Obamas New Initiative to Map the Brain: Realistic or Idealistic?

A New Goal Emerges

Last month, President Obama announced the start of new project: the BRAIN Initiative to map the Human brain. According to Obama, the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative aims to “do for the human brain what the Human Genome did for genetics.” To kick it off, Obama has allocated $3 billion towards the entire project of wide-spread neuron mapping, starting with $100 million in the first year, which he plans to split between the NIH (National Institute of Health), DARPA (Defense Advanced Research Project Agency), and NSF (National Science Foundation).

Why Global Mapping?

Why has Obama taken on this initiative to map the entire brain? According to Dr. Collins, director at the NIH (National Institute of Health), “the reality is we cant afford not to;  [we] dont want to stifle innovative thinking.” The scientific answer to this question is that our current available imaging techniques only allow for local mapping of neural circuits and connections—interactions between a few specific neurons in a targeted area, compared to all of the connections throughout the brain  (Saucan, 2008). Although these techniques have allowed us to discover some of the neuronal circuits underlying perception and sensation, our inability to create a global map leaves much room for error in what we think we know. Discovering a global map of these neuronal circuits therefore opens the door to a multitude of potential scientific advances, like the circuitry contributing to our perception and sensation, and—more importantly—the circuitry underlying diseases and disorders, such as PTSD, Schizophrenia, Alzheimers, and Parkinsons Disease.

What then, are the Problems?

Many scientists see this new incentive as potentially groundbreaking, but others see it as too ambitious, nearing unrealistically idealistic and somewhat erroneous in our current economic situation. Either way, the idea is excellent but there appears to be a few hurdles that need be jumped for the initiative to actually work:

1) Steep Taxes inhibit Sucess

According to the Wall Street Journal article by Gregory Sorensen, the BRAIN Initiative is actually hurt by a policy enacted in
Washington on Jan. 1. According the Affordable Care Act of 2010, the medical-technology industry is subject to a $30 billion annual tax on medical devices, making the “generous” $3 billion gift from Obama somewhat ridiculous.

The Reality

Over the past few years, we have definitely seen an increase in obsessive medical testing—in other words, with increased innovation, comes increases in unnecessary, wasteful, and expensive testing. But, taxing these companies at such high prices—although a smart attempt to combatting these issues—is actually decreasing the number of available jobs, and slowing down the rate of innovation.

As of Jan. 1, medical device manufacturers have already paid up to $450 million in taxes. Additionally, the Pacific Research Institute estimates the “health law’s medical-device tax will reduce American medical research and development by $2 billion a year, and the Manhattan Institute says the tax will cost 146,000 American jobs.” So then truly, how can science benefit from this initiative? According the Sorensen, “This tax decelerates and devalues innovation at the very moment when medicine is on the verge of historic breakthroughs. It is foolhardy to believe that the medical-technology community can spark new innovation while the government is overtaxing it.”

2) No Glia Mapping

In an article published in the Scientific American, Douglas Fields-neuroscientist at NIH- elaborates on a major problem with the BRAIN Initiative: the complete ignorance of non-neuronal cells in the brain, specifically Glia.  Glia are supporting cells with a variety of functions, from myelinating a cells axon, to regulating neuron-to-neuron communication. Furthermore, our current understanding of Glia is severely lacking compared to our understanding of neurons.

The Reality

By ignoring the role of Glia and other non-neuronal cells in the BRAIN Initiative, we are literally no better off than we were in our attempts at local mapping. By completely disregarding cells that we do not even fully understand, we cannot obtain a comprehensive understanding of the brains’ connections and their relationship to behaviors and disorders. Thus, we definitely cannot implicate any of the connectivity we do find as key to a particular disease, disorder, sensation, or perception. Similarly to completing only the boarders of a puzzle, we need to map all connectivity components to truly find solutions.

Good or Bad Idea?

These two considerations shine light on the idea that Obamas motives might not have been solely science-based. According to Obama, we are “giving scientists the tools they need to get a dynamic picture of the brain in action; a better idea of how we think, learn and perceive,” but without enough money and cell types, can we truly hope accomplish this feat?

