1. Hee Sok, Han Department of Biomedical Engineering, Kyung-Hee University BRAIN STIMULATION

2. 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

3. BRAIN STIMULATION TMS (Transcranial magnetic stimulation) Online: http://www.biotele.comhttp://www.biotele.com tDCS (Transcranial direct current stimulation) Online: http://www.biotele.comhttp://www.biotele.com TUS (Transcranial ultrasound stimulation) Online: http://www.mayfieldclinic.comhttp://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.comhttp://www.thehealthage.com

4. 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. Physiologicallyhormones environmentreflexesganglia

5. Donald Bliss, MAPB, Medical Illustration Terminal branches of axon Cell body (the cell’s life support center) Dendrites Myelin sheath Axon Neuronal Impulse THE NEURON : HOW THE BRAIN’S MESSAGING SYSTEM WORKS

7. dopamine transporters

8. 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

9. 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 techniques directed at basal ganglia targets in late 1980s, early 1990s.   Basal ganglia have been targeted for neuromodulation surgery since the 1930s.

10. 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) 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.

11. NEUROBIOLOGY Brain areas targeted in DBS: 1. 1. Vim = ventralis intermedius nucleus of the thalamus 2. 2. GPi = posteroventral portion of the internal segment of the globus pallidus 3. 3. STN = subthalamic nucleus

12. METHODS Stereotactic Surgery - Locate targeted brain areas - Stereotactic frame - MRI, CT, or ventriculography - Stereotactic atlas

13. 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

14. 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 withdrawal

15. 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

16. 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

17. 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

18. 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

19. 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.comhttp://www.biotele.com Technical illustration: Bryan Christie

20. 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

21. METHODS

23. ADVANTAGE VS. DISADVENTAGE Adventage : Non-invasive Focusing inexpensive Disadventage : Inject direct current(dargerous)

24. 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) WHAT IS TMS?

25. 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

26. 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 E : Electric field B : Magnetic field : Permeability of the head tissue I : Current along the coil path N : The number of turn : Conductivity of the head tissue J : Current Density

27. METHODS

28. ADVANTAGE VS. DISADVENTAGE Adventage : Non-invasive Ability to show causation Subjects conscious Disadventage : Can’t stimulate in one place(focusing)

29. WHAT IS TUS? 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) TUS (Transcranial Ultrasound Stimulation) : Low-intensity, low-frequency ultrasound are stimulated in the tissue

30. 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.

31. 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.

32. Online: 조선일보

33. ADVANTAGE VS. DISADVENTAGE Adventage : Non-invasive Ability to show causation Stimulate on target point(Focusing) Disadventage : Unknown(??)

34. COMPARED BRAIN STIMULATION DBStDCSTMSTUS 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

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