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Transcript of TMS lecture2
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Techniques in CognitiveNeuroscience
Transcranial Magnetic Stimulation (TMS)
Dr. Roger Newport
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Lecture Overview
Brief history of TMS and how it works
What can TMS add to Cognitive Neuroscience ?What advantages are there for TMS over other brain-behavior techniques?
Lesion sudies
Direct cortical stimulation
Imaging
TMS
Design ConsiderationsTMS safety
Contraindications
Acceptable risksEthics
Coil shape
Depth and spatial resolution of stimulation
Coil Localisation
Control conditions
Stimulation techniques and effects
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dArsonval (1896/1911) Magnusson &Stevens, 1911Thompson, 1910
History of TMS and obligatory funny pictures
Merton &Morton (1980). Successful
Transcranial Electrical Stimulation
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Barker, 1984
Transcranial MagneticStimulation allows the Safe,Non-invasive and Painless
Stimulation of the HumanBrain Cortex. Cadwell
DantecMagstim
Common rTMS machines
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Electromagnetic Induction
Introduces disorder into a normally ordered system
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Lecture Overview
Brief history of TMS and how it works
What can TMS add to Cognitive Neuroscience ?What advantages are there for TMS over other brain-behavior techniques?
Lesion sudies
Direct cortical stimulation
Imaging
TMS
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Lesion Studies
Dependence of serendipity of nature or experimental models in animals
Single or few case studies
might be more than a single lesion
lesion may be larger than the brain area under study
Cognitive abilities may be globally impaired
Lesion can only be accurately defined post mortem
The damaged region cannot be reinstated to obtain control measures that
bracket the lesion-induced effect
Comparisons must be made to healthy controls; internal double dissociations
are not possible
Given brain plasticity, connections might be modified following lesions
Other Brain-Behavior Techniques
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Cortical Stimulation Invasive
Limited to the study of patients with brain
pathologies requiring neurosurgical
interventions
Stressful situation in the OR and medications
might condition subjects performance
Time constraints limit the experimental
paradigms
Retesting is not possible
Other Brain-Behavior Techniques
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Other Brain-Behavior Techniques
Neuroimaging (Brain Mapping)
Non-invasive identification of the
brain injury correlated with a given
behavior
Association of brain activity withbehavior - cannot rule out
epiphenomenon
Cannot demonstrate the necessity of
given region to function
Neuroimaging techniques are usuallyonly good either temporally or
spatially, not both (e.g. Pet & fMRI
lack temporal resolution, EEG lacks
spatial resolution)
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Advantages of TMS in the Study of Brain-
Behavior Relations
Study of normal subjects eliminates the potential confounds of
additional brain lesions and pathological brain substrates
Acute studies minimize the possibility of plastic reorganization
of brain function
Repeated studies in the same subject
Study multiple subjects with the same experimental paradigm
Study the time course of network interactions
When combined with PET or fMRI, can build a picture of not
only which areas of brain are active in a task, but also the time atwhich each one contributes to the task performance.
Study internal double dissociations and network interactions by targeting
different brain structures during single a task and disrupting the same cortical
area during different related tasks
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Real lesion
Blue = sighted; Red = E blind
Cohen et al., 1997.
Occipital TMS
disrupts braille
reading in early blind,
but not control
subjects
Hamilton et al., 2000.
Reported case of blind
woman who lost ability to
read braille following
bilateral occipital lesions
Advantages of TMS: Virtual Patientscausal link between brain activity and behaviour
TMS lesion
Braille Alexia
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Advantages of TMS: Chronometry
Role of visual
cortex in tactile
information
processing in early
blind subjects
Hamilton and Pascual-
Leone, 1998
Chronometry:
timing the
contribution of focal
brain activity to
behavior
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Paus et al. TMS/PET
TMS to FEF - correlation between
TMS and CBF ati) stimulation site
ii) distal regions consistent with
known anatomical connectivity of
monkey FEF
Functional connectivity- relate behaviour to theinteraction between elements of a neural network
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Mapping and modulation of neural plasticity
- rapid changes
Serial Reaction Time Task
Cohen and colleagues.
Modulation of cortical excitability
in deafferentation studies.
TMS of plastic hemisphere
increases neural response,
TMS of non-plastic hemisphere
downgrades neural response of
plastic hemisphere.
Rapid plasticity - map changes incortical excitability using
TMS/MEPs during a learning task
(Pacual-Leone et al.)
