektive Sygdomme.
Transcranial magnetic stimulation (TMS) has been used as a diagnostic tool in neurology for more than a decade. Recent research indicates that it when applied repeatedly as repetitive transcranial magnetic stimulation (rTMS) has an antidepressant effect. RTMS is based on the principle of electro-magnetism. An electromagnetic coil placed on the scalp produces a time-varying magnetic field, which gives rise to a current in the proximity of the cerebral cortex. Unlike electroconvulsive therapy (ECT) rTMS does normally not give rise to epileptic seizures and does not require anaesthesia. This review covers a critical summary of the literature on the subject. The results of recent placebo-controlled, randomized trials are promising. However, further investigations are required, before rTMS can be fully integrated in the antidepressant therapeutic armamentarium.
PMID: 10827559

47: Curr Opin Neurobiol. 2000 Apr;10(2):232-7.
Transcranial magnetic stimulation in cognitive neuroscience–virtual lesion, chronometry, and functional connectivity.
Pascual-Leone A, Walsh V, Rothwell J.
Laboratory for Magnetic Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Fifteen years after its introduction by Anthony Barker, transcranial magnetic stimulation (TMS) appears to be ‘coming of age’ in cognitive neuroscience and promises to reshape the way we investigate brain-behavior relations. Among the many methods now available for imaging the activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with brain function. As illustrated by several experiments over the past couple of years, this property of TMS allows us to investigate the relationship between focal cortical activity and behavior, to trace the timing at which activity in a particular cortical region contributes to a given task, and to map the functional connectivity between brain regions.
PMID: 10753803

48: Exp Brain Res. 2000 Mar;131(1):1-9.
Transcranial magnetic stimulation studies of cognition: an emerging field.
Jahanshahi M, Rothwell J.
Department of Clinical Neurology, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
In this short review, we consider the application of transcranial magnetic stimulation (TMS) to the study of cognitive function. Following an introduction to the technique, we consider its possible mechanisms of action. We then review the studies that have applied TMS to the investigation of cognition. In the majority of these investigations, TMS has been applied to disrupt function and demonstrate that a particular cortical area is essential for performance of the task under study. Finally, we highlight pertinent design and procedural issues and consider other types of questions that can be addressed by future TMS studies of cognitive function.
PMID: 10759166

49: Depress Anxiety. 2000;12(3):135-43.
Electroconvulsive therapy in the treatment of neuropsychiatric conditions and transcranial magnetic stimulation as a pathophysiological probe in neuropsychiatry.
McDonald WM, Greenberg BD.
Geriatric Mood Disorders Program, Emory University Department of Psychiatry and Behavioral Sciences, Wesley Woods Geriatric Hospital, 1821 Clifton Rd., NE, Atlanta, GA 30329, USA.
It is a challenging task to review transcranial magnetic stimulation (TMS) studies in neuropsychiatric disorders alongside assessments of longstanding clinical applications of ECT as an empirical treatment. The task is challenging because TMS was developed as a probe of neural mechanisms, whereas, in marked contrast, ECT has been a clinical technique from its inception. Since the onset of modern psychopharmacology, the understanding of the potential applications of ECT to neuropsychiatric disorders is generally restricted to case reports of patients with intractable disease that have had at least a partial response to ECT. Studies of the possible efficacy of TMS in neuropsychiatric conditions have a significant advantage over ECT as the treatments are associated with less morbidity. The only serious known complication in TMS is a risk of seizures that may increase in patients with neuropsychiatric conditions such as course brain disease. Only cortical structures are themselves accessible to TMS using current technology. Present TMS techniques, however, seem capable of affecting activity in deeper brain structures that are functionally linked to cortical brain regions. TMS permits novel explorations of relationships between regional brain activity and symptoms of a number of neuropsychiatric disorders, as well as in research relating activity in functionally related brain regions to modulation of cognition and affective states in healthy individuals. This is particularly true at present because TMS and powerful neuroimaging and neuropsychological tools are all making rapid advances simultaneously.
PMID: 11126188

50: Depress Anxiety. 2000;12(3):178-87.
Animal models of the mechanisms of action of repetitive transcranial magnetic stimulation (RTMS): comparisons with electroconvulsive shock (ECS).
Lisanby SH, Belmaker RH.
Department of Biological Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 126, New York, NY 10032, USA.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive means of brain stimulation with a broad range of basic neuroscience and potential future clinical applications. Recent animal studies have shed some light on the mechanisms of action of rTMS, and broadened our understanding of how this intervention affects brain functioning acutely and chronically. Differences in the physical properties of magnetic and electrical stimulation result in marked disparities in the amount and distribution of electrical current induced in the brain; nevertheless, rTMS shares many of the behavioral and biochemical actions of electroconvulsive shock (ECS) and other antidepressant treatments. rTMS reduces immobility in the Porsolt swim task and enhances apomorphine-induced stereotypy, as does ECS. Although rTMS can induce a seizure when given at high enough doses, most studies have found subconvulsive levels of rTMS to be anticonvulsant. rTMS acutely modulates dopamine and serotonin content and turnover rates. Chronic rTMS modulates cortical beta-adrenergic receptors, reduces frontal cortex 5-HT2 receptors, increases 5-hydroxytryptamine1A receptors in frontal cortex and cingulate, and increases N-methyl-D-aspartate receptors in the ventromedial hypothalamus, basolateral amygdala, and parietal cortex. More work will be needed to clarify and explore the mechanism behind the early suggestions that rTMS may exert long-term-potentiation-like or long-term-depression-like action on hippocampal activity. Finally, rTMS is emerging as yet another intervention, like ECS and other antidepressants, that can regulate gene expression and may have an impact on neuronal viability and synaptic plasticity.
PMID: 11126193

51: J Physiol. 1999 Dec 15;521 Pt 3:565.
Comment on:
* J Physiol. 1999 Dec 15;521 Pt 3:749-59.
Experiments using transcranial magnetic brain stimulation in man could reveal important new mechanisms in motor control.
Edgley SA, Lemon RN.
Department of Anatomy, Cambridge, UK.
PMID: 10601488

52: Arch Neurol. 1999 Dec;56(12):1497-500.
Resetting of orthostatic tremor associated with cerebellar cortical atrophy by transcranial magnetic stimulation.
Manto MU, Setta F, Legros B, Jacquy J, Godaux E.
Department of Neurology, Hopital Erasme, Belgian National Research Foundation, Brussels, Belgium.
OBJECTIVES: To investigate the resetting effects of transcranial magnetic stimulation over motor cortex on orthostatic tremor, characterized by high-frequency electromyographic discharges in weight-bearing muscles, particularly orthostatic tremor (OT) associated with cerebellar cortical atrophy; and to compare our results with those obtained in primary OT, for which transcranial magnetic stimulation does not reset tremor. DESIGN: Study of 3 patients who clinically exhibited a sporadic pancerebellar syndrome associated with isolated cerebellar atrophy and features of OT. SETTING: Research hospital. MAIN OUTCOME MEASURES: Electromyograms and transcranial magnetic stimulation studies with a resetting index calculated on the basis of the timing of measured bursts and predicted bursts for a magnetic stimulus given at increasing delays. RESULTS: Surface electromyographic recordings in weight-bearing muscles showed tremor with a frequency of 14, 15, and 14 Hz in the 3 patients. Transcranial magnetic stimulus was able to reset OT. Resetting index was 0.72. CONCLUSIONS: Transcranial magnetic stimulus resets OT associated with cerebellar cortical atrophy, emphasizing the role of motor cortex in the genesis of OT associated with a cerebellar dysfunction. Our results argue in favor of a distinct pathophysiological mechanism of primary OT and OT associated with cerebellar cortical atrophy.
PMID: 10593305

53: J Neurol Sci. 1999 Nov 15;170(1):51-6.
Transcranial magnetic stimulation compared with upper motor neuron signs in patients with amyotrophic lateral sclerosis.
Schulte-Mattler WJ, Muller T, Zierz S.
Neurologische Klinik und Poliklinik, Martin-Luther-Universitat, Ernst-Grube-Strasse 40, 06097, Halle, Germany.
If patients with amyotrophic lateral sclerosis (ALS) present without upper motor neuron signs (UMNS) they do not meet current ALS research criteria. To compare how sensitively degeneration of upper motor neurons is detected clinically and by transcranial magnetic stimulation, 35 patients with ALS were studied. Nineteen patients had definite UMNS, nine patients had probable UMNS, and seven patients had no UMNS. Cortex, cervical nerve roots, and lumbar plexus were stimulated with a magnetic stimulator. Compound muscle action potentials from abductor digiti minimi and from anterior tibial muscles were recorded with surface electrodes. Responses to transcranial magnetic stimulation were considered abnormal if central motor conduction time was above the 99% upper limits or if there was no response to cortical but to peripheral stimulation. In all patients with definite UMNS central motor conduction was abnormal. In patients with probable UMNS it was abnormal in 67%, and in patients without UMNS it was abnormal in 71%. Abnormality of central motor conduction was neither correlated with the duration nor with the severity of the disease. The high rate of abnormalities of central motor conduction found in patients with ALS but without definite UMNS suggests that, in these patients, the diagnosis of ALS can be made more reliably if transcranial magnetic stimulation studies are performed.
PMID: 10540036

