Penetrating electrode arrays for retinal stimulation

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Mar 032011
 

On the heеls of the previous post, here is another news bit on the topic of retinal implants. Over the years, we have witnessed a variety of approaches being applied for retinal stimulation, including the epiretinal, subretinal, and suprachoroidal. One feature, however, remained unchanged in those varied types of implants – a planar geometry of the stimulation array.  At least until now. As the competition in the retinal implant sector is heating up,  the issues of low-power operation and improved electrode contact with retinal neurons is fueling the development of stimulation arrays featuring the 3D geometries. Improved charge delivery to retinal neurons has been achieved a few years ago by fabricating the protruding 3D nanoelectrodes in Daniel Palanker’s lab at Stanford University and at Dong-Il Dan Cho’s and Sung June Kim’s labs at Seoul National University. Now, preparing to reach even deeper into the retina, the Israeli company Nano-Retina Inc., co-founded by Rainbow Medical Ltd. and Zyvex Labs. , is developing the Bio-Retina implant featuring the array of 100-µm-sized penetrating electrodes. Their length should allow the electrodes to reach the layer of bipolar cells that are spared in AMD and other degenerating retinal disorders. The first-generation array will have 24×24 electrodes and the second – 72×72. Power to the device will be delivered wirelessly using the infrared light beamed from the glasses. To expedite their efforts in developing the low-power IC chip with the built-in photodetector array and power telemetry, Nano-Retina has teamed up with CMES (Centre Suisse d’Electronique et de Microtechnique), a non-profit R&D center in Switzerland. According to their (perhaps too optimistic) estimates they plan to have the functional device ready for clinical trials by 2013 and even have estimated the target price of $60K for the Bio-Retina implant. We wish the best of luck to this young ambitious company, hoping it has what it takes to develop a device from scratch in such a short period of time.

Organic film photodetectors for retinal implants

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Mar 022011
 

An important issue for the realization of retinal prosthetic devices is a conversion of light into electrical energy using photodetectors. The existing implants utilize the photodetectors made from semiconductors, either silicon or GaAs/AlGaAs, which exhibt moderate efficiency of photovoltaic energy conversion. Recently, the photodiodes based on nanoscale photo-ferroelectric thin films have been evaluated in order to overcome the charge injection limit of semiconductor photodiodes, imposed by the band gap of the p-n junction. However, the photovoltaic conversion efficiency of ferroelectric materials is too small to make them a viable option for retinal implants. The silicon-based photodetectors, although practical, provide the quantum efficiency of about 1000 times lower than the retinal photoreceptors, so that an intense eye irradiation, required for their operation, may be damaging (phototoxic) to remaining retinal photoreceptors. Faced with this challenge, Dr. Lanzani from Istituto Italiano di Tecnologia and Politecnico di Milano in Italy decided to evaluate the soft organic film photodetectors, which have the advantages of biocompatibility, flexibility, minimal heat dissipation, and inexpensive deposition by ink-jet printers. Dr. Lanzani used the fullerene–polythiophene film, commonly used in organic solar cells, patterned on one side with the indium tin oxide to form a transparent electrode for neuronal stimulation. The organic film photodetectors remained functional after a month of in vitro testing. Let’s hope that an upcoming in vivo testing in the eye will validate the efficacy and safety of novel photodetectors.

Innovative research in the field of brain-computer interface (BCI)

