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BRAIN STIMULATION
Hee Sok, Han
Department of Biomedical Engineering, Kyung-Hee
University
CONTENTS
1. INTRODUCTION
 What is Brain stimulation?
 Introduction-brain
 Neuron
 Brain Disease
2. TECHNIQUE OF STIMULATION
 DEEP BRAIN STIMULATION
 TRANSCRANIAL DIRECT CURRENT STIMULATION
 TRANSCRANIAL MAGNETIC STIMULATION
 TRANSCRANIAL ULTRASOUND STIMULATION
3. APPLICATION
BRAIN STIMULATION
Definition: Brain stimulation is a technique which involves electric currents to the brain to
interrupt brain function.
DBS (Deep brain stimulation)
Online: http://www.thehealthage.com
tDCS (Transcranial direct current stimulation)
Online: http://www.biotele.com
TMS (Transcranial magnetic stimulation)
Online: http://www.biotele.com
TUS (Transcranial ultrasound stimulation)
Online: http://www.mayfieldclinic.com
INTRODUCTION-BRAIN
• Physiologically, the function of the brain is to exert centralized
control over the other organs of the body. The brain acts on the rest of
the body both by generating patterns of muscle activity and by
driving the secretion of chemicals called hormones. This centralized
control allows rapid and coordinated responses to changes in the
environment. Some basic types of responsiveness such as reflexes can
be mediated by the spinal cord or peripheral ganglia, but sophisticated
purposeful control of behavior based on complex sensory input
requires the information-integrating capabilities of a centralized brain.
THE NEURON :
HOW THE BRAIN’S MESSAGING SYSTEM WORKS
Dendrites
Axon
Cell body
(the cell’s life
support
center)
Terminal
branches of
axon
Neuronal Impulse
Myelin
sheath
Donald Bliss, MAPB, Medical Illustration
dopamine
transporters
WHAT IS DBS?
 DBS (Deep Brain Stimulation)
: Application of weak electrical current through the inserted electrodes to modulate
the activity of neurons.
Inserted micro-electrodes in the Brain
Applied weak Voltage (2-3V) through the
electrodes to modulate the activity of neurons
Cortical excitability changes by DBS
Treat the brain disorders such as depression,
stroke, and Parkinson’s disease
HISTORY

Basal ganglia have been targeted for neuromodulation surgery since the
1930s.

1950s: Pallidotomy was the accepted procedure for the treatment of PD.

1960s: Levodopa therapy was introduced
- However, many PD patients remain disabled despite best available
dopaminergic treatment

Limitations of dopaminergic therapy led to a resurgence of new surgical
techniques directed at basal ganglia targets in late 1980s, early 1990s.
HISTORY

1993: Bilateral high-frequency stimulation of subthalamic nucleus (STN)
introduced in treatment of advanced PD
- Based on new insights into the pathophysiology of basal ganglia derived from experimentation on
animal models of PD

Siegfried & Lippitz (1994): Introduced DBS of globus pallidus internus (GPi)
for treatment of advanced PD

Pioneering studies & empirical observations during surgery showed that DBS
improved PD patient’s motor function and quality of life.

Today, DBS (electrical stimulation of basal ganglia structures via implanted
electrodes) has become a non-lesioning alternative to pallidotomy.
NEUROBIOLOGY
Brain areas targeted in DBS:
1.
2.
3.
Vim = ventralis intermedius nucleus of the thalamus
GPi = posteroventral portion of the internal segment of
the globus pallidus
STN = subthalamic nucleus
METHODS

Stereotactic Surgery
- Locate targeted brain areas
- Stereotactic frame
- MRI, CT, or ventriculography
- Stereotactic atlas
METHODS
Pre-Operative Stage:

Functional Stereotactic Surgery
- Electrophysiological exploration of
targeted regions via test electrodes
- Involves:
1. Microrecording
2. Test-stimulation
- Increases accuracy of localization (i.e.
finding optimum target in GPi or STN)
- Under local anesthesia
METHODS

Optimal Stimulation Sites:
- Dorsolateral STN border
- Posteroventral GPi
Implantation of Electrode:


DBS electrode stereotactically inserted with special rigid guide tube
Patient is awake and in the medication-“off” state after 12-hour
withdrawal
METHODS
Implantation of Electrode:


Electrode has 4 contacts on
its distal end
The effects of stimulation
from each combination of 2
contacts or monopolarly from
each contact are assessed
- Determine best contact(s) to
use to obtain optimal
therapeutic benefit
METHODS
Electrode-Stimulator Connection:



Electrode  Extension (passed under
skin to chest)  Chest: Batteryoperated stimulator
Patient turns stimulator “on” and “off” by
passing magnet over the skin overlying
stimulator
Typical stimulator settings:
- Voltage amplitude: 2-3 V
- Pulse width: 90 μs
- Stimulation frequency: 130-185 Hz
METHODS
Electrode-Stimulator Connection:


Stimulator parameters adjusted via a
computer-controlled probe placed
over stimulator
Pulse generator can be adjusted
post-operatively by telemetry:
(1) Electrode configuration
(2) Voltage amplitude
(3) Pulse width
(4) Frequency
ADVANTAGE VS. DISADVENTAGE
Adventage :
• it does not destroy any part of the brain(Focusing)
• New treatment is available that they’d like to participate in, turn off
the devices or have them removed
Disadventage :
• The presence of a foreign object in the body may increase the risk
of infection(Invasive)
• Repeat surgery every 3~5 years in order to replace the battery in
the device
• Uncomfortable sensations that may occur during stimulation
WHAT IS TDCS?
 tDCS (Transcranial direct current stimulation)
: Application of weak electrical current through the surface electrodes to modulate
the activity of neurons.
Attach two surface electrodes on the scalp
Applied weak current (1-2mA) through the electrodes to
modulate the activity of neurons
Cortical excitability changes by tDCS
Treat the brain disorders such as depression, stroke,
and Parkinson’s disease
Online: http://www.biotele.com
Technical illustration: Bryan Christie
HISTORY
•
Low-intensity electrical stimulation threusts of the 18 th century with studies of galvanic(i.e.,
direct) current in humans and animals.
•
aldini had assessed the effect of galvanic head current on himself(a;domo 1794).
•
He had reported the successful treatment of patients surffing from melancholia(aldini
1804)
•
Low-intensity DC was progressively abandoned in the 1930s when Lucino Bini and Ugo
Cerletti at the University of rome propesed the method of electroconvulsive therapy
METHODS
METHODS
ADVANTAGE VS. DISADVENTAGE
Adventage :
• Non-invasive
• Focusing
• inexpensive
Disadventage :
• Inject direct current(dargerous)
•
WHAT IS TMS?
TMS (Transcranial Magnetic Stimulation)
: Weak electric currents are induced in the tissue by changing magnetic fields
Pulse of current flow through a coil over the surface of
the head
Current make the time-varying magnetic field, which
induces the electric field in the head
Induced Electric field drives current in the brain which
stimulate neurons
Treat the brain disorder such as depression, stroke,
Parkinson’s disease
Transcranial magnetic stimulation (TMS)
HISTORY
Historical Background:
• About a century ago researchers first
stimulated retinal nerve cells with
magnetic fields to produce flashes of
light in subjects
• 1985 Barker and colleagues first
stimulate brain cells in the motor cortex
of subjects.
• By 1990’s develop repetitive TMS where
repeated magnetic pulses can be
delivered up to 50 times a second (50
hertz)
Thompson, 1910
Electric Principle in TMS
TMS (Transcranial Magnetic stimulation)
- Biot-Savart law
𝜇0𝑁
4𝜋
- Faraday’s law
𝐵 𝑅 =
▽× 𝐸 = −
- Ohm’s law
𝐼(𝑡)
𝑑𝑙
𝑅3
𝜕𝐵
𝜕𝑡
𝐽 = 𝜎𝐸
E:
B:
𝜇0:
I:
N:
𝜎:
J:
Electric field
Magnetic field
Permeability of the head tissue
Current along the coil path
The number of turn
Conductivity of the head tissue
Current Density
Induced electric fields by current through the coil
METHODS
ADVANTAGE VS. DISADVENTAGE
Adventage :
• Non-invasive
• Ability to show causation
• Subjects conscious
Disadventage :
• Can’t stimulate in one place(focusing)
WHAT IS TUS?
TUS (Transcranial Ultrasound Stimulation)
: Low-intensity, low-frequency ultrasound are stimulated in the tissue
Shinning focused ultrasound through a transducer into
the intact brain.
Ultrasound stimulate neural activity through a
combination of pressure/fluid/membrane actions in the
brain
Treat the brain disorder such as depression, stroke,
Parkinson’s disease
Transcranial ultrasound stimulation (TUS)
HISTORY
• Study of the ultrasonic existing were used ultrasound image, and bone
density measurements, etc.
• ‘Ultrasound Induced Increase in Excitability of Single Neurons’(30 th IEEE
EMBS Conference,Vancouver,British Columbia, Canada, August, 2008)
Massoud L. Khraiche publish in conference.
MECHANOSENSITIVE CHANNELS
•
Mechanosensitive channels (MSCs) are found in nearly all organisms.
Many of these channels are designed to sense pressure for various
reasons. For example, some MSCs sense osmotic pressure and
function to keep cells from rupturing. Other MSCs are involved in
sensory processes, such as transient receptor potential (TRP) channels
involved in the transducing the sense of touch.
•
Advances in our understanding of the biophysical behavior and
regulation of ion channels have revealed that nearly all ion channels
are mechanically sensitive to some degree. Even classic voltage-gated
channels, such as voltage-gated sodium, potassium, and calcium
channels exhibit gating properties, which are mechanosensitive.
•
Some neurotransmitter receptors like the glutamatergic NMDA receptor
has been shown to respond to stretch. Due to the integrated nature of
membrane bound ion channels in a phospholipid bilayer, stress,
bending, tension, compression, and expansion of the cellular
membrane can also influence the opening and closing of ion channels.
•
The degree to which the mechanosensitivity of ion channels impinge
upon neuronal activity and plasticity is not understood. However, such
consequences have critical ramifications on our conventional
understanding of brain function.
Online: 조선일보
ADVANTAGE VS. DISADVENTAGE
Adventage :
• Non-invasive
• Ability to show causation
• Stimulate on target point(Focusing)
Disadventage :
• Unknown(??)
COMPARED BRAIN STIMULATION
Advantages
DBS
tDCS
TMS
• Focusing
• Non-Invasive
• Focusing
• Non-Invasive • Non-Invasive
• harmless
• Focusing
• harmless
• Dangerous
• Inject Direct
current
• Unfocusing
Disadvantage • Invasive
• Dangerous
• Change Machine
(3~5years)
Direction of improvement Medical Engineering
TUS
• Unknown.
THANK YOU.
Q&A