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Other uses for TMS
Clinical - test speed, or existence of,
of corticospinal connections
(MS/stroke)
Therapy -rTMD has long term
effects on depression
Braille reader took 10-day holiday from
reading. Size of finger representation
shrank dramatically until she returned
to work even time off over the
weekend quantitatively reduced finger
representation.
Measure changes in motor
excitability in neurologic
disorders (e.g. PD, HD)
Mapping and modulation of neural plasticity
- slow changes
Amputee cortical excitability
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Summary: What can TMS add to Cognitive
Neuroscience ?
Virtual Patients: causal link between brain activity
and behavior
Chronometry: timing the contribution of focalbrain activity to behavior
Functional connectivity: relate behavior to the
interaction between elements of a neural network
Map and modulate neural plasticity
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Lecture Overview
Brief history of TMS and how it works
What can TMS add to Cognitive Neuroscience ?What advantages are there for TMS over other brain-behavior techniques?
Lesion sudies
Direct cortical stimulation
Imaging
TMS
Design ConsiderationsTMS safety
Contraindications
Acceptable risksEthics
Coil shape
Depth and spatial resolution of stimulation
Coil Localisation
Control conditions
Stimulation techniques and effects
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Safety
Seizure induction - Caused by spread of excitation. Single-pulse TMS
has produced seizures in patients, but not in normal subjects. rTMS hascaused seizures in patients and in normal volunteers. Visual and/or
EMG monitoring for afterdischarges as well as spreading excitation
may reduce risk.
Hearing loss - TMS produces loud click (90-130 dB) in the most
sensitive frequency range (27 kHz). rTMS = more sustained noise.
Reduced considerably with earplugs.
Heating of the brain - Theoretical power dissipation from TMS is fewmilliwatts at 1 Hz, while the brain's metabolic power is 13 W
Engineering safety - TMS equipment operates at lethal voltages of up
to 4 kV. The maximum energy in the capacitor is about 500 J, equal todro in 100 k from 50 cm on our feet. So dont ut our tea on it.
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Safety
Scalp burns from EEG electrodes - Mild scalp burns in subjects with
scalp electrodes can be easily avoided using, e.g., small low-conductivity Ag/AgCl-pellet electrodes.
Effect on cognition - Slight trend toward better verbal memory,
improved delayed recall and better motor reaction time
Local neck pain and headaches - Related to stimulation of local
muscles and nerves, site and intensity dependant. Particularly
uncomfortable over fronto-temporal regions.
Effect on Mood in normals - Subtle changes in mood are site and
frequency dependant. High frequency rTMS of left frontal cortex
worsens mood. High frequency rTMS of right frontal cortex may
improve mood.
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+ minimum inter-traininterval
e.g. at 20Hz @1.0-1.1
T leave >5s inter train
Frequency (Hz) Max. duration (s)
1 1800+
5 10
10 5
20 1.6
25 .84
Maximum safe duration of single rTMS train at 110% MT
Follow published safety guidelines for rTMS
Caution: Guidelines not perfect
Safety
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Safety -Contraindications
Metallic hardware near coil
Pacemakers
implantable medical pumps
ventriculo-peritoneal shunts
(case studies with implanted brain stimulators and abdominal devices have not shown
complications)
History of seizures or history of epilepsy in first degree relative
Medicines which reduce seizure threshold
Subjects who are pregnant
(case studies have not shown complications)
History of serious head trauma
History of substance abuseStroke
Status after Brain Surgery
Other medical/neurologic conditions either associated with epilepsy or in whom a seizure
would be particularly hazardous (e.g. increased intracranial pressure)
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Have you ever: had an adverse reaction to TMS?
Had a seizure?
Had an EEG?
Had a stroke?
Had a head injury(include neurosurgery)?
Do you have any metal in your head (outside of the mouth,) such as shrapnel, surgical
clips, or fragments from welding or metalwork? (Metal can be moved or heated by TMS)
Do you have any implanted devices such as cardiac pacemakers, medical pumps, or
intracardiac lines? (TMS may interfere with electronics and those with heart conditions are
at greater risk in event of seizure)
Do you suffer from frequent or severe headaches?
Have you ever had any other brain-related condition?
Have you ever had any illness that caused brain injury?
Are you taking any medications? (e.g. Tricyclic anti-depressants, neuroleptic agents, and
other drugs that lower the seizure threshold)
If you are a woman of childbearing age, are you sexually active, and if so, are you not using
a reliable method of birth control?
Does anyone in your family have epilepsy?
Do you need further explanation of TMS and its associated risks?
Safety TMS Adult Safety Screen
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Levels of Risk
Class I - Direct clinical benefit is expected, e.g. depression.
