Module A - Non-invasive brain stimulation Flashcards
Describe transcranial magnetic stimulation:
Use a plastic covered coil and a capacitor with a huge charge
This creates a brief magnetic field (2.2T ~50ms (most clinically induced magnetic fields are 1.5T)
The magnetic field strength decays exponentially
Perpendicular direction to coil has eddying currents in the opposite direction
Describe the side-effects of TMS:
Safe and painless for most people
A good way of activating cortical neurons in the brain
What results from local depolarisation of the axonal membrane induced by TMS and how are these results detected:
Evoked neural activity (EEG)
Changes in blood flow and metabolism (PET, fMRI)
Muscle twitch (EMG)
Behavioural changes
What type of waves are produced when a single TMS pulse is applied?
I waves (produced by interneurons) Inhibitory interneurons mainly synapse with interneurons
When does SICF occur?
Short interval cortical facilitation occurs when S2 follows S1 by temporal summation
Which types of stimulation induce D waves and late I waves?
Electrical stimulation induces D waves
LM and PA TMS induce late I waves
How can TMS be used to detect CNS conditions?
Can check if connections are present after stroke
Can observe a slowing of conduction velocities in MS
Where does the corticomotor pathway go?
From the motor cortex to the spinal cord to the motor unit
What is the motor threshold (MT)?
Weakest stimulus that will produce an MEP on 4/8 trials
Measured in % maximum simulator output
What are the MEP amplitudes at rest and during muscle activity?
At least 0.05mV at rest
At least 0.10mV during activity
Describe recruitment curves of the corticospinal projections:
Increasing stimulus intensity increases the amplitude of the MEP
Slope is a measure of corticomotor excitability
Recruitment of neurons (lowest firing threshold first)
Recruitment of motor units (smallest first)
Affected by background muscle activity
Describe paired-pulse TMS:
Test stimulus (produce an MEP) Conditioning stimulus (precedes test stimulus, effect depends on intensity and inter-stimulus interval)
Describe short interval intracortical inhibitions (SICI):
Interstimulus intervals between 1 and 5 ms
Conditioning stimulus between 60% and 100% of active motor threshold
GABAa-R activation
Reduced prior to movement
ISI (interspike intervals) 2-3ms
Sychronise to reduce inhibition or syncopate to increase inhibition
What is the output of the motor system a result of?
Inhibition (strokes are poor at this)
Describe long interval intracortical inhibition:
Interstimulus intervals 50-200ms Suprathreshold stimulus (conditioning stimulus BUT produces response) GABAb-R activation
Describe short interval intracortical facilitation:
Specific inter-stimulus intervals
Suprathreshold stimuli
Synchronised I-waves: I-wave facilitation
Describe the contralateral silent period:
Single test stimulus
During voluntary muscle activity
Silent period duration depends on GABAb-R activity
(shown as MEP followed by silent period)
Describe interhemispheric inhibition:
Interstimulus intervals 8-50ms Suprathreshold stimuli GABAb-ergic Task-dependent modulation In stroke, the normal side connections are lost
Describe the ipsilateral silent period:
Single test stimulus
Ipsilateral to activated muscle
Duration depends on GABAb-ergic activity
Describe the general features of TMS:
Versatile research tool
Can measure cortical excitability
Measure GABAA and GABAB function with sub-millisecond precision
Can be used to measure effects of aging, maturation, neurological disorders, interventions in drugs, rehab, learning
Safe, non-invasive and painless
Describe the properties of transcranial direct current stimulation (TDCS):
1-2mA current, up to 20 minutes
Moves ions through ECF
Shifts resting membrane potential
Alters spontaneous firing rate
Describe the roles of the anode and cathode in TDCS:
Anode - depolarisation and increased excitability
Cathode - hyperpolarisation and decreased excitability
Name the types of TDCS:
Direct current Alternating current (Bf 12.5-30Hz) Random noise (0.1-600Hz)
What can the full range of TMS techniques be used to measure:
Cortical excitability
Intracortical inhibition and facilitation
Interhemispheric interactions
Behaviour - learning, memory, mood, perception
Describe the use of TMS in diagnosis:
Conduction velocity, functional weakness (conversion disorder, where TMS can rule out a biological cause to localised weakness)
Acute injury - Stroke, spinal cord injury, peripheral nerve injury and functional weakness
Chronic conditions - multiple sclerosis, ALS
