I was chatting on Skype with a Japanese colleague who attended the Japanese Conference on Biomagnetism recently. I asked her if she noticed any TMS studies. Well, someone at the conference told her that it is “TMS world” currently. TMS may not be dominating the world affairs, but it is currently an influential and important method for understanding how does the brain work.
So why TMS is so appealing? As we all know, the fastest way understand how does something work is to break it.
Indeed, functional specificity of brain areas has been uncovered as a result of a break down in specific areas of the brain. Some of them are classics, such as Broca’s area involved in the production of speech, the frontal lobe damage of Phineas Gage and subsequent changes in his behaviour and personality. But how to study a living brain without breaking it permanently? This is where TMS is indispensible.
So what is transcranial magnetic stimulation? TMS is a method for stimulating cortical areas of the brain through the intact skull. The stimulation can temporarily and reversibly interfere with or break the functions of an isolated area in the brain being stimulated. This enables us to study both spatial and temporal characteristics of a brain area.
This talk consists of two major parts. In the first part I will introduce you to TMS: how it works, how it is being used for research purposes, safety issues, and the future of TMS.
In the second part I will be talking about some pilot data we have collected and improvements that we are implementing use the TMS apparatus more efficiently for research purposes.
In the first part I will introduce you to the principles of the transcranial magnetic stimulation and a short history of its development and then introduce you to the TMS apparatus.
Then I will talk about TMS as a tool for studying the brain mechanisms. I will also talk about safety and ethical issues. At then I will introduce you to TMS laboratory facilities and conclude with a few words about the future of TMS.
In the second part of the talk I will be talking about current projects. In particular, the experiment that we are currently piloting and also talk about improvements that we are trying to achieve by using a computer to control the TMS apparatus.
I will now give you more intimate introduction to the principles behind transcranial magnetic stimulation.
In 1831 Michael Faraday found that when two coils are in close proximity, but not touching each other, running an electrical current through the right coil magnetises the iron and the magnetic field of the iron induces brief electrical currents in the left coil. The current passing through the right coil is called primary current and the current passing through the left coil is called secondary current. TMS is based on the principle that the secondary current can be induced in any conductor: be it a potato, apple, orange, or a brain. It is important to note that the secondary current is induced only briefly when the circuit is close or open.
As the principle of the electromagnetic induction have been known since 1831, there have been early attempts to stimulate the brain. In 1896 d’Arsonval placed participants’ head in a big cylindrical coil and ran a current through the coil. As a result, participants reported seeing flashes of light which were possibly induced by stimulating retinal cells. These flashes of light are called phosphenes and I will talk more about them later on.
Silvanus Thompson experimented with electromagnetic stimulation of the brain in 1910. Like d’Arsonval, he observed flashes of light or phosphenes, which were possible result of stimulating the retinal cells.
To increase the strength of the magnetic field, Magnussen and Stevens in 1914, piled up a few coils on top of each other. However, they still couldn’t achieve requisite large, rapidly-changing electromagnetic fields.
An important engineering advance that enabled devising TMS was thyristor. Thyristor allows starting and stopping large electrical currents within microseconds. If you remember, electromagnetic induction takes place only when you start or stop the primary current.
A progenitor of modern TMS machines was developed Royal Halamshire Hospital and the University of Sheffield in 1980s. In 1985, Tony Barker and colleagues successfully demonstrated transrcanial magnetic stimulation of the brain by stimulating the motor cortex and observing finger twitches.
In TMS, a large primary current passing through the coil results in magnetic field. The magnetic field can efficiently pass through the scalp and skull, reach the cortex and induce the secondary current at the cortical level which results in cortical excitation.
On a microscopic level, as a result of stimulation, the induced secondary current causes electric charges being accumulated on neural membranes resulting in depolarisation. Depolarisation, in turn, can result in action potential.
The stimulated cortical area is estimated to be within 1 to 4 cubic centimeters and it is estimated that the stimulation affects 1 to 5 billion neuron.
In general, TMS machines consist of one, two, or three big briefcase-sized components, a coil for magnetic stimulation, and a user interface to control the machine. The upper component is the mainframe and it also contains a thyristor. The bottom component is a capacitor to store large electrical currents. The user interface let you control stimulation parameters, such as stimulation level or stimulation frequency.
If you look at the first TMS machine, you will notice that the stimulation coil was round. Intuitively, it may seem that the maximum magnetic field as in the centre of the coil.
However, the magnetic field is the strongest around the edges of the coil. Therefore, using a circular coil results in stimulating relatively large cortical area. While this may be useful in some cases, such as when treating patients presented with depression, a more focal stimulation is better suitable for research purposes.
The second major type of the coil is double coil also called figure-of-eight coil or butterfly coil. This coil was implemented by Ueno and colleagues in 1988. This type of coil is more preferable for research purposes because the magnetic field reaches its peak at the point between the two coils and it is more focal.
