Aug 272011
 

One does not need the future-telling skills of Ray Kurzweil to predict the rise and eventual dominance of China in manufacturing of neurotech devices. Outsourcing of medical device manufacturing to China has been on the rise in the last few years as evidenced, for example, by a reduced US export-import surplus for medical devices from $6 billion in 2005 to $3 billion in 2010 (according to US officials), of which $1.2 billion is the trade surplus with China. The market for medical devices in China is at $14 billion and is projected to double by 2014. The rise in China’s medical device market is fueled by an ongoing government-funded healthcare reform ($123 billion over the next four years), which aims, among other things, to make medical devices affordable by subsidizing their domestic manufacturing. The importance of such governmental  subsidies can be illustrated by the stunning revelation that in 2008 the number of cardioverter-defibrillator implants in China was fewer than 700 compared with 100,000+ implants annually in the United States.

Unlike the biomedical device industry as a whole, the implantable neural device industry has so far been resilient to migration to the land of rising dragon from its birthplaces in the US, Europe, and Australia. There are multiple reasons for that, which perhaps could be better explained by an economist. In my view, there had been two key obstacles: 1) assuring the regulatory conformance of the China-assembled medical device in the western countries; and 2) poor protection of intellectual property rights in China, making western device makers uneasy about sharing their fabrication secrets with Chinese subsidiaries. Both of these obstacles seem to be melting away. The regulatory conformance is rapidly improving as more reciprocal agreements are being ironed out between the US FDA and its Chinese counterpart, while inadequate IP rights protection no longer stops the leading electronics companies, such as Apple and Sony, from manufacturing their cutting-edge devices (e.g. iPhone, iPad, and PlayStation) in the Foxconn’s Chinese factories.  

With gradual dissolution of the economic barriers, we are now faced with a barrier of a different kind: an acceptance of the level-playing field in the emerging global medical device market. When Terry Gou, the CEO of Foxconn (the largest exporter and largest private employer in China), first approached Steve Jobs, the Apple’s CEO, he had to force Mr. Jobs to give him his business card. Now, a decade later, the relationship between the two companies has evolved from a contract manufacturing to a strong and dedicated partnership, with Foxconn being a main producer of iPhone and iPads. One can hope that a similar transformation is taking place in the mindsets of leading implantable neural device makers. China has recently begun fabrication of its own cochlear implants and DBS devices. The production rate of these domestically-made devices is not high enough to compete with large multinational companies, which still control 90+ percent of the Chinese market.

In anticipation of a looming challenge, the multinationals are expanding their operations in China. For example, Medtronic reported the opening a patient care center in Beijing in 2010 and its new regional headquarters in Shanghai earlier this year, with plans to double its workforce in China to 2,000 employees by 2015 (while reducing the same amount of workforce in other countries). Similarly, Boston Scientific announced a five-year, $150 million investment in China, including the construction of new manufacturing and research facilities and addition of 1,000 workers to the current 200. Following in the footsteps of its competitors, St. Jude Medical announced the opening of an R&D center in Beijing along with a manufacturing facility and training center in Malaysia. It makes sense for the neurotech device industry to embrace the Chinese emerging economy to utilize its consumers, labor, and innovation. According to this report from the Economist, Chinese R&D centers have already developed some innovative medical devices with a price tag one tenth of comparable products in the West. There’s no doubt that we’ll be seeing even more innovation from and investment in China’s neurotech industry. And with more than 1 billion of human capital at hand, it is easy to imagine the potential.

Aug 162011
 

In a recent piece in the journal Science and in a longer paper posted on the MIT website, Phillip A. Sharp and Robert Langer have spoken to the need for, and trend toward convergence in biomedical science. As these prominent researchers note, convergence “emerges” as the foci and activities of several disciplines fuse so that the sum of their research and outcomes is greater than its constituent parts. Such convergence is occurring among the disciplines that create, employ, and constitute the “field” of neurotechnology – and so we witness a merging of physics, chemistry, nanoscience, cyberscience and engineering, and the engagement of genetics, anatomy, pharmacology, physiology and cognitive psychology, in ways that biologist E.O Wilson might describe as “consilient.”

