Let’s (Briefly) Break the Brain

Introduction to TMS and an Overview of Current Projects

Arman Abrahamyan

Skype Chat

… are there TMS studies? Of course. There are a lot. Someone say

now is TMS world [unedited]

Break It … to Understand[1]

Accidental Brain Breakdown

[2] [3]

What is TMS?

[4]

Talk Structure

Introduction to TMS

Current Projects

Introduction to TMS

How does TMS work?TMS apparatus, major coil types, and

modes of stimulation“Virtual lesion” paradigmMRI guided coil positioningIs it safe?

How Does TMS Work?

Electromagnetic Induction

1831 [5]

[6]

Early Attempts: d’Arsonval

1896

Reported seeing

phosphenes

[7], [8]

Early Attempts: Thompson

1910

Replicated d’Arsonval’s

results

[9], [10]

Early Attempts: Magnusson & Stevens

1911

Electromagnetic field is still not large and

rapidly-changing enough

[11], [12]

Thyristor

Allows starting and stopping large

electrical currents within microseconds

[13]

First TMS apparatus

1985

[14, 31]

EM Induction and TMS[15, 31]

Microscopic Level

TMS causes depolarisation of neuronal membranes

Depolarisation can result in action potential

[16]

Macroscopic Level

Stimulated Area: 1-4 cm3

Affected Neurons: 1-5 billion

[17], [18]

TMS Apparatus, Coil Types, and

Stimulation Modes

TMS Apparatus

[4]

[14]

Circular Coil

Secondary Current Induced by Round Coil

Large Area of Stimulation

[19]

Secondary Current Induced by Double Coil

Focal Area of Stimulation

Induced Electric

Field

[33, 19]

Stimulation Modes

spTMS

Single pulse stimulation

Less than 0.2 Hz

Applied online

rTMS

Repetitive stimulation

Above or below 1 Hz

Can be applied online

or offline

[32, 21]

“Virtual Lesion” Paradigm

Use of TMS

Diagnosis & Treatment

Cognitive Neuroscienc

e

• Movement disorders• Epilepsy• Depression• Anxiety disorders• Stuttering• Schizophrenia• Dementia

• Perception• Attention• Memory• Learning• Emotions

“Virtual Lesion” or Breaking the Brain

[11, 20, 21]

Mechanisms of Interference

No TMS

[25]

Neural Activity: No TMS vs TMS condition

No TMS TMS

[26] [26]

Noise Injection or Signal Suppression?

NoiseInjection

Signal Suppression

[22] [23]

MRI Guided Stereotaxic

Navigation of the Coil

Brain is Difficult to See Through the Skull

[26]

MRI Guided Neuronavigation

[27] [28]

[29]

Safety

[27]

Risks of TMS

There are no known side effects associated with single-pulse TMS, when used properly

rTMS is known to cause seizure when stimulation parameters are well beyond accepted safety guidelines

[8, 11, 32]

Safety of Participants

Currently established safety guidelines for using TMS in rMTS mode are far below the risk margin for inducing a seizure

Participants undergo a screening check

[8, 11, 32]

Safety of Participants

Participants will be excluded if:◦Personal or family history of epilepsy◦Brain-related abnormal conditions◦Head or brain injuries◦Migraines or headaches◦Medications for a neurological or psychiatric

condition◦Implanted devices◦Heart condition◦Pregnancy

[8, 11, 32]

Conclusions

Conclusions

TMS operates on the principle of electromagnetic induction

TMS is relatively easy to operate and applyTMS can create a “virtual lesion” in a stimulated area of

the brain by interfering with a neural activity in that areaThe “virtual lesion” paradigm is useful approach for

mapping the temporal and functional characteristics of an area of the brain

Following currently established safety guidelines for TMS, it is possible to significantly reduce, if not eliminate, risks associated with TMS

Current Projects

Preliminary results of a pilot experiment

Improving phosphene threshold identification

TMS as a Pedestal in Visual Perception

Phosphene Threshold

Phosphene threshold◦Minimum stimulation level at the occipital pole

that induces phosphenesSuprathreshold TMS

◦Stimulation level above the phosphene threshold

Subthreshold TMS◦Stimulation level below the phosphene

threshold

Suprathreshold TMS

Impairs visual perception

Subthreshold TMS

But what about subthreshold TMS?