Obama states we “don’t want the next discovery to happen in India or China or Germany; we want it to happen in America; that’s what this initiative is about.” I understand the reasons behind this goal- pushing money and thus jobs into the economy- but “mapping the brain” might not be the most efficient way to achieve this goal. Unless the proposal for the BRAIN initiative is re-clarified and the tax attenuated, it looks like this endeavor might just be too idealistic.

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Pregnancy and Stress: Hormones Causing Mood-Disorders in Children?

It has been known for years that certain environmental factors—such as stress during pregnancy—can influence a baby’s development later on in life. On April 4th at the British Neuroscience Association Festival of Neuroscience in London, researchers presented very interesting findings on a possible mechanism negatively affecting fetuses. According to an article in Science Daily, Professor Megan Holmes, a neuroendocrinologist from the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science in Scotland (UK), has discovered a possible mechanism whereby a fetus’ exposure to high levels of stress hormones can result in mood disorders later in life.

The Study

Professor Holmes used genetic engineering in Rodents–the process of adding, removing, or manipulating a part of an animals genome via Biotechnology–to remove an enzyme she believed to be vital in correct pre-natal development. Holmes hoped to test how high levels of stress hormones affected both fetuses and puberty-age rodents—another time when drastic changes in development occur.

The Cellular Mechanics 

According to Holmes, increased levels of Glucocorticoids—the steroid hormones that increase a result of stress or abuse– might directly affect the programming of fetal cells, raising the chances of problems later on. The steroid, Cortisol, is believed to be a key factor in the fetal cell programing, for it reduces growth, changes tissues, and has long-term effects on gene expression (Davis, 2010).

The enzyme, 11β-HSD2 (11beta-hydroxysteroid dehydrogenase type 2),  usually found in the placenta and the fetal brain, has been implicated in breaking down Cortisol to inactive form, subsequently preventing it from harming a fetus during growth (Kajantie, 2003). By genetically engineering the mice to not have 11β-HSD2, and exposing them to high levels of stress hormones, Holmes was able to test if too little 11β-HSD2—or, better put, too much active Cortisol—was causing negative changes in programming.

What Holmes Found

The high levels of stress hormones directly reduced fetal growth and led to mood disorders later in life. More-so, the placentas of these 11β-HSD2 knockout mice were smaller, making nutrient transport more difficult in the developing fetus. Holmes therefore suggests that the placental 11β-HSD2 is key in inhibition of later mood disorders, acting as a shield to harmful stress hormones.

Holmes further states  “preliminary new data show that with the loss of the 11ß-HSD2 protective barrier solely in the brain, programming of the developing foetus still occurs, and, therefore, this raises questions about how dominant a role is played by the placental 11ß-HSD2 barrier. This research is currently ongoing and we cannot draw any firm conclusions yet.

The Implications…

You may think this is all great, yet Holmes bring an important issue to question: What implications do these findings have on current treatments? Specifically, for the past 20 years or so, we have treated pregnant mothers expected to prematurely deliver with dosages of synthetic glucocorticoids to stimulate fetal lung development. In trying to enhance the probability of life upon early birth,  we may be causing irreversible mood disorders in children later on. Homes emphasizes “while this glucocorticoid treatment is essential, the dose, number of treatments and the drug used, have to be carefully monitored to ensure that the minimum effective therapy is used, as it may set the stage for effects later in the child’s life.”

What About Adolescence? 

Holmes and her colleagues then decided to look at the affect of stress during early teenage years on mood and emotional behavior. They trained rats to respond to a specific learned task, and then exposed them to stressful environments, postulating that  high levels of glucocorticoids released during times of stress may cause changes in the brains neural networks associated with emotional processing.

The fMRI (Functional Magnetic Resonance Imaging) results successfully  “showed that in stressed ‘teenage’ rats, the part of the brain region involved in emotion and fear (known as amygdala) was activated in an exaggerated fashion when compared to controls.” Therefore, “altered emotional processing occurs in the amygdala in response to stress during this crucial period of development.”