 

To be sure, this fosters and necessitates the “multilingual” “convergence creole” capabilities of terminology, discourse and knowledge and resource inter-digitations that Sharp and Langer describe. I agree – a common language and working construct of convergence is vital if we realistically operationalize de-siloing of the disciplines that could develop and employ neurotechnological to maximize opportunities to define and solve novel problems in basic and translational biomedicine, and more broadly in the public sphere. That’s because this process is not merely a technical sharing, but instead represents a synthetic mind-set that explicitly seeks to foster innovative use of knowledge-, skill-, and tool-sets toward (1) elucidating the nature and potential mechanisms of scientific questions and problems, (2) de-limiting existing approaches to question/problem resolution; and (3) developing novel means of addressing and solving such issues.

 

I posit that in this way, convergence enables concomitant “tools-to-theory” and “theory-to-tools” heuristics, and the translation of both heuristics and tools to practice. This is important because the current utility of many neurotechnologies is constrained by factors including (1) a lack of specificity of action and effect (e.g. transcranial and/or direct magnetic stimulation), (2) size restrictions and cumbersome configurations of micro- and macroscale devices, and (3) difficulties of matching certain types of neurologic data (e.g. from neuroimaging, neurogenetic studies) to databases that are large enough to enable statistically relevant, and meaningful comparative and/or normative inferences. So the fusion of neuro-nano-geno-cyber science and technologies can be seen as an enabling paradigm for de-limiting current uses and utility, and fostering new directions and opportunities for use and applicability.

 

Once silos are dissolved, limitations can be diminished or removed, but so too may be the ability to recognize relative limits upon the pace and extent of scientific discovery, and the use of its knowledge and products. As I’ve previously mentioned in this blog and elsewhere, the result may be that we then encounter effects, burdens, and harms that were as yet unknown, and/or unforeseen. There is real risk that the pace, breadth and depth of neuroscientific and technological capability may outstrip that of the ethical deliberations that could most genuinely evaluate its social impact, and in response, appropriately direct such innovation and steer its use.

 

What is needed is a systematic method of and forum for inquiry about what the convergence approach in neuroS&T (neuroscience and technology) will and might yield, and how its outcomes and products may change the values and conduct of science and society. Appropriate questions for such inquiry would include: (1) how convergence approaches can be employed in neuroscience; (2) what practical and ethical issues, concerns, and problems might arise as a consequence, and (3) what systems of risk analysis and mitigation might be required to meet these challenges, and guide the employment of neuroS&T. Given the power of convergent science to affect the speed and scope of neuroscientific discovery and neurotechnological innovation, I argue that such an approach to the ethical, legal and social issues (ELSI) is needed now, and not after-the-fact.

 

But any meaningful approach to the ELSI of convergent neuroS&T would require an equally advanced, integrative system of ethics that can effectively analyze and balance positive and negative trajectories of progress, increase viable benefits, and militate against harm(s). Obviously, this would necessitate evaluation of both the ethical issues germane to the constituent convergent disciplines, and those generated by the convergence model of neuroS&T itself.  I believe that neuroethics can serve this role and meet this demand (although opinions on this certainly differ; see for example: “against neuroethics“) As a discipline, neuroethics can be seen as having two major “traditions” – the first being the study of neurological mechanisms involved in moral cognition and actions (what might be better termed, “neuro-morality”), and the second that examines, addresses and seeks to guide ethical issues fostered by neuroS&T research and use (see: “Neuroethics for the New Millennium“).

 

I’ve posed that these two “traditions” are not mutually exclusive, and that if and when taken together, may afford a meta-ethics that both informs how and why we develop and act morally, and uses this information to intuit ways to employ existing systems of ethics, and/or cultivate new ethical approaches to better reflect and decide upon the moral implications and ramifications of various uses and misuses of neuroS&T in the social sphere. Philosopher Neil Levy has claimed that neuroethics might be a new way of doing ethics, and this might be so. At very least, I think that neuroethics will allow a more explicit and purposive focus upon how change, uncertainty and progress in neuroS&T are affected by – and affect – progress, not only in genetics, nanoscience and cyberscience as stand-alone entities or simple concatenations of scientific methods, tools and techniques, but as a true convergence that conflates ideas, process and technologies, and in the event, change the human predicament, human condition, and the human being.

 

There are a number of excellent discussions about what neuroethics is and is not, and can and cannot do (see for example, Eric Racine’s fine book Pragmatic Neuroethics). My take on this is that in order to have any real value, neuroethics (as a discipline and practice) must (1) apprehend the changing realities of neuroS&T capability and effect(s); (2) identify which extant moral theories and systems may and/or may not be viable in ethical analyses and guidance; and (3) develop ethical tools that compensate for weaknesses in current ethical theories in order to more effectively weigh benefits and risks, and remain prepared for possible “less than best case” scenarios.