TMS can be used in two stimulation modes. Single-pulse TMS or sTMS is when the frequency of stimulation is less than 1 Hz. sTMS is usually applied online, while participants are doing the task. The sTMS is usually applied at 0 to 500 ms after the stimulus presentation depending on the functions being studied. Repetitive TMS, or rTMS refers to transcranial magnetic stimulation that is applied at a frequencies above 1 Hz. When stimulation is delivered while participants are doing the task, this is called online rTMS. When stimulation delivered before participants commit to the task, this is called offline stimulation. It is single-pulse stimulation that is usually used in vision research.
Broadly, TMS is used for diagnosis and treatment and in cognitive neuroscience. Here, I will introduce how TMS is being used in cognitive neuroscience for studying the brain mechanisms.
In 1989 Amassian and colleagues observed that the TMS applied over the occipital cortex between 80 and 100 ms is able to suppress visual perception. As a result of stimulation, TMS induced transient interruption of normal brain activity in the visual cortex. This experiment became a starting point for a concept of virtual lesion induced by TMS. In other words, TMS allows to break down the normal functioning of a part of the brain for a short duration of time, which usually lasts for about 100 ms.
So what causes the interference with the task as a result of transcranial magnetic stimulation? Let’s have a look at an example using a visual stimulus to understand the mechanisms. Let’s say a participant has to identify number of circles in the figure.
Picture on the right denotes a pattern of neural activity in some part of the visual cortex when the participants is doing the task without TMS. When participant is doing the same task combined with TMS, the pattern of activation changes because the dormant neurons are firing as a result of transcranial magnetic stimulation. The images are provided to explain the idea and are not based on actual TMS study.
This change in the goal-state of the stimulated area results in interference with the task. There are two competing theories as to what causes the interference.
The Noise Injection theory proposes that activation of dormant neurons as a result of TMS will inject noise into the system. Perceptually, this may manifest as seeing visual noise together with original stimuli, which may interfere with the task.
An alternative explanation is that the signal gets suppressed as a result of stimulation, which has been recently demonstrated by Harris and colleagues. According to the signal suppression theory, activation of dormant neurons as a result of TMS will result in signal suppression because the original information being encoded in a cluster of neurons has been distorted or suppressed.
Perceptually, signal suppression could manifest as loss in contrast, size, or shape.
Positioning the TMS coil on the skull to point at the desired anatomical landmark on the brain isn’t easy. Some areas of the brain are easier to locate while others are not. For example, observing phosphenes can tell us that we are stimulating the visual cortex. But what about other areas where there are no behavioural indicators to help to identify the area being stimulated?
One way to overcome this problem is to use participants’ MRI and a stereotaxic neuronavigation system to navigate the coil on the brain. This type of system consists of a neuronavigation equipment which allows to obtain coordinates of the coil and the head and we also need participant’s MRI to co-register with their brain. After the co-registration, it is possible to see on the screen in real-time where the coil is positioned. The precision of coil targeting can be within a few millimeters.
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
TMS has been in use for 23 years and there are currently more than 3000 TMS machines are in use around the world. Therefore, there are currently rigorous stimulation guidelines and participant screening procedures in place to ensure safety of participants.
Currently established safety guidelines for using TMS in rTMS mode are far below the risk margin for inducing a seizure
To lower the risk of a seizure, participants undergo a screening check using a questionnaire
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
1. Let’s (Briefly) Break
Introduction to TMS and an Overview of
2. Skype Chat
… are there TMS studies?
Of course. There are a lot. Someone say
now is TMS world
3. Break It … to Understand
4. Accidental Brain Breakdown
5. What is TMS?
6. Talk Structure
7. Introduction to TMS
How does TMS work?
TMS apparatus, major coil types,
and modes of stimulation
“Virtual lesion” paradigm
MRI guided coil positioning
Is it safe?
8. How Does
9. Electromagnetic Induction
10. Early Attempts: d’Arsonval
11. Early Attempts: Thompson
12. Early Attempts: Magnussen & Stevens
field is still not
large and rapidly-
Allows starting and
14. First TMS apparatus
15. EM Induction and TMS
16. Microscopic Level
TMS causes depolarisation of
Depolarisation can result in action
26. “Virtual Lesion” or Breaking the
[11, 20, 21]
27. Mechanisms of Interference
28. Neural Activity: No TMS vs TMS
No TMS TMS
29. Noise Injection or Signal Suppression?
30. MRI Guided
Navigation of the Coil
31. Brain is Difficult to See Through
32. MRI Guided Neuronavigation
34. Risks of TMS
There are no known side effects
associated with single-pulse TMS, when
rTMS is known to cause seizure when
stimulation parameters are well beyond
accepted safety guidelines
[8, 11, 32]
35. 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]
36. 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
◦ Implanted devices
◦ Heart condition
[8, 11, 32]
TMS operates on the principle of electromagnetic
TMS is relatively easy to operate and apply
TMS can create a “virtual lesion” in a stimulated
area of the brain by interfering with a neural
activity in that area
The “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
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