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Feb 172011
 

The BCI encompasses multiple types of neural technology united by a common purpose of assisting, augmenting, or repairing human cognitive or sensory-motor functions at the cortical level.  Taking its roots from the EEG interfaces in early 1970s, the BCI field has gradually grown to include other non-invasive techniques, such as the NIRS (near infrared-spectroscopy), fMRI (functional magnetic resonance imaging), and MEG (magnetoencephalogram). It has also evolved to include the invasive technologies, such as the electrocorticogram (ECoG) and penetrating cortical electrodes. In 2010, an international committee, headed by Dr. Gerwin Schalk of the Wadsworth Center (Albany, NY), critically evaluated the trends and developments in the BCIs by focusing on its novel applications and technological improvements. The  committee examined 57 submissions and selected the winner of 2010 BCI Research Award – a team led by Dr. Guan Cuntai from A*STAR, Singapore – for his work on motor-imagery based BCI coupled to a robotic arm and used for rehabilitation after stroke. The 2011 BCI Research Award will be awarded during the 5th International BCI Workshop on Sept. 22-24, 2011 in Graz, Austria. In the analysis of nominations for the 2010 award, the EEG is clearly the predominant technology accounting for 75% of nominations, while the fMRI and ECoG accounting for 3.5% each, NIRS accounting for 1.8%, and penetrating electrodes accounting for 0.9%. Current philosophy in the BCI development is dominated by four assumptions, stated in a recent article by Prof. Jon Wolpaw of the Wadsworth Center: (1) intended actions are fully represented in the cerebral cortex; (2) neuronal action potentials can provide the best picture of an intended action; (3) the best BCI is one that records action potentials and decodes them; and (4) ongoing mutual adaptation by the BCI user and the BCI system is not very important. According to Prof. Wolpaw, these assumptions are flawed. Indeed, much of the motor control occurs at the spinal cord, brainstem, and deep brain levels. Further complication for BCI is that the cortical involvement in the motor control is state-dependent and continually adapts to optimize the performance in different tasks. Present generation of BCI algorithms do not account for such state-dependent and performance-driven adaptations therefore their effectiveness quickly degrades over a period of several days. Yet another level of complexity for decoding of cortical signals stems from the profound slowly-developing plasticity in the motor cortex after the stroke or spinal cord injury. Fortunately, novel adaptive learning algorithms, like those in the IBM’s Jeopardy-winning computer Watson, continue to grow in sophistication and eventually should attain the adaptability needed for handling the challenges of BCI.

The amygdala as a possible neuromodulation target for treatment of PTSD

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Jan 062011
 

The fear is one of the strongest emotions that drive our behavior. And the amygdala is the central hub for processing the fear responses. How would our life be changed if we were to lose both of the amygdalae? While the animals can be deprived of fear by knocking out Stathmin, a cytoskeleton regulatory protein concentrated in the amygdala and other parts of the fear circuit, these animals cannot report on their internal subjective experience. Unfortunately, no drug is presently safe enough for a temporary amygdala inactivation in humans. Our understanding of a human condition without the amygdalae has been, therefore, rather limited, relying on a handful of patients with a rare genetic disorder, the Urbach-Wiethe disease, which produces bilateral calcifications on the medial temporal lobes, ultimately leading to a destruction of the amygdalae. One of these patients, a woman called S.M., has been studied extensively since 1994 and provided the wealth of psychological and neurological information about her condition. During the course of an extensive psychological evaluation, she reported feeling upset, angry, and irritable, but on no occasion did S.M. experience any fear, guilt, or shame, induced either by real-life experiences (being held up at knife point and at gun point) or by unpleasant thoughts (e.g. about dying). These findings suggest that because of her amygdala damage, S.M. became immune to the devastating effects of posttraumatic stress disorder (PTSD). Similarly to S.M., the Vietnam War veterans with considerable damage to the amygdala have a lower occurrence of PTSD, as described in this Nature Neuroscience 2007 paper. Moreover, when PTSD patients are provoked to recall their traumatic memories, they exhibit an increased activity in the amygdala and the head of the caudate nucleus, as reported in this recent fMRI study. Overall, there is a considerable body of knowledge suggesting that the amygdala inactivation, perhaps through chronic neuromodulation, could be an effective method for PTSD treatment.