 

A simple precautionary principle won’t work, for the simple reason being that neuroS&T pushes the boundaries at the frontier of the known and unknown, and (1) conditions “at the edge” are always risky; (2) while apparent benefits may compel each new step forward, burdens, risks and harms can be less than obvious because they often are consequential to our beneficent intentions (for those of you who are Sci-Fi fans, there are host of writings and movies that play to this, think for example of the films Mimic, Surrogates, and Limitless, just to name a few), and (3) the longer S/T remains in the public sphere, the greater the likelihood for it being influenced by economic, and/or socio-political agendas.

 

In other words, stuff happens, and we need to be aware that it can, likely will, and be prepared if and when it does. Not by trying to grind neuroS&T to a halt or by imposing unrealistic proscriptions, but by supporting a convergent approach to both neuroS&T and the ethical systems that guide its use in an ever-more pluralist society, and changing world stage.

Aug 022011
 

In another blog post, Victor Pikov raised provocative points  that speak to the iterative integration of neurotechnology (if not technology in general) into the fabric of human life and being. In this light, I think that we need to view Manfred Clynes and Nathan Kline’s conceptualization of the “cyborg” as a multi-step process, with renewed interest and vigor.  As humans, we use tools to gain knowledge and exercise the power of such know-how over our environment and condition.  Technology provides both investigative and articulative tools that allow us to both know and do at increasing levels of sophistication, complexity and capability.  Indeed, our current and future state might be seen as Homo sapiens technologicus (one aspect of which is Pikov’s somewhat tongue-in-cheek “twittericus”).

 

I agree with these perspectives, and offer that we are seeing the human-in-transition, a form of “trans-humanism” that is defined by and reliant upon technology and a technologically enabled worldview in the evolution and development of our species. This is evidenced by our technologically-enabled, rapid access to unprecedented amounts of information, increasing integration of technology into human embodiment, technologically-mediated engagement with each other, and capabilities for manipulation and control of our external and internal environments. As Victor Pikov notes, in this way, we are poised before a horizon of possibility, and potential problems.

 

Yet, any progression into and through a new era will incur individual and social attitudinal changes in relation to the capabilities and effects offered by new science and/or technology, and the effect(s) and our relationship to (and through)  neural interfacing would be no different.  It is interesting to speculate on how the cyborgization of homo technologicus will occur, and I wonder how we as individuals, communities and a species will direct and handle such change.   A “one-size-fits-all” approach to the employment of any neurotechnology – be it diagnostic or interventional – is at very least pragmatically inefficient, and at worse, inapt on both technical and ethical grounds. And while we might skirt some (but not all) of these technical issues when dealing with certain forms of neuroimaging (like fMRI/DTI), the possibility for runaway, a.k.a. Wexelblatt, effects (i.e. unanticipated consequences of nature) incurred by interventional neurotechnologies looms large, and ethico-legal and social issues become all the more prominent with increasing use of any neurotechnology in the public sphere. I believe that the issue boils down to an intersection of two major unknowns –first is the persistent uncertainties of the so-called “hard questions” of neuroscience (namely, how consciousness/mind originates in/from brain), and the second is how any neurotechnology can and does affect the nervous system. These uncertainties are not mutually exclusive – the tools-to-theory heuristics of neuroscience are sustained by the use of neurotechnology to forge ever-deepening understanding about the structure and function of the brain, and theory-to-tool heuristics enable the development of successively more complicated and capable neurotechnologies to assess, access and control neural functions. Yet, navigating the possibilities of what and how technologies can be used, versus what technologies should be used, in whom, and in which ways requires stringency in the guidelines and policies that direct neurotechnological research and its application(s).

 

As Don DuRousseau and I have recently noted, this may be increasingly important given a pervasive “market mindset” that has fostered more widespread use of neurotechnologies, and a tendency to side-step evidence-based, pragmatically grounded approaches and instead rely upon lore rather than the most currently validated science. Clearly, further research, development, testing and evaluation (RDTE) of various neurotechnologies is required to more fully define 1) what constitutes evidence-based versus non-evidenced based claims; and 2) the capabilities, limitations – and potential risks – of employing various neurotechnologies in both clinical and non-clinical settings.

