Report on the Neural Interfaces Workshop

Over 500 attendees gathered at the Hyatt Regency Hotel in Bethesda, MD, to participate in the workshop on November 15-17, 2004. This workshop combined the long-standing Neural Prosthesis Program Workshop, which was in its 35th year, with the annual meeting of the National Institutes of Health's Deep Brain Stimulation (DBS) Consortium.

Support for the Workshop came from the following Institutes within the NIH: the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the National Institute of Child Health and Human Development (NICHD), and the National Institute on Deafness and Other Communication Disorders (NIDCD). In addition, several organizations provided funding for refreshments during breaks and meals, where informal scientific discussions continued. The NIH gratefully acknowledges the contributions of California Neuroscience Institute, Cyberkinetics Inc., Medtronic Inc., National Parkinson Foundation, the Parkinson Alliance, Parkinson's Disease Foundation, and Plexon Inc.

In recognition of the fact that 30-40% of the DBS Consortium members had attended Neural Prosthesis Program workshops in past years as well as the shared interests of both groups, the meetings were combined to foster new collaborations. Both groups are multidisciplinary in composition, consisting of diverse groups of investigators representing the biological, engineering, and clinical aspects of neural interfaces. The opportunity for synergy was apparent from the complementary backgrounds of the two communities. While the DBS community has a larger proportion of clinicians, the Neural Prosthesis Program consists of basic and applied neuroscientists and engineers. By integrating these meetings, it was hoped that the state-of-the-art in microelectrode arrays, biomaterials, and data analysis tools being developed by the Neural Prosthesis Program would stimulate visions for next generation DBS systems. Likewise, the clinical experience of the DBS community would yield insight to Neural Prosthesis efforts, such as brain machine interfaces, that are moving rapidly beyond the laboratory bench to clinical testing. The Workshop was mainly organized into plenary sessions addressing the following cross-cutting issues: Neural Information Processing, Auditory Prosthesis as a Paradigm for Successful Neural Interfaces, Optimal Systems Design for Neural Interfaces, Optimizing Material Tissue Interactions for Neural Interfaces, Deep Brain Stimulation: Theoretical and Clinical Considerations, Practical Considerations for Neural Interfaces, and Future Challenges for Neural Interfaces. This report is not intended to be completely comprehensive, but to highlight several discussions and a few presentations from the plenary sessions.

During an introduction by Dr. Joseph J. Pancrazio, who organized the workshop with other NIH staff, he challenged the assembled attendees to take advantage of the complementary experiences and identify new potential collaborators to address critical barriers that limit the more widespread use of technologies to reduce the burden of disease. Dr. Story Landis, the Director of NINDS, spoke briefly to welcome the Workshop participants and recognize the role for neural technologies as a complementary strategy to cellular and molecular approaches for repair.

Dr. Michael Merzenich, from the University of California, San Francisco, a leader in the development of the cochlear prosthesis, delivered a keynote address on the topic of neural plasticity. He presented evidence for two epochs for brain plasticity: a critical period during the first 9 months of post-natal development and a second epoch during adult period. Dr. Merzenich's work has shown that receptive fields of the auditory areas of the brain can retune to accommodate to specific stimuli, raising the notion that brain can adapt to the prosthetic systems, especially when there is a behavioral advantage to doing so.

The theme of plasticity resonated through the duration of the Workshop, especially during the following plenary session entitled "Optimal Methods for Processing Information from Neural Signals", moderated by Dr. Grace Peng of NIBIB. Dr. Vasilis Marmarelis of the University of Southern California discussed nonlinear algorithm approaches (Volterra-Wiener models) for interpreting neural signals applied to the hippocampus. Dr. Chris Sackellares of the University of Florida discussed automated, nonlinear algorithms for prediction of seizures in patients with medically intractable epilepsy. Optimized algorithms could be used in a clinical setting to determine seizure focus in patients after only one seizure. Dr. Dawn Taylor of Case Western Reserve University reported on her efforts working towards a functional controller for motor cortical prosthesis, where a key question involves how information in the form of spike rates from multiple neurons encodes target positions of an upper limb. She provided evidence that the primate brain, at the level of single neurons within the motor cortex, could transform the spatial orientation to fit to a variety of coding schemes to drive a robotic limb.