Novel platform technology for neuromodulation applications

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Dec 282010
 

The present-day neuromodulation technology has been around for 25 years despite the advances in microfabricaion methods and electronics. In part that is due to a lack of novel scalable platform technologies with proven reliability of electrode-tissue interface, interconnects, and packaging. One of such platform technologies is now being developed by Dr. John Parker at the Sydney-based Implant Systems Group of the Australian research center NICTA. Leveraging from the cochlear implant technology, developed by the Cochlear Corp., Parker and his coworkers are developing a modular platform consisting of the multi-channel electrodes, sensors, actuators, processing elements, and packaging. Among the novel features of this platform are: a novel method for microfabrication of the electrode arrays involving the wire electrodes sawn into polymer yarn, novel biocompatible chip-scale hermetic packaging, and novel ASIC architecture for highly distributed neurostimulation systems employing optical data transmission. Targeted neuromodulation applications for this platform technology range from movement disorders (Parkinson’s disease and essential tremor) to obesity and depression. Perhaps because of a relative simplicity of epidural spinal implantation and a limited number of required stimulation channels, the chronic intractable pain was chosen as the first target application of the technology.  The INS2 device will include all key components of the platform including the yarn-woven electrodes with recording and stimulation capability, the ASIC chip, and a rechargeable battery with power telemetry. The human trials will begin sometime in 2011. If successful, the technology will be commercialized by a new spin-out company Saluda Medical.

Harvesting light and heat energy from the body with a hybrid device

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Dec 282010
 

Rechargeable batteries are increasingly more common in neural implants, removing the need for multiple surgeries to replace a depleted battery. Alternative strategies are being developed for replenishing the energy of the battery. The most established method of energy delivery is via radio waves. Recent shift toward the use of higher frequencies in the 0.1-1 GHz band made the rectenna (receiving antenna) extremely small. This allowed the implant to fit within an injectable needle for a minimally invasive delivery at a location near a peripheral nerve. In order to eliminate the need for coupling the implant with an external charging device, methods are being developed for harvesting the energy from the human body. These methods utilize the energy of light (visible or infrared), heat, or vibration.  Harvesting of visible light can be done most efficiently in the retina, while infrared light can penetrate the skin and be used for transcutaneous powering of the implants. In the body, amount of energy available for harvesting is rather limited, so that multiple forms of energy – such as light and heat, or light and vibrations – can be used simultaneously in order to collect a sufficient amount for practical use. This can be achieved by combining different kinds of energy transducers. In pursuit of this approach, Fujitsu Laboratories has developed a new hybrid harvesting device that captures energy from either light or heat in a single device. Their device is manufactured from inexpensive organic materials, keeping the production costs low. The device contains two types of semiconductor materials – P-type and N-type semiconductors – allowing it to function as a photovoltaic cell or thermoelectric generator. Importantly, their hybrid device can be fabricated on flexible substrate for easy accommodation into different implant shapes.  The company is currently refining the technology to increase its performance, and aims to commercialize it by around 2015.

Neurotech exploration setup for a curious child: price – $100, experience – priceless

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Dec 182010
 

Take a look at this self-explanatory video from Backyard Brains, a web store founded by two grad students at U. Michigan. It shows how to teach the basics of neural stimulation and recording on a slim budget. Their Spikerbox setup consists of a simple op-amp circuit, a few filters, an A/D, and a speaker, all connected to an iPhone for stimulus generation or recording. If you have a kid interested in neuroscience, don’t pass up this opportunity for a fun educational evening with the Spikerbox.

Neural probe with integrated microfluidics and pumps for intracranial drug delivery

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Dec 152010
 

Chemical stimulation using channels in a so-called “puffer” neural probe has been a challenging endeavor, originated by Prof. Kendal Wise’s laboratory in U. Michigan back in 1997. The early probes were fabricated using the reactive ion etching (RIE) technology, and despite their initial promise, so far have not been successfully used in chronic animal studies.  Multiple issues, ranging from the outlet biofouling to the hydraulic resistance inside a microfluidic channel, have been identified. A commercial probe combining the drug delivery and electrical recording/stimulation was recently developed by the NeuroNexus Technologies (D/DM-series); it consists of the silicone probe glued to the fused silica fluidic channel. Opting for an integrated probe solution, engineers at the Institute of Micromachining and Information Technology and the Institute of Microsystem Technology at the University of Freiburg etched the channels with heights of 50 µm and more inside the wafer using the deep RIE (DRIE) technology. Their effort is a part of the NeuroProbes project, funded by a European Sixth Framework Programme (FP6), which includes 13 other partners from Belgium, Germany, Sweden, Switzerland, UK, Italy, France, Hungary, Spain, and Netherlands. The probes, fabricated by German engineers, remained unclogged in an acute in vivo test, while the chronic implant studies are still ongoing. The fluid pumping action inside the microfluidic channels was achieved by a MEMS device built into the probe. The MEMS device functions by constricting fluid-filled micro-chambers (volume = 0.25 μL each) using a thermally expandable material coupled to heating microelements. The microchambers are connected in series and can be constricted individually with a 3-second temporal precision. Having the chemical stimulation and electrical recording on the same probe, may soon allow a detailed examination the chemical signaling inside the brain in vivo with a high spatiotemporal precision.

