1. Neuroprosthetics Week 5 Stimulating and recording of nerves and neurons

2. Realising an Action Potential Depolarization (synaptic transmission or external stimuli) causes ion channels to open Depolarization (synaptic transmission or external stimuli) causes ion channels to open Response of Na channels causes increase in outward current – depolarizes membrane further Response of Na channels causes increase in outward current – depolarizes membrane further Once opened, ion channels stay open for a while Once opened, ion channels stay open for a while Action potential achieved when depolarization exceeds a threshold – then outward current exceeds inward current Action potential achieved when depolarization exceeds a threshold – then outward current exceeds inward current Depolarization is reversed by closing of Na channels and opening of K channels Depolarization is reversed by closing of Na channels and opening of K channels Membrane potential is restored to resting value Membrane potential is restored to resting value

3. Electrical activation of ion channels Applying a negative current via a stimulating electrode depolarizes the membrane. Applying a negative current via a stimulating electrode depolarizes the membrane. Natural response is then evoked. Natural response is then evoked. Electrical stimulus can lead to action potential. Electrical stimulus can lead to action potential. Stimulating electrode serves as a cathode. Stimulating electrode serves as a cathode. Return electrode required to complete the current loop. Return electrode required to complete the current loop.

4. Intracellular Electrodes Technique used to inject current inside the cell is the patch clamp. Technique used to inject current inside the cell is the patch clamp. Glass pipette electrodes are used to penetrate the cell membrane. Glass pipette electrodes are used to penetrate the cell membrane. A high impedance seal is thus formed between the membrane and pipette. A high impedance seal is thus formed between the membrane and pipette. Very efficient method but difficult/impossible to form an implantable device! Very efficient method but difficult/impossible to form an implantable device!

5. Functional Magnetic Resonance Imaging (fMRI) Used to detect brain activity in response to a specific stimulus. Used to detect brain activity in response to a specific stimulus. No direct electrical interface - noninvasive. No direct electrical interface - noninvasive. Scans can be recorded. Scans can be recorded. Resolution typically more than 1mm. Resolution typically more than 1mm. Difficult to perform – expensive. Difficult to perform – expensive. Useful in assisting positioning of electrodes. Useful in assisting positioning of electrodes.

6. Charge balanced stimulation For a single stimulation waveform the total net charge must be zero. For a single stimulation waveform the total net charge must be zero. Either supply equal cathodic and anodic currents or better to use a blocking capacitor which slowly discharges. Either supply equal cathodic and anodic currents or better to use a blocking capacitor which slowly discharges. But capacitor size effects pulse duration. But capacitor size effects pulse duration. If charge is not balanced, bubbling can occur (oxygen + hydrogen produced). If charge is not balanced, bubbling can occur (oxygen + hydrogen produced).

7. Biphasic response

8. Example – Cochlear implants Use charge balanced, biphasic stimulation pulses to activate auditory nerve. Use charge balanced, biphasic stimulation pulses to activate auditory nerve. When a 200Hz signal is present, short pulses of 0.1msec at 200 Hz used to stimulate. When a 200Hz signal is present, short pulses of 0.1msec at 200 Hz used to stimulate. We will consider this more in lecture 7/8 We will consider this more in lecture 7/8

9. Stimulating Interface Electrodes form the interface between stimulus circuit and biological cells. Electrodes form the interface between stimulus circuit and biological cells. Material must be high conductivity - must deliver current at high charge densities without corroding or dissolving. Material must be high conductivity - must deliver current at high charge densities without corroding or dissolving. Charge injection capacity, electrochemical stability and mechanical strength are important. Charge injection capacity, electrochemical stability and mechanical strength are important. Need to be chemically inert. Need to be chemically inert. Small area electrodes for better resolution. Small area electrodes for better resolution. Platinum, Iridium, Gold are all good. Platinum, Iridium, Gold are all good.

10. Extracellular recording Stimulation is the basis for restoration of sensory and motor function. Stimulation is the basis for restoration of sensory and motor function. Recording/monitoring is also essential for a prosthesis. Recording/monitoring is also essential for a prosthesis. Usually extensive physiological recording research must be done to map an area into which a stimulation device will be implanted. Usually extensive physiological recording research must be done to map an area into which a stimulation device will be implanted. Recordings are also often used to validate efficacy and optimize design of implants. Recordings are also often used to validate efficacy and optimize design of implants.

