μblog: engineering from the trenches

I am spending the first half of this week in Cleveland, Ohio at the 2008 Neural Interfaces conference.

The first day was spent mostly discussing neural stimulation as an interface paradigm. Judging from the presentations, deep brain stimulation (DBS) is the most popular in both the research and medical communities. There are about five devices on the market that are FDA approved for DBS so many clinicians are looking to use these stimulators in various off-label applications to stimulate many targets within the brain as well as the vagus nerve in the periphery. The primary success story for DBS is continuous stimulation in the sub-thalamic nucleus and globus pallidus to alleviate effects of Parkinson’s disease. The same techniques are being applied with marginal success as a treatment for epilepsy, depression and obsessive compulsive disorder. It is still tough to show significant improvement for some of these latter diseases. Furthermore, it is equally tough to prove that the turning on the stimulation has any beneficial effects for those diseases. In some cases, implanting the stimulating electrode is good enough.

The second day has had some excellent coverage of the state-of-the-art prosthetic devices. One of the novel mechanisms that I was not aware of is nerve re-direction in the case of amputation. For example, there are surgical techniques to re-route nerve bundles that control arm movement in the case of amputation near the shoulder. The muscle groups on the chest become the targets and in some cases, the amputee can control those muscles by attempting arm movement and feel arm sensations through mechanical stimulation of their chest. If this type of surgery is successful, there are examples of external prosthetic arms which are controlled by electrically tracking muscle contraction on the chest and provide basic tactile feedback through mechanical stimulation.

On a side note, there was a luncheon focusing on commercialization of neurological devices. Translating an implantable device from academia to “mass product” seems to be a process that will test the designer’s patience and humility. The general feeling on the commercial side is that the academic designer should already have a working design that is undergoing human clinical trials when they approach a company for commercialization. Even then, the commercialization company will evaluate their potential for revenue generation and may provide a 0.25-0.5% royalty for the academic designer to take over the mass production of their product. This is while keeping in mind that the path from specifications to clinical trials is at least ten years. This may be the reason that many researchers try to create start-up companies and commercialize their own products to see more fruits of their labors. This approach, however, is perilous and may end up being unrewarding. This is clearly seen with the bankruptcy of Cyber-Kinetics, the company that has been receiving media attention for years for allowing several paraplegics control of an on-screen cursor by thought alone. (Their website has not been updated recently to disclose this.)

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As I have mentioned, the semester is winding down and projects are piling up. To help move things along, I have written a pair of documents that outline how to determine the conductivity of a plane (and volume) with a conducting disk (and sphere) of arbitrary size in the middle. I solved Laplace’s equations in both polar and spherical coordinate systems, then used boundary conditions to determine the electric potential and then determined the ratio of applied field to current density to determine the conductivity in the presence of the suspended object. I have checked these early drafts over a few times, however, there may still be some mistakes remaining, so please be warned. Also, feel free to post questions and I will make an attempt to answer them.

( disk-efield.pdf )

( sphere-efield.pdf )

P.S. The photo-op was staged during my last vacation, I would never use Classical Electrodynamics as a coaster.

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I have been working on spectral analysis of time series data and I am finding that (duh!) it is often easier to use someone else’s wheel than to invent a new one myself. That is, if their wheel has all of the necessary features and meets your performance criteria. I have been working with multi-taper spectral estimates and have found that the Chronux code (MATLAB scripts), available from Partha Mitra’s lab, to be fairly easy to use and effective for some continuous time-series analysis. The code also handles point process analysis, however, I don’t use that feature much.

The main reason that I like to use the multi-taper methods based on Slepian tapers, is that each taper gives a independent measurement of the signal spectra which then allows for computation of variances and therefore confidence intervals. This gives a certainty measurement to the analysis which can either make a strong case for its significance or will identify deficiencies in the data. Basically, these people put some years into writing this code and if you need to do coherence or spectral analysis in MATLAB, might as well give it a try.

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A little off topic, but some clever researchers at UCLA have created the Gene2Music project where they mapped classical music to genetic sequences and created some MIDI files (as well as sheet music). The image above is from one of the sheet music sections.

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Adding references, or data from, publications that are over a hundred years old seems to be a popular trend among scientific presentations these days. Sometimes it is to give a false sense of scholarship, however, it is often to remind us that some ‘new’ scientific breakthroughs may be simple re-interpretations of old discoveries. I try to note the references and look them up, when time permits. Here is the first paragraph from the preface of ‘Epilepsy and Its Treatments‘ (1904) by Spratling:

 The great progress made in the knowledge of epilepsy and its treatments during the past decade and a half, and in fact that no complete treatise on the subject has appeared in the United States since Echeverria’s work was published thirty-three years ago, was the chief reason that lead to the preparation of this volume.

