Guillermo Santamaria's List: Neurogenesis

• if we look back through human history what we see is we've come from an agricultural society to an industrial society, today we're living in an information society where political, economic, social changes, basically driven by information technology. If we look forward what we see is the convergence of multiple technologies that will allow us to develop effective tools for mental health. Now those tools are neurotechnology, the set of tools that allow us to manipulate our central nervous system, more specifically our brain. Our future society will be driven by neurotechnology. Now that's brain scanning technologies, neuroceuticals, which are advanced psycho-pharmaceuticals and those will create new industries. They will have political, economic and major ethical implications.
• when I talk about the neurosociety what we're really talking about is a time from about 2010 to 2060. This isn't something that's occurring now so when you're looking at how brain scanning technology is and neurotechnology is in its current state today.
• There would be sensoceuticals, emoticeuticals, and cogniceuticals. One example might be if you're a financial trader on Wall Street you might take a cogniceutical to improve memory retention, an a emoticeutical to sort of calm your emotional stability, or make you more emotionally stable and maybe a sensoceutical at the end to add a meaningful pleasure gradient to make the experience, if you will, fun.

• when I say neurotechnology it's not just neuroceuticals it's also neurofeedback systems. So for instance, one industry that should emerge relatively quickly is neurofinance. Let's say your GE Capital, you have 55 officers around the world with currency traders, you're in Singapore and you have a group of 5 traders who are leveraging cogniceuticals to again improve memory retention and emoticeuticals to ease the anxiety of making a trade. But at the same time you also have a neurofeedback system that's watching your emotional regulations in tying that back to previous trades that you've made in a similar emotional state. So you'll be getting this feedback on your emotional state, whereas today you don't really have you just sort of go by your gut. We have lots of information, but not information about our own eternal emotion and how that impacts our decisions.
• Neuroethics is an emerging field that's growing out of bioethics. In the United States we have in our Constitution, of course, freedom of speech, but it's not explicitly defined that we have freedom of thought. It's implied, but of course the framers of the Constitution had no capacity really at that time to imagine a world where we could potentially scan someone's brain and know, not necessarily the exact thing that they're thinking but whether or not they experience something at a particular point in time in their life.

• Neural warfare is a frightening concept and this is one of the issues going forward, as with any technology it's a double -edged sword. If you were able to selectively erase the memories of a town, let's say for a day or two, or sedate a town, there are broad implications for how we go about defending ourselves against these technologies and in terms of warfare in the offensive sense, what are the conventions that will be instituted to control this technology?

  Natasha Mitchell Well my impression is that DARPA have been looking into this sort of technology, so for example looking to erase selective traumatic memories in their soldiers.

  Zack Lynch: Yeah, currently they're using, in there some studies going on at Harvard in this area. They are using Propanol, if you give it to someone after an emotional event and what they're looking at it right now for is post-traumatic stress disorder for soldiers. Should we give soldiers these tools to help them mitigate the destructiveness of an event, if society asks them to be put in that position?

• Francis Fukuyama in his book Our Post Human Future, contemplates a future where we are modifying ourself in this way using say neuroceuticals, I don't think he contemplates that specifically but he does call for a red line to be drawn between the boundary between therapy and enhancement. He has real concerns that somehow we're coalescing the two. Technologies like neuroceuticals are really about enhancement.

  Zack Lynch: I would suggest that there may be a third term that should be injected into the discussion to move the debate forward and that would be the term 'enablement'. Enablement would sit between therapy and enhancement as an area where you could develop tools that would allow you to enhance or improve particular traits up to the point where that trait is seen in the general population of humanity. Now steroids is a classic example of enhancement, that's moving far beyond the natural capacity that's seen in a human whereas the tools that would be encompassed within the term enablement would not.

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• But in recent years Adderall and Ritalin, another stimulant, have been adopted as cognitive enhancers: drugs that high-functioning, overcommitted people take to become higher-functioning and more overcommitted. (Such use is “off label,” meaning that it does not have the approval of either the drug’s manufacturer or the Food and Drug Administration.) College campuses have become laboratories for experimentation with neuroenhancement, and Alex was an ingenious experimenter. His brother had received a diagnosis of A.D.H.D., and in his freshman year Alex obtained an Adderall prescription for himself by describing to a doctor symptoms that he knew were typical of the disorder. During his college years, Alex took fifteen milligrams of Adderall most evenings, usually after dinner, guaranteeing that he would maintain intense focus while losing “any ability to sleep for approximately eight to ten hours.” In his sophomore year, he persuaded the doctor to add a thirty-milligram “extended release” capsule to his daily regimen.

