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PYM0NS: Methods in Neuroscience, Lecture #5

Neurostimulation (TMS)

Thursday 8th Nov, 2012, 14:00-16:50


Session outline

  • 14:00-14:20 Background: Methods of stimulating the brain (in)directly
  • 14:20-14:25 Safety & ethics
  • 14:25-14:40 Peripheral neurophysiology (EMG, MEP, H-reflex, SAI/LAI)
  • 14:40-14:55 Central neurophysiology (paired-pulse, SICI/SICF, rTMS, theta-burst)
  • 14:55-15:15 TMS with other methods: EEG, fMRI & Discussion
  • 15:15-15:30 Break
  • 15:30-16:30 TMS demonstration & 'ask the experts'


Different methods (in order of invasiveness)

Whole-cell patch-clamping

Single neurons


Single units / multi-units


Nuclei / large areas (e.g., deep brain stimulation (DBS)


Area near cooling probes


Area/neurons/receptors exposed to or affected by drugs

Transcranial electrical stimulation (TES)

Brain areas between electrodes

Transcranial magnetic stimulation (TMS)

Brain areas ~1cm diameter

Transcranial direct current stimulation (TDCS)

Brain areas between electrodes

Transcranial random noise stimulation (TRNS)

Not sure yet...

(Transcutaneous) Peripheral nerve stimulation (PNS)

Single nerves

Static magnetic stimulation

~5cm of brain

Neurostimulation (& imaging)

Temporal & spatial resolution

Neurostimulation (& imaging)

Temporal & spatial resolution (& effects)

Neurostimulation (TMS)

Difficult beginnings

Neurostimulation (TMS)


Neurostimulation (TMS)

Modern history

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.

Barker AT, Jalinous R & Freeston I (1985). Non-invasive magnetic stimulation of the human motor cortex. Lancet 1:1106-1107.

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

Neurostimulation (TMS)

Electromagnetic discharge

Neurostimulation (TMS)

Coil shape

Neurostimulation (TMS)





aligned with axons




low <=1Hz vs high >1Hz


length & separation of pulse trains

Neurostimulation (TMS)



Mag & More

Brain Products' PowerMag(no more...)


Neurostimulation (TMS)


Strong, rapidly-alternating magnetic fields have the potential to induce seizures, both in healthy and in seizure-prone people.

All possible precautions must be taken to screen-out anyone to whom TMS presents an increased risk:

  • History of epilepsy
  • On some medications, alcohol, caffeine, other drugs
  • Neurological or psychiatric illness
  • Any metallic implants, injuries, surgery
  • Alert, well-slept, not doing multiple experiments

Neurostimulation (TMS)

International guidelines

Rossi et al., 2009 & Rossi et al., 2015

Required reading for all TMS users. Describes different methods & clinical uses of TMS. Collates all known data on adverse reactions to TMS. Attempts to standardise terminology. Sets safety guidelines.

Neurostimulation (TMS)

How many consecutive pulses?

Redrawn from Rossi et al. (2009)

Peripheral neurophysiology

TMS (& PNS) has been used most for studying cortico-motor transduction - the transmission of motor signals from primary motor cortex to muscles

And sensory-motor interactions

The key techniques are:

  • Electromyography (EMG)
  • Motor-evoked potentials (MEP)
  • M-waves & H-reflexes (& F-waves, I-waves...)
  • Short(long)-latency afferent inhibition (SAI/LAI)

Peripheral neurophysiology

Electromyography (EMG)

Peripheral neurophysiology

Motor-evoked potentials (MEPs)

MEP amplitude & latency tell you about the level of excitability in the cortico-motor pathway and the speed of conduction

Peripheral neurophysiology

MEP Recruitment curves

FDI muscle, right hand

Size (& variability) of MEPs varies with:

  • Level of muscle contraction
  • Intensity of TMS

Peripheral neurophysiology

Electrical stimulation of the median nerve at the elbow

The size & latency of M-waves and H-reflexes can tell you about peripheral nerve-spine conduction

Peripheral-central interactions

Short- & Long-latency afferent inhibition (SAI/LAI)

Central neurophysiology

Paired-pulse TMS

ppTMS comes in two forms: Two pulses from the same coil or two pulses from different coils

Two different coils:

And people are doing triple- and quadri- and other coil combinations now

Central neurophysiology

Short-latency intracortical inhibition & facilitation (SICI/F)

One coil, two pulses, close together (e.g., 1-50ms)

There's also LICI, LICF, and interactions among all these acronymns - see R Chen's work

Central neurophysiology

Repetitive TMS

Two main kinds:

  • Low frequency (<=1Hz)
  • Supposedly results in decreased activity of the brain area.

    Effects supposed to last about half as long as the stimulation

  • High frequency (>1Hz)
  • In long trains, supposedly results in increased activity of the brain area.

    In short trains, for interfering with a task during its performance: e.g., 2-5 pulses at 10-20Hz during your task

Central neurophysiology

Patterned TMS

TMS pulses are delivered in repeated trains of a certain frequency.

Each train has a certain duration.

Trains are separated by a certain duration

Theta-burst stimulation is the most popular...