 

We have called for uniform and enforced screening mechanism for all neurotechnology product developers to ascertain whether their products may incur potential risks to the general public, and regulation of the industry, as well as the clinical and public use of these technologies and devices (see: Giordano J, DuRousseau D. Use of brain-machine interfacing neurotechnologies: Ethical issues and implications for guidelines and policy. Cog Technol 2011; 15(2): 5-10).

 

But it’s important to note that the field – and use- of neurotechnology is evolving and with this evolution comes the development of new techniques, knowledge and capabilities. So, perhaps what is required is an “evo-devo” orientation to not only the ways that neurotechnology can affect the human condition, but also to the ongoing development and use of the technology itself. As more data become available, pre- and proscriptions regarding the use(s) of particular neurotechnologies should be re-examined, re-assessed, and altered as necessary, and as consistent with the spirit and dictates of science to remain self-reflective, self- critical and self-revising. To do otherwise would be anachronistic, if not downright de-evolutionary.

Jul 292011
 

The 2011 meeting of the International Neuromodulation Society, which took place in London, England in May 2011, featured a large number of oral and poster presentations offering updated technical and clinical information on neuromodulation topics. There was also a full day of sessions devoted to commercialization, investment, and industry issues affecting neuromodulation startup firms.

But as is the case with many meetings that draw attendance from different fields of endeavor, there was as much to learn from the informal scuttlebutt going on between sessions as there was from the posters and oral presentations themselves. We offer here some of our observations based on random comments from attendees.

After the Sunday session on future innovations in neuromodulation, some attendees were perplexed by Greatbatch Inc.’s efforts to launch a new spinal cord stimulation device company, called Algostim LLC. Given that Greatbatch supplies components such as batteries and leads to many manufacturers of implanted neurostimulation systems, it raised the question as to why Greatbatch would want to compete with its customers. Greatbatch CEO Tom Hook made the case that by incubating new device startups that will eventually be spun off, Greatbatch will cultivate a greater customer base in the future. It will be interesting to see how that situation plays out.

That controversy might have presented an opportunity for component supplier Cirtec Medical to drum up business, had they have more of a presence at the event. But that company has been hit by the departure of some key staff members, including its former president Barry Smith.

There was also some discussion on the competitive positioning of new entrants in the spinal cord stimulation business such as Nevro, Spinal Modulation, and Neuros Medical. Several attendees thought that Neuros has a sound technology base, though probably the smallest market opportunity of the three. There was speculation that Nevro and Spinal Modulation might be ripe targets for acquisition by existing players in the SCS market. It will be interesting to see if either firm makes it to the market approval stage, let alone profitability, before being snapped up by one of the big three.

Speaking of spinal cord stimulation, perhaps the most profound observation we heard at the conference was by Robert Levy of Northwestern University, who noted that the SCS systems that existed five to 10 years ago, which serve as the basis for many long-term pain studies, represent the worst case scenario. Today’s SCS systems, with their greater specificity, targeting capabilities, and control over stimulation parameters, offer a far better outcome for patients and vendors alike.

James Cavuoto
Editor and Publisher
Neurotech Reports
www.neurotechreports.com

Jul 182011
 

The University of Michigan is developing a minimally-invasive low-power brain implant, termed “BioBolt”, that transmits neural signals to a computer control station, and may someday be used to reactivate paralyzed limbs.

 

While the BioBolt carries enormous potential, the issues of intellectual property and market partnership raise a number of neuroethical questions. In our current era of fast-emerging innovative neurotechnology, we must critically confront the practical questions of how such technologies will be provided to those who need them. In our modern society, commutative justice theories establish the disproportionate provision of goods based upon relative (and unequal) need. Their fundamental assumption is that all patients who need such interventions would be provided access and means to acquire them. Implicit to this assumption are notions of neoclassical economics based upon Adam Smith’s construct of rational actors and unlimited resources (Smith, 1776). However, even a cursory analysis of the contemporary atmosphere of healthcare provision reveals such Smithian assumptions to be vastly unrealistic. In fact, resources are limited, and their provision is based upon a multidimensional calculus that determines the relative distribution of medical goods and services. Put simply, not everybody gets what they need, and this is particularly the case for high-tech medical interventions that are often only partially covered, and in some cases, not covered at all by the majority of health insurance plans. Moreover, some 57 million Americans are currently without health insurance (Wolf, 2010).