54: Psychiatr Pol. 1999 Nov-Dec;33(6):909-23.
[ECT versus transcranial magnetic stimulation (TMS): preliminary data of computer modeling]
Zyss T, Krawczyk A, Drzymala P, Starzynski J.
Katedry Psychiatrii Collegium Medicum UJ w Krakowie.
The essential issue of electroshock therapy (ECT) is the activity of physical stimulus, i.e., the electric current, on the disturbed structures of the brain. ECT sessions–when chronically applied for evoking antidepressive effects–are responsible for the appearance of excessive incitement in the neuronal net in the brain tissue in a form of self-sustaining after-discharge (SSAD) (convulsive attack characteristic for ECT). The study presents the computer research on basic biophysical phenomena of electroshock therapy (flow of electric current in the structures of the head just before convulsive attack). Five-layer 3-D model of the head was created in OPERA-3D (Vector Fields Ltd., Oxford), general 3 dimensional issues solver. Geometrical dimensions and electrophysical properties of each layer correspond with natural properties. The model was subjected to the action of electric stimulation (parameters identical to those applied in clinical conditions). Analysis of the flow in particular layers revealed the crawling/spreading effect present not only in the scalp layer but also in the layer of cerebrospinal fluid. The effect is conditioned by “deeper situated” lesser conduction of electricity-respectively skull bones, brain tissue. Crawling effect is the reason why only 5-15% of the electricity applied on the surface of the head reaches the surface of the brain. Electro-stimulation examinations also showed that the values of the so called density of the current in layers of brain tissue balanced between 1-10 mA/mm2. The current parameters of ECT were effective in evoking subsequent convulsive attack and safe for the brain tissue. The model was subjected to the action of magnetic stimulation according to the parameters of neurologic technique of transcranial magnetic stimulation (TMS). ELECTRA module was used to solve wire-current issues. The examination showed more regular distribution of current vectors in all layers of the head. The density of cerebral cortex was 0.1-1 mA/mm2, confirming markedly lesser current charge than that observed during ECT. The problem of magnetic stimulation efficacy in irritating deep structures of the brain demands further studies.
PMID: 10776027

55: Philos Trans R Soc Lond B Biol Sci. 1999 Jul 29;354(1387):1229-38.
Transcranial magnetic stimulation: studying the brain-behaviour relationship by induction of ‘virtual lesions’.
Pascual-Leone A, Bartres-Faz D, Keenan JP.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Transcranial magnetic stimulation (TMS) provides a non-invasive method of induction of a focal current in the brain and transient modulation of the function of the targeted cortex. Despite limited understanding about focality and mechanisms of action, TMS provides a unique opportunity of studying brain-behaviour relations in normal humans. TMS can enhance the results of other neuroimaging techniques by establishing the causal link between brain activity and task performance, and by exploring functional brain connectivity.
PMID: 10466148

56: Rev Neurol. 1999 Jul 16-31;29(2):165-71.
[Transcranial magnetic stimulation]
Tormos JM, Catala MD, Pascual-Leone A.
Laboratorio de Estimulacion Magnetica Cerebral, Centro Medico Beth Israel Deaconess, Universidad de Harvard, Boston, MA 02215, USA.
INTRODUCTION: Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS. DEVELOPMENT: The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans. CONCLUSIONS: In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.
PMID: 10528333

57: Arch Gen Psychiatry. 1999 Apr;56(4):300-11.
Comment on:
* Arch Gen Psychiatry. 1999 Apr;56(4):315-20.
Transcranial magnetic stimulation: applications in neuropsychiatry.
George MS, Lisanby SH, Sackeim HA.
Department of Radiology, Medical University of South Carolina, Charleston 29425, USA.
In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing. Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity–transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry’s diagnostic and therapeutic armamentarium.
PMID: 10197824

58: Anesth Analg. 1999 Mar;88(3):568-72.
A comparison of myogenic motor evoked responses to electrical and magnetic transcranial stimulation during nitrous oxide/opioid anesthesia.
Ubags LH, Kalkman CJ, Been HD, Koelman JH, Ongerboer de Visser BW.
Department of Anesthesiology, Academic Medical Center, University of Amsterdam, The Netherlands.
Transcranial motor evoked potentials (tc-MEPs) are used to monitor spinal cord integrity intraoperatively. We compared myogenic motor evoked responses with electrical and magnetic transcranial stimuli during nitrous oxide/opioid anesthesia. In 11 patients undergoing spinal surgery, anesthesia was induced with i.v. etomidate 0.3 mg/kg and sufentanil 1.5 microg/kg and was maintained with sufentanil 0.5 microg x kg(-1) x h(-1) and N2O 50% in oxygen. Muscle relaxation was kept at 25% of control with i.v. vecuronium. Electrical stimulation was accomplished with a transcranial stimulator set at maximal output (1200 V). Magnetic transcranial stimulation was accomplished with a transcranial stimulator set at maximal output (2 T). Just before skin incision, triplicate responses to single stimuli with both modes of cortical stimulation were randomly recorded from the tibialis anterior muscles. Amplitudes and latencies were compared using the Wilcoxon signed rank test. Bilateral tc-MEP responses were obtained in every patient with electrical stimulation. Magnetic stimulation evoked only unilateral responses in two patients. With electrical stimulation, the median tc-MEP amplitude was 401 microV (range 145-1145 microV), and latency was 32.8 +/- 2.3 ms. With magnetic stimulation, the tc-MEP amplitude was 287 microV (range 64-506 microV) (P < 0.05), and the latency was 34.7 +/- 2.1 ms (P < 0.05). We conclude that myogenic responses to magnetic transcranial stimulation are more sensitive to anesthetic-induced motoneural depression compared with those elicited by electrical transcranial stimulation. IMPLICATIONS: Transcranial motor evoked potentials are used to monitor spinal cord integrity intraoperatively. We compared the relative efficacy of electrical and magnetic transcranial stimuli in anesthetized patients. It seems that myogenic responses to magnetic transcranial stimulation are more sensitive to anesthetic-induced motoneural depression compared with electrical transcranial stimulation.
PMID: 10072007

59: Int J Neuropsychopharmcol. 1999 Mar;2(1):31-34.
The influence of rapid-rate transcranial magnetic stimulation (rTMS) parameters on rTMS effects in Porsolt’s forced swimming test.
Zyss T, Mamczarz J, Vetulani J.
Department of Psychiatry, Medical College of the Jagellonian University.
To assess the similarity of the behavioural effects of the rapid transcranial magnetic stimulation (rTMS) to those produced by other antidepressant treatments, in particular to repeated electroconvulsive shock (ECS), we carried out experiments on Wistar rats. The effects of a standard ECS procedure (9 daily treatments; the current parameters: 150 mA, 50 Hz, 0.5 s) were compared with 18 d treatment with rTMS of the same field intensity of 1.6 T but with different stimulation frequency (20 or 30 Hz) and a different number of sessions (9 or 18). Twenty-four hours after the last treatment the forced swimming test was carried out and the immobility time was recorded. The standard ECT reduced the immobility by 50%, the intensive rTMS (90 or 104 K impulses for the whole period of treatment) caused a significant effect, although smaller than that induced by ECT (reduction by 20-30%). The stimulation at 20 Hz required 18 treatment sessions to produce a significant effect, while only 9 sessions with stimulation at 30 Hz were sufficient to produce a comparable result. This suggests that the effectiveness of rTMS may be augmented by increasing the number or frequency of rTMS impulses.
PMID: 11281968

60: Neuropsychologia. 1999 Feb;37(2):207-17.
Transcranial magnetic stimulation and neuroplasticity.
Pascual-Leone A, Tarazona F, Keenan J, Tormos JM, Hamilton R, Catala MD.
Laboratory for Magnetic Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.
PMID: 10080378