11. Closed-Loop prostheses Monitoring is an essential part of any closed-loop prosthesis. Monitoring is an essential part of any closed-loop prosthesis. Example – for spinal cord injuries – biological control signals can be recorded to drive implanted stimulating electrodes. Example – for spinal cord injuries – biological control signals can be recorded to drive implanted stimulating electrodes. John Chapin’s work (rats) involved signals from the motor cortex driving a robot arm – reward/punishment in a maze!! John Chapin’s work (rats) involved signals from the motor cortex driving a robot arm – reward/punishment in a maze!!

12. Cellular level nervous system When a neuron receives stimuli from other cells its membrane depolarizes and causes ionic currents to flow. When a neuron receives stimuli from other cells its membrane depolarizes and causes ionic currents to flow. The action potential (voltage drop) associated with this current can be measured if a suitable electrode is located near enough. The action potential (voltage drop) associated with this current can be measured if a suitable electrode is located near enough. An action potential is typically 50 to 500 microvolts with a frequency content from 100Hz to 10 KHz. An action potential is typically 50 to 500 microvolts with a frequency content from 100Hz to 10 KHz.

13. Pipette Electrodes Electrode must approach the active neuron without damaging it or other cells acting with it. Electrode must approach the active neuron without damaging it or other cells acting with it. Electrode needs to be as small and noninvasive as possible. Electrode needs to be as small and noninvasive as possible. Glass micropipette – heating and pulling 1mm diameter glass capilary. Glass micropipette – heating and pulling 1mm diameter glass capilary. Tip tapered and bevelled to 1 microm. Tip tapered and bevelled to 1 microm. Filled with electrolyte solution for conduction. Filled with electrolyte solution for conduction. Forms a low pass filter – good for up to 1 KHz only. Forms a low pass filter – good for up to 1 KHz only.

14. Microelectrodes Preferred method for detecting action potentials is with a metal microelectrode. Preferred method for detecting action potentials is with a metal microelectrode. Use small diameter metal wire sharpened to a (less than) 1 microm tip Use small diameter metal wire sharpened to a (less than) 1 microm tip Examples: Tungsten, stainless steel, platinum Examples: Tungsten, stainless steel, platinum But single electrodes do not give information on cell networks. But single electrodes do not give information on cell networks.

15. Multichannel recordings Important to observe the activity and interaction of many neurons simultaneously. Important to observe the activity and interaction of many neurons simultaneously. Determine relationships between cells. Determine relationships between cells. Neurons can be separated by spatial distribution as well as waveform/time. Neurons can be separated by spatial distribution as well as waveform/time. Dealt with in Lecture 2 by Adam. Dealt with in Lecture 2 by Adam.

16. Multichannel methods Photoengraved microelectrodes Photoengraved microelectrodes Microelectrode arrays Microelectrode arrays SOI wafer fabrication SOI wafer fabrication Polymide electrodes Polymide electrodes Michigan probe Michigan probe Three-dimensional array Three-dimensional array Acute probes Acute probes

17. Example Microelectrode array Microelectrode array High density of penetrating shafts High density of penetrating shafts Each shaft is 0.5 to 1.5 mm long Each shaft is 0.5 to 1.5 mm long These project down from a glass/silicon composite base These project down from a glass/silicon composite base Silicon shafts are isolated from each other with a glass frit. Silicon shafts are isolated from each other with a glass frit. The 50 microm tip of each shaft is coated with platinum to form the electrode site. The 50 microm tip of each shaft is coated with platinum to form the electrode site. The shafts are spaced on 400 microm centres. The shafts are spaced on 400 microm centres.

19. Design Considerations Shank length – depends on depth of target and strength/stiffness. Shank length – depends on depth of target and strength/stiffness. Shank width – minimize for noninvasiveness but maximize for strength Shank width – minimize for noninvasiveness but maximize for strength Substrate thickness – insertion in tough tissue. Buckling force is important. Poss high velocity. Substrate thickness – insertion in tough tissue. Buckling force is important. Poss high velocity. Site spacing – could show correlated and uncorrelated activity. Site spacing – could show correlated and uncorrelated activity. Site area – smaller site/higher impedance, causing attenuation and noise. But larger site is less selective. Site area – smaller site/higher impedance, causing attenuation and noise. But larger site is less selective.

20. Future directions Solid-state devices – batch fabrication, reproducible characteristics, small size + on-chip processing. Solid-state devices – batch fabrication, reproducible characteristics, small size + on-chip processing. Bioactive coatings – improved interface + enhanced recording stability. Seed coating with neurotrophins to assist behaviour. Bioactive coatings – improved interface + enhanced recording stability. Seed coating with neurotrophins to assist behaviour. Reduced output leads – reduces motion, migration and adverse tissue response. Wireless operation + on-chip design. Reduced output leads – reduces motion, migration and adverse tissue response. Wireless operation + on-chip design.