• Chatterjee worries about cosmetic neurology, but he thinks that it will eventually become as acceptable as cosmetic surgery has; in fact, with neuroenhancement it’s harder to argue that it’s frivolous. As he notes in a 2007 paper, “Many sectors of society have winner-take-all conditions in which small advantages produce disproportionate rewards.” At school and at work, the usefulness of being “smarter,” needing less sleep, and learning more quickly are all “abundantly clear.” In the near future, he predicts, some neurologists will refashion themselves as “quality-of-life consultants,” whose role will be “to provide information while abrogating final responsibility for these decisions to patients.” The demand is certainly there: from an aging population that won’t put up with memory loss; from overwrought parents bent on giving their children every possible edge; from anxious employees in an efficiency-obsessed, BlackBerry-equipped office culture, where work never really ends.

• • neuroplasticity
• One of the strongest findings in neuroplasticity, the science of how the brain changes its structure and function in response to input, is that attention is almost magical in its ability to physically alter the brain and enlarge functional circuits. In a classic experiment, scientists found that when monkeys repeatedly practiced fine-tactile perception, the relevant brain region expanded, just as it does when people learn Braille or the violin. Similarly, a region of the auditory cortex expands when we hear a particular tone over and over. (Yes, the spot that processes your ringtone is encroaching on next-door areas.) But when monkeys simultaneously touched something and listened to tones, only the brain region controlling the input they were trained to focus on expanded. In other words, identical input—tactile sensations and sounds—produces a different result, expanding a brain area or not, depending only on whether attention is being paid.
• The holy grail of brain training is something that does transfer, and here there are three good candidates. The first is physical exercise. Simple aerobic exercise, such as walking 45 minutes a day three times a week, improves episodic memory and executive-control functions by about 20 percent, finds Art Kramer of the University of Illinois at Urbana-Champaign. His studies have mostly been done in older adults, so it’s possible the results apply only to people whose brain physiology has begun to deteriorate—except that that happens starting in our 20s. Exercise gooses the creation of new neurons in the region of the hippocampus that files away experiences and new knowledge. It also stimulates the production of neuron fertilizers such as BDNF, as well as of the neurotransmitters that carry brain signals, and of gray matter in the prefrontal cortex. Exercise stimulates the production of new synapses, the connections that constitute functional circuits and whose capacity and efficiency underlie superior intelligence. Kramer finds that a year of exercise can give a 70-year-old the connectivity of a 30-year-old, improving memory, planning, dealing with ambiguity, and multitasking. “You can think of fitness training as changing the molecular and cellular building blocks that underlie many cognitive skills,” he says. “It thus provides more generalizable benefits than specifically training memory or decision making.”
• what neuroscientists don’t know about the mechanisms of cognition—about what is physically different between a dumb brain and a smart one and how to make the first more like the second—could fill volumes
• he second form of overall mental training is meditation, which can increase the thickness of regions that control attention and process sensory signals from the outside world. In a program that neuroscientist Amishi Jha of the University of Miami calls mindfulness-based mind-fitness training, participants build concentration by focusing on one object, such as a particular body sensation. The training, she says, has shown success in enhancing mental agility and attention “by changing brain structure and function so that brain processes are more efficient,” the quality associated with higher intelligence.
• “There are lots of quick and dirty studies of cognitive enhancement that make the news, but the number of rigorous, well-designed studies that will stand the test of time is much smaller,” says neuroscientist Peter Snyder of Brown University Medical School. “We’re sort of in the Wild West.”
• The quest for effective ways to boost cognitive capacity is not hopeless, however. The explosion in neuroscience is slowly revealing the mechanisms of cognition. “We have accumulated enough knowledge about the mechanisms and molecular underpinnings of cognitionat the synaptic and circuit levels to say something about which processes contribute,” says James Bibb of the University of Texas Southwestern Medical Center, who organized a symposium on “cognitive enhancement strategies” at the 2010 meeting of the Society for Neuroscience. Greater cognitive capacity comes from having more neurons or synapses, higher levels of neurogenesis (the creation of new neurons, especially in the memory-forming hippocampus), and increased production of compounds such as BDNF (brain-derived neurotrophic factor), which stimulates the production of neurons and synapses, says neuroscientist Yaakov Stern of Columbia University. Both neurogenesis and synapse formation boost learning, memory, reasoning, and creativity. And in people who excel at particular tasks, Stern’s neuro-imaging studies show, brain circuits tend to be more efficient (using less energy even as cognitive demand increases), higher capacity, and more flexible.

