Apr 282013

In a typical cochlear implant, flexible lead with stimulating electrodes is inserted in the scala tympani, a fluid-filled cavity in the cochlea. When the electrical stimulation is applied, it propagates through fluid in the scala tympani and across the basilar membrane, separating the scala tympani and the scala media, an adjacent compartment of the cochlea containing the hair cells. Such rather remote operation of existing cochlear implants does not allow fine localized targeting of the hair cells, limiting their pitch resolution. Cochlear implants have not undergone significant changes in their design or function since 1985, when the first multi-channel cochlear implant was developed by Cochlear and approved by FDA. Since then, FDA approved similarly-designed cochlear implants by two other companies, one by Advanced Bionics in 1996 and another by MedEl in 2001. An apparent lack of innovation in cochlear implant is partially due to the fact that, despite their limited pitch resolution, they provide rather faithful reproduction of human speech. The remaining “holly grail” of the cochlear implant industry is a device with sufficient pitch resolution for listening to music. So far, that goal remains outside the reach, at least for the devices based on electrical stimulation of cochlea. As a welcome first step toward an alternative method of cochlear stimulation, a group of engineers at the Fraunhofer Institute for Manufacturing Engineering and Automation in Stuttgart, led by Dr. Kaltenbacher, developed a device that can be placed in the middle-ear to bypass the ossicles (the auditory bones) and provide direct acoustic stimulation of the fluid in the scala tympani. In theory, such a design can: 1) be less invasive, 2) be easily implanted in an outpatient procedure, and 3) potentially provide better sound quality than existing cochlear implants. The implant does require that at least some of the hair cells are still present in the cochlea (unlike the other types of cochlear implants). In order to bypass the bones in the middle ear, the sound is picked up by an externally-mounted microphone, converted to infrared light, passed through the tympanic membrane, picked up by a photo diode, and finally converted back to the sound waves with MEMS-based piezoelectric thin-film cantilevers (see the inset). So far, the engineers are testing individual components of the device, with a finished prototype tests planned for 2014.

Mar 082013

Most commonly used neuromodulation strategies, such as the DBS for treatment of Parkinson’s disease or spinal stimulation for chronic pain, use electrical stimulation to mask or override abnormal firing in disease-affected neuronal networks rather than to assist in repairing these networks.  In other words, the electrical stimulation is used to treat the symptoms rather than the disease itself. In contrast, two publications (one and two) by Dr. Hentall’s group at The Miami Project to Cure Paralysis describe a novel therapeutic role for electrical stimulation in the brainstem, a region of central nervous system between the brain and spinal cord. Specifically, the electrical pulses were used to stimulate activity of the raphe nuclei, which have an important role in orchestrating anti-inflammatory and neuroprotective effects throughout the central nervous system.  The raphe nuclei are composed primarily of serotonergic neurons that have extensive connections throughput the central nervous system, with the raphe magnus projecting to the spinal cord and medial/dorsal raphe nuclei projecting to cerebral cortex and subcortical structures. Due to a high concentration of serotonergic neurons in these nuclei and their common involvement in anti-inflammatory and neuroprotective functions, generalized stimulation of these nuclei results in synergic activation of these neurons and effective induction of biological repair mechanisms. It should be noted that presence of such homogenous neuronal population in the raphe nuclei is rather unique, as most brain regions have heterogenic populations with divergent (sometimes even opposite) functions.

Nov 142012

The Israel Brain Technologies (IBT) has announced the launch of one-million US$ B.R.A.I.N. Prize (Breakthrough Research And Innovation in Neurotechnology) to support the development of a disruptive and medically significant neural technology toward its commercialization. An international judging committee, composed of distinguished leaders in neurotechnology and business including two Nobel Prize Laureates, will select an individual or a group from across the globe to support continued development and commercialization of the technology in collaboration with Israeli researchers and entrepreneurs. The applicants must have already produced a working prototype and be able to demonstrate a clear path to commercialization.

“The B.R.A.I.N. Prize will bring together the best minds across geographic boundaries to create the next generation of brain-related innovation, from Brain Machine Interface to Brain Inspired Computing to urgently-needed solutions for brain disease,” says Dr. Rafi Gidron, Founder and Chairman of IBT. “It’s a global brain-gain. Our aim is to open minds…quite literally.”

