TheMillerCircle.org

Ever since David Hubel and Torsten Wiesel (Nobel Laureates in Physiology or Medicine for 1981) began their pioneering work on the function of the visual cortex, beginning in the 1960s, we have been confronted with trying to understand where it will all end–how sophisticated will our visual cells or any other cell type become and will we eventually build a single cell so sophisticated that it will be responsible for the identity of our grandmother? If so, should we lose our grandmother cell, will we also lose the capacity to recognize her? Individual neurons in the visual cortex show an increasing degree of sophistication and stimulus generalization as one goes upstream from the inputs that come from our retina. From circular, center-surround cells of retinal origin, the brain begins, not to extract a visual code from the retinal signal, like a morris code interpreter, but rather to use the building blocks of retinal origin and combine them in new ways, as if the visual cortex had access to a massive Lego set with which to construct a lot of different buildings of different architectures, vintages and colors with an increasing degree of sophistication and abstract representation of the visible world. Each building block as an input from the retina. One must keep in mind that the high speed movie we see in front of our eyes everyday, advancing at non-flickering frame rates (at least 30 frames/sec), in vivid color, with textures and contours that are often invented or exaggerated–that amazing scene in front of us is achieved because the brain is a massively parallel processing machine, which uses the continuous information provided by 1.2 million ganglion cell axons emanating from each eye, to achieve an unparalleled performance in visual display and art recognition. Not only are we continuously aware of the detailed visual information in front of our eyes, but we become instantly informed about the emotional content of our brain imagery: images can instantly evoke laughter or tears depending on their content, our visual memories and our emotional capacities. Each year, the Academy Awards fails all of us as humans for not recognizing the features of our visual system that make movie appreciation even remotely possible. Where’s the Oscar? What’s the category?