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• In the future, the scientists hope to investigate the possibilities of manipulating the brain's connectivity efficiency in order to create more efficient brain networks, and possibly boost IQ. Previous research has found a genetic component to white matter in the brain, which is also related to intelligence. By understanding how these genes work, scientists may be able to figure out how to manipulate the genes, leading to improved intelligence.

• Researchers at Columbia University Medical Center have developed a new way to stimulate neuron production in the adult mouse brain, demonstrating that neurons acquired in the brain's hippocampus during adulthood improve certain cognitive functions.
• In recent years, scientists have been exploring whether stimulating neurogenesis (the formation of new neurons) in the adult brain has a beneficial effect on cognition or mood. Until now, studies have relied on interventions, such as exercise and enriched environments, that affect numerous other processes in the brain in addition to increasing adult hippocampal neurogenesis.
• Earlier strategies for manipulating neurogenesis, according to the investigators, were broader and less specific. "In addition to stimulating neurogenesis, these earlier methods exerted many other effects on the brain. As a result, you never knew with these older manipulations what's due to neurogenesis, or what's due to the other effects that these manipulations cause, and, indeed, what we find is that when you stimulate just adult neurogenesis, you actually get a subtle effect. Unlike broader manipulations, it does not affect all forms of learning, it's very specific to tasks that require pattern separation," said Dr. Hen.
• "I think we're getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don't understand, regarding how the hippocampus can be involved with both cognition – which is its classic function – and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox," said Dr. Hen.

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• "This paper, as a consequence, may stimulate a whole area of research in humans to try to determine who in the population may have a pattern separation deficit, and whether it is restricted to the emotional domain, or is present even while performing tasks devoid of emotional salience. Once these studies are done in humans, it may be possible to treat these people with specifically targeted drugs or more personalized therapies," said Dr. Hen.

   

  The researchers say that the genetic strategy used to stimulate neurogenesis in their experiments can be mimicked pharmacologically, potentially leading to the development of new drugs to reverse pattern separation deficits. One such class of drugs the investigators are currently testing – BAX inhibitors – works by blocking cell death.

   

  "These drugs are basically doing the same thing that we did with our genetic manipulation–namely, increasing the survival of the young neurons which normally undergo a process of cell death that eliminates at least half of these neurons. Now instead of dying, the neurons will go on to survive," said Dr. Sahay.
• "I think we're getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don't understand, regarding how the hippocampus can be involved with both cognition – which is its classic function – and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox," said Dr. Hen.

• As we want to go on this journey of exploring what the heck we’re made out of, the first thing to do is to recognize that what you’re seeing out there is not actually reality. You’re not sort of opening your eyes, and voila, there’s the world. Instead, your brain constructs the world. Your brain is trapped in darkness inside of your skull, and all it ever sees are electrical and chemical signals. So all the colors you see, and so on, that doesn’t really exist; that’s an interpretation by your brain. (…)

   

  All we’re actually doing is seeing an internal model of the world; we’re not seeing what’s out there, we’re seeing just our internal model of it. And that’s why, when you move your eyes around, all you’re doing is updating that model.
• And for that matter, when you blink your eyes and there are 80 milliseconds of blackness there, you don’t notice that, either. Because it’s not actually about what’s coming in the eyes; it’s about your internal construction. And, in fact, as I mention in the book, we don’t even need our eyes to see. When you are asleep and dreaming, your eyes are closed, but you’re having full, rich visual experience —because it’s the same process of running your visual cortex, and then you believe that you are seeing. (…)

• And so, it turns out what the brain is really good at—and the cortex in particular —is in extracting information that has some sort of useful correlation with things in the outside world. And so, if you feed, let’s say, visual input into your ears, you will figure out how to see through your ears. Because the brain doesn’t care how it gets there; all it cares about is, Oh, there’s structure to this data that I can extract. (…)

   

  I think it’s sort of the most amazing thing about the way brains are built, is they’re constantly reconfiguring their own circuitry. (…)

   

  It turns out that one of the main jobs of the brain is to save energy; and the way that it does this is by predicting what is going to come next. And if it sort of has a pretty good prediction of what’s happening next, then it doesn’t need to burn a lot of energy when that thing happens, because it’s already foreseen it. (…)

