week 5- TMS Flashcards
Background of lesion studies and classic cases
-A lesion is said to have occurred when a localised region of the brain is damaged and ceases to function normally.
-By measuring what the subject can no longer do, you -can then deduce what function the lesioned area of the brain was responsible for.
-Classic examples of lesion studies include
Henry Molaison (HM)
Phineas Gage
Broca’s area
Wernicke’s area
problems for studying lesions after they occur
- The researcher had to wait for lesions to occur (small n)
- The researcher did not get to decide what was lesioned.
- Often, had to wait for the subject to be die before the true extent of the lesion could be precisely determined.
- Given time the brain would often compensate and the subject would (at least partially) recover – from that point on the researcher is then studying an abnormal brain.
- Many of these objections can be avoided by studying animals, but if you want to study humans, you need a better technique.
Why TMS?
It allows you to perform reversible lesions.
Thus, people are actually willing to participate.
The researcher can decide where the lesion occurs.
The subject can be tested before the brain compensates.
what does TMS do?
Uses a rapidly changing magnetic field to induce electrical currents in the brain
Sometimes this excites the brain (e.g. stimulation of the motor cortex can generate movement ticks)
More usually disrupts or hinders processing in that brain area creating a “virtual lesion”
The lesion is short-lived and can be made to occur at a precise place at a precise time.
History
-The first successful TMS experiment was by “The -Sheffield group” – Reza Jalinous, Ian Freeston and Tony -Stimulated the motor cortex using TMS
-Observed muscle twitches
Barker - 1985
Basic Principles
TMS is based on Faraday’s principle of electromagnetic induction.
In brief, a changing magnetic field will cause a current to flow in a wire that passes through the magnetic field
This is how dynamos, electrical generators and electrical transformers work
basic principles continued
A current flows around the TMS coil generating a brief (approx 1ms), very strong (2 tesla) magnetic field
2 tesla ≈ 40,000 times the earth’s magnetic field
Because the scalp is permeable to the magnetic field, the magnetic field penetrates the brain, inducing a brief electric current.
The electric current is usually confined to the upper layers of the brain (i.e. the cortex)
How To Deliver Such a Large Pulse
To generate such a large magnetic field requires a lot of energy
A TMS machine works by charging up a capacitor and then suddenly discharging it to create the current pulse required to generate the magnetic field
Types of Coil
For brain stimulation, one often uses a butterfly or figure-of-eight coil
Generates a more focused current
Each coil generates a magnetic field in the opposite direction, thereby generating offset current loops that also circulate in opposite directions
Thus, a large localized current is generated
Generative Effects of TMS
- When applied over the primary motor cortex, can produce an observable twitch
- When applied to visual cortex TMS can generate phosphenes
- Phosphenes are brief flashes of light perceived in the absence of any visual stimulus
- The pulse has to be very strong to elicit a phosphene
Inhibitory Effects of TMS
creates virtual lesions:Thus, if the brain region was critical to the particular task that the subject was performing, then performance on the task would be reduced.
neural noise
- Essentially, the TMS-induced current causes neurons to fire randomly, increasing the level of neural noise, thereby masking the neurons that are firing correctly
- These means that an areas cease to function correctly, though usually the processing is usually not totally disrupted
Advantages Of TMS Over Real Lesions
- It produces a focused “lesion” where and when you want it
- Does not give the brain time to reorganize
- Does not give the subject time to learn compensatory behaviours
- Because the TMS “lesions” are short-lived, each subjects serves as his own control – the perfect match. One simply has the subject perform the same task twice – once with TMS and once without – and compare his/her performance in the two conditions.
Why Not Just Do Neuroimaging (e.g. fMRI)?
- just because a brain area increases its activity when a subject performs a given task does not mean that it is essential to the performance of the task – it might be epiphenomenal
- TMS can be used to deactivate those brain areas “found” by an fMRI scan to investigate whether they really do play an essential role in the task being studied.
- TMS can also be used to determine WHEN a given brain area plays a role in a given task
Safety
- the brain structures essential to life (e.g. the pons which helps to control respiration rate) are located deep within the brain out of the range of TMS
- However, TMS can still cause seizures
- Single pulse TMS is considered very safe
- However, rTMS (repetitive TMS) is more likely to cause seizures
- Strict guidelines (Wasserman guidelines) are used to prevent seizures in rTMS.
Clinical Use of TMS
The Royal Australian & New Zealand College of Psychiatrists (position statement 79, October 2013) has endorsed TMS as a treatment option for depression.
This option is available in Victoria (e.g. the Victoria Clinic)
Typically this is a treatment of a last resort when all other treatments have failed
Perhaps still a bit controversial but getting increasingly accepted
Amassian et al. (1989)
- Amassian et al (1989) was one of the first studies to use -TMS to inhibit processing in a brain area
- “Virtual lesion” mode – the way TMS is typically used today
- Specifically, they used used TMS to mask a visual stimulus
- The stimulus was a trigram
- Each trigram contained 3 letters
- After a delay of 0-200ms from the presentation of the letters, a single TMS pulse was administered to the visual cortex, i.e. the rear of the head
Amassian continued
Data for one subject
Control was when no TMS pulse was applied
Incidentally, no subjects reported any phosphenes (pulse was not strong enough to induce phosphenes)
Thus, masking not due to phosphenes
Possible objection: The TMS can produce various non-specific effects that might account for the results.
how is the visual cortex organised?
The visual cortex is retinotopically organized.
Each part of it processes input from just one region of visual space
However, the mapping is inverted up/down and left/right
Amassian et al. (1989) control experiment
- Made use of this retinotopic organization in their control experiment
- They shifted the TMS coil from left to right thereby moving the virtual lesion
- They reasoned that when the “lesion” is removed from the the part of the visual cortex that process a particular letter, the letter should become visible.
- Their results were consistent with this
- As before, trigrams horizontally oriented. Delay between presentation of trigram and pulse was 100ms
Amassian moving tms coil left
Left letter processed in right visual cortex
Thus, the further left the TMS coil is moved, the less suppression of right visual cortex, the less suppression of the letter, the higher the accuracy for reporting that letter
A beautiful within-subject control for non-specific effects of TMS