With the exception of Manuel Echeverria (On Epilepsy: Anatomo-Pathological and Clinical Notes (1870)), the sentence can still be used in a modern book/review of Epilepsy without much alteration. The reason that the 1904 book was cited was to show that, a hundred years ago, physicians were aware that, on very rare occasions, were non-clinical. For example, it was noted that verbal interactions were sometimes enough to bring people out of seizure, something that researchers who seek alternative epilepsy treatments are rediscovering. (On a slight side note, there is an interesting personal account by Feydor Dostoyevsky starting at the bottom of page 466 where he links a pre-seizure state to a state of mental enlightenment.)

This long winded introduction was to present a pair of review articles from the early 1900s that covered what the authors thought were the highest achievements in physics and applied math of the previous century.

1905barus-the-progress-of-phsyics-in-the-nineteenth-century.pdf

1900woodward-the-centurys-progress-in-applied-mathematics.pdf

The image is from the IEEE and is of the Georgetown, CO steam/hydro powerplant.

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The last two days of the meeting started to blend together as the 8am to 8pm days started taking their toll. Sunday was mostly taken up by an investigators’ workshop dealing with basic principles behind epilepsy. Jack Parent had some interesting words to say about a protein called reelin. This protein has been implicated in limiting the process by which neurons form new connections, as though it somehow helped regulate “good” networking. The it seemed that, in animal models, seizures were associated with reduced reelin concentration and increased neuronal proliferation which led to more seizures.

Monday was divided between visiting Brian Litt’s and Marc Dichter’s labs at U Penn, presenting my poster, and more lectures. Visiting the labs made it apparent that while we have more space at Penn State, the U Penn labs have a more strategically located near civilization. The poster presentation went fairly smoothly with the toughest questions being about my choice of multi-taper spectral estimation approach over something like wavelet transform. The final lectures that I attended were covering new definitions of seizures. The basic idea was that clinicians had access to new equipment that could record more EEG channels at higher frequency as well as higher density electrode grids/arrays. The result was that neurological signals could be recorded with finer spatial and temporal resolution. These newer systems could pick up the huge electrographic seizures that have been recorded for decades, as well as shorter discharges termed “microseizures”. This could certainly give medical professionals better tools to diagnose neurological disorders and localize seizure foci, however, I think that the definition of a clinical seizure will consequently be broadened in the upcoming years to include some of these smaller discharges. This may lead to a broader definition of the disease and would lead to more people becoming clinically epileptic. This, coupled with an increased epilepsy risk as a result of traumatic brain injury,  will lead to a great jump in the number of reported clinical epilepsy cases of epilepsy in the upcoming decades which the analysts will probably attribute to things like mobile phones, wireless internet, and video games.

During the breaks, I had a chance to walk around the convention center visiting places like the city hall and the reading terminal market. In addition to the pictures of the city and the market, I am including pictures of the exhibitor section of the American Epilepsy Society meeting. Since the target audiences of the meeting are medical doctors, the drug companies really spend money on marketing and give away cell phone chargers, thumb drives, usb battery chargers and laser pointer pens which include usb flash drives which can also recharged through the usb connector.

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This day was split into three sections: Merritt-Putnam lectures, Engineering special interest group, and a set of lectures on high-frequency EEG recordings.

The morning was dedicated to the Merritt-Putnam lecture series, with this one focusing on traumatic brain injury (TBI) and the resulting possibility of epilepsy. The key theme was that there was a correlation between TBI, such as getting hit with a baseball, and developing epileptic seizures down the road (epileptogenesis). There are some clinical measures which can sort the severity of the TBI into mild, moderate and severe categories, however, the specifics were not presented. Various mechanisms, ranging from molecular to neural network organization, were implicated as potential targets for epileptogenesis, however, the key point that was reiterated by every presenter was that there was concern that troops coming back from Iraq were looking forward to epilepsy in their later years. Part of the reason for this is that explosives play a much larger role in modern warfare, as compared to bullets, which have a higher propensity to generate shock waves and thereby contribute to TBI. According to the statistics presented, there are over 2,000 “official” cases of severe TBI as of October 2007 with an estimated 10,000-20,000 more at risk.