Hypoglossal nerve stimulation for obstructive sleep apnea: revival of the old technology

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Dec 072010
 

Obstructive sleep apnea (OSA) is a condition in which breathing is periodically obstructed during sleep, often due to a prolapsed tongue or swollen throat. OSA affects 3-5% of people (18 millions in the US alone) and is often associated with obesity and old age. The hypoglossal nerve (HGN) controls the tongue and soft palate muscles. The closed-loop HGN stimulation, synchronized with the inspiratory phase of respiration, was shown (by Johns Hopkins U. researchers in mid-90es) to reduce the severity of OSA. In 1996-1997, Medtronic Inc. tested the first implantable HGN stimulator, Inspire I, in humans but soon abandoned the device due to concerns about its safety. Fast-forward to 2010: we have an expired patent on the HGN stimulation and several companies vying for dominance in this lucrative market. Charging ahead of the competition is a Medtronic’s spinout Inspire Medical Systems, with its device, Inspire II, that just received the CE Mark for clinical use in Europe. Not far behind are the Apnex Medical and ImThera Medical, who are undergoing clinical trials for their versions of the HGN stimulation devices. It is worth mentioning that other neurostimulation technologies are being applied for sleep apnea. Cardiac Concepts Inc. is developing a device for the phrenic nerve stimulation to restore a more natural breathing pattern in patients with the central sleep apnea, a related medical condition. Inspiration Medical Inc. holds several patents for the diaphragm pacing as yet another method for OSA treatment. Finally, there are some less-invasive approaches including tongue stimulation with sublingual electrodes and the repelling magnetic implants in the tongue base and posterolateral pharynx. Perhaps, it is too early to predict which of the technologies will ultimately prevail, so let’s not lose our sleep over this for now.

“Active Book” – an implant with active electronics for recording from and stimulation of lumbar spinal roots

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Nov 292010
 

A device prototype has been fabricated for implantation into human spinal column. It rests over the posterior and anterior (sensory and motor) spinal roots and allows recording from as well as selective stimulation of multiple spinal roots. The work is spearheaded by Prof. Nick Donaldson and Prof. Andreas Demosthenous at the University College London, UK. In collaboration with engineers from Freiburg University and the Tyndall Institute in Cork, they developed a device that includes a VLSI chip for processing the neural recordings and generating the electrical stimulation pulses. The VLSI chip is hermetically sealed into a can enclosure. Hermeticity of the enclosure is monitored using a humidity sensor. The chip feedthroughs are interconnected with the electrodes using wire bonds. The chip, wires, and electrodes are encapsulated into a soft shell, made presumably from silicone or epoxy. The electrodes are fabricated from platinum foil using laser etching and folded into a slot shape. There are four slots at the bottom of the implant, designed to bring the spinal roots (perhaps two anterior and two posterior ones) into close apposition with the electrodes. Such top placement of a neural interface is rather unusual as existing spinal root electrodes (e.g. Finetech-Brindley stimulators) have employed the cuff design. In order to be able to record neural activity and efficiently deliver the electrical current, the slots must be well-matched in size to the diameter of spinal roots. The initial application for the Active Book implant would be the control of bladder voiding in spinal cord injury. The effectiveness of the prosthetic bladder voiding will be similarly limited as in other sacral root stimulators, including the sensory perception of stimulation in people with residual below-injury sensation and concomitant activation of the bladder and urethral sphincter muscles, as well as other pelvic floor muscles. Other applications in paralyzed humans, such as the control of arm or leg muscles, are not unlikely to be successful with this implant as the applied surface stimulation would not be able to selectively activate a specific arm/leg muscle. Such lack of selectivity is inherent to the anatomy of the anterior spinal roots, which are comprised of mixed axonal bundles innervating different, sometimes antagonistic, muscles.

