Neural Prosthetic Engineering
Today- Nov. 7 th
• questions? Projects?
– (reserve enough time for the two days in Dec. (Dec.5th and 7th))
• Review
– Retina anatomy (Mr. Park) – Visual pathway
– Retinotopy
– Retinal degeneration – Electrical stimulation
– Stem cells and optogenetics
• Visual prosthesis continued
– Optic nerve and visual cortex approaches
– Epiretinal, Subretinal, Suprachoroidal approaches
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Retinal Prosthesis
Neural Prosthetic Engineering
Pros.
Favorable results
For patients with severe retinal damage
Cons.
Number of electrodes limited for High density of axons (1.2million/2mm diameter)
Difficult surgery, deep area and with tough dura
UCL (Universite Catholique de Louvain), Belgium
1998.4. Human Implantation
spiral cuff electrode (Au-Ti)
Visual restoration:
Electrical stimulation of Optic nerve
3 C Veraarta et al., Brain Research 1998
Good retinotopic
Correspondence
Poor spatial resolution
phosphene size and position
Different from what could have been expected on the basis of the the retinotopically activated axons in the optic nerve
Visual restoration:
Electrical stimulation of Optic nerve
Neural Prosthetic Engineering
Pros.
Therapeutic potential is great
Wider range of patients
Cons.
Difficult electrode placement due to complex topology of neurons
May cause Epilepsy
Utah, Dobelle Inst.,
Visual restoration:
Electrical stimulation of Visual cortex
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Dobelle & Mladejovsky (1974)
'acute' 38 experiments, succeeded in 15 patients undergoing brain surgery, using 11 Pt electrode
Dobelle (1974)
'Artificial Vision for the Blind' in Science
64 Pt electrode, 8 x 8 array on 3 mm centers in Teflon ribbon cable matrix
pattern recognition was unsuccessful
Visual restoration:
Electrical stimulation of Visual cortex
Neural Prosthetic Engineering
Can potentially exploit the natural
“encoding” of visual information
(which remains largely unknown)
Retinotopic visual mapping
• Stimulation at a particular location on the retina
Visual percept (phosphene) at known location
Less invasive(!) surgery
Retinal Stimulation!
Retina
Optic Nerve
LGN
Visual Cortex
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Epi-Retinal approach
Electrode is placed “on top of” the retina
Direct stimulation of Ganglion Cell
Cannot exploit retinal network
Difficulty in fixation- need a tack
Sub-Retinal approach
Electrode is inserted into the place of Photoreceptor cells
Benefit from intraretinal processing
Easy fixation
Surgical difficulty
Supra-Choroidal approach
Easy and safe surgery
Higher threshold
Lower resolution
Retina-where to Stimulate?
Neural Prosthetic Engineering 9/31
Retinal Prosthesis
skin
External unit
Camera DSP
Encoder Amplifier TX Coil
RX Coil Decoder
Rectifier
Current Stimulator
(ASIC) Electrode Array
Transmitter Coil on Glasses Camera on Glasses
Implanted unit
Electrode array
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USA SecondSight© “Argus II”
The first FDA-approved retinal prosthesis (in 2013 Feb.)
Epi-retinal: Argus II
Neural Prosthetic Engineering
USA SecondSight© “Argus II”
Implant unit:
Titanium package
• Stimulation generating circuit
• 11mm-diameter, 3 mm-thickness
Parylene-based electrode array
• 60 stimulating channels (6 x 10)
• 20° max. filed of view
Receiver coil
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Epi-retinal: Argus II
Subretinal stimulation
Neural Prosthetic Engineering
Artificial Silicon Retina (ASR) in (2000~2007)
2 mm diameter
~3500 pixels of microelectrode & microphotodiode array
Powered by incident light
Clinical trials with 6 RP patients
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Subretinal stimulation: ASR
A Chow et al., Clinical Sciences 2004
ASR results in 2004
Reported visual function improvements in all subjects!!
However,
Improved vision included retinal area far from the implant location
What caused the vision improvement ?
Not by direct stimulation of the implant
But by “neurotrophic effect”
• ASR’s presence in retina acted as an indirect effect
(possibly release of growth factors improving the health of retina)
Subretinal stimulation: ASR
Neural Prosthetic Engineering
Why the ASR could not work well?
Photovoltaic current was not sufficient to stimulate retina
Theoretical current output of subretinal microphotodiode in sunny environment is:
• < 1 nA (nano Ampere)
• Far below the activation threshold of retina neurons (~mA)
We need external power
To generate photo-current greater than neural threshold
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Subretinal stimulation: ASR
Alpha-IMS (Dr. Zrenner group, Tuebingen Univ. in Germany)
1,600 microphotodiode array(MPDA)
Implanted into subretinal space
• Targeting to activate bipolar cells
• bypassing the degenerated photoreceptors
No external camera is needed
Acquired European CE mark
Subretinal Implant (Alpha-IMS)
Neural Prosthetic Engineering
1500 channel Microphotodiode Array (MPDA)
Single channel
• photodiode + amplifier + electrode
Photodiode itself is not sufficient for neural activation
• Each diode acts as “gating” the current driver
Advantages
• No external camera is needed
• Vision changes following the eye-movement
• High scalability
Subretinal Implant (Alpha-IMS)
E Zrenner, Proc. R. Soc. B. 2013 17
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stgeneration (percutaneous)
2st generation (wireless)
Clinical trials in 9 patients
Subretinal Implant (Alpha-IMS)
Neural Prosthetic Engineering
Alpha IMS (similar tests with Argus 2)
Light perception threshold
Light source localization
Motion detection
Grating acuity
Landolt-C ring (visual acuity
Retinal Implant Clinical trials
E Zrenner, Proc. R. Soc. B. 2013 19
Clinical Trials (9 patients)
Light perception threshold (8/9)
Light source localization (7/9)
Motion detection (5/9)
Grating acuity (6/9)
Landolt-C ring (2/9)
Subretinal Implant (Alpha-IMS)
Neural Prosthetic Engineering
Both subretinal and epiretinal prostheses demonstrated
Feasibility and reasonable safety
Ability to convey patterned vision through electrical stimulation of degenerated retina
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Summary of Clinical trials
Argus II:
Epiretinal
Camera + stimulator
60 channels
current stimulation
Reported visual acuity:
20/1260
Clinical trials
Alpha-IMS:
Subretinal
Photodiode array
1,500 channels
Voltage stimulation
Reported visual acuity:
20/2000 and 20/546
Similar performance :
Light perception
Discrimination of grating pattern
Detection of moving light source
Read large characters
Detection of large objects in everyday life
Neural Prosthetic Engineering
Optic Nerve and Visual Cortex
Three places to do retinal prosthesis
Epiretinal Implant: Argus 2
Subretinal Implant: ASR and Alpha IMS
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