 

Now more than ever, we face the pragmatic charge of access: who will receive state-of-the-art neurotechnological interventions, such as the BioBolt? Will these approaches become part of a new ‘boutique neurology,’ or will there be active assertion and effort(s) to increase the utility and use of these interventions, so as to make them more affordable and more widely accessible within the general population of those patients who might require them? Will some newly developed medical criteria accommodate these decisions and actions, or, as is more likely, will the tipping points be governed by healthcare insurance provisions? How can and/or should healthcare reform(s) be adjusted and adjudicated in order to accommodate rapidly advancing science and the potential benefit(s) it might confer? While certain provisions of the new federal healthcare plan might support such directions, real availability and access will only be sustainable through a real shift toward a more demand-side health economics, which would constitute something of a sea change in our overall economic infrastructure. But rarely does such change occur all at once. Instead, it may be more viable to dedicate efforts to developing realistic designs for more equitable allocation of neurotechnologies. Such efforts, if appropriately subsidized and sustained, could be important droplets towards the sea change that may be necessary.

 

For further reference, see:

Giordano, J. (2010). Neuroethical Issues in Neurogenetic and Neuro-Implantation Technology: The Need for Pragmatism and Preparedness in Practice and Policy. Studies in Ethics, Law, and Technology. Vol. 4 (3): Article 4.

Giordano, J., Benedikter, R., and Boswell, M. V. (2010). Pain Medicine, Biotechnology and Market Effects: Tools, Tekne and Moral Responsibility. Ethics in Biology, Engineering, and Medicine. Vol. 1 (2): 135-42.

 

Jun 192011
 

In the DARPA-led project REMIND, Prof. Ted Berger from the University of Southern California and Prof. Samuel Deadwyler from Wake Forest University have been developing an innovative type of neural prosthetic device for restoring and enhancing the formation of long-term memories. Their strategy is to build a computational model of the information processing in the hippocampus and use it as a substitute for normal memory encoding in people with brain trauma, dementia, stroke, and other disorders affecting learning. In their new work, the scientists have described achieving an important milestone –  improving the memory formation in laboratory rats. In the performed behavioral tests, the rats were trained to remember the lever location and, after being distracted, had to recollect which lever to push. Two 16-electrode devices were implanted bilaterally for recording communication between the CA3 and CA1 sub-regions of the hippocampus. After the CA3 neuronal activity was recorded during successful recollection of the lever location, it was played back during the next recollection trial by stimulating the neurons at the CA1. And the rats displayed an amazing 20% improvement in their memory recollection (see the figure). Then, the scientists did something even more remarkable. They temporarily blocked the intrinsic CA1 activity (using a glutamate receptor antagonist), fully substituting it by the electrical stimulation. And the animals were able to remember the lever location equally well or even better than with their natural CA1 processing! These findings generate a lot of excitement, but the scientists are still facing a long road ahead to develop a fully functional replacement for hippocampus. One major challenge would be to build a scaled-up device for recording the activity of thousands of neurons in the hippocampus.  Another hurdle, perhaps even more significant, would be to create a memory encoder that can go beyond replaying the previously-remembered tasks and to create brand new memories. After all, learning something new is a lot more exciting than, say, reciting the Pythagorean theorem for the N-th time.

Jun 082011
 

It wasn’t that long ago that magnetic stimulation was looked at as somewhat suspect by many in the neurotechnology industry. But now the number of new entrants in the magnetic neuromodulation space is growing steadily, supplementing existing players using magnetic devices in stimulation, neurodiagnostics, and research.

Some of the credit for this upsurge in interest in magnetic stimulation can be attributed to Neuronetics, Inc., the Malvern, PA manufacturer of transcranial magnetic stimulation systems. The company’s NeuroStar system received FDA approval for major depressive disorder in 2008, and in 2011 Neuronetics announced that Category I CPT codes were available for the procedure, making reimbursement much easier.

