Explain the difference between 2 types of TMS
Single pulse is used to explore brain function, while rTMS is used to induce changes in brain activity that can last beyond stimulation period
What does TMS evoke?
corticospinal acticity
What are the 2 measures of corticospinal activity?
Motor threshold
Motor-evoked potential
Explain motor threshold
The minimum stimulation capable of causing a twitch; minimum TMS intensity required to evoke MEP of at least 50 mV in 5/10 consecutive trials
What are volleys?
Descending volleys; signals sent from brain’s motor cortex down through the spinal cord - down descending tracts (neural pathways responsible for controlling voluntary movement)
How are the neurons TMS activates oriented and where do they send signals?
TMS activates neurons oriented horizontally that are parallel to the coil and the brain surface
Explain motor evoked potential
When TMS activates neurons parallel to the coil and induces descending volleys down the corticospinal tract, motor neuron activation causes the target muscle to contract. This produces an MEP which can be recorded on EMG.
EMG recorded by placing surface electrodes on muscle belly.
What is used to estimate the excitability of the corticospinal tract?
The peak-peak amplitude of the MEP
MT depends on cortico-cortico axon excitability and their input to corticospinal neurons
What does MT depend on?
On cortico-cortical axon excitability and their input to corticospinal neurons
This is influenced by agents blocking voltage gated Na+ channels
What can MT be lowered by and what is the mechanism?
By anything that increases the excitability of a neuron; for example, by enhancing glutamatergic (NMDA) transmission, reducing GABAergic inhibition, or applying excitatory stimulation protocols such as anodal tDCS or high-frequency rTMS
What can MT be increased by?
by agents blocking voltage gated Na channels, which decreases excitability and thus more TMS intensity is needed to evoke an MEP
By what can MEP be depressed and what is the mechanism for the depression?
By agents that inactivate Na+ channels such as volatile anaesthetics
Mechanism: Na+ channel inactivation, fewer action potentions, lower Ca2+ entry, reduced synaptic transmission
By modulators of GABA receptors
By what can MEP be increased?
By dopamine agonists and various norepineprhine agonists
Explain single pulse TMS and what it is used for
Single magnetic pulse through wire coil over motor cortex: causing MEP (twitch) recorded via EMG
Used to explore brain functioning
Explain paired pulse TMS and what it is used for
It is a type of single pulse TMS where two successive pulses are applied over the same point on the motor cortex
Also used to explore, especially inhibitory/excitatory intracrotical networks
Explain the difference between single pulse and rTMS
rTMS uses biphasic pulse waveforms because of their lower energy requirements, compared to monophasic waveforms used in single-pulse experiments
Explain rTMS, what it is used for and its mechanisms
Used to induce changes in activity that go beyond stimulation period.
Mechanisms are poorly understood but thought to involve synaptic plasticity, similar to LTP and LTD.
Low frequency rTMS has inhibitory effect; decreases excitability or cortico-cortical neurons and has LTD like effects
High frequency rTMS has excitatory effect; increases excitability and has LTP like effects
Explain theta burst stimulation
A type of TMS protocol that stimulates pattern based on brain’s theta waves; involves bursts of high-frequency stimjulation, intensity threshold set to 80% of motor threshold.
Used to induce synaptic plasticity in animal studies
The effects on excitability depends on the pattern (iTBS vs cTBS)
How to TBS results compare to regular TMS methods?
they are more consistent, because stimulation intensity and number of puses is roughly equal, unlike simple TMS
Explain difference between cTBS and iTBS
Theta burst stimulation with different patterns and excitatory/innhibitory resutls.
cTBS: bursts repeated for 40s without pause. causes depression of MEP for approx 60 min.
iTBS: burst of 2s then repeated every 10s. increases cortex excitability and MEP.
Relationship between cortical excitability, MT and MEP
MT measures how easily neurons fire; MEP measures how strongly they respond once they do.
↓ excitability → ↑ MT and ↓ MEP amplitude
↑ excitability → ↓ MT and ↑ MEP amplitude
What is Paired Association Stimulation (PAS) method
This is a type of TMS protocol. It combines peripheral electrical nerve stimulation (somewhere on the body) with TMS over the corresponding region of the motor cortex. It can induce Hebbian plasticity.
How does PAS work?
Each pairing = one peripheral electrical pulse (e.g., median nerve) followed by a TMS pulse to the contralateral motor cortex after a fixed interstimulus interval (ISI).
The timing (ISI) determines whether synaptic strength increases or decreases.
What are the timing dependent effects of PAS?
If the TMS pulse follows the peripheral input (around 25 ms later), cortical excitability increases (Hebbian, LTP-like effect). If the TMS pulse occurs before the peripheral input (shorter ISI, less than the afferent delay), cortical excitability decreases (anti-Hebbian, LTD-like effect).