Lecture 2: TMS Flashcards
What are brain perturbations?
They impair or influence cognitive functions
Wht can brain perturbations arise from?
e.g., perturbations from brain damage in stroke patients, disease or trauma but perturbations induced experimentally using pharmacological or electrical methods
Infromation from brain perturbations have
greatly advanced our understanding of the neural underpinnings of cognitive functions
What is lesion studies?
When a specific brain region is purposefully or incidentally damaged, and consequentially specific cognitive functions are affected, these functions are causally connected to processing in this region.
Lesions and TMS give advantage, over fMRI EEG being correlaiton, is that
causal
Example of lesion study - (3)
In 1948, Phineas Gage had a workplace accident in which an iron tamping rod entered and exited his skull.
He survived but it is said that his personality changed as a result, leading to a greater understanding of the brain regions involved in personality, namely the frontal lobe
famous patient with frontal cortex lesion - accidental lesion
There are two types of lesion studies - (2)
- Invasive methods
- Non-invasive methods
Invasive methods of lesion studies - (4)
- Destory processing in brain region of interest –> advantage can tightly control ROI
- Can for instance be done by remving brain tissue or cooling region
- Ethically very problematic
- Done in animals
What are non-invasive methods of lesion studies? - (2)
- Studying patients with incidental lesions(e.g., due to stroke/posioning) in specific parts of their brain e.g., phineas gage
- Using brain stimulation to temporarlly impair neural processing (TMS)
What does lesion mapping in patients require?
use of structural imaging (e.g., structural MRI)
What is involved in lesion mapping? - (2)
Carefully mapping the damaged cortical regions allows for establishing spatially specific and causal relationships between brain activations and cognitive functions
mapping where the lesions is happening
There is database in lesion mapping across the world which - (2)
have structural images and where the lesion is and catalogue of functions assessed
if interested what causes arithmetic difficulties and find list of patients with this in database and overlap their lesions in MRI and find common area impaired in all of them
Lesion Mapping in Patients
What does this diagram show? - (2)
MRI scans of patient D.F (on right) and healthy volunteer)
D.F had damage to visual cortex called lateral occipital and not acivated vs healthy volunteer L0 activated in task that activates it
Whats a single dissociation in lesion studies?
A lesion to a specific region leads to an impairment in a specific task (but not in other tasks)
What is the problem with single dissociations? - (2)
Single dissociations my be found when the two tasks are differently sensitive (e.g., different task demands or difficulty
e.g., has a patient who is deficit in factual arithemtic e.g., 2+2 = 4 but okay in comparing numbers then say task is quite difficult and different from each other
The problem of single dissociation that they are found when 2 tasks are differently sensitive (e.g., different task demands/difficulty) is aggravated/increased by
fact that participants may have unspecific impairments that impair their performance in various tasks with high sensitivity
Whats example of single dissociation? - D.F - (3)
Single dissociation between dorsal and ventral stream functions in the visual system
Traumatic lesion in human ventral stream (patient D.F.) leads to impaired object perception (matching card in the angle of slot), but leaves object-guided action intact (posting - card through angular slot)
healthy volunteers good at both
What is a double dissociation? - (2)
A lesion to one region leads to an impairment in a specific task (but not the second task), and a lesion to another region leads to an impairment in another specific task (but not the first task)
e.g., patient who can do arithmetic 2+2 = 4 but not number comparison and patient who can do number comparison and not arithmetic and have lesions in different areas
What does double dissociation reveal?
Reveals unequivocal links between lesion and putative (supposed) brain function, that are not explicable by the tasks’ sensitivity
What is an example of double dissociation?
: Double dissociation between dorsal and ventral stream functions in the primate visual system - (3)
- Trained macaque monkeys in two tasks: 1) object discrimination of always picking up Toblerone shape object wherever it is, 2) landmark discrimination of monkeys always pick up the piece closer to cylinder
- Artificial lesions in macaque animals’ ventral stream (temporal lobe) leads to an impairment in object discrimination but not in landmark discrimination
- Artifical lesions in macaque animal’s dorsal steam (parietal cortex) leads to impairment in landmark discrimination but not object discrimination
What does this graph show in terms of single vs double dissociation? - (2)
- single dissociation, region A is reduced in function X but not in function Y
- In double dissociation , region A is reduced in function X but not in function Y, region B is reduced in function Y and not X
What are the 2 advantages of lesion studies? - (2)
- Reveals causal links between brain regions and functions esp in double dissociation in patients
- High spatial precision (when done invasively - in animals artifical lesions)
What are the weaknesses of lesion studies? - (4)
- Low temporal precision
- Low spatial precision (when studying incidental lesions)
- Confounding impairments are not unlikely –> e.g., patients have number of processing deficits but may also have speech problems - lesions may not just impair one function so lesion mapping is useful
- Experimentation can be difficult, costly, and unethical (animals in lab)
What is brain stimulation?
