Lecture Four: Principles of non-invasive brain stimulation Flashcards
What is the function of TMS?
- Stimulates the brain directly
- The effects of this can be measured in the periphery i.e alpha motor neurons -> spinal cord activation -> peripheral nerve activation
What is brain stimulation divided into?
Invasive and non-invasive techniques
What is an example of an invasive brain stimulation technique?
Deep Brain Stimulation (DBS)
i.e Used in parkinsons to stimulate the sub thalamic nucleus
Activates local neural effectors and passing neuron axons
What are some examples of non-inasive brain stimulation?
1) Transcranial Magnetic Stimulation
2) Transcranial Direct Current Stimulation
Describe the TMS setup;
- Figure 8 coil
- Huge capacitor (discharges 450v)
- Magnetic field reaches 4cm (2.2T)
Describe how TMS functions;
The coil + current induces a brief rapidly changing magnetic field.
This decays exponentially from the coil
What does the rapidly changing magnetic field in TMS do?
Rapidly changing = induces current flow of ECF and neurons. Therefore causing depolarisation by changing resting membrane potential
What is used to record the effects of TMS?
EEG surface electrodes can record motor evoked potential to infer the state of the motor cortex (commonly used in stroke)
i.e How big, quick, how does it change when the participant thinks something
What does the intensity of the TMS stimulus depend on?
Depends on the geometry of the participants brain
Threshold intensity is variable between people with brain folds
Describe where in the brain TMS is most effective?
TMS is most effective at inducing a current in bending locations such as fissures
Describe what the induction of local current in TMS does?
Induction of a local current activates chains of interneurons. It is there summations of inputs at the dendrites / axons that determines neuron depolarisation.
Not a selective process.
What layer of neurons is TMS most effective at activating?
TMS is most effective by activating the horizontal layer of intercortical interneurons, in cortical layers 1+2.
These synapse onto pyramidal motor + dendritic trees
In the grand scheme of things what sort of pathways is the pyramidal and dendritic trees?
These are indirect pathways and if the stimulus is increased pyramidal neurons can be activated directly.
What does the depolarisation of pyramidal neurons from TMS look like?
Evidence from humans suggests that we can activated different types of waves in neurons.
D wave = Direct wave
Followed by;
I wave
II wave
What are we interested in when depolarising pyramidal neurons using TMS?
Interested in the latency and amplitude because latency can be effected by: Health of neurons i.e stroke, MS, ALS, Peripheral nerve injury etc
Also height
Amplitude it proportional to the umber of nerves recruited.
What is a measured product of TMS?
Corticomotor pathway
Motor cortex -> Spinal cord -> Motor unit
What is the motor threshold?
The weakest stimulus that will produce a MEP (motor evoked potential) on 4/8 trials
What is motor threshold measured in?
- Measured in % max stimulator output (MSO)
- MEP amplitude at least 0.05mV at rest
- MEP amplitude at least 0.10mV when muscle is active
What is also seen on a MEP?
The stimulus artefact prior to main response
What does the recruitment curve for TMS tell us? Page 9
- Increasing stimulus intensity increases the amplitude of the MEP
What does a recruitment curve slope indicate about MEP and being in an active or resting state?
The slope
- Measure of corticomotor excitability
- Recruitment of neurons (lowest firing threshold first)
- Recruitment of motor units (size principle) - Smallest first
- Affected by background muscle activity
How does the slope change between resting and active muscle states?
Steeper during active muscle states
How does EMR threshold change between resting and active states?
In an active state EMR threshold decreases as active state increases
What is paired pulse TMS?
Delivery of two pulses (one coil) (2 capacitors)
Can be at different intensities
Interstimulus interval b/w 1-5ms
In pair pulse TMS what is the first pulse also known as?
First pulse; Conditioning stimulus
- Precedes Test Stimulus (second pulse)
- Effects depend on intensity and inter stimulus interval
What is paired pulse TMS most commonly used for?
Short interval intracortical inhibition
Write some short notes on SICI;
- Interstimulus intervals b/w 1-5ms (PPTMS)
- Conditioning stimulus is b/w 60-100% of active motor threshold
- GABAa-R activation (A)
- Reduced prior to movement
Describe how SICI works;
Conditioning stimulus is sub threshold (weak) but can still activate gaba-ergic interneurons
Therefore when the test stimulus comes in fewer neurons fire (GABA rich environment = inhibition = Decreased MEP.