61: Electroencephalogr Clin Neurophysiol Suppl. 1999;51:55-64.
Performance of a system for interleaving transcranial magnetic stimulation with steady-state magnetic resonance imaging.
Shastri A, George MS, Bohning DE.
Department of Radiology, Medical University of South Carolina, Charleston 29425, USA.
PMID: 10590936

62: Am J Psychiatry. 1998 Nov;155(11):1608-10.
Comment in:
* Am J Psychiatry. 2000 May;157(5):835-6.
Transcranial magnetic stimulation in mania: a controlled study.
Grisaru N, Chudakov B, Yaroslavsky Y, Belmaker RH.
Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
OBJECTIVE: Left prefrontal transcranial magnetic stimulation has been reported to have ECT-like effects in depression; therefore, the authors planned a study of transcranial magnetic stimulation in mania. METHOD: Sixteen patients completed a 14-day double-blind, controlled trial of right versus left prefrontal transcranial magnetic stimulation at 20 Hz (2-second duration per train, 20 trains/day for 10 treatment days). Mania was evaluated with the Mania Scale, the Brief Psychiatric Rating Scale, and the Clinical Global Impression. RESULTS: Significantly more improvement was observed in patients treated with right than with left prefrontal transcranial magnetic stimulation. CONCLUSIONS: The therapeutic effect of transcranial magnetic stimulation in mania may show laterality opposite to its effect in depression.
PMID: 9812128

63: Electroencephalogr Clin Neurophysiol. 1998 Oct;109(5):397-401.
Comparison of descending volleys evoked by transcranial magnetic and electric stimulation in conscious humans.
Di Lazzaro V, Oliviero A, Profice P, Saturno E, Pilato F, Insola A, Mazzone P, Tonali P, Rothwell JC.
Istituto di Neurologia, Universita Cattolica, Rome, Italy.
OBJECTIVES: The present experiments were designed to compare the understanding of the transcranial electric and magnetic stimulation of the human motorcortex. METHODS: The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of two conscious human subjects. These volleys were termed D- and I waves, according to their latency. Magnetic stimulation was performed with a figure-of-eight coil held over the right motor cortex at the optimum scalp position, in order to elicit motor responses in the contralateral FDI using two different orientations over the motor strip. The induced current flowed either in a postero-anterior or in a latero-medial direction. RESULTS: At active motor threshold intensity, the electric anodal stimulation evoked pure D activity. At this intensity, magnetic stimulation with the induced current flowing in a posterior-anterior direction evoked pure I1 activity. When a latero-medial induced current was used, magnetic stimulation evoked both D and I1 activity. Using electric anodal stimulation, at a stimulus intensity of 9% of the stimulator output above the active motor threshold (corresponding approximately to 1.5 active motor threshold), a small I1 wave appeared only in subject 1. Using magnetic stimulation with a posterior-anterior induced current, at a stimulus intensity of 21% of maximum stimulator output above the active motor threshold (corresponding approximately to 1.8 times threshold in subject 1 and to two times threshold in subject 2), a small D wave appeared in subject 1 but not in subject 2. CONCLUSIONS: Present results demonstrate that, in conscious humans at threshold intensities, electric stimulation evokes D waves and magnetic stimulation (with a posterior-anterior induced current) evokes I waves, while magnetic stimulation (with a latero-medial induced current) evokes both activities.
PMID: 9851296

64: Curr Opin Neurol. 1998 Jun;11(3):205-9.
Brain excitability in migraine: evidence from transcranial magnetic stimulation studies.
Aurora SK, Welch KM.
Henry Ford Hospital and Health Sciences Center, Department of Neurology, Detroit, Michigan, USA.
PMID: 9642537

65: Neurosci Lett. 1998 Apr 24;246(2):97-100.
Modulation of upper extremity motoneurone excitability following noxious finger tip stimulation in man: a study with transcranial magnetic stimulation.
Kofler M, Glocker FX, Leis AA, Seifert C, Wissel J, Kronenberg MF, Fuhr P.
Department of Neurology, University Hospital Innsbruck, Austria.
Little is known about nociceptive reflex mechanisms in the upper limb in humans. To investigate nociceptive effects on spinal motoneurone excitability, a conditioning noxious stimulus was applied to the index finger of five healthy subjects. Motor evoked potentials (MEPs) following contralateral transcranial magnetic stimulation (TMS) were recorded from thenar eminence (TE) and biceps brachii (BB) muscles ipsilateral to finger stimulation. TMS was randomly applied alone or combined with preceding finger stimulation at an interstimulus interval of 100 ms. MEP amplitudes were profoundly suppressed in TE and augmented in BB. We conclude that nociception produces a differential effect on different spinal motoneurone pools, which may be part of a complex protective reflex mechanism in the upper limb of humans.
PMID: 9627189

66: Brain. 1998 Mar;121 ( Pt 3):429-35.
Comment in:
* Brain. 1998 Mar;121 ( Pt 3):397-8.
Transcranial magnetic stimulation over the posterior cerebellum during smooth pursuit eye movements in man.
Ohtsuka K, Enoki T.
Department of Ophthalmology, Sapporo Medical University, School of Medicine, Japan.
Recent neurophysiological experiments in the monkey have demonstrated that the flocculus and the posterior vermis, lobules VIc-VII (oculomotor vermis), are involved in the generation of pursuit eye movements. Whereas the functions of the flocculus in the control of smooth pursuit have been intensively investigated, sufficient data are not available for a profitable discussion of the functions of the oculomotor vermis in the control of smooth pursuit. We previously indicated that the posterior vermis can be electrically stimulated by a focal transcranial magnetic stimulation (TMS) device through the skull in man, and that focal TMS of the posterior vermis can modulate saccadic eye movements. In this study we investigated the effects of cerebellar stimulation on smooth pursuit metrics in man using a focal TMS device. Focal TMS was applied over the posterior cerebellum in an area approximately 7 mm lateral and caudal to the inion, where saccadic eye movements are modulated by TMS, during horizontal smooth pursuit elicited by a step-ramp target with a constant velocity of 15 degrees/s in four normal subjects. The TMS device was triggered after the onset of smooth pursuit during the initial acceleration phase (latency range = 40-80 ms) or the steady-state tracking phase (latency range = 300-340 ms). We investigated the effect of TMS on the velocity and acceleration of smooth pursuit. For smooth pursuit directed ipsilateral to the stimulation side (ipsiversive), focal TMS of the posterior cerebellum produced abrupt acceleration of pursuit in both initial acceleration and steady-state tracking phases. On the other hand, TMS produced abrupt deceleration of contraversive pursuit in both initial acceleration and steady-state tracking phases. These findings suggest that the posterior vermis controls smooth pursuit velocity in a direction-selective manner in both initial acceleration and steady-state tracking phases.
PMID: 9549519

67: Epilepsy Res. 1998 Mar;30(1):11-30.
Transcranial magnetic stimulation: its current role in epilepsy research.
Ziemann U, Steinhoff BJ, Tergau F, Paulus W.
Department of Clinical Neurophysiology, University of Gottingen, Germany.
This paper reviews the current role of transcranial magnetic stimulation (TMS) in epilepsy research. After a brief introduction to the technical principles, the physiology and the safety aspects of TMS, emphasis is put on how human cortex excitability can be assessed by TMS and how this may improve our understanding of pathophysiological mechanisms in epilepsy and the mode of action of antiepileptic drugs (AEDs). Also, potential therapeutical applications of TMS are reviewed. For all aspects of this paper, a clear distinction was made between single-/paired-pulse TMS and repetitive TMS, since these two techniques have fundamentally different scopes and applications.
PMID: 9551841

68: Am J Psychiatry. 1997 Dec;154(12):1752-6.
Comment in:
* Am J Psychiatry. 1999 Apr;156(4):669; discussion 669-70.
Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial.
George MS, Wassermann EM, Kimbrell TA, Little JT, Williams WE, Danielson AL, Greenberg BD, Hallett M, Post RM.
Biological Psychiatry Branch, NIMH, Bethesda, MD 20892, USA.
OBJECTIVE: Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design. METHOD: Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment. RESULTS: Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted. CONCLUSIONS: These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action.
PMID: 9396958

