Introduction to TMS Transcranial Magnetic Stimulation Lisa Koski, PhD, Clin Psy TMS Neurorehabilitation Lab Royal Victoria Hospital 2009-12-14 BIC Seminar, MNI
Overview History, basic principles, instrumentation Basic TMS For investigation For intervention Advanced TMS For investigation For intervention
Overview History, basic principles, instrumentation Basic TMS For investigation For intervention Advanced TMS For investigation For intervention
History of TMS - Faraday (1831)
History of TMS d Arsonval (1896) Thompson (1910) Magnussen & Stevens (1911)
History of TMS - Barker (1985) Powerful electric charge creates time varying magnetic field, inducing electric current in adjacent conductors, including neural tissue Induced current depolarizes nerve cells, causing firing of neurons and muscles Cortical Stimulation Cervical Stimulation
Basic Principles From current in coil to induced charge density with Magstim 200 & circular coil
Stimulation Efficiency Stimulation Characteristics Device Circuit - hi inductance Risetime Waveform: mono / bi Coil Geometry: shape, size, winding Induced electric field
Stimulation Efficiency Factors Contributing to Response Characteristics Conductor / Brain / Nerve Distance and angle of the Coil to Conductor Size and shape of Conductor Length, and Bending Angle of Conductor Surrounding Resistivity Shape Length and bending angle Resistivity Gray matter CSF White matter Skull Scalp
Modeling Electric Field Potentials Intensity = 120% motor threshold (45% Maximum Stimulator Output) Cortex modeled at 1.5 cm Red = Effective stimulation = 100 V/m At 150% intensity, the figure 8 coil is effective to 2.5 cm New H coils vs. Fig 8 Less drop-off in effectiveness with distance Lower power Roth et al., J Clin Neurophysiol, 2007
Figure-8 Cooled for rtms Coil Types Circular nonfocal Most focal Motor mapping H-coil Depth stimulation (6 cm) Stimulate midline (leg)
Methods for Locating Stimulation Sites Empirical Primary motor cortex: Muscle twitch or EMG Primary visual cortex: Phosphenes Scalp anatomic Image-guided with MRI (structural or functional)
Resolution Spatial 0.5 cm with 5 cm fig.8 coils 1.5 cm depth from scalp Distant effects? Temporal Current: 0.5 ms Behavior: 50-150 ms rtms:?
Overview History, basic principles, instrumentation Basic TMS For investigation For intervention Advanced TMS For investigation For intervention
Single Pulse TMS Investigating Motor System Activity Probing the integrity and excitability of the corticomotor pathway Single TMS pulse over primary motor cortex 5 ms Motor threshold (MT) Motor evoked potential (MEP) Measure output of surface EMG from contra-lateral muscle Variables: - Latency - Amplitude or area
Single Pulse TMS Cortical Motor and Visual Excitability Thresholds
Single Pulse TMS Corticomotor Excitability After Stroke Related to location of damage and disuse of the affected hand 100 1400 90 * Unlesioned side Lesioned side Lin, Koski et al. 2005 % stimulator output MEP latency (ms) 80 70 60 50 40 30 20 10 0 40 35 30 25 20 15 10 5 0 Lesioned Side * Lesioned Side Unlesioned Side Unlesioned Side 1200 1000 N = 10, Post-stroke > 4 months, Age 32-83 Koski et al., NNR, 2004 MEP amplitude uv Map Area (cm2) 25 20 15 10 800 600 400 200 5 0 0 * Lesioned Side Lesioned Side Unlesioned Side Unlesioned Side Conclusions: Return to normal excitability on the lesioned side is associated with better functional recovery for at least a year after stroke
Paired-pulse TMS Investigating Intracortical Excitability of the Motor Cortex SUB-threshold conditioning pulse SUPRA-threshold test pulse % change in MEP size relative to a single pulse Intracortical Inhibition Intracortical Facilitation LICI = Long-interval Intracortical Inhibition SUPRA-threshold conditioning pulse; GABAb mediated
Intervention: Repetitive TMS (rtms) Modulating Neural Activity Beyond the Time of Stimulation 10 Hz Intensity Frequency Intertrain Interval Train Duration Total # trains Bestmann et al., 2005 1 Hz Intensity - Frequency Total # pulses Ridding & Rothwell, 2007
Modifying Motor Excitability by rtms Single-pulse TMS Evidence Sham 1 Hz 10 Hz Sham 1 Hz 10 Hz Pascual-Leone et al, 1998
TMS Investigations of Interventional rtms Examples from Stroke 10 Hz Intensity Frequency Intertrain Interval Kim et al., Stroke 2006 Train Duration 1 Hz Intensity Frequency Total # trains Takeuchi et al., Stroke 2005 Total # pulses
Intervention with multiple rtms sessions SPECT evidence Reason: Depression Target: Left DLPFC Coil : fig-8 Pre Treatment Frequency: 10 Hz # Trains: 10 Pulses / day: 1600 # sessions: 10 days Post Treatment Pascual-Leone et al, 2000
ONLINE TMS rtms for Investigation in Cognitive Neuroscience Virtual lesion technique Critical region for function: Brief train of pulses over Broca s area disrupts speech Chronometry: Single carefully-timed TMS pulse over visual cortex disrupts perception of visual stimulus Amassian et al, 80 s OFFLINE TMS Region involved in the task: Performance on cognitive task changes after administration of rtms
Limitations of TMS Surface structures activated preferentially Not a good exploratory tool: requires strong a priori hypotheses about Structures involved Behavioral effects - beyond muscle twitches Safety issues Stimulation parameters Contraindications
Selecting Stimulation Intensity Options: Relative to motor threshold Relative to visual threshold visible? EMG? subjective? But what if the motor or visual system is not my target?
Selecting Stimulation Intensity McConnell et al. Biol Psychiatry, 2001 Motor thresholds to TMS Distance from scalp to cortex on MRI No correlation between motor threshold and prefrontal Cx distance!
Sham Stimulation To prove that the effect evoked by rtms is due to activation of some brain structure, the sham procedure must mimic Method Visual Cutaneous sensation Scalp & facial muscle twitch Boneconducted sound Airconducted sound Coil at 90 0 + + - Partial + Ineffective intensities + + Partial Partial Partial Magstim sham coil + + - Partial Partial Sandwich sham coil + + Partial Partial + Electric scalp stimulation Sham + Electric scalp stim - Partial + - - - + + Partial Partial Control site + + Partial + +
Sham Stimulation Real Electro-magnetic placebo (REMP) Rossi et al. Clin Neurophysiol 2007 Conditions Real rtms REMP w/o electric pulse REMP w/ electric pulse Sham coil Real coil tilted at 900 At Varying frequencies and intensities Results Experts: 100% chose Real rtms consistently Novices: 25-50% chose Real rtms consistently 40% consistently chose REMP as real No-one picked the sham coil or tilted coil as real
Cognitive Neuroscience Zeimann, Cortex, Jan 2010 Interesting reviews Walsh & Cowey, Nature Neuroscience Reviews, 2000 Clinical Neurology Chen et al., The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee, Clin Neurophysiol 2008 Psychiatry Lam et al., Repetitive transcranial magnetic stimulation for treatmentresistant depression: a systematic review and metaanalysis, Can J Psychiatry, 2008