The main focus of the SIG was to demonstrate to try to define what a seizure was. Several groups were presenting data from tiny electrodes embedded in standard electrode arrays to help get better spatial resolution of EEG measurement for seizure focus detection. The most entertaining talk, however, came at the very end and provided an overview of stimulation efficacy for seizures. The point was that in many cases, simply implanting the electrodes was enough to stop seizures. It didn’t statistically matter if the stimulator was turned on or not, providing that the seizure focus was located correctly.

The last session was titled “Broadband EEG”, but the range of talks was very wide. Gyorgy Buzsaki gave the first talk part of which dealt with qualitative energetics. The idea can be explained with this analogy: when people clap at the end of a musical performance, they clap randomly at first, then, a pattern develops and people clap rhythmically. When people clap in unison, they typically clap slower than they did before, expending less energy. The same can be seen on functional MRI (something that measures metabolism) where things like the hippocampus, a popular seizure focus, shows decreased energy usage during seizure activity.

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Today is the first day of the American Epilepsy Society annual meeting and I attended some lectures on sleep-related epileptic events and another one on the impact of the immune system on epileptic activity. The first part, dealing with sleep and seizures, was mostly clinical results and a strong ties with abnormal electroencephalogram (EEG) recordings during non-REM sleep and cognitive impairment in children. Several specific pathologies were discussed, the main topic being speech impediment. It is known that many children experience epilepsy-like events when they are young, however, most grow out of their seizures and go on to lead normal lives. For some, the speech impediment becomes life-long if the night-time seizures are untreated. The interesting aspect is that the children can read and write, even use sign language, but they cannot understand spoken word or speak. The consensus from the group of people at this special interest group was that it is important for children with sudden speech impediments and a family history of epilepsy to undergo night-time EEG recording to determine if their speech problems can be linked to things like autism, or if it is actually an epileptic event. If clinical epileptic activity is observed, it is suggested that the child is monitored for an extended period of time (12-18 months) to see if there is a natural improvement in their speech, and only start thinking about drug therapy if there is none. The thinking is that if the EEG signals can be brought back to normal early enough, providing they were not on course to do this themselves, the impediment would be reversed.

The second part, dealing with immune response and seizures, was somewhat out of my league. The talks were mostly covering basic science and all seemed to link increased immune response with increased occurance of seizures. Various pathways were demonstrated, mostly in animal models, from linking temperature increases to seizures all the way to demonstrating antibody binding to and blocking ion channels.

I am fairly busy at the conference so today’s IC Friday may become next weeks IC Tuesday or later. With the bad news comes some good news. The chip I have lined up is one that is very close to my heart, the Graphics Synthesizer chip from the Playstation 2. I have most of the images on my laptop already, I mainly need to stitch them, format and upload, so I apologize for the wait.

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I am going to the 2007 American Epilepsy Society annual meeting in Philadelphia, PA next weekend and intend to present a poster half of which will deal with multi-taper spectral analysis. I am presenting it next Monday morning, from 8:00AM to 2:00PM (poster #3.165). I could also use some suggestions for a good place to get a cheese steak.

The novelty of this presentation is that I am using orthogonal Slepian tapers to determine both the amplitude and phase of a complex transfer function, where most of the previous research deals with amplitude spectra alone. The difficulty is that the various tapers have different phase-bias characteristics, so averaging them and then computing the phase and amplitude would not work. Nevertheless, if we first compute the power in different bands, per taper, and then average, the phase dispersion will not play an important role. The second part of the presentation will deal with causing the activity of an on-going, epileptic seizure to become temporarily phase-locked to applied electrical stimulation (entrainment). The technical abstract for the poster presentation is below.

( nchernyy-abstract.pdf )

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I had spent some time yesterday at a NIH grantsmanship seminar so here is a small digest.

Firstly, the NIH is split up into 24 administrative units/institutes each of whom have their own individual budgets and fund their own grants. Although NIH has standardized grants (F, K, R, P series), their funding criteria and value different from institute to institute. For this reason, it is paramount to have your grant sent to the appropriate institute for consideration after it is reviewed by the Center for Scientific Review. It is highly recommended that those who are planning to submit a grant contact a program officer in the individual institute to discuss the scope of the grant to make sure that it complies with the activities of the institute. If not, the program officers can typically recommend a better place to submit your grant. Below are a few useful links.

• Neuroscience research funding contacts in the federal government
• Federal grants clearing house
• NIH program announcements and requests for applications
• “All about grants“
• NIH grant writing tips
• Quick guide for grant applicants

The image above is of gold ore taken from USGS mineral resources program.

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