69: Neuropsychologia. 1997 Aug;35(8):1121-31.
Temporal aspects of visual search studied by transcranial magnetic stimulation.
Ashbridge E, Walsh V, Cowey A.
Department of Experimental Psychology, Oxford University, UK.
Transcranial magnetic stimulation was applied over the parietal visual cortex of subjects while they were performing ‘pop-out’ or conjunction visual search tasks in arrays containing eight distractors. Magnetic stimulation had no detrimental effect on the performance of pop-out search, but did significantly increase reaction times on conjunction search when stimulation was applied over the right parietal cortex 100 msec after the onset of the visual display for trials when the target was present. Target absent reaction times were elevated when stimulation was applied 160 msec after array onset. Stimulation had no effect on the number of errors made. The results suggest that a sub-region of the right parietal lobe is important for conjunction search but not for pre-attentive pop-out. The result from target present trials is consistent with timing data from studies of single cells in monkeys and the hypothesis that parietal areas generate a signal that projects back to extrastriate visual areas to enhance the processing of features in a restricted part of the visual field. The timing of the effect indicates that transcranial stimulation disrupts the mechanisms underlying the focal attention necessary for feature binding in conjunction search. The effects of TMS on target absent trials are interpreted in terms of fronto-parietal connections and the role of frontal cortex in decision-making. The results also highlight the efficacy of transcranial magnetic stimulation as a complement to other spatial and temporal imaging techniques.
PMID: 9256377

70: Am J Psychiatry. 1997 Jun;154(6):867-9.
Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.
Greenberg BD, George MS, Martin JD, Benjamin J, Schlaepfer TE, Altemus M, Wassermann EM, Post RM, Murphy DL.
Laboratory of Clinical Science, NIMH, Bethesda, MD 20892-1264, USA.
OBJECTIVE: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms. METHOD: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients’ symptoms and mood were rated for 8 hours afterward. RESULTS: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation. CONCLUSIONS: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.
PMID: 9167520

71: Brain Res. 1997 May 2;755(2):181-92.
Motor cortex involvement during choice reaction time: a transcranial magnetic stimulation study in man.
Romaiguere P, Possamai CA, Hasbroucq T.
Centre National de la Recherche Scientifique, Laboratoire de Neurobiologie Humaine, Marseille, France.
It has been shown that transcranial magnetic stimulation can delay simple reaction time; this happens when the stimulation is delivered during the reaction time and over the cortical area which commands the prime mover of the required response. Although it is agreed that magnetic stimulation could be a useful tool for studying information processing in man, we argue that, because of the use of simple reaction time, the results reported so far are difficult to interpret within this theoretical framework. In the present paper, three experiments are reported. Six subjects participated in experiment 1 in which magnetic stimulation was delivered, at different times, during choice reaction time. The effects of the magnetic stimulation of the cortical area involved in the response (induced current passing forward over the motor representation of the responding hand), were compared to the effects of an electrical stimulation of the median nerve (H-reflex). In a first control experiment (experiment 2a; 5 subjects), the coil was placed over the ipsilateral motor cortex (induced current passing backward over the motor representation of the non-responding hand) thus minimizing the probability to excite the same neural nets as in the first experiment. In a second control experiment (experiment 2b; 4 subjects), the coil was placed a few centimeters away from the subject’s scalp thus ensuring no stimulation of any neural nets. The results show that: (1) the noise and the smarting of the skin associated with the coil discharge produce an intersensory facilitation thereby shortening reaction time (experiment 2a), (2) actually, the noise produced by the stimulation is sufficient to produce such a facilitatory effect (experiment 2b), (3) a stimulation over the area at the origin of the motor command causes a reaction time delay which counteracts this intersensory facilitation effect (experiment 1), (4) in this latter case, the closer the stimulation to the actual overt response, the longer the delay and (5) there is no trace of correlation between the amplitude of the motor evoked potential and the reaction time change.
PMID: 9175886

72: Aust N Z J Psychiatry. 1997 Apr;31(2):264-72.
Transcranial magnetic stimulation as therapy for depression and other disorders.
Kirkcaldie MT, Pridmore SA, Pascual-Leone A.
Department of Anatomy and Physiology, University of Tasmania, Hobart, Australia.
OBJECTIVE: To provide an overview of the progress and prospects of transcranial magnetic stimulation as a psychiatric therapy for depression. METHOD: Published and unpublished studies of the usefulness of transcranial magnetic stimulation as a therapy for depression were assessed, and characterised in terms of a consistent measure of dosage. Additional information was obtained through correspondence, personal meetings and visits to facilities. RESULTS: Transcranial magnetic stimulation, a means for inducing small regional currents in the brain, has been used in clinical neurology for some time, and can be used on conscious subjects with minimal side-effects. Early researchers noticed transient mood effects on people receiving this treatment, which prompted several inconclusive investigations of its effects on depressed patients. More recently, knowledge of functional abnormalities associated with depression has led to trials using repetitive transcranial magnetic stimulation to stimulate underactive left prefrontal regions, an approach which has produced short-term benefits for some subjects. The higher dosage delivered by high-frequency repetitive transcranial magnetic stimulation appears to produce greater benefits; scope exists for more conclusive studies based on extended treatment periods. CONCLUSIONS: Repetitive transcranial magnetic stimulation is a promising technology. The reviewed evidence indicates that it may be useful in the treatment of depression, and perhaps other disorders which are associated with regional hypometabolism. Should repetitive transcranial magnetic stimulation prove an effective, non-invasive, drug-free treatment for depression, a range of disorders could be similarly treatable.
PMID: 9140635

73: Electroencephalogr Clin Neurophysiol. 1996 Dec;101(6):478-82.
The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain.
Kaneko K, Kawai S, Fuchigami Y, Morita H, Ofuji A.
Department of Orthopedic Surgery, University of Yamaguchi, School of Medicine, Japan.
Evoked spinal cord potentials (ESCPs) from the cervical epidural space and motor evoked potentials (MEPs) from the hand muscles were recorded simultaneously in 6 subjects following transcranial magnetic stimulation in two different coil orientations on motor cortex. The onset latency of the MEPs was approximately 1 ms shorter when the induced current flowed in a latero-medial direction (L-M stimulation) on the motor cortex as compared to a postero-anterior direction (P-A stimulation). Hence, L-M stimulation elicited an earlier component of the ESCPs than that induced by P-A stimulation. During general anesthesia with Sevoflurane, only the first component of the ESCPs could be elicited routinely following L-M stimulation. In contrast, all components of the ESCPs were dramatically attenuated following P-A stimulation. Moreover, first component latency of the ESCPs induced by L-M stimulation was almost the same as that induced by transcranial anodal electrical stimulation. These results suggest that if the induced current following transcranial magnetic stimulation flows in a latero-medial direction on motor cortex, it preferentially stimulates the corticospinal tract non-synaptically (producing a D-wave). However, if the induced current flows in a postero-anterior direction, it preferentially stimulates the corticospinal tract trans-synaptically (producing I-waves). Therefore, the direction of magnetically induced current is crucial in determining corticospinal excitability in the human brain.
PMID: 9020819

74: J Neurol Sci. 1996 Jul;139(1):131-6.
Effect of stimulus intensity and voluntary contraction on corticospinal potentials following transcranial magnetic stimulation.
Kaneko K, Kawai S, Fuchigami Y, Shiraishi G, Ito T.
Department of Orthopedic Surgery, University of Yamaguchi, School of Medicine, Japan.
Following magnetic transcranial stimulation, motor-evoked potentials (MEPs) from the abductor digiti minimi muscle, and evoked spinal cord potentials (ESCPs) from the cervical epidural space were recorded simultaneously in 9 subjects in the awake and anesthetized condition. In the awake condition, during voluntary contraction, one (n = 5) or two (n = 4) components of the ESCPs were elicited at the threshold stimulus intensity of the MEPs. As the stimulus intensity increased, an early response (n = 7) and multiple late components were recorded. The first component at high stimulus output (average 80%) preceded the small potentials elicited at threshold stimulus intensity. The latency of each component of the ESCPs during voluntary contraction was the same as that during the resting condition. In addition, the enhancement of amplitude of the ESCPs during voluntary contraction was not significant compared with that recorded at rest. During general anesthesia with volatile anesthetics, the first component of the ESCPs could be elicited at high stimulus intensity, but later components were markedly attenuated. In paired transcranial magnetic stimulation, the amplitude of this first potential following the test stimulus completely recovered within the 2 ms interstimulus interval. From these results, we hypothesized that the first component was generated non-synaptically (D-wave), but later components were generated transsynaptically (I-waves). Compound muscle action potentials (CMAPs) and F-waves also were recorded following supramaximal ulnar nerve stimulation at the wrist. Peripheral conduction time, which included synaptic delay in spinal motor neurons, was measured as follows (latency of CMAPs+ latency of F-wave + 1)/2 (ms). The central motor conduction time (CMCT) was measured by subtracting the peripheral conduction time from the onset latency of the MEP at high stimulus intensity in the awake state. During voluntary contraction, the calculated CMCT (4.9 +/- 1.0 ms) was the same as the onset latency of the second component of the ESCPs (I-wave, 4.3 +/- 0.2 ms) recorded from the C6-C6/7 epidural space. These results suggest that transcranial magnetic stimulation generates I-waves preferentially when the stimulus intensity was set at just the threshold level of the MEPs during voluntary contraction in the awake condition. At high stimulus intensity, transcranial magnetic stimulation can elicit both D- and I-waves, but most spinal cells require I-wave activation to fire. Facilitatory effects of voluntary contraction on the muscle response following transcranial magnetic stimulation mainly originates at a spinal level.
PMID: 8836984