Vision rules! We are overwhelmingly visual animals, with a visual brain that developed so much power, we eventually learned how to read and through that medium, we began to change the world we live in. Except for hurricanes, volcanoes, tornadoes and the coming global climate change and mass species extinction, we learned to rule the world and turn the tables on the remaining species that had previously hoped to dine on us. Vision controls our brain, even though it tells lies about the visible world around us, through mechanisms such color-constancy, Mach Bands for enhancing edges, contrast gain, chromatic adaption and movement distortion to name just a few deceptive tactics of our visual apparatus. The brain is a plastic organ, waiting to change and develop according to the experiences we present to it. The “lies” are actually generated by the retina’s commitment to improve our edge detection, recognizes boundaries and colors and detect the movement and project the estimated arrival times of moving objects. From stationary retinal inputs, the cortex begins to build larger regions of visual field receptivity. From small circular receptive fields, larger regions of light sensitivity are constructed that are made of lines of different orientation covering a larger retinal region and these respond preferentially to movement in one direction, as well as prefer information from one eye over the other in an organized set of repeated columns. All of the processing that takes place within the visual cortex, with multiple parallel streams of Lego block construction, still represents early coding for some of our most important visually related events.
Brain imaging studies have revealed that a “letterbox” region lies, on the left side of the brain, near the occipito-temporal border that is associated with the identification of letters of the alphabet and words we have learned. It’s estimated that the human word capacity is somewhere between 50,000 and 100,000 words accomplished when we are adults, through the repetitive, daily act of reading and challenging our brain with new words and their meaning. Written language has fundamentally changed the world and contributed substantially to the growth in intellect and the recognition that reading and writing are fundamental to progress. In the hundred years between the 20th and the 21st century, the percentage of people who are literate has increased dramatically and will continue to grow, given the essential entree it provides into advanced cultures.
Outside of the visual cortex per se, in the medial temporal inferior  lobes, close to the hippocampus that plays a big role in laying down memories that are eventually stored in the cerebral cortex, memories of the declarative type, available to our verbal recall, researchers have determined the encoding properties of single brain cells which turn out to display surprisingly specialized and unique properties. In the less than 1% of epileptics that do not respond to the litany of antileptic medications, removing the localized offending tissue is the only way to reduce or eliminate seizure activity. But since the legendary patient H.M., neurosurgeons carefully explore an epileptic focus with recording electrodes to make sure they don’t remove essential structures committed to the patient’s memory. At the cellular level, no two brains are wired alike, so one has to be careful and record from the cells near the lesion and avoid removing brain tissue that has stored or can store part of the human engram. These studies, which often require hours with a patient’s brain exposed and recording electrodes inserted into brain structures to explore single cell properties near the epileptogenic site, have revealed surprising properties of human neurons that contain memory information about people. One such cell recently described (Quiroga et al., Invariant visual representation by single neurons in the human brain, Nature, 435,1102-1107,2005) in a patient was the “Jennifer Aniston Cell.” This cell responded to images of Jennifer Aniston very distinctly; it did not require her face in any particular position or special clothing. An image of Jennifer Aniston in any position or posture fired the cell vigorously, whereas other similar images of famous people did not.  Interestingly, when the image of Jennifer Aniston was coupled with Brad Pitt, the cell was silent. Not only did the cell respond to an image of Jennifer Aniston, but it responded as well to the auditory or written form of her name. Was this then the long lost grandmother cell we had been searching for during the last 50 years? If you destroyed that single cell, would the patient lose all memory of Jennifer Aniston? Naturally, it was unethical to do something like that, but the authors did feel that their results, with included 993 units, with about 14% of cells committed to human identities (Halle Berry was also popular, as was Bill Clinton, the Beatles and cartoons from The Simpsons and Michael Jordan); to qualify as a human identity cell the cellular response to the picture had to equal to the mean plus five standard deviations of the baseline, with a least two spikes in the post-stimulus time interval.  Repetition is the means we have for forming strong, long-term memories. So perhaps all of us have Jennifer Aniston, Halle Berry and Bill Clinton cells. Since the study was done in 2005, the experimenters did not have a chance to look for Obama cells, but by now they are probably there, perhaps in all of us, maybe even more strongly integrated into the brains of tea baggers. The authors argue that their findings favor the interpretation that the cells from which they recorded are in fact, the missing grandmother cells that were postulated to exist, but have never really been found until now.  The  obvious question that comes up is whether there is more than one representation of Jennifer Aniston? And if one Jennifer Aniston cell is knocked out, will another one quickly takes its place through the methods of laying down a new long-term memory from the background neural engram already active in the brain? One of the most riveting of all issues related to brain function involves the question about the grandmother cell, or in this case the Jennifer Aniston cell. The fact that such a cell exists, when the theory to which I ascribed for many years held that Jennifer Aniston was represented by an overlapping population of cells, so that her identity was determined by a network, not a single, cell has been seemingly shattered by this report. Thus we must now acknowledge the likely fact that we store images of people we know or have seen enough times and encode the representation of these individuals into the discharge properties of a single cell. That cell is so sophisticated that it responds to Jennifer Aniston independent of position, expression, hair style, clothing or facial expression. But, do we have one or many Jennifer Aniston cells in our brain and can those cells be recalled for updating to new folks, once we lose interest in Jennifer Aniston? Of greater relevance is the question about who or what is it that reads the Jennifer Aniston cell to report it to our consciousness? Is the Jennifer Aniston cell one cell removed from our conscious identity? Is consciousness the readout of our cortex, with specialized Jennifer Aniston cells making the task more simplified? Stay tuned! There’s a notable human issue residing in these discoveries. Recordings from awake humans during surgical exploration for epilepsy-related surgery is about the only way we can get at this question and the results of Quiroga et al., have come down pretty hard in favor of us having brains with grandmother cells! But what if we find the same cells in the Chimpanzee? Will that give us pause? Do Chimps care about Jennifer Aniston if they see her on TV enough times? Do we also need language, both written and verbal to even form a Jennifer Aniston cell? All these questions remain in the future, but we can no longer deny the grandmother cells of our present and future brain.

RFM

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When I began my training in medical school in the 1960s, many of the drugs that would become the mainstay, front-line agents in the fight against cancer and other diseases, were just coming into play and some of them, such as methotrexate, which was initially used to treat leukemia, have remained viable drugs for treatment of cancer, psoriasis and rheumatoid arthritis. For the past 50 years or so, we have been living in what I refer to as the chemical age of medicine–in which we search for magic chemical compounds that selectively attack only one type of diseased cell or source of viral/bacterial infection, while leaving all others untouched.  In truth, this phase of medicine began during WW II, when large scale fermentation plants in the United States began producing huge quantities of penicillin from the fungus Penicillium chrysogenum, which proved, for many, to be one of the first miracle drugs available. Yet, decades later, we are still searching for the perfect miracle drug, one whose target of action is so selective that it has no side-effects or harmful untoward reactions.  The “better living through chemistry” mentality still grips contemporary  medicine, as it drives the pharmaceutical industry to search for better magic bullets in the form of improved drug design. And, over the decades, we have gotten much better at drug design because we are increasingly able to construct and visualize the three-dimensional structure of a targeted receptor or enzyme we want to modify and design a drug that will fit neatly into the critical key and lock combination leading to a desired pharmacological effect (blocking or enhancing its action). Through very special efforts, we are beginning to target specific cells with drugs by pre-selecting the cell, say a cancerous cell,  for targeted destruction using manufactured minicells that can deliver specific toxins to the wayward cells which can be identified through immunolabeling methods (It’s pretty cool and the link above goes to an article I wrote earlier on the topic).

