Transcranial Magnetic Stimulation ( TMS ) Log Scale (mm) Brain Map Column Layer Neuron Dendrite Synapse 3 2 1 0-1 -2-3 -4 ERP & MEG TMS Optical Dyes Single Unit Recording Patch Clamp Functional MRI Light Microscopy PET -3-2 -1 0 1 2 3 4 5 6 7 Millisecond Second Minute Hour Day Log Time (sec) 2DG Lesions Microlesions History of TMS Modern Era 1985 Barker et al., non-invasive, painless, cortical stimulation with magnetic fields Barker AT, Jalinous R & Freeston I. 1985. Non-invasive magnetic stimulation of the human motor cortex. Lancet 1:1106-1107. 1984 David Cohen, 1988 Shoogo Ueno, the idea and realization of the figure-of-eight coil Cohen D. 1984. Feasibility of a magnetic stimulator for the brain. In Biomagnetism: applications and theory. Editors: Weinberg H, Stroink G & Katila T. Pergamon press, p. 466-470. Ueno S, Tashiro T & Harada K. 1988. Localized stimulation of neural tissue in the brain by means of a paired configuration of time-varying magnetic fields. J Appl. Physics 64:5862-5864. 1987/88 Cadwell Laboratories Inc., repetitive stimulation with water-cooled coil Walsh V & Cowey A. 2000. Transcranial magnetic stimulation and cognitive neuroscience. Nat Rev Neurosci 1: 73 79. 1
( TMS ) Transcranial Magnetic Stimulation TMS Coil Rapid magnetic field changes >> electric current Magnetic field created at scalp with figure-8 coil Electric current induced in neurons in cortex Adds noise, disrupts coordinated activity Temporary lesion Without the kind of compensation that develops w/ long-term lesions Maximum magnetic field at center of figure-8 Naeser et al. (2004), Fig 2, p 100 Rapid-onset brief electrical current generated in coil Produces rapid-onset brief magnetic ( Tesla field pulse (up to 2 Induces rapid-onset brief electrical field Induces rapid-onset brief electrical ( cortex current in brain (mostly Which has an effect on some task Walsh & Cowey (2000), Fig 2, p 76 Bailey CJ, Karmu J, Ilmoniemi, RJ. 2001. Scand J Psych 42: 297 306. 2
TMS: Terminology TMS: general term for all modes of transcranial magnetic stimulation rtms: repetitive magnetic stimulation Single-pulse TMS: non-repetitive TMS Low-frequency (slow) TMS: repetition rate below 1 Hz High-frequency (rapid-rate) TMS: repetition rate above 1 Hz Dual (paired)-pulse TMS: stimulation with two distinct stimuli through the same coil at a range of different intervals; the intensities can be varied independently Double TMS: stimulation with two stimulation coils applied to different cerebral loci; the timing and stimulus intensity are adjusted separately Multichannel TMS: TMS with multiple (say, 20-100) coils that are independently controlled TMS mapping: performed by changing the coil position above the head while observing its effects Bailey CJ, Karmu J, Ilmoniemi, RJ. 2001. Scand J Psych 42: 297 306. http://www.biomag.hus.fi/tms/terminology.html TMS: Basic Idea Apply to different areas of scalp & see what functions disrupted Disruption does NOT mean brain regions directly under coil responsible for function Only that it s involved somehow in the function OR connected to regions involved in the function ( diaschisis ) Get distal effects through connections Necessary (sort of) but not sufficient Repetitive versus Single Pulse TMS Many early studies used rapidly repeated trains of magnetic pulses Because single pulses weren t found to have much effect on gross measures of behaviour More recently, single pulse studies have found effects with constrained hypotheses & more sensitive behavioural measures Can time single pulse at different steps in a process to see when it has the most effect Mostly studying vision & motor processes ( retrieval Also working memory (encoding, maintenance, 3
Amassian, V.E., Cracco, R.Q., Maccabee, P.J., Cracco, J.B., Rudell, A.P. and Eberle, L., 1989. Suppression of visual perception by magnetic coil stimulation of human occipital cortex. Electroencephalography and Clinical Neurophysiology 74, pp. 458 462. Each point is one TMS stimulation. No effect. Error reporting right letter but correctly reporting left letter. Error reporting left letter but correctly reporting right letter. Feredoes et al (2007) Journal of Neuroscience Feredoes et al (2007) Journal of Neuroscience 4
A [17F]-fluoromethane PET/TMS study of effective connectivity Ferrarelli et al Brain Research Bulletin 2004 Ferrarelli et al Brain Research Bulletin 2004 Safety If used properly, single-pulse TMS has no known harmful side effects. TMS has been used since 1985 and today some 3,000 stimulators are in use. Protocols should always exclude patients and volunteers with: intracranial metallic or magnetic pieces - The magnetic field present in TMS will generate forces on objects exposed to it: magnetic objects will be attracted and nonmagnetic repelled. The force may be substantial, but decreases quickly with decreasing cross-sectional area and conductivity of the object and with distance from the coil. pacemaker, or any other implanted device - The magnetic field pulse will disturb nearby electronic devices. http://www.biomag.hus.fi/tms/safety.html Safety Single-pulse TMS has produced seizures in patients, but not in normal subjects rtms has caused seizures in patients and in normal volunteers Hearing loss - During TMS there will be a loud clicking sound from the coil. The peak sound pressure is 120-130 db 10 cm from the coil. Most sound energy is in the frequency range 2 7 khz where the human ear is the most sensitive. The noise may exceed criteria limits for sensorineural hearing loss. Heating of the brain - Heating of the brain is unlikely to cause deleterious effects. Theoretical power dissipation from TMS is few milliwatts at 1 Hz, while the brain's metabolic power is 13 W Headache - A frequent harmless, but uncomfortable, effect is a mild headache, which is probably caused by activation of scalp and neck muscles. Engineering safety - TMS equipment operates at lethal voltages of up to 4 kv. It is hence important not to keep coffee cups or ice bags on the stimulator. 5
Safety Recent literature lists indicative ranges for safe use of rtms. The following parameters are of main importance: Stimulus strength Repetition rate Train duration Train interval Total number of pulses Chen R, Gerloff C, Classen J, Wassermann EM, Hallett M and Cohen LG. 1997. Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters. Electroen Clin Neuro 105:415-421. Wassermann EM. 1998. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroen Clin Neuro 108:1-16. Summary: TMS High spatial and temporal resolution Can be used repeatedly in humans Provides information about the functional significance of a brain region ( virtual lesion ( technique Restricted to brain regions close to the skull Difficult to interfere with higher order cognitive processes distributed processes? 6