• You’re not passively just watching the river of time flow by. Instead, just like with visual illusions, your brain is actively constructing time. (…)

   
• It’s not only the way we see vision and time, but it’s all of our cognition: it’s our morals, it’s what we’re attracted to, it’s what we believe in. All of these things are served up from these subterranean caverns of the mind. We often don’t have any access to what’s going on down there, and why we believe the things we do, why we act the way we do. (…)
• As far as nature vs. nurture goes, the answer nowadays is always both. It’s sort of a dead question to ask—nature vs. nurture—because it is absolutely true that we do not come to the table as a blank slate; we have a lot of stuff that we come to the table with predisposed. But the whole rest of the process is an unpacking of the brain by world experience

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• "The fear is that if you start putting very large numbers of human brain cells   into the brains of primates suddenly you might transform the primate into   something that has some of the capacities that we regard as distinctively   human.. speech, or other ways of being able to manipulate or relate to us,"   he told a news briefing in London.

• Let's start by acknowledging that there's no way just administering a drug or fiddling with a few genes can confer human-type intelligence or language ability on chimpanzees or other non-human primates. "The scientific notion is preposterous," Jon Cohen, author of the book "Almost Chimpanzee," told me today.

   

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  Cohen said the oft-cited claim that there's a 1 percent difference between the human and chimp genetic code has led people to believe mistakenly that the two species are separated only by a few molecular tweaks here and there. When the differences in non-coding DNA are taken into account, that difference rises to 4 or 5 percent. Chimps and humans don't even have the same number of chromosomes (48 for chimps vs. 46 for humans).

  "We have to get away from this vastly oversold notion that we're the same," Cohen said. "Let's grow up, and let's stop that."
• Humanized species: It's becoming more common to transplant our genes into other species — for instance, the mice who were given a "humanized" version of the gene linked to language and speech. Humanized mice are even being created in college science projects. The trend has rung alarm bells at the British Academy of Medical Sciences, which is calling for a ban on experiments that might give human characteristics to other primates. (Note the "Planet of the Apes" angle in this video.) Last year, U.S. bioethicists made a similar call for regulation, saying that it would be "ethically unacceptable" to conduct humanization research with apes. (Here's a scary sentence: "Imagine the life of the transgenic chimpanzee that, while no more self-aware than other chimps, is hairless, walks erect, lacks long canine teeth, or vocalizes like a human.")

• The mice with the human FOXP2 gene didn't start babbling like babies of course, but they showed changes in brain circuits that have previously been linked to human speech. The genetically altered mouse pups also showed differences in ultrasonic vocalizations they use when placed outside the comfort of their mothers' nests. But not enough is known about mouse communication to read too much into what those changes mean, Enard noted.

• After two years of heated debate on how to protect animal welfare without scuppering scientific research, the new limits, updating regulations from 1986, were adopted by the European Parliament despite objections from Green MEPs.

   

  Under the new legislations, experiments on great apes such as chimpanzees, gorillas and orangutans are to be banned and "strict" restrictions set on the use of primates in general.

• The legislation notably allows the use of primates in testing illnesses such as Alzheimer's, cancer or Parkinson's disease if there is scientific evidence that the research cannot be achieved without using these species.

  To avoid repeated suffering by an animal, it lists different categories of pain that may be inflicted during a test (non-recovery, mild, moderate or severe) and proposes that the same animals be reused only if the pain is classed as "moderate," and provided a vet is consulted.

• The historical value of the chimpanzee as a disease model is indisputable. It was important in developing the Sabin polio vaccine; instrumental in discovering the infectious nature of the spongiform encephalopathies; and essential to both the creation of a vaccine against hepatitis B and the identification, in 1989, of the hepatitis C virus (HCV).

