Transcranial Magnetic

Stimulation (TMS)
Changes in membrane potential due to inward(left) and outward(right)
transmembrane current flow.
• TMS is based on the principle of electromagnetic
induction
• If a pulse of current passing through a coil placed
over a person’s head has sufficient strength and
short enough duration... rapidly changing magnetic
pulses are generated that penetrate scalp and
skull to reach brain with negligible attenuation
• These pulses induce a secondary ionic current
(transmembrane) in brain (neurons). A sufficient
current causes depolarisation of its membrane
*The capacity of TMS to depolarise straight nerves
depends on the “activating function”

*Activation function causes transmembrane

current to flow and can be described mathematically
as spatial derivative of Electric Field along the nerve

*Thus, stimulation will take place at a point where

spatial derivative of induced Electric Field is
maximum
*In case of a bent nerve, the situation is a little
different
*Although nerve fibre bends across induced
Electric Field, the current will continue in a
straight line and pass out of the fibre across
membrane (figure 1)
*Thus, spatial derivative of Electric Field along the
nerve is critical, causing the bend to be a
preferential point of stimulation
How TMS works
How TMS effects a nerve fibre
MEP = Motor Evoked Potentials
Anisotropy : Variation in physical properties
 TMS
• TMS is a technique for
noninvasive stimulation of the
human brain.

• Stimulation is produced by
generating a brief, high-intensity
magnetic field by passing a brief
electric current through a
magnetic coil.

• A magnetic field is produced with

lines of flux passing
perpendicularly to the plane of
the coil.
 TMS

An electric field is induced perpendicularly to

the magnetic field.

The voltage of the field itself may excite

neurons, but more important are the induced
currents.

Spatial change of the electric field will cause

current to flow in loops parallel to the plane of
the coil.

The loops with the strongest current will be

near the circumference of the coil. The current
loops become weak near the center of the coil,
and there is no current at the center itself.
 TMS
• The magnetic field can reach up
to about 2 Tesla and typically
lasts for about 100 µs.

• The field can excite or inhibit a

small area of brain below the coil

• All parts of the brain just

beneath the skull can be
influenced, but most studies
have been of the motor cortex
where a focal muscle twitch can
be produced, called the motor-
evoked potential (MEP).
 TMS
• Delivering a single pulse of TMS to the brain is very safe.

• repetitive TMS (rTMS) is capable of delivering high-frequency (1–50

Hz) stimulus. This can produce powerful effects that outlast the
period of stimulation.

• rTMS at slow rates, approximately between 0.2 and 1 Hz, will cause a
decrease in brain excitability.

• rTMS at faster rates, approximately 5 Hz or faster, will cause an

increase in brain excitability.

• rTMS, however, has the potential to cause seizures even in normal

individuals.
 Magnetic Coils
• Magnetic coils have different shapes.

• Round coils are relatively powerful.

• Figure-of-eight shaped coils are more

focal, producing maximal current at the
intersection of the two round
components.

• Cone-shaped coil is figure-of-eight-

shaped coil with the two components
at an angle, has increased power at the
intersection.
 Magnetic Coils
• H-Coil with complex windings
that permit a slower fall-off of
the intensity of the magnetic
field with depth.

• In another design, the windings

of a coil are around an iron core
rather than air; this focuses the
field and allows greater strength
and depth of penetration.
 Magnetic Coils

The geometry of the coil

determines the focality of
the magnetic field and of the
induced current, and hence
also of the targeted brain
area.
Rest motor threshold (RMT):
The minimum stimulation intensity needed to elicit a
recordable EMG response (Motor Evoked Potential
usually 50 to 100 uVolts)) from the target muscle with the
muscle at rest with a 50% probability in a cascade of 10 to
20 consecutive stimuli (Rossini et al EEG J. 1994)
Active motor threshold (AMT):
The minimum stimulation intensity needed to elicit a
recordable EMG response (Motor Evoked Potential) from
the target muscle during tonic contraction (usually 10%
less intensity needed than for RMT)
Frequent conditions that may alter Excitability
Thresholds
• Age
• Wakefulness, drowsiness, sleep
• Body Position and Posture
• Drugs (psicoactive drugs (decreases),
benzodiazepines, barbiturates, antiepileptic
drugs (increases))
Example: Subjects were
shown letters briefly on a
monitor, and TMS was
delivered after the visual
stimulus.
When delivered at an
interval less than 40–60
ms or more than 120–
140 ms, letters were
correctly reported.
When delivered at
intervals of 80–100 ms, a
blur or nothing was seen.
Most probably this
indicates important
visual processing during
that time interval.
TMS Protocols
Stimulus of lower intensity can induce a transient scotoma
 Applications – Antidepressant
• Using fMRI, it was found that
– The hyperactivity of the right dorsolateral prefrontal
cortex (RDLPFC) correlates with the severity of the
depression, which is also related to attention
modulation
– The hypoactivity of the left dorsolateral prefrontal cortex
(LDLPFC) is related to the presence of negative emotions