How can TMS and TDCS be used in treatment:
TMS - depression, stroke, chronic pain
TDCS - stroke aphasia and neglect, tinnitus, ambylopia
Describe the predication accuracy of non-invasive applications:
PT - 41% incorrect
Model - 30% incorrect
PREP - 17% incorrect
Describe the use of the PREP algorithm for stroke patients:
Accurate 83% of the time (vs. 50 PT scanner)
More specific prognosis
Measures brain (not just arm)
Describe the 72 hour mark of the PREP algorithm:
SAFE score >= 8 = Complete recovery (predicted recovery of upper-limb function at 12 weeks)
SAFE score < 5 progress to TMS at 5 days
Describe the 5 days mark of the PREP algorithm:
TMS –> MEP present –> Notable recovery (SAFE 5, 6, 7)
MEP absent –> progress to MRI at 10 days
Describe the 10 days mark of the PREP algorithm:
MRI asymmetry index limited recovery
MRI asymmetry index >0.15 –> no recovery
Describe how to induce suppression and facilitation of repetitive TMS:
Low-frequency rTMS (~1Hz) = suppression
High frequency rTMS (5Hz) = facilitation
Describe how to induce suppression and facilitation of theta-burst stimulation:
Continuous (40s) = suppression
Intermittent (every 10s) = facilitation
Describe how to induce suppression and facilitation of paired associated stimulation (PAS):
Given every 3 seconds
ISI of ~10ms = suppression
ISI of ~25ms = facilitation
Describe how to induce suppression and facilitation of transcranial direct-current stimulation (TDCS):
Given continuously for >5 min
Cathodal = suppression
Anodal = facilitation
Describe the mechanism responsible for the effects of TMS:
NMDA-R dependent, effects are blocked by NMDA-R antagonists dextro methorphan and memantine
Calcium influx - rapid influx promotes LTP
- slow influx promotes LTD
Describe the results of a rapid and slow influx of calcium on AMPA receptors:
Rapid influx causes increase in number and density of AMPA-R (LTP)
Slow influx causes decrease in number and density of AMPA-R (LTD)
How do we know the effects of TMS work?
Motor practice (stimulus-response) With rTMS see a shift (definitely less excitable and opposite of motor practice) rTMS resets people when M1 active (interferes)
Is their learning suppression or facilitation in the following TBS situations:
iTBS
imTBS
cTBS
Learn fasted
Suppressed
Suppressed
rTMS can be used to disrupt signalling to ______ learning and facilitate signalling to ______ learning:
Decrease
Increase
Describe the use of rTMS in depression:
Suppresion of prefrontal cortex
Usually subthreshold 1Hz rTMS (weak –> no MC response –> suppressive LTD)
Several session required
FDA approved treatment as a last resort
Describe the use of rTMS in stroke:
Helps people learn better during physiotherapy
Brain stimulation needs to be combined with physical therapy for motor rehabilitation
Most studies are at the chronic stage (caveat)
Describe how TMS can overcome the effect of the good side of the brain becoming overactive and oversuppressing the stroke side in stroke:
Facilitate ipsilesional cortex (same side) TMS facilitation
Suppress contralesional cortex (opposite side) TMS inhibtion
Describe the effects of rTMS and TDCS in stroke:
Can improve upper limb function
Can improve communication
Can reduce visuospatial neglect (where people stop attending to one side)
Describe how TDCS affects learning:
TDCS improve and activates whole motor network
Met carriers (BDNF) have reduced skill (10%)
Val/Val in 2/3 population, higher level of learning
Changes through use and experience (promote more permissible environment to LTP learning synapses)
Describe the use of TDCS in tinnitus:
10% of people have it but can be incredibly disabling for some people
Can reduce the loudness and annoyance of symptoms
Anode to facilitate left temporoparietal area
Dose response
Describe the use of TDCS in ambloyopia (lazy eye):
Can improve depth perception when combined with visual training
What is the intensity in rTMS and TDCS?
% threshold
Up to 2mA
What is the duration of rTMS and TDCS?
How many stimuli?
How many minutes?
Describe the strengths of non-invasive brain stimulation:
Targeted to specific part of brain
Specific effect depending on protocol
Describe the limitations of non-invasive brain stimulation:
Equipment
Contraindications
Describe the interindividual variability of non-invasive brain stimulation:
Suppressing contralesional M1 with cTDCS in stroke patients
- Mild patients get better
- Worse patients get worse
Why should TMS not be tried at home?
Electrodes are very small
TDCS affects a lot of the brain
No idea of maximum safe dose
Brain doping?