Driving neural activation to understand brain function
What is the idea of brain stimulation - (2)
When neurons communicate, they change their membrane potentials and eventually fire action potentials.
By inducing electrical currents into neurons, we can either push neurons to fire more (or to be more excitable) or induce chaotic activations that prevent coordinated firing.
What are the two methods of methods in brain stimulation - (2)
- Invasive
- Non-invasive
What are inasive methods of brian timulation - (2)?
- Electric stimulation of neurons in particular brain regions
- In humans: Rarely possible for patients with implanted electrodes (e.g., for informing epilepsy treatment)
Disrupting the neural processing using direct electrical stimulation of specific brain region (i.e., perturbation by intracranial brain stimulation)
the technique in humans is limited to
patients with serious medical problems
Direct cortical stimulation is an important technique for
estbalishing the necessity of brain region for cognitive construct
How does direct cortical stimulation work? - (2)
electrical current is introduced using electrodes that are placed on the surface or the brain or directly into deeper brain tissue
The current is delivered via a relatively large electrodes that stimulate a large region or via a small electrodes that stimulate a few neurons
What are the modern uses of direct cortical stimulation - (3)
- Today, direct cortical stimulation is most frequently used to map areas of critical functions (e.g., language, motor abilities) in patients awaiting undergoing neurosuregrey
- Based on function of brain regions located near the surgical target, neurosurgeons may change the path taken through the brain surface to leave critical area s intact while removing a deep tumour
o It reduces the change the patient will suffer from motor, language or other deficits
Modern methods of direct stimulation - (5):
- In modern practice of direct cortical stimulation, a pair of stimulating electrodes are placed on the surface of the cortex (Figure 13.1A):
- One electrode (anode) provides the source of electrical current
- The second electrode (Cathode) provides the sink to which current will flow
- Stimulation consist of weak current pulses that are rapidly presented
- Surgeon moves electrode to different locations on exposed cortical surface and tests effect of stimulation on regions of interest
Modern methods of direct cortical stimulation - grids - (3)
- Some epilepsy patients have grids of electrodes implanted subdural for over a period of days or weeks as shown on the right:
- By recording the frequency and locations of seizures within this grid, the patient’s physicians can determine whether a particular surgical excision would reduce or eliminate seizures
- Since patients are conscious, alert and comfortable during direct stimulation studies much useful info is obtained about their higher cognitive functions from these procedures
Limitation of direct cortical stimulation - (3)
- Invasive and bring on seizure on patients who suffer epilsepy
- High electrical currents sufficient to depolarise neurons and may spread from stimulating electrodes to excite brain regions distant away –> thus cathode and anode kept in close proximity
- Positive or negative effects does not ncessairly indicate surgical removal of stimulated region cause corresponding deficits
Whats non invasive methods of brain stimulation - (2)
- Using fast changing magnetic fields (Transcranial Magnetic Stimulations) to stimulate neurons
- [Using transcranial direct (tDCS) or alternating (tACS) current stimulation across the head to modulate activity outside of the brain]
How does tDCS work? - (2)
- tDCS protocol involves 2 small electrodes placed on different parts of the scalp – often with one over target site and another at distant reference location
- Weak direct current is delivered over extended periof of time
TMS is less invasive method than
tDCS (transcranial direct stimulation)
A far less invasive approach as compared to perturbation by intracranial brain stimulation is to
disrupt cognitive processing in normal subjects is transcranial magnetic stimulation (TMS)
For studies in humans electrical activity in brain influenced by
by either directly by applying an electrical current (tDCS) or a focal magnetic field (TMS) to surface of the scalp
What is the difference between TMS or tDCS/tACS?
One uses magnetic fields (TMS) and another uses electrical currents (tDCS/tACS)
Diagram of history of TMS
History of TMS - (13)
- In 1832 Farady discovers electromagnetic induction
- Took a while to produce machines for high enough magnetic fields to go through the skull
- 1848 Du Bois-Reymond shows link between electric current and nerve-cell activity
- In 1875, Ferrier uses electrical currents to stimulate the cortex and map cortical responses in dogs and monkeys
- In 1In 1896 “d’Arsonval presents the first report of magnetically induced phosphenes in human subjects by stimulation of the retina, not the cortex”. - painless stimulation of nervous system by electromagnetic induction
- In 1910 “Silvanus P. Thompson experiments on himself. Again, the phosphenes were due to retinal, not cortical, stimulation. - First successful generation of magnetically induced phosphenes by d’Arsonval (1896), 1902 Beer, 1910 Thompson
- Mangussen and Stevenson - arrangment of coils to provide a magnetic field of sufficient strength to induce phosphenes
- In 1974, Baker begins using brief magnetic pulses to stimulate peripheral nerves and report msucule contractions and skin sensations
- In 1985 “Barker and colleagues report the first successful magnetic stimulation of the human motor cortex”. - current era of TMS machines begins
- In 1989, Amassian et al and Day et al publish first studies on TMS as virtual lesion technique in visual and motor cortex
- In 19991, Pascual-Leone et al report TMS induced speech arrest in population of epiletic subjects
- In 1994, Pasucul Leone et al produce visual extinction using repetitve pulse TMS
- In 1996, George et al report TMS related improvements in mood and concomitant changes in blood flow of prefrontal cortex in depression
- TMS lab at YNiC with TMS at Nov 2008
TMS operates on Faraday’s principle of electromagnetic induction - (2)
- Faraday showed that an electrical current passed through one coil could induce a current in a nearby coil. The current in the first coil produces a magnetic field that in turn causes current to flow in the second coil
- In TMS, that second coil is replaced by brain tissue and the induced electric field elicits neuronal activity
What is phosphenes? - (2)
a sensation of a ring or spot of light produced by pressure on the eyeball or direct stimulation of the visual system other than by light.
