Techniques in Cognitive Neuroscience

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Techniques in Cognitive Neuroscience

• 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 Considerations
• TMS safety
• Contraindications
• Acceptable risks
• Ethics
• Coil shape
• Depth and spatial resolution of stimulation
• Coil Localisation

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History of TMS and obligatory funny pictures
Merton Morton (1980). Successful Transcranial
Electrical Stimulation
Magnusson Stevens, 1911
Thompson, 1910
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Barker, 1984
Common rTMS machines
Dantec
Magstim
Transcranial Magnetic Stimulation allows the
Safe, Non-invasive and Painless Stimulation of
the Human Brain Cortex.
Cadwell
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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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Other Brain-Behavior Techniques

• 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

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Other Brain-Behavior Techniques

• 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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Other Brain-Behavior Techniques

• Neuroimaging (Brain Mapping)
• Non-invasive identification of the brain injury
  correlated with a given behavior
• Association of brain activity with behavior -
  cannot rule out epiphenomenon
• Cannot demonstrate the necessity of given region
  to function
• Neuroimaging techniques are usually only 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 at which 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
Advantages of TMS Virtual Patients causal link
between brain activity and behaviour
Braille Alexia
TMS lesion
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
Blue sighted Red E blind
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Advantages of TMS Chronometry
Chronometry timing the contribution of focal
brain activity to behavior
Role of visual cortex in tactile information
processing in early blind subjects
Hamilton and Pascual-Leone, 1998
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Functional connectivity- relate behaviour to the
interaction between elements of a neural network
TMS to FEF - correlation between TMS and CBF
at i) stimulation site ii) distal regions
consistent with known anatomical connectivity of
monkey FEF
Paus et al.
TMS/PET
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Mapping and modulation of neural plasticity -
rapid changes
Rapid plasticity - map changes in cortical
excitability using TMS/MEPs during a learning
task (Pacual-Leone et al.)
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.
Serial Reaction Time Task
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Mapping and modulation of neural plasticity -
slow changes
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.
Other uses for TMS Clinical - test speed, or
existence of, of corticospinal connections
(MS/stroke) Therapy -rTMD has long term effects
on depression
Amputee cortical excitability
Measure changes in motor excitability in
neurologic disorders (e.g. PD, HD)
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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 focal
  brain 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 Considerations
• TMS safety
• Contraindications
• Acceptable risks
• Ethics
• Coil shape
• Depth and spatial resolution of stimulation
• Coil Localisation

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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 has caused 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 few milliwatts 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 to
dropping 100 kg from 50 cm on your feet. So dont
put your 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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Safety
Follow published safety guidelines for rTMS
Maximum safe duration of single rTMS train at
110 MT
minimum inter-train interval e.g. at 20Hz
_at_1.0-1.1 T leave gt5s inter train
Caution Guidelines not perfect
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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 abuse
• Stroke
• 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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Safety TMS Adult Safety Screen
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?
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Levels of Risk
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

• 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.

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Practical considerations Coil shape
The geometry of the coil determines the focality
of the magnetic field and of the induced current
- hence also of the targeted brain area.
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Practical Considerations - stimulation depth
70x60
55x45
40x30
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Cannot stimulate medial or sub-cortical areas
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Caution! All the figures quoted on the previous
page are estimated.
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
The presumed intensity of TMS is usually based on
motor threshold But this assumes a uniform and
constant threshold throughout cortex
It is possible that differences in brain anatomy
may lead to inter-individual differences in the
substrates of TMS effects
Temporal effects depend on recovery rate of
neural area
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Further Caution! Spread of activation and the
path of least resistance
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Coil localisation - hitting the right spot
Find functional effect M1 - hand twitch (MEP) V5
- moving phosphenes
Find anatomical landmark inion/nasion-ear/ear
vertex EEG 10/20 system
Move a set distance along and across (e.g. FEF
2-4 cm anterior and 2-4 cm lateral to hand area)
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Coil localisation - hitting the right spot
But not all brains are the same
Paus et al.
MRI co-registration
Functional and structural scan
Frameless Stereotactic System
e.g. eye movement test from functional and map
onto structural, then co-reg
v. expensive and laborious
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Stimulation techniques and possible effects
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Paradoxical effects
Connected effects
Expected effect
Single pulse rTMS (low/high fr.)
Paired pulse
Paired pulse
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Control Conditions
Real
Different hemisphere
Different effect or no effect
Sham
Different site
Or interleave TMS with no TMS trials
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Major advantages summary Reversible 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
Major limitations summary Only 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
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Suggested Readings
Walsh 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 - 135 Paus (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 neuroscience virtual
lesion, chronometry, and functional connectivity
Current Opinion in Neurobiology 2000,
10232237 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 57, 1996
Electroencephalography and clinical
Neurophysiology 108 (1998) 116