Neuroprosthetics Week 8 Visual Neuroprostheses

History Brindley (Cambridge) tried a series of experiments in the 1950s – limited success, but opened the field Brindley (Cambridge) tried a series of experiments in the 1950s – limited success, but opened the field Last 15 years – lots of initial tests Last 15 years – lots of initial tests Mostly animal studies – proof? Of concept Mostly animal studies – proof? Of concept Limited human studies Limited human studies First generation will be pixelated vision for the profoundly blind (avoid guide dog?) First generation will be pixelated vision for the profoundly blind (avoid guide dog?) Mostly still speculation/experimental Mostly still speculation/experimental

Physiology of Visual Pathway - 1 Best site for an implant yet to be resolved Best site for an implant yet to be resolved Different sites – different characteristics Different sites – different characteristics Anatomy – Anatomy – Light falls on the retina – located at the back surface of the eye Light falls on the retina – located at the back surface of the eye Photoreceptor neurons (in the retina) convert electromagnetic (light) energy into electrochemical signals Photoreceptor neurons (in the retina) convert electromagnetic (light) energy into electrochemical signals These are first stage retinal neurons These are first stage retinal neurons

Physiology of Visual Pathway - 2 Output of retinal ganglion cells (last) collected together on the optic nerve Output of retinal ganglion cells (last) collected together on the optic nerve Fibres reorganised at the optic chiasm Fibres reorganised at the optic chiasm Majority form synapses in the lateral geniculate nucleus (LGN) of the thalamus Majority form synapses in the lateral geniculate nucleus (LGN) of the thalamus LGN neurons project to cerebral cortex LGN neurons project to cerebral cortex Region called visual cortex Region called visual cortex

Jargon Receptive field- type of visual stimulus that causes neuron to respond Receptive field- type of visual stimulus that causes neuron to respond Visuotopic – map from visual to neural space Visuotopic – map from visual to neural space Visual pathway – massively parallel? signal processing Visual pathway – massively parallel? signal processing M (large) and P (small) are two segregated pathways thought to represent (M) where object is and (P) what object is M (large) and P (small) are two segregated pathways thought to represent (M) where object is and (P) what object is

Blindness Mainly age-related degeneration, retinitis pigmentosa (RP), accidents and cancers Mainly age-related degeneration, retinitis pigmentosa (RP), accidents and cancers Also glaucoma, diabetes but treatable Also glaucoma, diabetes but treatable Age related leading cause (2M in USA) – mainly loss of fine detail – central photoreceptors degenerate Age related leading cause (2M in USA) – mainly loss of fine detail – central photoreceptors degenerate RP – inherited, affects peripheral + night vision – leads to tunnel vision – rod photoreceptors go RP – inherited, affects peripheral + night vision – leads to tunnel vision – rod photoreceptors go Accidents + cancer more difficult as whole eye may be lost or visual pathway affected Accidents + cancer more difficult as whole eye may be lost or visual pathway affected

Prosthesis - Key Elements Recipients must be aware that their resultant sight will not be perfect/normal Recipients must be aware that their resultant sight will not be perfect/normal Acceptable system must be almost invisible Acceptable system must be almost invisible Components integrated into glasses etc Components integrated into glasses etc First generation experimental systems may not satisfy these criteria First generation experimental systems may not satisfy these criteria

Video Encoder Mimics photoreceptors in the retina Mimics photoreceptors in the retina For cortical or optic nerve based - CCD array or photodiode array: For cortical or optic nerve based - CCD array or photodiode array: Conventional, cheap video cameras good for lab exp. Conventional, cheap video cameras good for lab exp. For retinal based – could be integrated into the neural interface, so reside in the plane of the retina: For retinal based – could be integrated into the neural interface, so reside in the plane of the retina: Latter has advantage of using natural acquisition, so no robotic head movements Latter has advantage of using natural acquisition, so no robotic head movements Spatial resolution low – limited no. of electrodes Spatial resolution low – limited no. of electrodes

Signal Processing Visual system organised as a hierarchical sequence of maps Visual system organised as a hierarchical sequence of maps Visuotopy: close points in space excite close together neurons – low resolution conformal but locally random Visuotopy: close points in space excite close together neurons – low resolution conformal but locally random Prediction of light spots only ½ degree Prediction of light spots only ½ degree Signal encoded into discrete signals – one for each neural electrode Signal encoded into discrete signals – one for each neural electrode Light adapted into range of stimulus levels – must not be affected by ambient light Light adapted into range of stimulus levels – must not be affected by ambient light Image compression + remapping for perception Image compression + remapping for perception