Two concurrent breakout sessions were held to allow Neural Prosthesis Program contractors to report on progress over the last year.Dr. Roger Miller of NIDCD moderated the session entitled "Auditory Prostheses", where recent progress over the year was reported. Dr. Douglas McCreery of Huntington Medical Research Institute and Bob Shannon of House Ear Institute described a landmark in their 15 year effort to produce an implant with electrodes that penetrate into the cochlear nucleus, a promising technique for providing better speech recognition to patients with a damaged auditory nerve. The penetrating auditory brainstem implant uses cochlear implant technology that has been adapted for microstimulation of the surviving neural pathways ascending from cochlear nucleus, rather than the cochlea. Promising results from five patients implanted with this investigational device were presented. Dr. Paul Abbas, from the University of Iowa, summarized studies in an animal model of cochlear implant patients with substantial residual hearing. These results could be used in the clinic to identify patients in need of special processing to provide an optimal mix of electric and acoustic hearing. Dr. Russell Snyder described ongoing work at the University of California at San Francisco to advance the state of the art in the design of cochlear implant electrodes. These tests utilize novel combinations of currents applied with custom built electrode arrays; multichannel recording probes are then used to assay the patterns of neural activation during animal studies. It is hoped that these studies will provide new ways to mimic the neural activation patterns driven by normal hearing for future cochlear implant users. The session concluded with presentations from Dr. Patricia Leake, from the University of California at San Francisco, and Dr. Robert Shepherd, from the Bionic Ear Institute, which described studies on the protective and plastic effects of patterned electrical stimulation on the deafened auditory system. These researchers are working to identify neurotrophic agents and patterns of stimulating currents that promote auditory nerve survival following damage to the inner ear.

Drs. Daofen Chen and Naomi Kleitman of NINDS led the "Cortical Prosthesis/Functional Neural Stimulation" breakout session. Among the highlights of this session was the presentation by Dr. Robert Kirsch of Case Western Reserve University who reported on progress in restoration of hand and arm function through functional neuromuscular stimulation. A systematic evaluation of command interfaces has been performed which shows that, it is possible to use remaining electromyographic signals as an input to an artificial neural network to drive an implanted functional neuromuscular stimulation system for mid-level tetraplegia. Drs. Doug McCreery and Arthur Prochazka (University of Alberta) reported progress on related projects of intraspinal stimulation to induce coordinated bladder and sphincter control after spinal cord injury. Each reported that optimizing electrode placement remains key to producing coordinated micturition, however, larger fixed arrays have additional issues with electrode movement over time in this spinal application. Dr. Kensall Wise of the University of Michigan presented their progress towards micromachined microelectrode arrays, which are capable of multi-channel recording and in vivo drug delivery. These assemblies are rapidly evolving towards three-dimensional probes that are wireless, which may make complete implantation possible. Dr. Florian Solzbacher of the University of Utah introduced his newly NINDS funded research effort based on the Utah/Cyberkinetics microelectrode array that will integrate a wireless recording flip-chip technology. Both the University of Utah and the new University of Michigan efforts seek to the demonstrate multi-channel wireless in vivo within the first 18 months of support, while the long-term goal of the contracts is for a robust, chronic recording capability defined as longer than 6 months.

The plenary session entitled "Auditory Prosthesis as a Paradigm for Successful Neural Interfaces," which was moderated by Dr. Miller, addressed valuable lessons learned for what is widely considered the most successful neural prosthetic from a clinical perspective. Dr. Donald Eddington of the Massachusetts Institute of Technology described his groups approach to identifying optimal stimulation paradigms based on functional performance measures. Dr. Blake Wilson of Research Triangle Institute described the history of cochlear prosthetics, identifying major obstacles and how they were surmounted with recognition of the visionary leadership of the NIH resulting in a success story of modern medicine. Dr. Wilson also highlighted the theme of plasticity, showing increased performance on learning curves over a one-year period.

Dr. William Heederks of the NIBIB introduced Dr. John Donoghue of Brown University as the Chair for the plenary session entitled "Optimizing System Design for Neural Interfaces", where various types of multi-channel array formats were discussed. Dr. Donoghue presented evidence based on the Utah/Cyberkinetics array where the recording sites are at the tips of 100 silicon spike-like columns. He reported that very little tissue response to the implants has been detected, based on 45 implants in non-human primates. After implantation, the arrays are encapsulated which appears to provide some mechanical stability. Multi-channel recordings showing spikes on many electrodes with multiple units on each electrode site were presented. These recordings spanned well over a year, with a maximum of one case extending for over 4 years. The only failures identified for 3 of the 45 tests involved mechanical connectors and a case of bleeding/infection. Dr. Rio Vetter, representing Dr. Daryl Kipke of the University of Michigan, described advantages of the Michigan probe technology, which has multiple recording sites along multiple shanks of the dagger-like implant, allowing the recording of neural activity in three-dimensions. Dr. Vetter reported that the recent focus of the Michigan group has moved towards chronic, long-term recording where issues that are of principal interest include: characterization of tethering forces and micromotion through finite element analysis, integration of wireless components, and exploration of conductive polymeric recording sites. Dr. Donald Woodward from Wake Forest University showed a historical overview of electrode development and discussed his current work with platinum-indium microwires and electrochemical sensing platforms.

Following this session, Dr. Donoghue presented a special report on preliminary observations from the Braingate pilot clinical trial. He described the system developed at Cyberkinetics Neurotechnology Systems, Inc. that allows direct cortical control of devices by patients with spinal cord injury. He was able to record neural activity three years after injury and showed examples of the first patient using the device to control simple computer programs.