“We invite innovators around the world to enter the B.R.A.I.N. Prize competition, so we can tackle some of the most exciting challenges facing our planet,” said IBT Executive Director Miri Polachek. “Our aim is to bring Israeli technology to the world, and the world to Israeli technology. We want to turn the ‘Start-up Nation’ into the ‘Brain Nation.’”

In the words of Israeli President Shimon Peres, a leading proponent of brain research and technology. “There is no doubt that brain research in the next decade will revolutionize our lives and impact such major domains as medicine, education, computing, and the human mind, to name but some. Moreover, it will not only relieve the suffering of patients of such debilitating diseases as Parkinson’s and Alzheimer’s, but it will also engender large economic rewards as well.”

Prize winners could, for example, help treat neurological disorders like Alzheimer’s, Parkinson’s, depression, PTSD or even sports-related brain trauma. Or they could create the next cutting-edge brain-inspired technology that will alter our day-to-day lives.

Interested contestants can visit www.IsraelBrain.org to receive more information and to apply online. The submission deadline is March 15, 2013, and the Prize will be awarded at IBT’s International Brain Technology Conference in October 2013.

Sep 292012

Earlier this year, the National University of Singapore (NUS), Singapore’s Agency for Science, Technology and Research (A*STAR) and the Ministry of Defense joined their efforts in establishing the SINAPSE: Singapore Institute for Neurotechnology.  With the initial funding of 20M SGD (~16M USD) and allocated space of 1000 square meters in the NUS Center for Life Science, the newly-formed institute already has 5 primary and 5 affiliated faculty members as well as 10 postdoctoral fellows and research assistants.  The Institute’s director is Prof. Nitish V. Thakor, who is also the BME professor at Johns Hopkins University, Editor-in-Chief of IEEE Trans Neural Rehab Eng, and founder of 3 startups.  The SINAPSE institute has specific interest in the development of peripheral and central neuroprosthetics, neuromorphic systems and neurochips, and other research areas in clinical and cognitive neuroengineering. The director’s over-arching vision is to create the environment for interaction among basic scientists, computational scientists, experimentalists and clinicians, engineers, innovators and entrepreneurs. Prof. Thakor is presently in a recruitment mode, aiming during the next 1-2 years to hire 4 additional faculty members and 10 postdocs, essentially doubling the institute’s manpower. He is looking for researchers that pursue clinically-applied brain research, technology development, and commercial translation of devices. For detailed job offerings, please visit the NTZ Jobs page and the official SINAPSE site. If you plan to attend our ICNPD-2012 meeting in Freiburg, Germany this November, you can stop by SINAPSE’s booth and discuss the job requirements and benefits with Prof. Thakor.

Sep 272012

NTZ blog has been paying close attention to neural prosthetic devices aimed at improving cognitive functions. We have presented the beneficial effects of direct current stimulation (tDCS) of the temporal lobe and frontal cortex, DBS of the fornix, and recording in CA3 region coupled with stimulation of CA1 region in the hippocampus.  The last-mentioned study was performed using a rat preparation in 2011 by a Prof. Ted Berger at the University of Southern California and Prof. Samuel Deadwyler at Wake Forest University. Merely a year later, the same group of researchers has accomplished a new feat – a closed loop recording and stimulation in the rhesus monkey’s prefrontal cortex, an important location for decision-making and short-term memory processes. The same nonlinear dynamic model (MIMO) was applied for decoding, enhancing, and re-encoding of the firing patterns. To access the prefrontal cortex, the ceramic-substrate multisite electrodes were chronically implanted, targeting the supra-granular layer 2/3 and infra-granular layer 5. Cocaine was used to disrupt cognitive activity, simulating the brain injury. As you can see in the graph above, the memory task performance was fully restored by MIMO-patterned electrical stimulation during the task execution. The far-reaching goal of the project is to replace the memory forming process in the brain area damaged by stroke, dementia or other disorder by using a neuroprosthetic device interfaced to the healthy decision-making area of the brain.

