Bat and Bird Songs for Systems Neuroscience

This week’s Science features an article about the songs of bats – not the ultrasonic echolocating calls most often associated with these wonderful creatures but complex vocalizations that bats use socially.

The most well-studied “songsters,” as the author, Virginia Morell, calls them, are songbirds. In species like canaries, zebra finches and starlings, the male sings a courtship song that he learns from his father to woo females.

Male zebra finches, for example, learn just one song, which typically consists of several syllables, and repeat the same song throughout their lives (hundreds or thousands of times per day). Each rendition is virtually indistinguishable from another, and yet finches can learn to modify the pitch of any given syllable on a millisecond timescale. Canaries also sing to woo females, but their songs are long and complex, with relationships among different syllables that imply nontrivial syntax. Continue reading

Coordination Between Motor and Sensory Systems

One interesting problem in systems neuroscience is how the nervous system’s motor output interacts with its sensory systems. Sensory inputs that result from motor commands must be either filtered out or used to guide future motor actions. In other words, the organism must distinguish between sensory inputs that are self-generated and those from the outside world. In the juvenile songbird, for example, motor commands for song generation must be sent to some internal critic (likely basal ganglia) so the bird can compare the actual song output to some internal tutor model and improve subsequent renditions.

The weakly electric fish produces regular electric pulses – electric organ discharge or EOD – to actively locate objects within its environment, not unlike a dog sniffing or a blind person feeling objects with his hands. The EOD produces an electric field around the fish that activates electroreceptors on the fish’s body, which the electroreceptors must cancel out (otherwise each EOD pulse would confuse the fish into thinking that a foreign object is nearby – imagine if every time you say something, you can’t tell if it was you speaking or someone else). Continue reading

Milk Does Not Cause Autism

The radical organization whose supposed mission is to protect animal welfare now says that cow milk not only worsens autistic symptoms but can actually cause autism too. PETA’s campaign to stop people from using animal products latched on to obscure studies of dietary influences on autistic symptoms.

A PETA blog post refers to two studies that found a link between autistic children’s behavior and consumption of cow milk (or proteins found in cow milk), and jumps to conclude that “dairy foods may worsen or even cause autism.”

One of the cited studies followed two groups of children, one of which had the kids on a gluten- and casein-free diet. The experimenters quantified poorly-defined things such as “whether the child at times could be aloof (1), was easily distracted (2), needed routines and rituals (3), and how the child responded to teaching.” The results section poetically describes how these traits were defined:

Aloofness is a characteristic symptom in the behaviour of many people with autistic syndromes, reflected in the expression ‘the child in the glass bulb’. The child is physically close, but yet impossible to reach. All the participants showed this trait prior to the experimental period

Unnecessary literary attempts aside, this (and other) studies that found links between autism and diet were poorly designed.  Anyone who’s ever given a kid a bag of M&M’s can tell you that diet can affect behavior, but there is no reason at all to believe that milk (or vaccines…) causes autism. Obviously parents should be wary of what their children eat. A bigger threat than milk proteins might be hormones that cows and chickens are fed, or pesticides that conventional fruits and vegetables are sprayed with. Trumping all these concerns might be Congress’s dubious ideas that tomato sauce or french fries count as servings of vegetables in school lunches; or the ever soaring numbers of prescriptions for drugs like Ritalin and Adderall, which act in the brain could have long-term developmental effects.

Using the Brain to Treat the Body’s Diseases

There’s an article in New York Times Magazine about using electrical signals in the nervous system to signal to the rest of the body to somehow alter molecular signaling outside the nervous system. Neuroscientists have known for a while that neurons transmit messages by electro-chemical signals: at each synapse, an electrical impulse arrives from a cell body, is converted to a chemical message via neurotransmitters. The chemical message jumps across the synapse, where it is again converted into an electrical signal at the next (postsynaptic) neuron. For some reason though, the thought that electrical signals interact with non-nervous system elements (like the immune system) has not been very popular; the idea that one could manipulate the electrical signals to “hijack” downstream molecular signaling without affecting neural communication itself seems like magic.

The NYT article describes how Kevin Tracey, a neurosurgeon, hooked up stimulating electrodes around a rat’s vagus nerve and injected a toxin that increases tumor necrosis factor (TNF), a cytokine that promotes cell death. He found that stimulating the vagus greatly reduced TNF production in the liver (original paper can be found here) and reduced inflammation. Tracey is currently pursuing clinical therapies using such “bioelectronics” to treat diseases like rheumatoid arthritis, which don’t respond well to drugs (drugs go all over the body and usually act in different tissues, despite being designed to target specific targets).

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How does sensory experience change cortex?