75: Fortschr Neurol Psychiatr. 1996 Jun;64(6):205-11.
[Triggered transcranial magnetic stimulation in high cognitive functions]
[Article in German]
Kammer T, Spitzer M.
Psychiatrische Universitatsklinik Heidelberg.
Transcranial magnetic stimulation (TMS) can be triggered and thereby allows the reversible manipulation of cortical information processing. A magnetic field is induced by a coil which produces a current which has an excitatory or inhibitory effect on the underlying cortex. Triggered TMS has been used to assess the visual system and lately the method was also applied to higher cognitive functions. The method has good spatial and temporal resolution and it can be combined with other neuroscience and experimental psychological methods. We provide an overview on TMS research and present the results of a study. Possible applications and limitations of the method are discussed with respect to basic research as well as diagnostic and therapeutic implications.
PMID: 8766993

76: Neurosci Lett. 1996 May 24;210(1):45-8.
Direct and indirect activation of human corticospinal neurons by transcranial magnetic and electrical stimulation.
Nakamura H, Kitagawa H, Kawaguchi Y, Tsuji H.
Department of Orthopedic Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Corticospinal volleys and surface electromyographic (EMG) responses evoked by magnetic and electrical transcranial stimulation were recorded simultaneously in three conscious human subjects. For magnetic stimulation, the figure-of-eight coil was held on the hand motor area either with the induced current through the brain flowing in a postero-anterior direction (P-A stimulation) or in a latero-medial direction (L-M stimulation). For electrical stimulation, the anode was placed 7 cm lateral to the vertex and cathode at the vertex (anodal stimulation). The P-A stimulation that was generally used preferentially evoked I waves, whereas the L-M and anodal stimulation preferentially evoked D wave. The results suggested that the mode of activation by transcranial magnetic stimulation altered, depending on its current direction, and the difference between P-M magnetic and electrical stimulation can be explained by the context of the D and I hypothesis.
PMID: 8762188

77: Neurol Neurochir Pol. 1996 May-Jun;30(3):399-408.
[Transcranial magnetic stimulation neurophysiological and biochemical response in man]
[Article in Polish]
Zyss T, Witkowska B.
Katedry Psychiatrii Collegium Medicum Uniwersytetu Jagiellonskiego w Krakowie.
Ten adult volunteers had EEG recordings and serial serum prolactin/cortisol estimations performed during repetitive transcranial magnetic stimulation. No significant changes in either the hormone values or in the EEG traces were detected.
PMID: 8965974 [PubMed – indexed for MEDLINE]

78: Neuroreport. 1996 Feb 29;7(3):734-6.
Functional magnetic resonance imaging shows localized brain activation during serial transcranial stimulation in man.
Brandt SA, Davis TL, Obrig H, Meyer BU, Belliveau JW, Rosen BR, Villringer A.
Department of Neurology, Charite, Humboldt-Universitat, Berlin, Germany.
Area and depth penetration of transcranial stimulation methods such as transcranial electrical stimulation (TES) are poorly defined. We investigated the feasibility of a simultaneous TES and fMRI measurement. The aim was to compare the signal intensity changes measured using BOLD fMRI during sequential finger movement with the signal response during artificial transcranial stimulation. Tes induced contralateral finger contractions and in T2* weighted images a transient signal increase was observed in the area underlying the electrodes. Compared with the signal obtained during sequential finger movements, the area activated by TES was more localized, signal amplitude, was smaller and there was no post-stimulus undershoot. These data indicate that TES induces a local blood flow increase associated with a drop in the concentration of deoxyhaemoglobin.
Publication Types:
* Clinical Trial
PMID: 8733733 [PubMed – indexed for MEDLINE]

79: Electroencephalogr Clin Neurophysiol. 1996 Feb;101(1):48-57.
Corticospinal direct response to transcranial magnetic stimulation in humans.
Fujiki M, Isono M, Hori S, Ueno S.
Department of Neurosurgery, Oita Medical University, Japan.
The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5-72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recordings of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.
PMID: 8625877 [PubMed – indexed for MEDLINE]

80: Spine. 1995 Oct 15;20(20):2233-9.
Magnetic-evoked compound muscle action potential neuromonitoring in spine surgery.
Kitagawa H, Nakamura H, Kawaguchi Y, Tsuji H, Satone T, Takano H, Nakatoh S.
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan.
STUDY DESIGN. Muscle action potentials elicited by paired transcranial magnetic stimulation were recorded during spine surgery in 34 patients. Anesthesia was based on ketamine and fentanyl. OBJECTIVES. To evaluate the optimal anesthetic regimen to be used for transcranial magnetic stimulation, and to determine the clinical import of magnetic-evoked compound muscle action potentials. SUMMARY OF BACKGROUND DATA. Muscle action potential by transcranial magnetic stimulation has been difficult to record under general anesthesia. Ketamine is known to not suppress the muscle responses, although no conclusive clinical study has been reported. METHODS. Paired transcranial magnetic stimulation was delivered as muscle action potentials were recorded from the limb musculature. RESULTS. Neuromonitoring was reliable in 56% of total cases and in 82% of the recent cases after reducing fentanyl dosage. Paired magnetic stimulation was an excellent facilitation technique for reliable monitoring. At higher dosages, fentanyl and ketamine decreased the reproducibility of the responses. CONCLUSIONS. Magnetic-evoked compound muscle action potential neuromonitoring is a sensitive and selective motor pathway monitoring method that covers the entire motor pathway, including the white and gray matter of the spinal cord. Ketamine-based anesthesia is a good choice for this purpose.
PMID: 8545718 [PubMed – indexed for MEDLINE]

81: Rinsho Byori. 1995 Sep;43(9):965-70.
[Excitability of motor cortex with transcranial magnetic double stimulation in the intact man]
[Article in Japanese]
Yoshino A, Yokota T.
Department of Medical Technology, Tokyo Medical and Dental University.
To evaluate the excitability of central motor tract, we studied a transcranial magnetic double stimulation with short conditioning-test (C-T) interval of 1-10ms in eight normal volunteers. In addition, H-reflex of the forearm muscle was used to study the effect of the magnetic cortical conditioning stimulus on alpha-motoneuron, and the test response evoked by electrical cortical stimulation was also used to examine the effect of the magnetic cortical conditioning stimulus. The subthreshold conditioning and suprathreshold test stimuli were applied, and compound muscle responses were recorded in the relaxed abductor pollicis brevis muscle. There was a decrease of the test response size by the conditioning stimulus at C-T interval of 1-5ms. This attenuation was probably caused by intracortical inhibition. Because the identical magnetic cortical conditioning stimulus produced increase in H-reflex size. Moreover, the test response evoked by electrical cortical stimulus was not suppressed by the magnetic cortical conditioning stimulus; whereas, response evoked by the magnetic cortical test stimulus was suppressed at C-T intervals of 2ms. With the technique of transcranial magnetic double stimulation, therefore, it is possible to evaluate the inhibitory function in the motor cortex. The technique may be of use for pathophysiology, diagnosis and estimation of treatment in the diseases.
Publication Types:
* Clinical Trial
PMID: 7474462 [PubMed – indexed for MEDLINE]

82: Ann Neurol. 1995 Aug;38(2):264-7.
Increased sensitivity to ipsilateral cutaneous stimuli following transcranial magnetic stimulation of the parietal lobe.
Seyal M, Ro T, Rafal R.
Department of Neurology, University of California, Davis, Sacramento, USA.
Transcranial magnetic stimulation of the sensorimotor cortex results in decreased sensitivity of threshold electrical stimuli to fingers of the contralateral hand. It has been suggested that one factor contributing to neglect contralateral to a unilateral parietal lesion is a release of the normal hemisphere from reciprocal interhemispheric inhibition by the damaged hemisphere. Consistent with this account, the current study demonstrated that transcranial magnetic stimulation over the parietal cortex results in increased sensitivity to cutaneous stimulation ipsilateral to the stimulation. The likely mechanism is a transcranial magnetic stimulation-induced transient dysfunction of the ipsilateral parietal cortex that then results in disinhibition of the contralateral parietal cortex.
PMID: 7654076 [PubMed – indexed for MEDLINE]