Sep 092012

Bionic Vision Australia is a consortium of Australian scientists who are working together on suprachoroidal retinal stimulation device for restoring the lost vision. This effort involves about 150 researchers at the Bionics Institute, Centre for Eye Research Australia, NICTA, University of Melbourne, and University of New South Wales in Sydney. The suprachoroidal approach shares some similarities with the cochlear implants, as in both cases the implants are placed in a fluid-based cavity adjacent to the compartment with sensory neurons. The suprachoroid approach is considered safer and easier than surgically-challenging placements directly above the retina (epiretinal) or below it (subretinal). The analogy with the cochlear implants is not a coincidence, as the Australian researchers have leveraged from their extensive experience in developing the first FDA-approved multi-channel cochlear stimulation device for restoring the hearing more than 30 years ago.
Toward their ultimate aim of implanting the 98-electrode suprachoroidal implant, in May 2012, the Australian researchers reached a significant milestone with an implantation of the early-prototype device in three patients with profound vision loss due to retinitis pigmentosa, an inherited condition. While the functionality of the prototype is rather limited (24-electrodes and a lack of wireless interface to the camera), it will enable psychophysics studies to carefully examine the visual percepts and allow researchers to develop appropriate visual processing strategies in preparation to implantation of the fully-functional device in 2013 or 2014. The R&D effort is being supported by a $42 million grant from the Australian government and technology-sharing agreements from Cochlear Ltd.

Aug 022012

Two students, Eran May-raz and Daniel Lazo, studying at the Bezalel Academy of Arts and Design in Jerusalem, created the short film above. It offers a glimpse of near-future augmented visual perception in a form of visual overlays for the world in front of our eyes. Every aspect of our daily activities, from cutting vegetables to picking an outfit for a date, becomes a part of the game. The proposed visual overlays and communication link to a PC/smartphone can potentially be implemented using the contact lenses with embedded OLED screen and a Bluetooth chip. However, even inclusion of motion tracking inside the contact lens probably would probably not be able to provide smooth tracking of eye movements and saccades. For more natural integration of external visual information and an OLED overlay, the latter could be placed in front of the retina (epiretianlly). Alternatively, the retinal stimulation chip coupled to the videocamera and the smartphone can be placed subretinally or suprachoroidally. Augmented visual perception is likely to gain more interest in a near future as the retinal implant market is rapidly expanding worldwide.

Jul 082012

Transcranial magnetic stimulation (TMS) is a well-established method of modulating neuronal activity in the brain. The TMS coil usually spans several centimeters and produces a lot of heating, making it unsuitable for intracranial implantation. The study, led by Dr. Fried at the Massachusetts General Hospital, aimed to develop a sub-millimeter sized coil that can be implanted into deep brain targets, such as the basal ganglia. Their prototype micro-coil was based on a commercial multilayer copper coil (ELJ-RFR10JFB, Panasonic) that was coated with a dielectric varnish, placed on a tip of a needle, and manually positioned above the freshly dissected rabbit retina. With the photoreceptor side down and the ganglion cell layer on top, the patch electrode was positioned on a ganglion cell to record the light-stimulated activity of individual retinal neurons. The micro-coil was oriented in two positions, either parallel or perpendicular to the retinal surface, and the DC voltage (0.5-10 V) was applied for 20 μs to induce a circulating electric field (E-field) in the retinal tissue (see the figure).  The parallel orientation was considerably more effective in inducing the neuronal activation that the perpendicular one. The train of action potentials was readily induced in the parallel orientation as far as 1.1 mm from the retinal surface.  Even more intriguingly, essentially the same amount of DC voltage (6V) was required at the micro-coil to induce the neuronal response at different distance from the retina, ranging from 0.3 to 1.1 mm. The finite element method (FEM) modeling of the electric field distribution around the micro-coil indicated that the magnetically-induced E-field was ~1 V/m at a radial distance of 1 mm from the coil core and was only slightly decreasing with distance. In contrast, the E-field decreased rather rapidly in the vertical dimension form the coil, being only 0.1 V/m at a 1 mm distance. This study provides an initial ex vivo proof of the principle and opens up a possibility of developing novel implantable neuroprosthetic devices with several features that are superior to the electrical stimulation. Among such desirable features are: 1) less steep E-field gradient, resulting in more uniform stimulation of neurons over a larger volume, and 2) absence of electrochemical reactions at the electrode-tissue interface, resulting in longer electrode lifetime and healthier tissue. Other, perhaps unexpected, benefits of the magnetically-induced electrical stimulation may become evident once the in vivo evaluation study is completed.