At least one new entrant hopes to follow in Neuronetics’ footsteps. NeoStim Inc., a startup in San Mateo, CA, cites the existence of an FDA-cleared TMS therapy and the CPT codes as reasons why NeoStim is a sound investment. NeoStim’s device features an array of coils that the company says offers greater target selectivity than the NeuroStar system because of the multiple overlapping fields. The company plans to pursue other indications besides depression, including pain and addiction. Another startup, Israeli-based Neuronix Ltd., is developing a TMS system for treatment of mild to moderate Alzheimer’s disease.

eNeuras Therapeutics (formerly Neuralieve) in Sunnyvale, CA is developing a single-pulse TMS device for home use for treatment of migraine. Its SpringTMS Total Migraine System is placed at the back of the head for less than a minute, generating a focused, single magnetic pulse that induces a mild electric current in the back of the brain.

Magnetic stimulation devices are also gaining popularity in neurosensing and presurgical planning applications. Nexstim Ltd., the Finland-based manufacturer, markets its MRI-guided TMS system NBS to neurosurgeons as an alternative to direct cortical stimulation. The company is investigating other neurodiagnostic and therapeutic applications of its system, including stroke recovery and pain.

One of the oldest TMS product lines in existence is the MagVenture’s MagPro system, first introduced in 1992 (previously marketed under Dantec, Medtronic, and Natus Medical brand names).  UK-based MagStim Ltd. has also been marketing its line of TMS stimulators for many years. In 2010, the company teamed with the Dutch ANT B.V. (Advanced Neuro Technology) to market a magnetic neuronavigation system called Visor, which features integration with MRI, fMRI, and EEG.

We suspect that there will be even more magnetic ventures forthcoming in the years ahead as the road to FDA approval for more invasive forms of neuromodulation continues to be difficult.

Originally published in Neurotech Business Reports, May 2011, p2

Jun 052011
 

About one third of epilepsy sufferers are refractory to drug treatment.  When drugs are ineffective, these people find their hope in brain-applied electrical stimulation. Several commercial neuroprosthetic devices have been successful in providing at least partial relief. They include a vagal nerve stimulator (VNS) from Cyberonics Inc., and a deep brain stimulator from Medtronic Inc., and cortical stimulation device from NeuroPace Inc. These devices are surgically implanted and cut the number of seizures in half or more in about 40% of drug-resistant patients. Currently, there is no neurological test to predict who will benefit from electrical stimulation. To solve this problem, Dr. Christopher DeGiorgio, a neurologist at UCLA, decided to use an external stimulator to estimate whether the epilepsy sufferers would benefit stimulation therapy before an invasive surgery is performed to implant a permanent device. His stimulator activates a superficially-located trigeminal nerve, a large cranial nerve that projects to key parts of the brain that modulate seizure and mood. The stimulation is applied at the forehead, while the electrode leads are connected to a small wearable pulse generator. According to the initial clinical test, the stimulator has similar efficacy to the implantable VNS. A positive side-effect of trigeminal nerve stimulation is an improvement in mood, which is important as many epilepsy patients suffer from depression. A startup company NeuroSigma Inc. has licensed the approach to stimulate the trigeminal nerve for epilepsy, depression, and PTSD, and is developing an implantable version for those who find relief with the externally-applied device.

Apr 172011
 

Stroke is the third-leading cause of death in the U.S. and the leading cause of disability. While some 1.5 million people in the US report stroke-like symptoms annually, half of them have actually not suffered a stroke. Making a reliable assessment of stroke in just minutes would provide timely information for treating the victims faster, at lower cost, and with less risk. Jan Medical developed the first and so far the only portable brain sensing device for rapid detection of ischemic stroke. The device is aimed to be used in the ER or ambulance, before a thorough evaluation can be made in a hospital setting with a CT or MRI. The device operation is based on an interesting principle of detecting the ultrasonic waves emitted by the skull. The device does not measure back-reflection of the emitted ultrasound from the brain; instead, it measures natural mechanical vibrations of the skull. These vibrations are generated by a pressure wave of blood rushing from the heart toward the skull during each pulse.  In 5 minutes, the device collects enough information to detect a variety of cerebrovascular anomalies: an intracerebral or subarachnoid hemorrhage, epidural or subdural hematoma, intracranial aneurysm, arteriovenous malformations, ischemic stroke, or transient ischemic attack. The device consists of two primary components: a headset with sensors and a controller for decoding the collected ultrasonic information connected to a computer. Jan Medical markets its device primarily for early detection of stroke as well as the traumatic brain injury, such as sports-related concussion that is often not detected on the field leaving it to a discretion of a team physician to clear the player for return to the game. The device can also be used for rapid military diagnostics of traumatic brain injury at the battlefield.