Hypothesis

Subthreshold magnetic stimulation of the occipital pole will act as a pedestal for a visual stimulus and lower stimulus detection threshold

Method

2-interval forced-choice taskTask: “Left Shift” button when stimulus is

in the first interval, “Right Shift” button when stimulus is in the second interval

Adaptive staircase to identify detection threshold in 30 trials

Stimulus: plaid (2 x ±450 Gabor)Stimulus duration: 40 ms

Method

Single-pulse TMS to occipital pole100 ms after stimulus onsetStimulation intensities:

◦Varied from 80% - 120% of phosphene threshold

Control: no TMS or stimulation at CzPlaid was positioned where phosphene

was located

Preliminary Results

no TMS 120% 80% 70%0.000

0.010

0.020

0.030

0.040

0.050

0.060

0.070

0.080EA

EL

No TMS 120% 80% 60%0.000

0.020

0.040

0.060

0.080

0.100

0.120

no TMS 100% 90% 85%0.000

0.010

0.020

0.030

0.040

0.050

0.060

0.070

EL

HP

Individual data Average detection threshold

by condition

Conclusions

Result seem to support the hypothesis that subthreshold TMS can act as a pedestal

It is contended that the noise injection, as a results of stimulation, acts as a pedestal which improves the stimulus detection threshold

We are devising a final protocol for more systematic testing and data collection◦Manipulating levels of subthreshold stimulation◦Manipulating the timing of the TMS pulse

Acknowledgements

Justin HarrisColin CliffordEhsan ArabzadehIrina HarrisAlexandra Murray

Participants:Evan LiveseyHannah Pincham

Thank you[4]

References

1. http://news.bbc.co.uk/1/hi/health/2293179.stm 2. http://www.nature.com/nrn/journal/v5/n10/full/nrn1521.html3. Damasio, H., et al., The return of Phineas Gage: clues about the brain from the

skull of a famous patient. Science, 1994. 264(5162): p. 1102-5.4. http://www.magstim.com/downloads/imagegallery.html 5. http://www.tamu-commerce.edu/physics/links/faraday.jpg6. http://micro.magnet.fsu.edu/electromag/electricity/inductance.html7. d'Arsonval, A. Dispositifs pour la mesure des courants alternatifs de toutes

fréquences. C.R.Soc.Biol.(Paris) 3:450-457, 1896. 8. http://www.csbmb.princeton.edu/tms_orientation.ppt9. Thompson, S.P. A physiological effect of an alternating magnetic field. Proc R Soc

Lond [Biol] B82:396-399, 1910. 10. http://www.scholarpedia.org/article/Transcranial_magnetic_stimulation11. Walsh, V. and A. Cowey, Magnetic stimulation studies of visual cognition. Trends

in Cognitive Sciences, 1998. 2(3): p. 103-110.12. Magnusson, C.E. and Stevens, H.C. Visual sensations created by a magnetic

field. Am J Physiol 29:124-136, 1911. 13. http://www.global-b2b-network.com/direct/dbimage/50298013/

Thyristor_Modules.jpg 14. http://www.scholarpedia.org/article/Transcranial_magnetic_stimulation

References

15. http://brainstimulant.blogspot.com/2008/05/tms-video.html16. http://en.wikipedia.org/wiki/Action_potential17. http://berkeley.edu/news/media/releases/2007/09/27_TMS.shtml18. Kammer, T., M. Vorwerg, and B. Herrnberger, Anisotropy in the visual

cortex investigated by neuronavigated transcranial magnetic stimulation. Neuroimage, 2007. 36(2): p. 313-21.

19. Bailey, C.J., J. Karhu, and R.J. Ilmoniemi, Transcranial magnetic stimulation as a tool for cognitive studies. Scand J Psychol, 2001. 42(3): p. 297-305.

20. http://www.joelertola.com/tutorials/brain/index.html 21. Amassian, V.E., et al., Suppression of visual perception by magnetic coil

stimulation of human occipital cortex. Electroencephalogr Clin Neurophysiol, 1989. 74(6): p. 458-62.

22. Walsh, V. and A. Cowey, Transcranial magnetic stimulation and cognitive neuroscience. Nat Rev Neurosci, 2000. 1(1): p. 73-9.

23. Harris, J.A., C.W. Clifford, and C. Miniussi, The functional effect of transcranial magnetic stimulation: signal suppression or neural noise generation? J Cogn Neurosci, 2008. 20(4): p. 734-40.

References

24. http://www.wpclipart.com25. http://www.physics.lsa.umich.edu/zochowski/images/Neurons.jpg26. http://www.boneclones.com/BC-092-Set.htm 27. http://www.medcat.nl/Research/softaxic.htm28. http://www.ant-neuro.com/products/visor 29. http://www.youtube.com/watch?v=NQG-ml4aZ_s30. http://medicine.mercer.edu/Research/safety31. Barker, A.T., Jalinous, R., and Freeston, I. Non-invasive magnetic

stimulation of the human motor cortex. Lancet 1:1106-1107, 1985.32. Wassermann, E.M., 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. Electroencephalogr Clin Neurophysiol, 1998. 108(1): p. 1-16.

33. Ueno, S., Tashiro, T. & Harada, K. Localised stimulation of neural tissue in the brain by means of a paired configuration of time-varying magnetic fields. J. Appl. Phys. 64, 5862–5864 (1988).

Questions

Improving phosphene threshold identification

Finding a threshold using a computer