Jun 172012

The team of MIT researchers, led by Rahul Sarpeshkar and Jakub Kedzierski, reported developing a Si-based fuel cell that can break down glucose and harvest its energy. The device operates by collecting the electrons liberated during electrooxidation of glucose at the anode, while the liberated protons travel to the cathode through the solution. The subsequent reduction of protons and electrons, catalyzed at the cathode, restores the net charge neutrality in the solution (or tissue). Since glucose is present in the brain and spinal cord, including the cerebrospinal fluid, the fuel cell can operate autonomously at the implantation site, without the need for supplying the fuel. Moreover, the catalyzing agent for the anodic reaction can be produced by a bacterial biofilm, which has a self-regenerating capability (although this approach might not be suitable for humans due to the biosafety concerns). Researchers calculate that a very small fraction of available glucose will be used, therefore not impacting normal brain consumption of glucose. The prototype device was able to harvest the energy at the power density up to 100 µW/cm2, which is sufficient for operation of the ultra-low-power analog electronics that is also being developed by Dr. Sarpeshkar. Harvesting the biological energy is important for removing the batteries or inductive coils from the implanted neuroprosthetic device, and consequently shrinking its size and reducing the number of feedthoughs and leads from the device. Harvesting the energy of organic compounds, such as glucose, it just one possible method of collecting the energy from biological environment, while other groups are evaluating the absorption of light, heat and mechanical vibration.

May 302012

The FCC recently allocated a dedicated RF spectrum for Medical Body Area Network (MBAN) technologies. The MBAN spectrum can be used for low-power and short-range medical applications as well as other, perhaps unprecedented, uses in consumer electronics, personal entertainment, gaming, sport training, and social network applications. The transmitting/emitting devices can be implanted or placed on the surface or around the body of humans (or animals). The MBAN adheres to IEEE 802.15.6-2012 standard and supports the data rates up to 10 Mbps. The allocated frequency bands include 402–405, 420 –450, 863 –870, 902 –928, 950 –956, 2360 –2400, and 2400 –2483.5MHz. Creation of the MBAN spectrum has been driven by the “last meter” challenge of untethering the patient from the bedside monitoring and treatment equipment. In addition to the bedside applications of MBAN spectrum, the neural interface devices are also likely to benefit from the new bandwidth. MBAN can spur the development of novel data-intensive neural interfaces, ranging from EEG and ECoG to cochlear and retinal implants. The newly-allocated bandwidth can be readily utilized for sending the wide-band neural signals from hundreds of recording electrodes or for sending the control signals to hundreds of stimulation electrodes. Use of the bandwidth reduces the need for incorporating the multiplexing and signal-processing circuits inside the implantable device and, instead, sending the raw data to an external controller, such as a body-worn smartphone-like device. My personal hope is that simplification and standardization of the implantable electronics will lead to the considerable price reduction and eventual emergence of consumer-oriented implantable neural interfaces for non-medical use.

May 242012

One and a half years ago, NeuroTechZone reported on initial success of subretinal implants from the Retina Implant AG in three retinitis pigmentosa (RP) patients from Germany. The international multi-center phase of the clinical trial with the wireless implant Alpha-IMS was initiated in late 2011, involving two additional sites in Germany, two sites in London, UK and one site in Hong Kong, China. Altogether, 26 patients have received subretinal implants in the trial. The first two UK patients with RP were implanted in April 2011 and the UK doctors are recruiting additional 10 patients. The first Chinese patient was implanted on February 2012, with two more to follow. Additional sites in Hungary, Italy and the United States will soon join the trial. The data from recently implanted patients indicate a restoration of useful vision in daily life. Many of them experience visual perception in both dim and bright environments. Some patients have reported the ability to see objects 30 feet away and to read numbers on a pair of dice. Unexpectedly, one of the British patients reported having dreams in color for the first time in 25 years since becoming blind.