Apr 132011
 

Earlier this month, DARPA released a call for proposals addressing a key challenge in the brain-machine interfaces (BMI) – the reliability of cortical electrode-tissue interface. As seen in the chart above (taken from this DARPA presentation by Prof. Jack Judy), existing intracortical electrode arrays (such as BrainGate) can extract a lot of information from the cortex (1500 events/s and more) but their performance drops off by 50% in about one year after their implantation. By 3-5 years after implantation, performance further deteriorates to a point where their informational flow is no longer above that of peripheral nerve electrodes. The DARPA initiative aims to explore novel revolutionary approaches to improve the long-term reliability of neural recordings to sustain high information flow needed for controlling an artificial hand or arm. The ultimate goal of the initiative is to develop the intracortical array that can provide the life-long information flow of 2000+ events/s to control the 22-degrees-of-freedom artificial arm recently developed by DARPA. Achieving this very ambitious goal will likely require a concerted effort of multiple research groups working together on different aspects of the problem, ranging from the design of novel biocompatible and neurotropic/ immuno-suppressive electrode materials to development of robust non-linear state-dependent decoding algorithms and advanced techniques for device packaging and wireless telemetry.

Mar 232011
 

According to a recent MedGadget post, a Colorado-based company Clarimedix has developed a BandAid-looking device that can be attached on the neck’s skin and emits infrared light onto the carotid artery. The device is being evaluated for treatment of Alzheimer’s disease. The company’s website provides scant scientific explanation for its therapeutic action indicating just that light modulates the production of nitric oxide (NO) in the brain . To expand on their rationale, I examined recent literature on this subject and sketched the diagram (see the image) illustrating the hypothetical mechanism of device’s action. According to one recent review, NO has two opposing effects on neurons. On one hand, NO is involved in neuroprotection by activating the Akt, Bcl-2, and MAP kinase survival pathways. On the other hand, NO inhibits mitochondrial respiration (by blocking the activity of cytochrome c oxidase), therefore depleting neurons of energy and ultimately leading to their inflammation and death. The harmful effect of NO on mitochondrial respiration can be reversed by light, at least in vitro. So, by illuminating the carotid artery, the Clarimedix device modulates the NO release and possibly helps to suppress the progression of neuroinflammatory diseases, such as multiple sclerosis,  Alzheimer’s and Parkinson’s diseases. The evidence for its therapeutic action is very weak at the moment but non-invasive nature of the therapy will hopefully allow for a quick and inexpensive clinical trial.

Mar 202011
 

Glioblastoma is the most common type of brain tumor affecting 0.002-0.003% of general population. In glioblastoma, the astrocytes (neuron-supporting glial cells) turn into cancerous cells, start to divide frequently  and gradually form a large mass pressing against the brain. Glioblastoma is a challenging disease to treat as dosages of radiotherapy and chemotherapy are limited by their toxicity to the brain tissue. The use of alternating electrical fields is a novel approach that aims to suppress the division (mitosis) of malignant cells while sparing non-dividing neuronal cells in their vicinity. An Israeli-based company NovoCure Ltd. developed a stimulation device, Novo-TTF, which delivers alternating electric fields through insulated electrodes attached on the scalp surface. The scientific foundation of this approach comes from the study by the Technion scientists showing that alternating electrical fields can stop the cells from dividing and can even destroy them, if the cells are oriented roughly along the field direction. Importantly, the dividing cells inside the blood vessels appear to be unaffected. The key concern for the therapeutic use of alternating electric fields relates to their effects on neurons. At low frequencies, under 1 kHz, alternating electric fields stimulate neurons. As the frequency of the electric field increases above 1 kHz, the field can better penetrate through the cellular membrane, and its effect on neuronal excitability is diminished. At even higher frequencies, above 100 MHz, the brain exposure becomes localized and significant local heating can occur. Faced with these possible side-effects of low and high frequencies, the scientists decided to stick with intermediate frequencies of 100–200 kHz.  The electric fields at these frequencies might be relatively safe as long as their intensity is kept below the threshold for inducing the pore formation in the cellular membrane, through a phenomenon called electroporation. A recently completed phase III trial of the Novo-TTF device alleviates some of these concerns by showing no change in incidences of headaches or seizures in patients. The device is likely to be approved for use in the US within the next three months.