Central neurophysiology

Theta-burst TMS

Designed to mimic the tetatic stimulation that is most effective at inducing long term potentiation (LTP) and depression (LTD) in neurons of hippocampal slices (N=9)

A recent article from the same group suggests that these effects depend on the subjects... (N=56)

References (APA style)

Chen, R. (2004). Interactions between inhibitory and excitatory circuits in the human motor cortex. Experimental Brain Research, 154(1), 1–10. [NB]

Churchland, P. S., & Sejnowski, T. J. (1988). Perspectives on cognitive neuroscience. Science, 242(4879), 741–745. [NB]

Classen, J., Steinfelder, B., Liepert, J., Stefan, K., Celnik, P. A., Cohen, L. G., Hess, A., Kunesch, E., & Chen, R. (2000). Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent. Experimental Brain Research, 130(1), 48–59. [NB]

Cohen, D. (1984). Feasibility of a magnetic stimulator for the brain. In: Weinberg, H., Stroink, G., & Katila, T. (Eds). Biomagnetism: applications and theory. Pergamon Press. [NB]

Funke, K., & Benali, A. (2011). Modulation of cortical inhibition by rtms – findings obtained from animal models. Journal of Physiology, 589(18), 4423–4435. [NB]

Hamada, M., Murase, N., Hasan, A., Balaratnam, M., & Rothwell, J. C. (2013). The role of interneuron networks in driving human motor cortical plasticity. Cerebral Cortex, 23(7), 1593–1605. [NB]

Huang, Y., Edwards, M. J., Rounis, E., Bhatia, K. P., & Rothwell, J. C. (2005). Theta burst stimulation of the human motor cortex. Neuron, 45(2), 201–206. [NB]

Koch, G., Del Olmo, M. F., Cheeran, B. J., Ruge, D., Schippling, S., Caltagirone, C., & Rothwell, J. C. (2007). Focal stimulation of the posterior parietal cortex increases the excitability of the ipsilateral motor cortex. Journal of Neuroscience, 27(25), 6815–6822. [NB]

Mars, R. B., Klein, M. C., Neubert, F., Olivier, E., Buch, E. R., Boorman, E. D., & Rushworth, M. F. S. (2009). Short-latency influence of medial frontal cortex on primary motor cortex during action selection under conflict. Journal of Neuroscience, 29(21), 6926–6931. [NB]

Neubert, F., Mars, R. B., Buch, E. R., Olivier, E., & Rushworth, M. F. S. (2010). Cortical and subcortical interactions during action reprogramming and their related white matter pathways. Proceedings of the National Academy of Sciences USA, 107(30), 13240–13245. [NB]

Neubert, F., Mars, R. B., Olivier, E., & Rushworth, M. F. S. (2011). Modulation of short intra-cortical inhibition during action reprogramming. Experimental Brain Research, 211(2), 265–276. [NB]

Oliviero, A., Mordillo-Mateos, L., Arias, P., Panyavin, I., Foffani, G., & Aguilar, J. (2011). Transcranial static magnetic field stimulation of the human motor cortex. Journal of Physiology, 589(20), 4949–4958. [NB]

Rossi, S., Hallett, M., Rossini, P. M., Pascual-Leone, A., & The Safety of TMS Consensus Group, . (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical Neurophysiology, 120(12), 2008–2039. [NB]

Rossini, P. M., Burke, D., Chen, R., Cohen, L. G., Daskalakis, Z. J., Di Iorio, R., di Lazzaro, V., Ferreri, F., Fitzgerald, P. B., George, M. S., Hallett, M., Lefaucheur, J. '., Langguth, B., Matsumoto, H., Miniussi, C., Nitsche, M. A., Pascual-Leone, A., Paulus, W. E., Rossi, S., Rothwell, J. C., Siebner, H. R., Ugawa, Y., Walsh, V. Z., & Ziemann, U. (2015). Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. an updated report from an i.f.c.n. committee. Clinical Neurophysiology, 126(6), 1071–1107. [NB]

Rothwell, J. C., Day, B. L., Thompson, P. D., & Kujirai, T. (2009). Short latency intracortical inhibition: One of the most popular tools in human motor neurophysiology. Journal of Physiology, 587(1), 11–122. [NB]

Ueno, S., Tashiro, T., & Harada, K. (1988). Localised stimulation of neural tissue in the brain by means of a paired configuration of time-varying magnetic fields. Journal of Applied Physics, 64, 5862–5864. [NB]

Vucic, S., Cheah, B. C., & Kiernan, M. C. (2009b). Defining the mechanisms that underlie cortical hyperexcitability in amyotrophic lateral sclerosis. Experimental Neurology, 220(1), 177–182. [NB]

Walsh, V. Z., & Cowey, A. (2000). Transcranial magnetic stimulation and cognitive neuroscience. Nature Reviews Neuroscience, 1(1), 73–79. [NB]

Walsh, V. Z., & Cowey, A. (1998). Magnetic stimulation studies of visual cognition. Trends in Cognitive Sciences, 2(3), 103–110. [NB]

Walsh, V. Z., & Cowey, A. (2000). Transcranial magnetic stimulation and cognitive neuroscience. Nature Reviews Neuroscience, 1(1), 73–79. [NB]

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