TMS lecture2

7/30/2019 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



Lesion sudies


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



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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



Lesion sudies


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

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