Mar 122011
 

The US Department of Energy-funded Artificial Retina project is geared toward developing an epi-retinal prosthesis. To date, the effort resulted in fabrication of Argus I and Argus II devices with, respectively, 16 and 60 sites for retinal stimulation. The Argus II device has been commercialized by the company Second Sight and already gained the marketing approval in Europe with plans for the US approval in 2012.  Meanwhile, the continued effort is underway at the Center for Microtechnology and Nanotechnology at the Lawrence Livermore National Labs (LLNL) to fabricate the third-generation device, Argus III, that will have 1000 or more stimulation sites.  Those who are curious about the advanced microfabrication steps involved in making the Argus III can have a look at this video produced by the LLNL. The video is shot at spectacular 1080p and details all major steps from patterning the layers to device release from the wafer and its integration with a wireless chip.

Mar 072011
 

Dr. Stephen Oesterle, Medtronic’s senior vice president for medicine and technology, made an announcement about an interesting new device at works at the world’s largest medical device company – the tiny injectable pacemaker. Judging by the provided photo of the prototype, its width is ~2 mm and length is ~6 mm, allowing it to be implanted into the heart via a small catheter rather than an invasive surgery. Medtronic’s R&D department has already developed an ASIC chip featuring most of the components—an oscillator to generate current, a capacitor to store and rapidly dispense charge, memory to store data, and a data telemetry system. “What we don’t have that is fundamental to a pacemaker is a way to power the chip,” said Oesterle. It is not clear whether Medtronic will try to develop this crucial piece of technology in-house or to buy the patent rights from others. Considering that the device would have to deliver tens of mA of current (perhaps more), the power telemetry development might be not an easy task. Additional challenges facing the device developers include deep device placement and limited space for the antenna given the small device size. For these reasons, it might not be feasible to use the existing RF inductive-coupling power telemetry technologies developed for superficially-placed neurostimulation devices, such as the RF-BIONTM Implantable Microstimulator from AMF and the SAINTTM from MicroTransponder Inc. Other possibilities do exist, such as the resonant antennas operating at microwave frequencies, but these technologies have a long way to go before they are applied for any biomedical applications. I guess, we will be more certain about the Medtronic’s plans once they start hiring the microwave antenna engineers.

Mar 052011
 

Since 2005, DARPA (the Defense Advanced Research Projects Agency) has invested more than $100M into development of the brain-machine interfaces (BMIs) by sponsoring two programs, Revolutionizing Prosthetics and Human-Assisted Neural Devices. Most of that funding went into creation of two BMI-controlled artificial arms – the 10-degrees-of-freedom (DoF) DEKA “Luke” Arm by DEKA R&D Corp. and the 22-DoF Modular Prosthetic Limb (MPL) by Johns Hopkins University together with University of Pittsburgh and California Institute of Technology. A smaller effort to develop the 3-DoF BMI-controlled artificial arm is also underway in Germany by the company Otto Bock HealthCare GmbH. It now appears that DARPA’s investment into neuroprosthetic control of the arm may begin to materialize as early as this summer. The BMI control of the MPL arm will be made possible by the array of penetrating electrodes implanted into the motor cortex of five quadriplegic patients. The silicon-based array will record the multi-unit activity in the cortical area that controls the arm movement and the recorded information will be used to predict the intended direction and force of movement. Penetrating silicon-based arrays have been already successfully tested in monkeys, demonstrating the feasibility of decoding the intent of different movements from cortical signals. The biggest remaining problem is a rapid deterioration in the quality of neural recordings from cortical arrays, ranging from several months to a year.  A range of strategies can potentially overcome this problem: 1) by making the electrodes less stiff, 2) by removing the wires tethering the array to the skull, and 3) by using a biomimetic array coating to improve its biocompatibility and reduce the immune response. It is unlikely that any of these novel strategies will actually be used in the first generation of cortical arrays for the MPL control. Nevertheless, the upcoming clinical trial will be a positive event for the BMI R&D community after suffering a setback from the failed BrainGate trial three years ago. Progression of the BMI-MPL clinical trial will be closely monitored and guided by the FDA, which, after extensive talks with DARPA, recently created the Innovation Pathway specifically for such pioneering and transformative medical technologies. By utilizing this Pathway, the FDA aims to cut the premarket approval process time in half (to 150 days or less), suggesting a smooth commercialization path for the BMI-MPL after conclusion of its clinical trials.