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The latest NYTimes/CBS News Poll should warm the hearts of those intent on making the public option component part of our healthcare reform package. After being distracted by the Republican goons of August, whose mission was to distort and destroy healthcare reform, no matter what the plan, the latest poll provides us with some glimpse of how successful they were in derailing a serious reform effort. The NYT/CBS Poll asked a very straightforward and general question: “Would you favor or oppose the government offering everyone a government-administered health insurance plan–something like Medicare coverage that people 65 and older get–that would compete with private insurance plans?” The beauty of this poll question is that it was phrased generally, without reference to a specific bill. The results indicate that, despite what the press wanted to portray as a mounting healthcare reform failure, the respondents to that question overwhelmingly endorsed the public option plan with 65% in favor of the public option–one like medicare–26% opposed and 9% without an opinion. In short, the support of the public option has grown and must be viewed as a plan favored by most Americans. And, with that level of support, derived from a question that wasn’t linked in some devious way to a confusing healthcare plan subtlety, the NYT/CBS Pollsters will apparently use that same question to follow the debate in the coming months of what is  shaping up to be a modern political food fight.

The Baucus bill that was in the Senate finance committee emerged without any Republican support, turning Obama’s  position of insisting on bipartisan support, into a non-entity: this will be a Democratic bill and we can win the public support option in two ways. First, floor amendments to the Baucus bill will bring up the public option plan, though it is currently unclear whether the Senate will vote their version of the healthcare plan with that component in it. But, this is up to the Democrats and the pressure on conservative Democrats who do not favor the public option plan, will be to face the prospects of not getting a decent bill passed at a time when the Democratic Party controls all three branches of government. Though the planned healthcare bill will not go into force until 2014, a failure to achieve a decent healthcare bill could doom the prospects for Democrats’ re-election bids on any one of a number of legislative failures. Passing a bill in which the public becomes increasingly aware that it favors the for-profit insurance companies, as analysis trickles in over the next few years,  could be the single greatest element of destruction for the Democratic Party in the election of 2010. All Democratic Senators are aware of this dilemma and we should continue to remind those conservative Democrats that the NYT/CBS polling data favors a solution with the public option plan as a major component.

The second pathway to insure the public option is through the House, where several bills have already come out of committees that have a public option plan. Nancy Pelosi insists that a healthcare reform bill that lacks the public plan cannot pass the House because of pressure by progressive democrats and union support.  By increasing our pressure on Democrats who are wavering on this issue (again, we are unlikely to see any Republican votes in the House, unless we apply pressure and keep the poll numbers pointing in the direction of the public plan as an essential element to healthcare reform), a strongly endorsed healthcare plan coming out of the House with the public option intact, will force acceptance of that component in the House/Senate conference meeting–the Senate will not be able to avoid it. So the margin of victory in the House now becomes an important component of our reform prospects.  Now is the time to write to your Senators and House legislators, to keep the pressure and drive the issue into a state of redundant acceptance. I believe that the public option plan is more achievable now than at any other time in the last few months. We may have passed through the dimly lit tunnel of the goons into a brighter light of new hope for decent healthcare reform. The lobbying against the public option is running out of gas and it’s time to energize our legislators and force our news media to talk about the new polling data and explore the ethical failure of our current healthcare system. For the past two months, opponents of healthcare overhaul have outspent those supporting the bill, but that tide has now shifted, with more advertising money spent on support of the legislation, even though we don’t yet have a specific bill to fight over. One can almost predict that the Senate/House conference committee  will be the site at which the public option succeeds or fails and, if so, no conference in history will be in the public spotlight more than that one. Energize yourself–the battle for healthcare supremacy is about to begin!

RFM

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