The neocortex is an evolutionarily new part of the brain unique to mammals and is responsible for high level sensation, movement and cognition. It wouldn’t be fair to summarize in a sentence or two what cortex “does,” but it is clear that it is an important part of the brain. Korbinian Brodmann famously divided the human cortex into about 50 areas based on histology of the six cortical layers in different parts of the brain; Brodmann’s areas are still used today because their functions follow their histological structure.

While cortical areas have largely stereotyped wiring patterns, some connectivity “motifs” are thought to be area-specific, varying based on the type of input the area receives. It is unknown whether the type of input (i.e. statistics of incoming activity that vary with types of sensory stimuli) to a given cortical area determines the types of connectivity motifs present in that region. And while classical cortical “rewiring”experiments from Mriganka Sur’s lab have shown that primary sensory cortices are somewhat tolerant to process foreign inputs, it is not clear to what extent those circuits constitute basic computational units or if foreign inputs cause reorganization of connections within the circuit. Continue reading

Connectomic Reconstruction of Direction-Selective Circuit in the Retina

Connectomics is the area of neuroscience that aims to collect and curate the entirety of the connections made by all neurons in a brain (the product being called a “connectome”). For the human brain, that would be a data set of 100 billion neurons, each of which is estimated to make 1000-10000 synapses with other neurons (on the order of 1017 connections). The roll-up-your-sleeves-this-will-get-really-messy way of collecting that kind of data is to slice the brain into nanometers-thick sections and to image each slice with an electron-microscope, which has resolution below the nanometer range, and can reveal the structure of cells on a fine scale. In the image from Kristen Harris’s lab below you can see a part of a neuron’s dendrite making a synapse with an axon filled with neurotransmitter vesicles; EM images however cannot show individual proteins or molecules).

Stack of EM images of brain slices from Kristen Harris’s lab.

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Oklahoma’s Torture-execution

With the world in shock over the botched execution of Clayton Lockett in Oklahoma last week, rather than questioning the morality of capital punishment, we should reevaluate America’s prison system as a whole. With an ever-growing population of inmates, America’s prisons are operating under the arcane notion that punishment deters crimes, while ignoring a growing body of scientific work that could be used to understand why people commit violent crimes and how to reinstate criminals into society successfully.

On the question of what causes people to commit horrible crimes, we know that damage to the frontal lobes of the brain (the areas responsible for impulse-control, reasoning, foresight and other “higher” cognitive functions) can cause severe behavioral problems and violent outbursts. Perhaps it isn’t surprising then, that prison inmates seem to have higher rates of brain damage. This does not mean that having brain damage absolves one of responsibility for crimes; nor does it mean that criminals with mental problems aren’t bad people. Rather, knowing that violent or criminal behavior has a mechanistic basis allows us to treat that behavior mechanistically too. The brain is a machine after all, and like all machines its parts and function can be analyzed so it can be repaired. Neuroscience gives us the toolbox to do those repairs. One promising avenue of research is on treating post-traumatic stress disorder (PTSD), which is a form of damage to the brain that has been linked with violent outbursts. Some researchers are testing drugs that could separate a memory of an event from its emotional connotation, which one day could give peace to those troubled by their experiences.

While we may soon find biomedical routes to prevent some violent crimes, no crime prevention strategy is perfect. So, we should have a plan for what to do with people who do commit crimes. Our current system works on the idea that prison punishment is a way to deter convicts and would-be criminals from committing future crimes. The data tells us that this approach doesn’t work: according to the Bureau of Justice Statistics, between 2005 and 2010, 76% of released prisoners in 30 states had been arrested for new crimes. It doesn’t take brain science to recognize that in some way or another, our justice system is failing. We know that a part of the problem is that people getting out of prison aren’t welcomed by society; their opportunities for an honest and prosperous life are greatly reduced by the fact that they have criminal records. On the other hand, a high rate of recidivism is a sign that time in prison could be better spent. Science comes in when we start asking what type of educational methods work best for prisoners to lead productive lives. Experiments on prisoners should be done by scientists with the goal of finding best strategies for behavioral modification rather than by prison officials looking for new sources of lethal drugs.

For some convicts though, re-education may not be in the cards. Killers and child rapists like Clayton Lockett and Charles Warner were sentenced to death for their crimes. The purpose of capital punishment is in part to deter people from committing horrible crimes. Does it work? U.S. states that do not have the death penalty tend to have lower homicide rates than those that do. Notably, these data are correlative; they do not mean that the link is causative. One prominent study used more intricate statistics to come to the conclusion that the death penalty does have a deterrent effect – the authors estimate that every execution prevents 3-18 homicides. If we accept their argument and agree that capital punishment deters violent crime, we still have to ask if we want, as a society, to be in the business of killing people. Just because it works, does not mean it is what we should be doing. What if a scientific study shows that torturing people to death deters crime even more than a quick painless death? What if an agonizing death like Clayton Lockett’s prevents the next thousand would-be murders?