Hi-def and infrared vision in a subretinal implant from Retina Implant AG

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Nov 122010
 

A remarkable milestone has been reached in the resolution of retinal implants – a whopping 1520 pixels (38×40)! Following on the heels of a recent success of Argus II retinal implants developed by the Second Sight, this implant by the German Retina Implant AG brings a 25-fold increase in resolution and several other unique features. Its subretinal placement is closer to the retinal pigment epithelium than can be achieved with epiretinal placement. This provides more selective stimulation of photoreceptors and results in further improvement in the implant’s resolution. The light sensing circuitry (silicon photodiodes) is built into the implant allowing it to move along with the eye movements.  This is beneficial for more natural cortical processing of visual information, as the visual map in the visual is adjusted during each saccade. Other types of retinal implants use an external videocamera (usually mounted on the glasses) that does not adjust the video information during the eye movements. The implant is 3 x 4 mm and 50 µm thick.  In addition to vision restoration, the implant provides a first-ever vision-enhancing capability – the sensitivity to near-infrared light. Extending the spectrum of perceived light can have some interesting implications, such as the ability to see a thermal shape of the object (the black body radiation) even in complete darkness. The ongoing research by Prof. Eberhart Zrenner at the University of Tuebingen aims to evaluate these implants to develop strategies for further improvements in the sensitivity and targeting of the implants. According to the paper published in the November issue of Proceedings of Royal Society B, the implants have been tested in three patients with hereditary retinal degeneration. All patients could locate bright objects on a dark table, and one patient discerned shades of grey with only 15% contrast. An important question for the retinal implant community, so far not answered by the study, is: how many pixels in the implant provide truly unique information to the retina and whether this spatial threshold has been reached with a 70-µm spacing used in the implant. The answer to this question has far-reaching implications for further technology developments: 1) whether further improvements in the density of planar arrays will translate into more focal stimulation and 2) whether the stimulating sites should be microfabricated to extend from the chip toward the retina in order to achieve the intended 70-µm spatial resolution.

Modified cochlear implant restores vestibular function

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Nov 062010
 

Cochlear implants have been around for decades restoring hearing in profoundly deaf people. Now, with the help of Jay Rubinstein, James Phillips, and other scientists at University of Washington, the old “dog” from Cochlear Ltd has learned a new trick: restoring the sense of balance. The Nucleus® cochlear implant was modified to include three leads with multiples stimulation sites. The leads are implanted into all three semicircular canals of the inner ear to restore the 3D rotational information. The details of the implant design and surgery are provided in this video.

Brain-machine interface for declarative memory in humans

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Nov 032010
 

Caltech-BMI-2010

Development of brain-machine interfaces (BMI) greatly accelerated in the last decade, shifting from the monkey feasibility studies toward actual human testing. The pioneering studies with the BrainGate implantable array of microelectrodes proved the usefulness of BMI to a paralyzed person for variety of everyday functions. The latest study, published in October 28, 2010 issue of Nature, provides further evidence that BMI can be used for providing access to specific visual memories.  Researchers at the California Institute of Technology and UCLA Ronald Reagan Medical Center evaluated the single-unit neuronal activity from the microelectrode arrays implanted in the medial temporal lobe of patients with severe treatment-resistant epilepsy. The recording sites spanned the parahyppocampal cortex, hippocampus, and amygdala. These brain regions are intimately involved in declarative memory processes. Accessing declarative memory with a closed-loop BMI interface is challenging to setup in monkeys as it requires sophisticated behavioral methods for reading out the animal’s responses. In contrast, visual memories in human subjects can be easily interrogated using images projected on a computer monitor and their feedback for decoding algorithms can be collected by pressing the keyboard buttons. Looking a bit into the future, one can speculate that larger BMI arrays can be used for a comprehensive cognitive interface allowing paralyzed humans to apply their conscious thoughts for controlling their environment.

