Hee Sok, Han

Department of Biomedical Engineering, Kyung-Hee University

BRAIN STIMULATION

CONTENTS1. 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

TMS (Transcranial magnetic stimulation)Online: http://www.biotele.com

tDCS (Transcranial direct current stimulation)Online: http://www.biotele.com

TUS (Transcranial ultrasound stimulation)Online: http://www.mayfieldclinic.com

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

INTRODUCTION-BRAIN

• Physiologically, the function of the brain is to exert centralized con-trol 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 driv-ing the secretion of chemicals called hormones. This centralized con-trol 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 sophis-ticated purposeful control of behavior based on complex sensory in-put requires the information-integrating capabilities of a centralized brain.

Donald Bliss, MAPB, Medical Illustration

Terminalbranches of

axon

Cell body(the cell’s life

support center)

Dendrites

Myelinsheath

Axon

Neuronal Impulse

THE NEURON :HOW THE BRAIN’S MESSAGING SYSTEM WORKS

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 elec-trodes to modulate the activity of neurons

Cortical excitability changes by DBS

Treat the brain disorders such as depression, stroke, and Parkinson’s disease

HISTORY

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 tech-niques directed at basal ganglia targets in late 1980s, early 1990s.

Basal ganglia have been targeted for neuromodulation surgery since the 1930s.

HISTORY

Today, DBS (electrical stimulation of basal ganglia structures via implanted electrodes) has become a non-lesioning alternative to pallidotomy.

1993: Bilateral high-frequency stimulation of subthalamic nucleus (STN) in-troduced in treatment of advanced PD - Based on new insights into the pathophysiology of basal ganglia derived from experimentation on ani-mal 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.

NEUROBIOLOGY

Brain areas targeted in DBS:

1. Vim = ventralis intermedius nucleus of the thalamus2. GPi = posteroventral portion of the internal segment of

the globus pallidus 3. 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 tar-geted 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

Implantation of Electrode:

Optimal Stimulation Sites:- Dorsolateral STN border- Posteroventral GPi

DBS electrode stereotactically inserted with special rigid guide tube Patient is awake and in the medication-“off” state after 12-hour with-

drawal

METHODS

Implantation of Electrode:

Electrode has 4 contacts on its distal end

The effects of stimulation from each combination of 2 con-tacts or monopolarly from each contact are assessed- Determine best contact(s) to use to obtain optimal thera-peutic benefit

METHODS

Electrode-Stimulator Connection:

Electrode Extension (passed under skin to chest) Chest: Battery-operated 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)

•

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 in-duces 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)

WHAT IS TMS?

HISTORYHistorical Background:

• About a century ago researchers first stimulated retinal nerve cells with mag-netic fields to produce flashes of light in subjects

• 1985 Barker and colleagues first stimu-late brain cells in the motor cortex of sub-jects.

• By 1990’s develop repetitive TMS where repeated magnetic pulses can be deliv-ered up to 50 times a second (50 hertz)

Thompson, 1910

TMS (Transcranial Magnetic stimulation)

Electric Principle in TMS

- Faraday’s law

- Biot-Savart law

Induced electric fields by current through the coil

- Ohm’s law

𝐵 (𝑅 )=𝜇 0𝑁4𝜋 ∮ 𝐼 (𝑡)

𝑅3𝑑𝑙

▽×𝐸=−𝜕𝐵𝜕𝑡

𝐽=𝜎 𝐸E : Electric fieldB : Magnetic field : Permeability of the head tissue I : Current along the coil pathN : The number of turn : Conductivity of the head tissueJ : Current Density

𝜇0

𝜎

METHODS

ADVANTAGE VS. DISADVENTAGE

Adventage :

• Non-invasive

• Ability to show causation

• Subjects conscious

Disadventage :

• Can’t stimulate in one place(focusing)

WHAT IS TUS?

Shinning focused ultrasound through a transducer into the intact brain.

Ultrasound stimulate neural activity through a combina-tion of pressure/fluid/membrane actions in the brain

Treat the brain disorder such as depression, stroke, Parkinson’s disease Transcranial ultrasound stimulation (TUS)

TUS (Transcranial Ultrasound Stimulation) : Low-intensity, low-frequency ultrasound are stimulated in the tissue

HISTORY

• Study of the ultrasonic existing were used ultrasound image, and bone den-sity 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 rea-sons. 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 trans-ducing 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 in-fluence 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 conse-quences 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 STIMULATIONDBS tDCS TMS TUS

Advantages • Focusing • Non-Invasive• Focusing

• Non-Invasive• harmless

• Non-Invasive• Focusing• harmless

Disadvantage • Invasive• Dangerous• Change Machine(3~5years)

• Dangerous• Inject Direct

current

• Unfocusing • Unknown.

Direction of improvement Medical Engineering

THANK YOU.

Q & A