This is where science stops being useful. We can use statistics to measure complex patterns and neuroscience to explain and modify the mechanics of behavior, but science does not tell us how to use its conclusions. Deciding whether torturing criminals in order to deter future crime is a moral judgment that we have to make.

 

Congress to Peer Review Science Funding?

There is a bill circulating in the House of Representatives, sponsored by Lamar Smith of Texas, that aims to give Congress the power of oversight over government grants for scientific research. Grants from the National Science Foundation are given out to basic research projects based on their scientific merit, as determined by a system of peer review. Lamar Smith’s legislature hopes to “improve” science funding (= reduce government spending) with this proposal:

CERTIFICATION.—Prior to making an award of
any contract or grant funding for a scientific research project, the Director of the National Science Foundation shall publish a statement on the public website of the  Foundation that certifies that the research project—

(1) is in the interests of the United States to  advance the national health, prosperity, or welfare, and to secure the national defense by promoting the progress of science; 

(2) is the finest quality, is ground breaking, and answers questions or solves problems that are of utmost importance to society at large; and 

(3) is not duplicative of other research projects
being funded by the Foundation or other Federal
science agencies

 

Perhaps the effort is genuine and Smith wants to boost scientific research and output in the U.S. Perhaps it is out of a naive micro-manager tendency that he’s proposing to overtake the peer review process (which is definitely far from perfect), just as he did with the SOPA (“Stop Online Piracy Act”) bill. Or maybe the underlying motivation is more sinister.

Regardless, the point of basic science is that it does not promise to bring about any specific advances or cures for social or medical ailments. Rather, basic science advances society by a more stochastic process – two steps forward, one step back. Many scientific projects either don’t work out at all or the results are negative or un-interpretable; but all information produced through the scientific process is useful. If my experiment produces confusing results, the conclusion shouldn’t be that I wasted the government’s money; on the contrary, that money (and time!) are saved for the next person who wants to test a similar hypothesis – that person doesn’t have to duplicate my failed effort and can design a better (or different) experiment.

The National Science Foundation is distinguished primarily from the National Institutes of Health in that the latter aims to improve human health through science, while the NSF simply aims to fund scientific projects in order to produce knowledge. (By the way, the NSF’s budget is ~$7 billion compared to the NIH’s $32 billion). With the tight budgets, the funding agencies are already forced to choose only the most competitive and promising proposals. The agencies must be accountable, but holding them at gunpoint won’t produce any innovation.

More on the issue on The Huffington Post, American Science Blog and The New Yorker.

The President’s BRAIN Initiative

At three pounds, 100 billion cells, 10,000 as many connections, the human brain makes Facebook look like child’s play of a network, not without reason: our brains are solely responsible for our every thought, emotion and action. The human brain is the most complicated machine in the known universe.

It is fitting then, that President Obama announced this week that the state of our knowledge of brain function is in a sort of swamp despite tremendous progress in the past century, and it is time to pave our way out in an effort to solve how the brain functions.

The BRAIN Initiative seeks $100 million for the next fiscal year to fund new research into mapping connections between nerve cells, with the ultimate aim of curing monstrous diseases like Alzheimer’s, Parkinson’s, autism and PTSD. The cornerstone of the proposal, based on two idea-papers published by top neuroscientists in the last few months, in Science and Neuron, is to create new technologies capable of measuring the electrical activities of millions of brain cells at a time (the current state of the art is hundreds of cells).

The President hopes this sort of “big science” project will follow the Human Genome Project’s success in creating jobs and boosting the US economy, while unifying neuroscientists around the world in the pursuit of cures for major diseases (according to a Times article, a $600 billion annual worldwide toll for dementia care alone). While well-intentioned, the proposal is ripe with serious problems. Neuroscientists, like Prince Herbert, must be cautious.

One problem with the proposal – and a way in which it differs from previous Big Science projects – is that it’s not clear what victory would look like. With the Moon Shot and Human Genome Project, we had clear goals to work toward and knew exactly when those were achieved. On the other hand, how will we know when we’ve understood the brain? The Initiative’s aim to record from every neuron involved in a behavior doesn’t help its case – surely there are millions of possible behaviors one could study, with even more states in which the appropriate networks start the behavior, not to mention the multitude of ways a neural network can progress through learning. The proposal doesn’t clarify how such experiments could be set up or what information they would provide.