83: No To Shinkei. 1995 Apr;47(4):363-7.
[Transcranial magnetic stimulation of the accesory nerve–investigation of the site and mechanism of excitation in the cat]
[Article in Japanese]
Gotoh K, Ohira T, Ishihara M, Kobayashi M, Nakamura A, Toya S, Takase M.
Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
The site where transcranial magnetic stimulation excites the accessory nerve was studied in 5 cats. Transcranial magnetic stimulation of the accessory nerve was recorded from the right trapezius. The accessory nerve was stimulated electrically at the C1 level, jugular tubercle and jugular foramen. The latencies of the compound muscle action potentials (CMAPs) for each portion were measured and compared with the magnetic response, which was coincidental with that of the jugular tubercle. The accessory nerve was then transected in steps distally from the C1 level, and CMAPs following magnetic stimulation were recorded at each step. The CMAPs disappeared following the nerve transection at the jugular tubercle. The results of both approaches in this study conclude that transcranial magnetic stimulation excites the accessory nerve at jugular tubercle. This stimulation site was anatomically coincidental with that of the facial nerve and trigeminal nerve in being right before the point where the nerve bends. Following the accessory nerve transection at the C1 level, the amputation stump was moved cranially, and CMAPs disappeared. CMAPs recorded after the accessory nerve was returned to its original position. These examinations suggested that sudden alteration of the traveling lie of the nerve participates in the mechanism of transcranial magnetic stimulation.
PMID: 7772404 [PubMed – indexed for MEDLINE]

84: Electroencephalogr Clin Neurophysiol. 1994 Dec;93(6):417-20.
Facilitation and disfacilitation of muscle responses after repetitive transcranial cortical stimulation and electrical peripheral nerve stimulation.
Claus D, Brunholzl C.
Department of Neurology, University of Erlangen-Nuremberg, Germany.
Compound muscle responses were recorded after repetitive electrical stimulation of the peripheral nerve and after transcranial electrical and magnetic stimulation in 5 healthy persons. The enlargement of the second response at intervals between 30 and 50 msec is more pronounced after cortical magnetic and electrical stimulation than after peripheral nerve stimulation. This difference is believed to be a result of facilitatory mechanisms involving the summation of effects from conditioning and test stimuli along the entire central motor pathway. The facilitation at 10 msec interval, which is only seen after magnetic, but not after electrical transcranial stimulation could indicate an intracortical mechanism.
PMID: 7529690 [PubMed – indexed for MEDLINE]

85: Exp Brain Res. 1994;101(1):153-8.
Quantification of D- and I-wave effects evoked by transcranial magnetic brain stimulation on the tibialis anterior motoneuron pool in man.
Awiszus F, Feistner H.
Orthopadische Universitatsklinik, Magdeburg, Germany.
Transcranial stimulation in man evokes multiple descending volleys in the spinal cord giving rise to multiple subpeaks in a peri-stimulus-time histogram (PSTH) obtained from a cross-correlation of motor unit discharges with transcranial stimuli. The first volley is termed the D wave, as it is assumed to be evoked by direct excitation of pyramidal tract neurons, whereas the subsequent I waves appear to be generated by indirect excitation of the pyramidal tract neurons via cortical interneurons. It was the aim of this study to obtain an estimate of the effect induced by multiple volleys evoked by transcranial magnetic stimulation on the entire motoneuron pool of the tibialis anterior in awake subjects. A considerable part of a particular motoneuron pool was investigated by sampling responses of a large number (at least 19) from each muscle investigated. In total, three tibialis anterior muscles from three normal volunteers were studied. From each of the 63 units included in this study, a PSTH to 100 transcranial magnetic stimuli and a PSTH to 100 electrical stimuli given to the peroneal nerve were compiled. From the motor unit response to the peripheral nerve stimulation, the latency of the single-unit H reflex peak was obtained. This yielded, the timing of the subpeaks in response to the magnetic stimulation relative to the timing of the H reflex of the same unit, thus eliminating the influence of the peripheral conduction time from the motoneuron to the recording electrode. It was found that 50 (79%) of the motor units exhibited at least two subpeaks in response to the cortical stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 7843294 [PubMed – indexed for MEDLINE]

86: No To Shinkei. 1993 Jul;45(7):655-60.
[Transcranial magnetic stimulation of the facial nerve–identification of the actual excitation site in the cat]
[Article in Japanese]
Gotoh K, Ohira T, Namiki J, Ajimi Y, Ishikawa M, Shiobara R, Toya S, Takase M.
Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
The site where transcranial magnetic stimulation excites the facial nerve was studied in 6 cats. Transcranial magnetic stimulation of the facial nerve was recorded from the left mentalis muscle. A figure-of-eight shaped magnetic coil was used, and coil induction direction had more influence on the facial nerve evoked compound muscle action potentials (CMAPs) than the coil position. No change could be detected in the CMAPs before and after craniotomy, after cerebellar lobectomy and after exposure of the facial nerve in the facial canal. The facial nerve was stimulated electrically at the porus, meatal portion, geniculum and horizontal portion. The latencies of the CMAPs for each portion were measured and compared with the magnetic response, which was coincidental with that of the meatal portion. The facial nerve was then transected distally from the porus, and CMAPs following magnetic stimulation were recorded at each step. The CMAPs disappeared when the nerve was transected at the fundus. The results of both approaches in this study led to the conclusion that transcranial magnetic stimulation excites the facial nerve at the meatal portion.
PMID: 8398386 [PubMed – indexed for MEDLINE]

87: Electroencephalogr Clin Neurophysiol. 1993 Apr;89(2):131-7.
Transcranial electric and magnetic stimulation of the leg area of the human motor cortex: single motor unit and surface EMG responses in the tibialis anterior muscle.
Priori A, Bertolasi L, Dressler D, Rothwell JC, Day BL, Thompson PD, Marsden CD.
MRC Human Movement and Balance Unit, Institute of Neurology, London, UK.
We compared single motor unit and surface EMG responses in the active right tibialis anterior following anodal electrical or magnetic stimulation of the motor cortex over the vertex. Magnetic stimulation used a monophasic current pulse through a circular coil centred 3 cm anterior to the vertex. Lowest threshold magnetic stimulation occurred when the current in the coil flowed from the left to the right side at the posterior rim of the coil. Such stimulation produced single unit and surface EMG responses which had the same latency as those produced by anodal electric stimulation. If the direction of the magnetic stimulating current was reversed, response latencies became more variable from unit to unit, and on average they occurred 1.0 +/- 0.5 msec later. In single motor units anodal and magnetic post-stimulus time histogram (PSTH) peaks had the same duration. This was similar to the duration of the PSTH peaks produced by a single low intensity stimulus given to the common peroneal nerve. We conclude that magnetic stimulation can produce direct activation of corticospinal neurones to the tibialis anterior if the direction of induced current flow is optimal. This projection is likely to be either monosynaptic or oligosynaptic.
PMID: 7683603 [PubMed – indexed for MEDLINE]

88: Neurosurgery. 1993 Mar;32(3):414-6; discussion 415-6.
Comment in:
* Neurosurgery. 1994 Dec;35(6):1186-8.
Transcranial magnetic stimulation excites the root exit zone of the facial nerve.
Tokimura H, Yamagami M, Tokimura Y, Asakura T, Atsuchi M.
Department of Neurosurgery, Faculty of Medicine, University of Kagoshima, Japan.
The actual site of excitation of the facial nerve by transcranial magnetic stimulation was investigated in five patients with hemifacial spasm who underwent microvascular decompression. The facial nerve was stimulated preoperatively and intraoperatively by transcranial magnetic stimulation and intraoperatively by electrical stimulation at its root exit zone with a minimum of surgical invasion of the facial nerves. The onset latency of compound muscle action potentials recorded from the nasalis muscle was 5.06 +/- 0.44 ms by magnetic stimulation and 5.08 +/- 0.43 ms by electrical stimulation. The latency difference was 0.06 +/- 0.08 ms. Therefore, transcranial magnetic stimulation was basically the same as electrical stimulation in onset latency. From this study, it appears that the root exit zone of the facial nerves is stimulated by transcranial magnetic stimulation.
PMID: 8384326 [PubMed – indexed for MEDLINE]