Neurotech for achieving supernatural memorizing skills

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Nov 022010
 

Centre for the Mind at the University of Sydney NSW, directed by Prof. Allan Snyder, in collaboration with Neuromodulation Lab of Spaulding Rehabilitation Hospital in Boston, has undertaken an interesting study to demonstrate how neuromodulation can unleash supernatural sensory abilities hidden in normal people.  Their study, published in September issue of Brain Research, shows that a 13-minute application of transcranial direct current stimulation (tDCS) – with cathodal current (inhibitory) on the left anterior temporal lobe and anodal current (excitatory) on the right anterior temporal lobe – results in twice as accurate visual recollection as compared to sham stimulation or stimulation with reversed current polarities. Interestingly, the autistic people with a deficit in left anterior temporal lobe also have better visual memory. It is conceivable that improved visual memory is due to a diminishing left hemisphere dominance leading to a right hemisphere compensation. This hypothesis is supported by the finding that people without strong hemisphere dominance have better memory for semantically related words. Right hemisphere is important for recalling specific details without their understanding, which is important for arts, music, mathematics, mechanical and spatial skills – the skills that autistic people are exceptional at. Perhaps, we are all capable of accessing such raw information in the right hemisphere but our abilities are greatly inhibited by our conscious left-dominated awareness. With the help of neuromodulation technology, we can, perhaps, unleash the savant-like mental state, the autistic genius inside of us. For more information about this, please see this comprehensive review by Allan Snyder, published in Phil. Trans. R. Soc. B in 2009.

Neuro-enhancing neurotechnologies: what lies ahead?

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Nov 012010
 

Development of new neurotechnologies is driven by a paramount goal of restoring neural functions. Presently, no commercial companies or government-funded research laboratories are actively pursuing the technologies aiming at augmenting and enhancing the functions of the brain or spinal cord in able-bodied humans. Yet, such technologies can readily be developed with minimal modifications of the existing neuro-restorative technologies. Let’s consider, for example the retinal implants (e.g. from Second Sight) that use an external video camera mounted on the glasses. The video camera sensor can be easily replaced with the near-infrared sensitive one to enable perception of thermal signatures in complete darkness (heat vision is actually not that unnatural, just think of the snakes). More peculiar sensory enhancement can be achieved by employing terahertz sensors to enable x-ray-like vision, similar to the full-body scanners deployed recently in airports.  Other types of supernatural sensitivity can be soon be possible with some creativity and engineering ingenuity, by adapting other types of sensors (e.g.  narrow-band spectral detection, ultrasound, accelerometers, etc) and by using the sensors with faster response time as compared with the perception delay of our natural five senses. On the other end of the spectrum of the neuro-restorative devices are the one providing rehabilitation, mobility, and muscle reanimation in paralyzed patients. Novel motor control modalities are already being explored, ranging from a forthcoming powerful neurally-controlled robotic arm (Revolutionizing Prosthetics project by DARPA) to a tongue-implanted joystick (by Prof. Ghovanloo at GATech). There is a great potential for developing a range a supernatural skills using the motor-control neurotechnologies. The researchers behind novel sensory and motor technologies are really trying to “play God”, rather they are using the technical resources at their disposal to get to the maximal clinical benefit. Philosophical and ethical concerns will inevitable rise as a result of wider adoption and acceptance of the neuroprosthetic devices.  I foresee a particularly sharp debate in the Christianity-dominated societies, stemming from their strong beliefs in subordinate position of a man relative to God. In parts of Asia, situation is rather different. Buddhist and Hindu religions have a less defined relationship between a man and God, and, as a possible result of that, the Buddhist and Hindu-dominated societies have already become more receptive to novel forms of biotechnology, such as stem cells and genetic engineering. Countries like Singapore and China provided heavy centralized investments to become leading innovation incubators of the 21st century (see “Biotech Without Borders” by Parag and Ayesha Khanna).

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