Therefore this indicates the state of gabaergic interneurons in the patient.
What happens prior to movement with SICI?
SICI is reduced prior to movement (much less inhibition). These neurons have been turned down prior to movement
PPTMS can act as SICI
Whens a situation that was used in the lab to increase SICI?
Syncobate (out of time beating) increases inhibition from static state i.e more inhibiton more GABAergic state
What is LICI?
Long interval intracortical inhibiton
How does LICI work?
- Interval stimulus is 50-200ms
- Conditioning stimulus is suprathreshold
- GABAb-R activation (B)
What is SICF?
Short interval intracortical Facilitation
Describe the conditions for SICF?
- Specific inter-stimulus intervals
- Suprathreshold stimuli
- Synchronised I-waves : I wave facilitation
How does SICF work?
The specific timing of interneuron activation, when correct can boost the signal. i.e when excitation is arriving at pyramidal cells (facilitation)
Poor timing = no effect
What is the use of dual coil TMS?
Dual coil TMS;
- Can activate different parts of cortical network based on stimulus interval
- Motor Cortices linked through corpus colossum (Mostly inhibitory)
What is the contralateral silent period?
A period of time following an MEP that as very little / no electrical activity.
- Refractoriness potentially
- B/c TMS activates GABAb-R interneurons which in the long term create an inhibitory environment
- Changes with age and disease
What are the conditions for contralateral silent period?
- Single test stimulus
- During voluntary muscle activity
- Silent period duration depends on GABAb-R activity
What is interhemispheric inhibition?
The task dependant inhibition of the other hemisphere
What is the conditions for interhemispheric inhibition?
- Interstimulus intervals 8-50ms
- Suprathreshold stimuli
- GABAb-R activity
What did the experiments by morishita show regarding interhemispheric inhibition?
Setup; - One hand = fine motor manipulation task (Active M1 receives conditioning TMS) - Other hand = MEP (resting M1 receives Test TMS)
Expectation = FM task inhibits other side. Interhemispheric inhibition is more pronounced when FM task is used over IA task or rest.
What is the ipsilateral silent period?
The use of TMS to inhibit motor output via interhemispheric communication (Corpus collosum)
- Measure the state of corpus collosum and GABAergic neurons
What are the conditions for the ipsilateral silent period?
- Single test stimulus
- Ipsilateral to activated muscle
- Duration depends on GABAb-ergic activity
Summerise TMS;
- TMS is a versatile research tool
- It can measure cortical excitability
- It can measure GABAa and GABAb function with sub millisecond precision (impressive for non-invasive)
What can TMS be used to measure?
It can be used to measure the effects of;
- Maturation
- Age
- Neurological disease and disorders
- Interventions such as drugs, learning, rehabilitation
- It is safe, non-invasive and painless
What are all the tests TMS can be used for;
SICI LICI SICF Contralateral Silent Period Interhemispheric Inhibition Ipsilateral Silent Period
What are the conditions for Transcranial Direct Current Stimulation?
- 1-2mA current delivered
- Up to 20 mins duration
Electrodes are located in the cup
How does TDS work?
Delivers current from anode to cathode through ECF of brain therefore shifts resting membrane potential of neurons in this pathway and alters their spontaneous firing rate. (not synchronised firing)
What happens at the anode and cathode during TDS?
Anode
- Depolarisation
- Increased excitability
Cathode
- Hyperpolarisation
- Decreased Excitability
Cant predict parts of electric field in patients brains
What are the types of TDS?
- Direct Current (brain adapts to this though)
- Alternating current (13Hz, 12.5-30Hz)
- Random Noise (0.1-600Hz (range))
What is measured in TDS?
All the same stuff as in TMS (same tests)
- Cortical excitability
- Intracortical excitability and facilitation
- Interhemispheric interactions
TMS = Mainly Motor TDS = Psychiatric
What is TDS used in?
- Learning
- Memory
- Mood
- Dexterity
- Perception
What are some safety concerns of non-invasive brain stimulation?
Non-invasive brain stimulation cant be used by people with;
- Pacemakers
- Epilepsy
- Brain surgery patients
- cochlear implants
- aneurysm clips
- DBS
- medication pumps
- pregnancy