  Humankind has benefited handsomely. Since the United States instituted universal childhood vaccination for hepatitis B in 1991, there has been a 98% decline in the disease in children under the age of 15 years. And with the identification of HCV, screening of donated blood for the virus reduced the risk of transfusion-associated hepatitis in the United States from 4% in 1989 to almost zero in 2000.
• The chimpanzee is the only animal model in which human strains of HCV can replicate, making it especially important in work to develop a vaccine. And studies in this animal have propelled at least one hepatitis C vaccine into human trials. Other chimpanzee experiments are making inroads in developing better therapies for the disease. The case for chimpanzee use in some other circumstances — such as the effort to develop a vaccine against respiratory syncytial virus, which mainly affects infants and young children — is less strong, but is at least arguable.
• chimpanzee studies are under fire (see page 268). Public discomfort over the use of chimpanzees in research has reached a historic high, with the result that the United States is now the only country save Gabon in which invasive experiments are conducted. Legislation has now been introduced in the US Congress that would prohibit invasive chimpanzee research. Although the bill is unlikely to become law any time soon in a Congress distracted by wars, debt and a moribund economy, the Great Ape Protection and Cost Savings Act is nonetheless a sign of the times.
• One thing is almost certain: if the NIH and scientists do not engage with the ethical and animal-welfare issues that are so clearly at the forefront of the public mind, Congress will do it for them, and the result may well be to shut down virtually all research using great apes, as happened in the European Union in 2010.

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• In response to a request from the National Institutes of Health (NIH), the Institute of Medicine, in collaboration with the National Research Council, will assemble an ad hoc expert committee that will conduct a study and issue a letter report on the use of chimpanzees in NIH-funded research that is needed for the advancement of the public’s health. The primary focus will be animals owned by the National Institutes of Health, but will also include consideration of privately owned animals that are currently financially supported by NIH.

• A chimpanzee cannot be declared a person, Austria's Supreme Court has ruled, activists said Tuesday. 

     

  An animal rights group had sought to have the chimp, Matthew Hiasl Pan, declared a person in hopes of gaining guardianship of the animal.

   

  The shelter where Matthew has lived for 25 years is going bankrupt, threatening to leave him homeless. Donors have offered to help support him, but under Austrian law, only a person can receive personal gifts.

• It wasn't speech that Terrace was after: The vocal cords of chimpanzees weren't designed to replicate human speech. But if the behaviorists were correct, chimps, our nearest genetic relatives, should be able to learn and communicate using the grammatical rules and expressive elements that American Sign Language and spoken languages shared if they were brought up among people. 

• Terrace was writing up his findings for the journal Science when one day, as he watched a well-worn tape of Nim signing with his teacher, he began to notice that something was off. “Then I realized the teachers were prompting him,” Terrace told me. “They weren’t even aware of this. But Nim was.” 

  In a “quarter of a second,” years of observations came crashing down, Terrace told me. "My understanding of Nim signing the grammatical rule was wrong," he said. "Eventually I concluded that our minds are fundamentally different from a chimp's."

  It had to do with our understanding of ourselves as individuals. "We’re aware of our mind," Terrace said. "With a chimpanzee, I don’t think there’s any awareness of one’s own mind and another mind out there. That means you can’t have any concept in a chimpanzee of a self and other." 

  Nim used the concepts of “I” and “Nim” interchangeably. When he wanted cookies, Nim's second caretaker Petitto told me, the chimp would take Petitto’s hand and lead her to the kitchen, to the locked cabinet in which the cookies were stored. While his message was clear, Petitto said, Nim could never take himself out of the picture. “He took me through the motions. It was physical. He couldn’t say, 'On Monday could you buy the cookies,'" she explained. 
• Bringing a chimpanzee home to teach it human language was all the rage once upon a time, but that’s old hat now, he said. Communication studies on chimp behavior now look at the many and varied ways in which chimps and other primates interact naturally. The Nim project was pivotal in giving scientists an early glimpse of those rich possibilities. “We feel like the language studies have opened up an enormous amount of knowledge about cognition, but not about linguistics,” de Waal said. 

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• Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users [10]. Experiment 2 tested “impossibly unspeechlike” [3] sine-wave (SW) synthesis, which reduces speech to just three moving tones [11]. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human

• A talented chimpanzee called Panzee can recognise distorted and incomplete words spoken by a computer, scientists have discovered.

   

  That suggests that apes may be more capable of perceiving spoken sounds than previously thought, and that the common ancestor of humans and chimps may also have had this ability.

   

  It also refutes the idea that humans have brains uniquely adapted to process speech, say the scientists who have published their findings in the journal Current Biology.

   

  Panzee was raised from 8 days old, by humans, and was spoken to and treated as if she were human. At the same time, she was taught to use symbols called lexigrams to communicate.

   

  "This has resulted in Panzee showing proficiency in understanding approximately 130 English words," researcher Lisa Heimbauer told BBC Nature.

• They played Panzee noise-vocoded speech, which alters the frequencies of the spoken words. This produces a sound similar to what people with cochlear implants hear.

   

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