i.e., stimulate visual cortex in dark room getting phosphenes
How does TMS work? - (2)
- Figure 8 TMS head coil over participants’ head
- In the coil, current which induces magnetic field that goes through the skull and induces electric field in opposite direciton in underlying brain tissue
Why do we use Figure 8 coil in TMS? - (2)
- graph of electric field
- The problem with using circular coil is that field is not specific as compared to Figure of 8 which targets specific region maximally and peak
What does this graph show in terms of principles of TMS? - (4)
- Important for TMS is the quick rise time of magnetic field pulse in milliseconds –> reason why it took long for TMS machines to develop
- Coil goes from 0 to 2.5 T in magnetic field pulse graph less than 0.2 milliseconds –> quick rise time
- The rate of change in magnetic field is what induces the electric field
- So stimulating coil current current goes have to go quickly and down as well as magnetic field pulse
Diagram of cortical effects of TMS how TMS affects brain processing- Baker’s model - (5)
- How TMS affects brain processing depends on the orientation of the magnetic field to the axons
- Some regiosn axons are more organised and some regions are not
- In A, if we have magnetic field going along the axon then there is no change/effect on brain
- In B, if we have magnetic field crossing the axons perpendicular then see hyerpolarisation/depolarisation and if its strong enough then lead to action potential and see change in brain
- Same for if axon is bent across magnetic field in C and get differential which may induce change in AP
What do we use in YNIC lab for registering MRI scan wtih TMS - (3)
Brainsight2 –> used for neurosuregrey
Participant come in lab with MRI scan done and already ahve their structural image and what you do is participant come in and coregisters the participants’ structural MRI scan with participant in space of lab
Then put TMS coil and shows trajectory where magnetic field going in and target to area you want to target
TMS based on 10-20 EEG system in which - (2)
its anatomical landmark approach of where to put electrodes on cap uses inion and naisan of the participant
International 10-20 system for EEG placement is used (e.g. TMS stimulation site would be P4 for example)
2 examples of functional TMS localiser - (2)
- want to find motor cortex by finding itroughly by using participants’ hand jerking response
- can find area known as forsal angular gyrus is important for visual searching by having participants do visual search task and hover coil and find area when participants have impairments in the taks in finding red line which was present in some trials (picture)
Sack et al., (2008) compared number of participants required to reach signifiance for methods 1-4 and found
Need less participants for methods 1 (5) than methods 4 (~43) to reach sig
In Silvanto et al., (2007) TMS experiment subjective report of control participants –> where perceive phosphenes
A. unilateral
B. Bilateral TMS
A participants see phopshenes in left visual field when stimulating right in A
In B when stimulating both sides seeing phopshenes across both visual field
In Silvanto et al., (2007) TMS experiment subjective report of control participants -> where perceive phosphenes
A. unilaterla
B. Bilateral TMS - (2)
in A stimulating the right in which has right V1 seeing percepts of phosphenes in left visual field hes not blind in like in control pps
In B, however, stimulated both motion areas for very first time in time he reported seeing flasshes in his blind right visual field
In combining TMS and fMRI they did 2 tasks of select and execute in which - (2)
In the execute task the participants had to press a button index finger when they saw a circle or a square.
In the select task the participants had to press buttons with two different fingers, depending on which forms they saw - task where premotor task is involved in
Diagram of brain activation in healthy participants in combining fMRI and TMS experiment:
Healthy participants had higher activation in select task than execute task in right and left pre motor cortex
In combining TMS and fMRI
How to answer the question
After a unilateral stroke affecting the dorsal premotor cortex in one hemisphere the dorsal premotor cortex in the intact hemisphere is often more active
Is this due to altered brain structure/connectivity?
Or is it related to reorganisation of brain function?
- (2)
- did fMRI tasks of select and execute pre TMS then TMS then fMRI tasks post TMS
- in TMS, applied TMS to pps left premotor cortex