May 132012

Combining several therapies to build a rehabilitation treatment plan for neurological conditions is nothing new.  However, combining a variety of technologies into a treatment plan to produce functional outcomes is an emerging theme among innovative rehabilitation professionals. The roots of combining the rehabilitation with electrical stimulation to improve motor re-learning come from the pioneering work by Dr. Randolph Nudo and Dr. Alvaro Pascual-Leone in 1990es.

Recently, this approach was applied by combining the robotic therapy with electrical or magnetic stimulation by a team of researchers lead by Dr. Lumy Sawaki at the University of Kentucky in Lexington. This new neural rehabilitation technique capitalizes on “neuroplasticity,” which refers to the brain’s ability to reorganize itself by forming new neural connections to compensate for injury and disease.  Dr. Lumy Sawaki, MD, PhD, an Associate Professor in the Department of Physical Medicine and Rehabilitation at the University of Kentucky, has been exploring how combining technologies in the rehabilitation setting may help her patients regain functional movements. This new therapy is based on previous work she had done involving CIMT, constraint-induced movement therapy.  Dr. Sawaki was the lead author on a CIMT study published in the journal Neurorehabilitation and Neural Repair.   In this study, each of the 30 participants was evaluated using transcranial magnetic stimulation (TMS), a non-invasive method to excite neurons in the primary motor cortex. In the CIMT therapy study, Dr. Sawaki and collaborators used TMS to map the area of the brain that controls a particular muscle and compared this map to previous patterns of activity. As the patient’s ability to perform a certain movement improves, these brain maps confirm the reorganization of the associated area of the brain. Focusing on hand motor function of sub-acute stroke survivors, they observed changes within the functional activity of the brain for those who used CIMT.

Building on this previous work, Dr. Sawaki and her research team are evaluating the combined approach to stimulate the brain with two painless and non-invasive methods: the magnetic stimulation with TMS and the electrical stimulation with transcranial direct current stimulation (tDCS), to develop a new neural rehabilitation therapy for chronic survivors of neurological trauma from stroke, brain and spinal cord injuries. In this new therapy, the TMS and tDCS is applied along with robotic movement therapy, such as body weight supported treadmill training. Dr. Sawaki is using TMS and tDCS to stimulate the area inside the motor cortex that controls movement of a targeted muscle. By applying multiple stimuli and monitoring the muscle response combined with robotic therapy, the investigators are attempting to determine if this combination will result in higher functional benefit.

Conclusive evidence is still lacking but it brings the promise of combined neural rehabilitation therapies paving a new path for how we approach complex neurological conditions in the rehabilitation setting.  Click here to read more about Dr. Lumy Sawaki’s research and new neurorehabilitation therapy.

Mar 292012

It is well known that building a setup for recording neural spikes is not trivial. Many older electrophysiological systems are bulky, expensive and difficult to use. Their system components require elaborate shielding and grounding  to reduce the electromagnetic interference. Recently, the technology advances have been quite rapid. It has become possible to build the millimeter-scale electrophysiology amplifiers from commercial off-the-shelf components. Here, I would like to share an amplifier design that is capable of intracellular and extracellular recording, as well as LFP, EMG, and EEG. It is small, easy to build and extremely cheap. The system uses differential mode of recording, thus eliminating the need of extensive shielding from environmental noise. The circuit had been tested on freely-moving animal exposed to their regular environment and was able to record neural spikes with a good signal-to-noise ratio (SNR).

The amplifier is divided into two stages. The first stage is an Instrumentation Amplifier (IA) with the differential input. The input signals have DC removed (with a high-pass filter) with highly tuned RC components. It is important to have very closely matched components to have high Common Mode Rejection Ratio (CMRR). The capacitors Cpf and Cnf are for power supply regulation with typical value of 0.1µF. The gain of the instrumentation amplifier is typically set in the range from 100 to 1000. The second stage is a second order low-pass filter (sellen-key). The gain of this filter should be maintained about 10; resulting in a total gain of the amplifier of ~10,000.

Following are the example values for the filter amplifier:

Chp1 = CHR = 100nF, RH1 = RHR = 4.68MΩ; Low Cut-off frequency = 0.34Hz;

R1= 10kΩ, R2= 150kΩ, C1= 1nF, C2= 1nF, R3= 10kΩ, R4= 100kΩ; High Cut-off frequency = 4,109Hz;

NOTE: For multiple channels build the same circuit and use them in parallel. For single reference electrode just short all the inverting terminals (-) of all instrumentation amplifiers and use only one reference high-pass filter (CHR, RHR) instead.

