Neural Prosthetic Engineering

Today- Nov. 7th

• 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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Neural Prosthetic Engineering

Retinal Prosthesis

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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

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C Veraarta et al., Brain Research 1998

Neural Prosthetic Engineering

Good retinotopicCorrespondence

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

4C Veraarta et al., Brain Research 1998

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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Neural Prosthetic Engineering

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 mmcenters in Teflon ribbon cable matrix

pattern recognition was unsuccessful

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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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Neural Prosthetic Engineering

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

8/31

Retina-where to Stimulate?

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Neural Prosthetic Engineering 9/31

Retinal Prosthesis

skin

External unit

Camera DSP

Encoder

AmplifierTX Coil

RX CoilDecoder

Rectifier

Current

Stimulator

(ASIC)

Electrode Array

Transmitter Coil on Glasses Camera on Glasses

Implanted unit

Electrode array9

Neural Prosthetic Engineering

USA SecondSight© “Argus II” The first FDA-approved retinal

prosthesis (in 2013 Feb.)

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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

Neural Prosthetic Engineering 12

Subretinal stimulation

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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

Neural Prosthetic Engineering

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)

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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

Neural Prosthetic Engineering 16

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)

E Zrenner, Proc. R. Soc. B. 2010

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

Neural Prosthetic Engineering

1st generation (percutaneous)

2st generation (wireless) Clinical trials in 9 patients

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Subretinal Implant (Alpha-IMS)

E Zrenner, Proc. R. Soc. B. 2013, 2010

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

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Neural Prosthetic Engineering

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)

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Subretinal Implant (Alpha-IMS)

E Zrenner, Proc. R. Soc. B. 2013

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

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Argus II:

Epiretinal

Camera + stimulator

60 channels

current stimulation

Reported visual acuity: 20/1260

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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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Summary