Level of acceptable risk (i.e. sz) is moderate Class II - Potential, but unproven benefit, e.g. PD. Level
of acceptable risk is low.
Class III - No expected benefit. Will advance general
understanding. Requires stringent safety guidelines.
Ethics Guidelines
Informed Consent - disclosure of all significant risks, both
those known and those suspected possible
Potential Benefit must outweigh risk
Equal distribution of risk - Particularly vulnerable patient
populations should be avoided
i
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The geometry
of the coil
determines thefocality of the
magnetic field
and of the
induced current
- hence also of
the targeted
brain area.
TPractical
considerationsCoil shape
P i l C id i
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25mm
15mm20mm
70x60
55x4540x30
0
5mm
Practical Considerations - stimulation depth
Cannot stimulate medial or sub-cortical areas
Ca tion!
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Knowledge of the magnetic field induced by the coil is not
sufficient to know the induced current in the brain - and that is
very difficult to measure
It is possible that differences in brain anatomy may lead to inter-
individual differences in the substrates of TMS effects
The presumed intensity of TMS is usually based on motor threshold
But this assumes a uniform and constant threshold throughout cortex
Caution!
All the figures quoted on the previous page are estimated.
Temporal effects depend on recovery rate of neural area
Further Caution! Spread of activation
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Further Caution! Spread of activation
and the path of least resistance
C il l li ti hitti th i ht t
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Find anatomical landmark
inion/nasion-ear/ear vertex
EEG 10/20 system
Coil localisation - hitting the right spot
Move a set distance along and
across (e.g. FEF = 2-4 cm anterior
and 2-4 cm lateral to hand area)
Find functional effect
M1 - hand twitch (MEP)
V5 - moving phosphenes
C il l li ti hitti th i ht t
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But: not all brains are the same
Functional and structural scan
e.g. eye movement test from functional
and map onto structural, then co-reg
v. expensive and laborious
MRI co-registration
Coil localisation - hitting the right spot
Frameless
Stereotactic
System
Paus et al.
Sti l ti t h i d ibl ff t
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--
++
Stimulation techniques and possible effects
Single pulse
rTMS (low/high fr.)
Paired pulse Paired pulse
Paradoxical effectsConnected effectsExpected effect
C t l C diti
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Real
Sham
Control Conditions
Different hemisphere
Different site
Different
effect or
no effect
Or interleave TMS with no TMS trials
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Major limitations summaryOnly regions on cortical surface can be stimulated
Can be unpleasant for subjects
Risks to subjects and esp. patients
Stringent ethics required (cant be used by some institutions)
Localisation uncertainty
Stimulation level uncertainty
Major advantages summaryReversible lesions without plasticity changes
Repeatable
High spatial and temporal resolution
Can establish causal link between brain activation and behaviour
Can measure cortical plasticity
Can modulate cortical plasticity
Therapeutic benefits
S t d R di
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Suggested ReadingsWalsh and Cowey (1998) Magnetic stimulation studies of visual cognition. Trends in Cognitive
Sciences 2(3), 103 -110
Vincent Walsh and Matthew Rushworth (1999) A primer of magnetic stimulation as a tool for
neuropsychology. Neuropsychologia 37, 125 - 135Paus (1999) Imaging the brain before, during and after transcranial magnetic stimulation.
Neuropsychologia 37.
Paus et al. (1997) Transcranial magnetic stimulation during positron emission tomography: a new
method for studying connectivity of the human cerebral cortex. Journal of Neuroscience 17, 3178
- 3184.
Cohen, L.G. et al. (1997) Functional relevance of cross-modal plasticity in blind humans Nature
389, 180183
Pascual-Leone, Walsh and Rothwell. (2000) Transcranial magnetic stimulation in cognitive
neurosciencevirtual lesion, chronometry, and functional
connectivity Current Opinion in Neurobiology 2000, 10:232237
Hamilton et al., (2000).. Alexia for Braille following bilateral occipital stroke in an early blind
woman. Neuroreport 11: 237-240, 2000
Hamilton and Pascual-Leone (1998). Cortical plasticity associated with Braille learning, Trends
in Cognitive Sciences, Volume 2, Issue 5, 1 May 1998, Pages 168-174
Eric M. Wassermann. (1998). Risk and safety of repetitive transcranial magnetic stimulation:
report and suggested guidelines from the International Workshop on the Safety of Repetitive
Transcranial Magnetic Stimulation June 5 7 1996 Electroencephalography and clinicalN h i l 108 (1998) 1 16