The plenary session "Optimizing Tissue Interactions with Neural Interfaces" included a presentation by Dr. David Martin of the University of Michigan teamed with Dr. Patrick Tresco of the University of Utah dealing with the biological response to implanted neural probes. Dr. Martin described progress in the development of probes that incorporate conducting polymer electrochemically grown on hydrogel scaffolds. Dr. Tresco showed a systematic and quantified characterization of the tissue response to implanted modified neural probes including both Michigan and Utah/Cyberkinetics microelectrode arrays. One remarkable finding was that the principal sites of inflammation of both tethered and non-tethered arrays are centralized along the shanks of the arrays. The fact that the recording sites for the Utah/Cyberkinetics array are at the tip rather than along the shank, unlike the Michigan probe, may explain in part why there has been more anecdotal evidence of chronic recording with the Utah/Cyberkinetics array format to date. Nevertheless, research by Dr. Tresco and efforts by Dr. Ravi Bellamkonda of the Georgia Institute of Technology suggested that there is a time window for the inflammatory process such that long-term damage can be abated. The initial wound response due to electrode array insertion may be managed through pharmacologic and material choices, such that the sequence leading to neurodegeneration near electrode recording sites can be diminished. A spirited discussion resulted as the speakers of this session considered the implications of these findings for DBS. While the discussion facilitator, Dr. Jerrold Vitek of the Cleveland Clinic, acknowledged that tissue damage associated with DBS was generally thought not to be a major issue based on the limited published literature, however, it was unclear to what extent the area had been comprehensively explored.

In the plenary session entitled, "Deep Brain Stimulation: Theoretical and Clinical Considerations," Dr. Elena Moro of the University of Toronto described multiple clinical uses of DBS systems whereas Dr. Marjorie Anderson of the University of Washington and Dr. Warren Grill of Duke University discussed mechanisms of DBS action. Using a modeling approach, Dr. Grill has been able to recapitulate a feature of DBS effectiveness, i.e., the frequency dependent responsiveness of intrinsically active neurons, suggesting that the stimulation modulates neuronal output to become more regular and effectively decrease information transfer.

Dr. Michael Weinrich of the NICHD moderated the session entitled "Practical Considerations for Neural Interfaces" where presentations primarily focused on existing and near term clinical applications of neural interfaces, with an emphasis on brain-machine interfaces. Dr. Andrew Schwartz's team at the University of Pittsburgh presented recent work on the use of motor cortical electrode arrays to drive a robotic limb, where a non-human primate can sufficiently manipulate the system to feed retrieve and consume food rewards. Dr. Jon Joseph from Cyberkinetics described initial findings from the first human implant of the Cyberkinetics BrainGate system, which relies on the Utah/Cyberkinetics microelectrode array system implanted in the motor cortex. Dr. Joseph showed videos of a high-level spinal cord injured tetraplegic controlling a computer cursor to perform a limited set of tasks. Dr. William Marks of University of California San Francisco discussed practical issues for DBS, in particular the need for microelectrodes for more precise neuronal targeting and better steering control to deal with sub-optimal electrode implantation and reduce the likelihood of stroke during brain penetration.

The final plenary session entitled "Future Challenges for Neural Interfaces" featured Dr. Ali Rezai and Dr. Hunter Peckham, both from Case Western Reserve University. Following an overview of DBS and its effectiveness, Dr. Rezai identified the needs for electrode materials that can withstand mechanical stresses and confer patient safety during high resolution magnetic resonance imaging. Dr. Peckham presented a vision for a fully implantable upper limb neural prosthetic system that integrates functional neuromuscular stimulation with systems capable of assessing the paralyzed individual's will to move the limb. He identified the need for robust and reliable microelectrode arrays suitable for implantation in the motor cortex that can be used in clinical studies. This plenary session closed with a brief presentation about a new prosthetic limb related program. Dr. Jon Mogford representing Dr. Geoffrey Ling of the Defense Advanced Research Projects Agency briefly described the Human Adaptive Neural Device (HAND) program currently in the planning stages.

Students were encouraged to attend the Neural Interfaces Workshop and apply for the Student Assistance Program. Students selected for the program were recognized on the first day by Dr. Meredith Temple-O'Connor of NIBIB. Of approximately 40 applications, 20 students were selected to receive assistance and most of these students presented a poster at the meeting. Overall student attendance was relatively high; approximately 12% of the participants identified themselves as students.

Feedback from the participants strongly indicated that the Neural Interfaces Workshop fills a unique and important role, distinct from other meetings or workshops. Building on the experience of 2004, planning is underway for the Neural Interfaces Workshop 2005, which will again bring these communities together but provide more structured content. Tentatively, Day One will focus on current progress in DBS with presentations from the Consortium members. In addition, there will be a session on emergent microelectrode stimulation technology and a discussion to identify critical issues limiting progress in DBS and potential future approaches for surmounting those obstacles. In the preliminary agenda, Day Two will focus on current progress in neural prosthetics with plenary sessions on microelectrode array technology, surgical considerations for neural prosthetics, and neural interfaces for sensory information. Day Three will address current goals as well as potential future advances in neural prosthetics, such as nanotechnology. It is also expected that the Student Assistance Program will continue. Plans will be finalized over the next several months and updated information will be made available on the Neural Prosthesis Program site.