89: Neurosci Lett. 1993 Feb 5;150(1):21-4.
Activation of high-threshold motor units in man by transcranial magnetic stimulation.
Schubert M, Dengler R, Wohlfarth K, Elek J, Stallkamp A.
Department of Neurology, University of Bonn, FRG.
Motor units (MUs) with low voluntary recruitment thresholds are the first to be activated by transcranial magnetic stimulation. It is not clear, however, if high-threshold MUs can also be activated and if they contribute to motor evoked potentials (MEPs). We therefore studied 11 high-threshold motor units in the first dorsal interosseous muscle of 11 healthy subjects. Voluntary recruitment thresholds ranged from 22 to 41% (29.5 +/- 5.6%; mean +/- S.D.) of maximal muscle force. When MUs were driven at their recruitment thresholds, transcranial magnetic stimuli were applied to the vertex. Peri-stimulus time histograms of MU discharges were constructed. All MUs studied revealed a period of increased firing probability at 19-27 ms after the stimulus (primary peak). Stimulus intensities were lower by 10-57% of the maximal stimulator output than required to produce near maximal MEPs in conventional surface EMG recordings in the same subjects. We conclude that high-threshold MUs can be activated by transcranial magnetic stimulation and that they contribute to conventionally recorded MEPs.
PMID: 8469397 [PubMed – indexed for MEDLINE]

90: Laryngorhinootologie. 1993 Jan;72(1):32-5.
[Transcranial magnetic stimulation in perioperative damage to the facial nerve]
[Article in German]
Kotterba S, Tegenthoff M, Malin JP.
Neurologische Klinik und Poliklinik, Ruhr-Universitat Bochum, BG-Krankenanstalten Bergmannsheil.
5 patients (3 men, 2 women, aged from 28 to 51 years) with unilateral facial palsy after surgery of a cerebellopontine angle tumour have been investigated by transcranial magnetic stimulation. The purpose was to evaluate the prognostic aspects of this method, which was compared with the electrical stimulation of the facial nerve and the elicitation of an orbicularis-oculi reflex. The components of the blink reflex were absent in all cases. In 3 patients electrical stimulation was possible (compound muscle action potentials were delayed). With transcranial magnetic stimulation ipsilateral short-latency and contralateral long-latency responses (stimulation of the cortex) were elicited and registered from the M. mentalis as well as 3 times from the M. orbicularis oculi. The short-latency response revealed no prognostic aspects. Despite the missing response, a recovery was possible. Long-latency responses could be evoked in all patients. The extent of delay in latency was strongly correlated with clinical improvement of the paresis. Interestingly, this correlation could also be observed in the single rami of the facial nerve when two muscles were investigated in a patient. Transcranial magnetic stimulation is an important improvement in electrophysiological diagnosis of perioperative lesion of facial nerve to prove continuity of the nerve and to evaluate the clinical course.
PMID: 8439354

91: Electromyogr Clin Neurophysiol. 1992 Oct-Nov;32(10-11):521-30.
Inadequacy of transcranial magnetic stimulation in the neurophysiologic assessment of Bell’s palsy.
Cocito D, De Mattei M.
Department of Neurologic Emergency, Ospedale Molinette, Turin.
Transcranial magnetic stimulation is a non-invasive procedure which to stimulate the brain cortex and the peripheral nerve pathways. A new technique was recently introduced to record the muscle action potential of facial muscles by means of transcranial magnetic stimulation of the facial nerve. The experimental data that was obtained indicate that this technique allows to stimulate the facial nerve above the stylomastoid foramen: a greater tract of the nerve can therefore be explored than what was possible with the traditional electrical stimulation at the mastoid. Until now no comparison data was available on the clinical usefulness of the two methods. We decided to study 14 normal controls and 26 patients suffering from unilateral idiopathic facial palsy (Bell’s palsy) and to submit these two groups to magnetic transcranial stimulation and electrical stimulation of the facial nerve in the mastoid region, to the purpose of observing where the nerve is stimulated by the magnetic impulse and which of the two techniques can be of accurate prognostic value in the study of the evolution of the clinical lesion. The electromyographic responses were elicited by the electrical stimulation at the mastoid and by transcranial stimulation after positioning the coil on the parieto-occipital scalp. A recording was taken from the ipsilateral orhicularis oculi muscle utilising two cupped electrodes. The latency and the amplitude of the compound muscle action potential were measured bilaterally in order to compare the results obtained on both the affected and the healthy sides. The patients were scheduled to two neurophysiological and clinical evaluations at about 30 days interval one from the other: the first test was not carried out before 20 days from the onset of the deficit; further clinical examination was carried out only 6 months later. The analysis of the results obtained in the normal controls submitted to transcranial magnetic stimulation indicate that the nerve is activated at the point where it originates from the brainstem. The study carried out showed that transcranial magnetic stimulation of the facial nerve, does not provide data which can be correlated to the clinical situation observed at the time of the study; furthermore, transcranial magnetic stimulation does not supply any prognostic data on the clinical evolution of the lesion.
PMID: 1446584

92: Rinsho Shinkeigaku. 1992 Apr;32(4):385-7.
[Transcranial magnetic stimulation of the facial nerve]
[Article in Japanese]
Tokimura H, Nomaguchi S, Hirahara K, Kadota K, Asakura T.
Department of Neurosurgery, Faculty of Medicine, University of Kagoshima.
It was the object of the present study to determine whether transcranial facial nerve stimulation using a magnetic coil can be clinically applicable, and to find the site where the facial nerve is best stimulated. A magnetic coil was placed over the parieto-occipital skull of the subjects for stimulation, and the facial nerve was electrically stimulated in its intracranial and peripheral courses. Then an electromyogram was recorded from the nasalis muscle of the face on the stimulated side. In 9 healthy volunteers, 18 facial nerves received magnetic and electric stimuli in the peripheral region, and the actual site of stimulation was estimated from the conduction velocity of the nerve. The conduction velocity was 56.6 +/- 4.8 m/s, and the latency between CMAPs for electric at the magnetic stimuli to the posterior tragus was 1.23 +/- 0.21 ms. Therefore, the position stimulated by magnetic coil was estimated to be 70.0 +/- 11.4 mm central to the posterior tragus, i.e., near the root exit zone. In two patients undergoing surgery in the cerebellopontine angle, transcranial magnetic stimulation and electrical stimulation of the intracranial facial nerve were compared intraoperatively. The CMAP produced by transcranial magnetic stimulation coincided closely with that produced by direct electrical stimulation of the root exit zone. Thus, the facial nerve was stimulated at the root exit zone, and this method could be expected to be useful for evaluation of disorders of the intracranial facial nerve.
PMID: 1395323

93: Neurology. 1992 Mar;42(3 Pt 1):647-51.
No evidence of hearing loss in humans due to transcranial magnetic stimulation.
Pascual-Leone A, Cohen LG, Shotland LI, Dang N, Pikus A, Wassermann EM, Brasil-Neto JP, Valls-Sole J, Hallett M.
Human Cortical Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Prompted by the description of hearing loss in rabbits exposed to the acoustic artifact of magnetic stimulation, we compared the results of audiologic studies before and after exposure to transcranial magnetic stimulation in humans. We found no evidence of temporary or permanent threshold shifts in any of the subjects, even in those exposed to transcranial magnetic stimulation repeatedly for several years. Risk of hearing loss from the acoustic artifact of magnetic stimulation, as evaluated by audiograms, tympanograms, acoustic reflexes, and auditory evoked potentials, seems to be small in humans.
PMID: 1549231

94: Electroencephalogr Clin Neurophysiol. 1991 Oct;81(5):389-96.
Electrical and magnetic transcranial stimulation in patients with corticospinal damage due to stroke or motor neurone disease.
Berardelli A, Inghilleri M, Cruccu G, Mercuri B, Manfredi M.
Dipartimento Scienze Neurologiche, Universita La Sapienza, Rome, Italy.
Twenty patients with hemiplegia and 13 patients with motor neurone disease were studied with electrical and magnetic transcranial stimulation. Motor evoked potentials were recorded from the biceps, thenar and tibialis anterior muscles. In both groups of patients magnetic stimulation with a Novametrix stimulator revealed fewer abnormalities than electrical stimulation with a Digitimer D180 stimulator. In patients with hemiplegia, motor evoked potentials after electrical stimulation were absent in 70% of muscles, delayed in 22% and normal in 8%; after magnetic stimulation, they were absent in 53% of muscles, delayed in 28% and normal in 19%. In patients with motor neurone disease, motor evoked potentials after electrical stimulation were absent in 62% of muscles, delayed in 10%, and normal in 29%; after magnetic stimulation, they were absent in 45% of muscles, delayed in 15%, and normal in 40%. The reason why magnetic stimulation reveals fewer abnormalities than electrical stimulation could be that magnetic stimulation repetitively discharges the pyramidal cells and, because of temporal summation mechanisms, produces more powerful excitatory potentials at the lower motoneurone synapse.
PMID: 1718725 [PubMed – indexed for MEDLINE]