• rTMS exerts antidepressant effects either

– by enhancing LDLPFC excitability with 10 Hz rTMS or
– by decreasing RDLPFC excitability with 1 Hz rTMS
 Applications – Motor Conduction
• With TMS, it is possible to study the speed of
conduction in central motor pathways.

• This method has been applied in the evaluation of

patients with multiple sclerosis.

• Example: Motor conduction to the abductor digiti

minimi (ADM) muscle.
 Applications – Motor Conduction
• ADM responses were recorded using • The latencies of the potentials are
EMG after stimulation of similar in the patient and normal
– ulnar nerve at the wrist subject following stimulation at the
– C-7 level of the spinal cord wrist and spine, but the latency is much
(activating the nerve roots) longer following cortex stimulation in
the patient, implying prolonged central
– TMS of the cortex over the hand conduction time.
area
 Applications
• TMS is used to map brain function and explore the excitability of different
regions.

• rTMS of 10 Hz of the LDLPFC has been useful in the treatment of

Parkinson’s disease.

• PET and fMRI lack time resolution and cannot alone prove that an area is
essential for a particular function. TMS can transiently disrupt activity in
focal brain regions, allowing researchers to assess function on a millisecond
scale.

• TMS studies, unlike functional imaging, can also be frequently repeated.

 Applications

• In the visual system, TMS has been used to study perception.

(a strong TMS of occipital cortex can produce phosphenes)

Example: TMS of V5 selectively interfere with the perception of motion

of a stimulus without impairing its recognition.
This support the concept arising from imaging studies that V5 is the
motion perception region of the brain.
 Applications – Plasticity
• TMS can be used in a variety of ways to induce plastic changes in the
brain, and this can be utilized to assess the capability for plasticity.

• An effective way to modulate synaptic efficacy is to activate a cell

with two or more inputs at close to the same time

• If the stimuli come on the same synaptic pathway, this is called

homosynaptic, and, if on different synaptic pathways, this is called
heterosynaptic.

• Increased synaptic strength is called long-term potentiation (LTP);

decreased synaptic strength is called long-term depression (LTD).
 Applications – Plasticity
• Heterosynaptic plasticity can be
realized in humans with a peripheral
stimulus paired with a TMS brain
stimulus.

• Example: If a median nerve stimulus at

the wrist is paired with a TMS to the
sensorimotor cortex at 25 ms, then the
two stimuli arrive at about the same
time, and the MEPs will be facilitated
(=> LTP).

• If the interval is about 10 ms, the TMS

comes about 15 ms before the median 90 pairs of median nerve stimulation and TMS were
nerve volley arrives, and the MEP will given with an interstimulus interval (ISI) of 25 ms.
The post-test MEP has become larger than the pre-
be depressed (=> LTD) test MEP
 Applications – Stroke
• In the acute stage, when the patient is paralyzed, the presence of an
MEP is a good prognostic sign.

• The absence of the MEP in this situation can be a bad sign.

• The presence of an MEP in the face of paralysis has also been

sometimes useful in the diagnosis of psychogenic paralysis.
 Applications – Stroke
• Much of the spontaneous recovery from stroke after the acute phase
involves plastic changes in the brain.

• The task for rehabilitation is to find ways to facilitate plasticity so that

the changes occur more rapidly and more completely.

• Since much of good recovery depends on plasticity in the lesioned

hemisphere, one therapeutic approach is to try to increase brain
plasticity in the lesioned region with brain stimulation.
 Side Effects
• Treatment discontinuation because of side effects is very less (~4.5%).

• There have been no deaths or epileptic seizures reported after

thousands of treatment sessions in published studies.

• The side effects are minimal and well tolerated, consisting principally
of migraines and minor skin injuries in the application area.

• There are no verified auditory or cognitive deficits after rTMS