Telemetry & Power Wireless link for power and video signals in implant Wireless link for power and video signals in implant RF or light transmission – cellphone tech RF or light transmission – cellphone tech Telemetry – bidirectional, circuitry informs external electronics of power needs Telemetry – bidirectional, circuitry informs external electronics of power needs Transmitter + Receiver only 1cm apart Transmitter + Receiver only 1cm apart Receiving coil implanted in eye or scalp Receiving coil implanted in eye or scalp Frequency must be limited to avoid heat and radiation damage to tissues Frequency must be limited to avoid heat and radiation damage to tissues Implanted receiver small, high reliability Implanted receiver small, high reliability Low BW better but more electrodes means more BW Low BW better but more electrodes means more BW

Neural Stimulator Video signals processed before stimulating neurons Video signals processed before stimulating neurons External stimulator electronics easier External stimulator electronics easier Preferable for complete implant – problems Preferable for complete implant – problems Requires on-chip memory locations Requires on-chip memory locations Each location dedicated to each electrode Each location dedicated to each electrode VLSI device prototyped VLSI device prototyped Hermetic sealing of electronics difficult Hermetic sealing of electronics difficult

Neural Interface Same problems as with other neural interfaces Same problems as with other neural interfaces Biological Biocompatibility Biological Biocompatibility Physical Biocompatibility – implant density, barriers, mechanical compliance, wire tethering Physical Biocompatibility – implant density, barriers, mechanical compliance, wire tethering Percutaneous – v - implant Percutaneous – v - implant

Four Approaches Subretinal Subretinal Epiretinal Epiretinal Optic Nerve Optic Nerve Cortex Cortex

Subretinal Approach Replication of photoreceptors – good approach for most cases, uses remnant bipolar cells Replication of photoreceptors – good approach for most cases, uses remnant bipolar cells Array of phototransducers is placed in the subretinal space (Artificial Silicon Retina) Array of phototransducers is placed in the subretinal space (Artificial Silicon Retina) Each element is photodiode + electrode Each element is photodiode + electrode Resultant voltage gradient from light source stimulates bipolar cell dendrites Resultant voltage gradient from light source stimulates bipolar cell dendrites No external power or control needed No external power or control needed Little/no signal processing required Little/no signal processing required Presently undergoing human trials Presently undergoing human trials

Epiretinal Approach Stimulating electrodes on inner retina surface – excite remnant ganglion cells Stimulating electrodes on inner retina surface – excite remnant ganglion cells Array of electrodes attached to inner retina surface Array of electrodes attached to inner retina surface Patterns of electrodes stimulated electrically Patterns of electrodes stimulated electrically Simple, linear organisation Simple, linear organisation Still just ideas – can it be permanently attached? Can useful signals be obtained at safe currents? Still just ideas – can it be permanently attached? Can useful signals be obtained at safe currents?

Optic Nerve Approach Optic nerve sole visual conduit from retina to lateral geniculate nucleus in thalamus Optic nerve sole visual conduit from retina to lateral geniculate nucleus in thalamus Only one human study – spiral cuff electrode array with four surface electrodes Only one human study – spiral cuff electrode array with four surface electrodes Biphasic pulses, thresholds 350 microA Biphasic pulses, thresholds 350 microA Stimulus rate 8 to 10 Hz Stimulus rate 8 to 10 Hz Identify simple objects via a head mounted camera Identify simple objects via a head mounted camera Method not good for high resolution – MEA better ? Method not good for high resolution – MEA better ?

Cortically Based Approach Yet to be developed – practically?? Yet to be developed – practically?? Dobelle – stimulation via electrode arrays under the dura on visual cortex Dobelle – stimulation via electrode arrays under the dura on visual cortex percutaneous connector behind the ear percutaneous connector behind the ear Each electrode connected to one of 64 pins Each electrode connected to one of 64 pins Subjects able to perceive points of light Subjects able to perceive points of light Currents 1 to 10 mA (unsafe for chronic implant?) Currents 1 to 10 mA (unsafe for chronic implant?) Local electrodes alter image – nonlinearities – so large spacings required Local electrodes alter image – nonlinearities – so large spacings required Recently single electrodes – 10 microA Recently single electrodes – 10 microA MEA thought to be the way to go! MEA thought to be the way to go!

Final Words Four poss sites – subretinal, epiretinal, optic nerve and visual cortex Four poss sites – subretinal, epiretinal, optic nerve and visual cortex Passive photodiode arrays cannot produce currents that excite retinal neurons Passive photodiode arrays cannot produce currents that excite retinal neurons Stimulating electrodes must be positioned close to neurons to excite them – electrodes must have same dimensions Stimulating electrodes must be positioned close to neurons to excite them – electrodes must have same dimensions Stimulation best with highly localised current injections – penetrating electrodes Stimulation best with highly localised current injections – penetrating electrodes Electrode arrays felt to be the way ahead – first human trial was in 2002!!!!!! Electrode arrays felt to be the way ahead – first human trial was in 2002!!!!!!

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