95: Exp Brain Res. 1991;83(2):403-10.
Effects of electric and magnetic transcranial stimulation on long latency reflexes.
Deuschl G, Michels R, Berardelli A, Schenck E, Inghilleri M, Lucking CH.
Neurologische Klinik und Poliklinik, Universitat Freiburg, Federal Republic of Germany.
The interaction of transcranial electric and magnetic brain stimulation with electrically elicited short- and long latency reflexes (LLR) of hand and forearm flexor muscles has been investigated in normal subjects. In the first paradigm, the motor potential evoked in thenar muscles by transcranial stimulation was conditioned by median nerve stimulation at various conditioning-test intervals. At short intervals (electric: 5-12.5 ms, magnetic: 0-7.5 ms) facilitation occurred that corresponded to the H-reflex and at longer intervals (electric: 25-40 ms, magnetic: 22.5-35 ms) there was a facilitation corresponding to the LLR. Electric and magnetic stimulation resulted in a similar degree of facilitation. A second paradigm investigated the facilitation of the forearm flexor H-reflex by a cutaneo-muscular LLR elicited by radial superficial nerve stimulation and transcranial stimulation used separately or together. When electric and magnetic brain stimulation were compared, magnetic brain stimulation was followed by significant extrafacilitation but electric stimulation was not. This result favours an interaction between the afferent volley eliciting the LLR and transcranial magnetic stimulation most likely at supraspinal level.
PMID: 2022246

96: Neurosci Lett. 1990 Nov 13;119(2):153-5.
Safety aspects of transcranial brain stimulation in man tested by single photon emission-computed tomography.
Dressler D, Voth E, Feldmann M, Benecke R.
Department of Clinical Neurophysiology, Georg-August-University, Gottingen, F.R.G.
Single photon emission-computed tomography (SPECT) using 99mTc-labelled hexamethylpropyleneamine oxime (99mTc-HMPAO), a new method to visualize regional cerebral blood flow (rCBF) and epileptogenic foci, was used to study acute and long-term effects of transcranial brain stimulation. Magnetic and electric brain stimulation increase rCBF not more than voluntary muscle activation mimicking the motor effects of transcranial brain stimulation. Focal rCBF increase, typical for epileptogenic foci, or other pathological findings could not be detected even when the subject had received several thousand stimulations in the past. Transcranial brain stimulation does not produce rCBF patterns indicating acute or chronic adverse effects.
PMID: 2280887

97: Otolaryngol Head Neck Surg. 1990 Sep;103(3):439-42.
Magnetic transcranial and electric direct stimulation of the facial motor cortex in dogs.
Estrem S, Haghighi S, Davis WE.
Division of Otolaryngology, University of Missouri-Columbia 65212.
Magnetic stimulation may allow noninvasive study of the entire course of the facial nerve. Our goal was to determine if evoked muscle action potentials can be obtained in facial musculature using electric direct cortical and noninvasive transcranial magnetic stimulation of the canine motor cortex. Thirty-four dogs were studied with electric direct cortical stimulation through a craniotomy and magnetic transcranial stimulation of the facial motor cortex. Facial nerve stimulation in the cerebellopontine angle allowed comparison to cortical responses. Latencies of 6.08 and 9.52 msec for orbicularis oculi and levator nasolabialis, respectively, were determined with magnetic transcranial stimulation, compared with 4.22 and 5.78 msec with electric direct cortical stimulation. In conclusion, magnetic stimulation of the facial motor cortex is possible in dogs, with longer central conduction times than with electric direct stimulation.
PMID: 2122375

98: Neurosci Lett. 1990 Apr 20;112(1):54-8.
Descending volley after electrical and magnetic transcranial stimulation in man.
Berardelli A, Inghilleri M, Cruccu G, Manfredi M.
Dipartimento Scienze Neurologische, Universita di Roma La Sapienza, Italy.
The descending volley evoked by electrical and magnetic transcranial stimulation was recorded with spinal electrodes in 3 subjects undergoing spinal surgery. The descending volley evoked by electrical stimulation, as previously described, was composed by a short-latency initial wave followed by later waves. In two subjects magnetic stimulation evoked an initial wave of slightly longer latency (0.2-0.3 ms), smaller amplitude and higher threshold than the initial wave evoked by electrical stimulation. In these two subjects, magnetic stimuli probably activated the pyramidal axons directly. In the third subject the initial wave evoked by magnetic stimulation had a latency of 1.4 ms longer and a considerably smaller amplitude than that evoked by electrical stimulation. In this case magnetic stimulation may activate the pyramidal axons indirectly.
PMID: 2385364

99: Ann Neurol. 1990 Jan;27(1):49-60.
Activation of the epileptic focus by transcranial magnetic stimulation of the human brain.
Hufnagel A, Elger CE, Durwen HF, Boker DK, Entzian W.
Department of Epileptology, University of Bonn, Federal Republic of Germany.
To establish whether transcranial magnetic stimulation is able to activate the primary epileptic focus preferentially, 13 patients who had medically intractable complex partial seizures were examined prior to surgical therapy. Single or a series of magnetic stimuli were applied to various regions of the skull. The effects of transcranial magnetic stimulation were monitored via subdurally implanted electrodes. In the process of presurgical evaluation, the dosage of anticonvulsant medication had been reduced in all patients but one. Transcranial magnetic stimulation was able to activate the epileptic focus (or foci) in 12 of the 13 patients. Distinct patterns of focal activation were observed in 3 patients who had several foci. No epileptiform potentials were induced outside epileptic foci, which had been identified by corticographic recordings. In one patient a complex partial seizure that was induced was identical to her habitual seizures. In another patient, a complete transition from a nonactive theta focus to a self-sustained epileptic focus occurred. A facilitation of epileptiform afterdischarge was seen with sequential stimulation. No adverse effects were either reported by the patients or observed by the investigators. In summary transcranial magnetic stimulation is able to activate the epileptic focus (or foci) and consequently may be an additional tool for the localization of epileptic foci in presurgical evaluation.
PMID: 2301928

100: J Neurol Neurosurg Psychiatry. 1989 Oct;52(10):1149-56.
Investigation of facial motor pathways by electrical and magnetic stimulation: sites and mechanisms of excitation.
Rosler KM, Hess CW, Schmid UD.
Department of Neurology, University of Bern, Inselspital, Switzerland.
A refined technique is described for non invasive examination of the facial motor pathways by stimulation of the extra- and intracranial segment of the facial nerve and the facial motor cortex. Surface recordings from the nasalis muscle rather than from the orbicularis oris muscle were used, since the compound muscle action potential (CMAP) from this muscle showed a more clearly defined onset. Electrical extracranial stimulation of the facial nerve at the stylomastoid fossa in 14 healthy subjects yielded a mean distal motor latency of 3.7 ms (SD 0.46), comparable with reported latencies to the orbicularis oris muscle. Using a magnetic stimulator, transcranial stimulation of the facial nerve was performed. The mechanism of transcranial magnetic facial nerve stimulation was studied using recordings on 12 patients who had facial nerve lesions at different locations, and with intraoperative direct measurements in four patients undergoing posterior fossa surgery. The actual site of stimulation could be localised to the proximal part of the facial canal, and a mean “transosseal conduction time” of 1.2 ms (SD 0.18) was calculated. The cerebrospinal fluid (CSF) played an important role in mediating the magnetically induced stimulating currents. Finally, with transcranial magnetic stimulation of the facial motor cortex, clearly discernible CMAPs could be produced when voluntary activation of several facial muscles was used to facilitate the responses. From this, a central motor conduction time of 5.1 ms was calculated (SD 0.60, 6 subjects).
PMID: 2795040

See also: Sandyk R, Anninos PA , Jacobson JI; three pioneers of electromagnetic field therapy to treat Parkinson’s, Alzheimer’s and Epilepsy.