Interestingly, there is an effort already underway to map connections between brain cells to the resolution of the approximately 10,000 inputs per neuron in whole circuits or brains; the Connectome Project, led by Sebastian Seung, Jeff Lichtman and Winfried Denk, is quite controversial because its goal is to create static pictures of the connections rather than ever-evolving ones of electrical activity, but it is also very well defined and promises clear answers, much like the Human Genome Project did. One of the experiments proposed by the Connectome team, according to Jeff Lichtman, is to create diagrams of the circuit responsible for generating songbirds’ songs (a highly complex and well-defined learned behavior) before and after learning. Such data would be tremendously important for our understanding of how neurons organize themselves during learning to produce sequences of complex movements.

In addition to the vagueness of the BRAIN Initiative’s goals, its promise to cure diseases like Alzheimer’s reveals either a misunderstanding of how basic science works, or simply a dangerous exaggeration that will discredit neuroscientists in the public eye. If we fail to find cures in the next decade, will conservatives in Congress conclude that science just doesn’t work?

And while the proposed “mapping” of activity will provide great scientific insight into brain function, it won’t find cures horrible diseases such as Alzheimer’s because those are rooted in molecular and genetic failures rather than in neuronal electrical activity itself. Aberrant activity is a result, not a cause, of molecular and genetic problems; manipulating activity, such as Deep Brain Stimulation for Parkinson’s, is a temporary fix. The Initiativewill likely make the highest impact in cases of mechanical damage to the brain like stroke, where circuit function goes awry because dead neurons don’t make critical computations. In such cases, measuring activity in healthybrains will be enormously helpful to treatments.

Elements most critical to the Initiative’s success will not be those that define it, but those outside of it. The organizers must ensure that funding for BRAIN does not syphon money from existing projects or alternative and independent future proposals. Scientists must have the freedom to pursue their interests without having to follow the government’s vision.

Idolatry in Science

Gary Marcus recently celebrated Noam Chomsky in an essay about the famous linguist’s life and influence on the field of linguistics over the past fifty years. There is no doubt that Chomsky has had tremendous impact on American intellectual life over the years, from work on language to political and philosophical ideas. However, Gary Marcus’s description of Chomsky’s influence on the field and his colleagues is somewhat troubling and unfortunately not unique to Chomsky but prevalent in the sciences. In every scientific sphere, it seems, a handful of individuals have excessive sway; these one-percenters are revered to an extent that their opinions go unquestioned (unchallenged) at best or as dogma, at worst.

As Marcus points out, young linguists have a hard time studying what Chomsky finds uninteresting, the tragedy of which manifests itself in those people either not getting jobs and recognition in the field, or abandoning their interests in favor of Chomsky’s: “A good way for a young linguistics graduate student to make a name is to develop an intriguing idea that Chomsky mentions in one of his footnotes; it’s a riskier move to study something that Chomsky doesn’t find to be important.”

This is also the case in the life sciences, where such idols serve on funding committees and editorial boards of journals, which not only serve as gatekeepers to young investigators’ professional lives, but also have huge influence on the technological and medical progress in Western society.

Growing up (i.e. in college), I had the impression or dream that scientists were in many ways removed from the regular vices that the rest of humanity was suffering from. I mean the need for social status. The typical scientist, in my imagination, was a disheveled person wearing ragged, ripped clothes, sometimes overdue on a shower. Presumably these people are so immersed in their thoughts and experiments that they simply don’t care to follow social customs; they have no need to impress people with fancy designer clothes; they forget to be social and polite not because they’re rude or too cool, but simply because they’re living on another plane, etc. Scientists don’t care to know what Lindsay Lohan did last night because they don’t look up to celebrities in the way that others do.

That was my imagination; the reality is not as cute. As the Chomsky example shows, scientists do have idols and status symbols. The most obviously silly status is what journals one publishes in. Over the years, a handful of journals have accumulated such reverence that even one paper published in them can make a scientist’s career. Publishing in Nature or Science is the equivalent to owning a Porsche or dating a supermodel or [fill in whatever people want for the sole reason that other people want it]. Everyone is guilty. Knowing that this is a problem is not enough; I am still impressed by papers published in such journals and would be ecstatic if my work appeared in those glossy pages. (The counterargument is that top journals publish scientific papers based on their merit, so it only makes sense that those publications should be bellwethers of good science. For this to be true, the editors at those journals would have to be blind to the authors’ and universities’ identities (which they’re not).

As far as idolatry goes, the real victims may be scientific theories that get shut down simply because the Chomskys of science don’t care for them (or have their own counter theories); or young scientists who need to publish and get grants (“the rich get richer”). I wish Dr. Chomsky all the best for his birthday and future, and can only hope for the sake of science that the old maxim attributed to Max Planck does not stay true much longer: Truth never triumphs — its opponents just die out.