Mar 282012

Central-nervous-system based neuromotor prosthesis (NMP) holds a great deal of promise for complete spinal cord injury (SCI) yet is still far from the clinical use.  Cortical-level NMP uses direct cortical recording and requires craniotomy for implanting a microelectrode array in the motor cortical area of an injured person. First successful human trial of the cortical NMP in a quadriplegic person, the BrainGate, was done by Dr. Donoghue and colleagues back in 2006. Last year, Dr. Edgerton and colleagues have applied a spinal NMP to train a paraplegic person to stand and walk on a treadmill.  As these cortical and spinal NMPs are reaching maturity, the question emerges, whether all people with SCI can benefit from this technology. In this post, I will try provide my perspective about the potential technology users.

SCI has different severity, motor complete or incomplete, and occurs at different spinal levels, from cervical to thoracic and lumbosacral, resulting in quadriplegia or paraplegia. NMP is potentially most viable for motor-complete SCI since people with incomplete SCI can benefit from extensive rehabilitation training. Quadriplegics with motor-complete SCI would likely benefit the most from this technology. One of major challenges for implementation of cortical NMP for quadriplegics is the availability of real-time adaptive decoding algorithms for controlling the body balance, needed to enable standing and locomotion. As a quadriplegic person completely loses his/her posture control, it is unlikely that they could use existing decoding algorithms for cortical NMP for standing and stepping. Still, such a person can use the cortical NMP for controlling an external device or an upper limb (through stimulation of peripheral nerves or muscles). Volitional control of an individual hand muscle by this kind of cortical CNMP has already been demonstrated in non-human primates by Dr. Fetz and colleagues.

It is not clear whether paraplegics can benefit from the NMP technology to the same degree as quadriplegics. As paraplegics have useful hand and arm functions, cortical NMP might be too risky and invasive of a procedure to justify the potential benefits. Perhaps, a spinal NMP controlled by a hand or a processor that interprets the person’s movement intent can be more beneficial for standing and walking. In a spinally-intact person, the leg movements and locomotion require no visual feedback and are adjusted in time and space through a local feedback circuitry in lumbo-sacral region of spinal cord. Provided that this feedback loop is intact in the paraplegic person, would be extremely beneficial to use this loop along with the spinal Central Pattern Generator (CPG) for enabling the locomotion. Recent human studies by Edgerton and others indicate simply turning these spinal neural circuits ON and OFF might not be enough for standing and/or stepping. Hopefully, with more robust decoding and encoding algorithms, the spinal NMP might become a viable clinical solution for paraplegics.

Considering these arguments, I would like to suggest that an ideal candidate for cortical NMP would be a quadriplegic, while an ideal candidate for spinal NMP would be a paraplegic.



Mar 252012

An international research team from Japan, Germany, and United States reported creating a flexible organic transistor that features good thermal stability at temperatures up to 150°C. The new transistor has been fabricated with a biocompatible polymeric substrate (Parylene), making it potentially useful for ECoG and other types of implants. Fabrication of many implantable devices involves some steps that have to be performed at elevated temperatures (e.g. parylene annealing). In addition, device sterilization is also commonly done at elevated temperatures of 130-170°C and (optionally) an elevated chamber pressure, in a process called autoclaving. The autoclaving, done at 150°C and atmospheric pressure, takes less than 3 hours, faster than room-temperature sterilization using ethylene oxide (24 hours).

The key technological achievement in the reported study is the use of an ultrathin (2 nm) heat-resistant monolayer film for insulation between the organic semiconductor and its gate. The monolayer is synthesized by a self-assembly of long-tailed phosphonic acids and has a densely packed crystalline (rather than amorphous) structure. Such ordered chemical structure prevents a formation of pinholes during heating. The use of ultrathin monolayer between the semiconductor and its gate instead of thicker dielectric films allowed the researchers to reduce the transistor driving voltage from 20V to 2V, making it more suitable for neuroprosthetic applications. Main limitation of the reported study is the short duration of the applied heat stress (20 sec), which does not evaluate a possibility of a slow heat-induced degradation of the self-assembled monolayer.