Closing Thoughts…

Holmes emphasizes that “determining the exact molecular and cellular mechanisms that drive fetal programming will help us identify potential therapeutic targets that can be used to reverse the deleterious consequences on mood disorders. In the future, we hope to explore the potential of these targets in studies in humans.” Additionally, she hopes the results will promote awareness that “children exposed to an adverse environment, be it abuse, malnutrition, or bereavement, are at an increased risk of mood disorders” later, and the “children should be carefully monitored and supported to prevent this from happening.”

-Adapted from Science Daily Article

– Abstract title: “Perinatal programming of stress-related behaviour by glucocorticoids”.

– Symposium: “Early life stress and its long-term effects-experimental studies”, at 15.15 hrs BST on Sunday 7 April, Cinema 1.

Mosquitoes Quickly Develop a Resistance to DEET

On February 13th, a study published in the open access journal PLOS ONEby James Logan, Nina Stanczyk, and colleagues at London School of Hygiene & Tropical Medicine, UK, exposed a somewhat scary truth about our current methods for preventing bug bites and insect-carried diseases: mosquitos that are exposed to DEET, or N,N-Diethyl-m-toluamide, are developing a tolerance to the drug within three hours.

What We Thought… 

For years prior to the study, the resistance of the aegypti mosquitos was believed to be due to a genetic trait that was passed down through generations. According to an article published in 2010 in the Nature Journal, researchers had used selective breeding to breed females with, what they believed to be, a genetic resistance to DEET. Furthermore, the researchers believed the gene to be dominant, meaning that only one parent has to have the gene for the offspring to inherit the DEET resistance (Stanczyk, 2010).

Now, after additional experiments, Logan and Stancyk conclude the resistance in these mosquitos is actually due to a habituation process similar to that in Humans.

But What Does This Mean?

When you walk into a room and are immediately presented with a foul smell, although absolutely intolerable at first, 20 or 30 seconds later, you no longer smell it. This is habituation.

Within our noses, we have receptors for different odors. When an intense odor enters our nose, the receptors that are sensitive to the odor saturate (respond maximally).This causes the receptor to, in a sense, readjust its baseline to ignore subsequent stimulation by the same odor.This preserves our ability to smell novel odors in the room that would be masked by the intense odor otherwise.

Logan and Stancyk have now concluded that the aegypti mosquitoes develop a resistance to DEET, in the same way as humans.

The Findings…

Logan and Stancyk repeatedly exposed 20 female aegypti mosquitos to DEET in four different experiments to look at their behavioral and physiological responses (Stancyk, 2012).

According to an excerpt from a press release from the Public Library of Science, Logan says  “Our study shows that the effects of this exposure last up to three hours. We will be doing further research to determine how long the effect lasts.” This means that after one exposure, the mosquitoes showed insensitivity to subsequent DEET exposures–they attacked the hosts’ arm, although it had been re-sprayed with DEET. Additionally, supporting these behavioral findings, the researchers performed an electroantennography—a technique measuring the output from an antenna to the brain for a specific odor—and discovered that the olfactory receptor neurons actually did respond less to the DEET.

Since these neurons’ responses were altered by the pre-exposure to DEET, we now have proof that even one presentation of certain olfactory stimuli can modulate the olfactory system of certain mosquitoes, making the stimuli less effective, and creating potential problems for insect-carried illness prevention.

Implications for the Future…

   Apart from the nuisance of having one, two or twelve bug bites, the newly discovered ineffectiveness of DEET leaves Humans in tropical areas at risk to illnesses such as West Nile VirusMalaria, or Dengue Fever, carried by these mosquitos. Although the study specifically looked at the resistance of Aedes aegypti mosquitoes, other recent studies have also shown Drosophila melanogaster-the household fruitfly (Reeder, 2001)-and Rhodnius prolixus-a tritanopia bug (Sfara, 2011)- to also develop DEET resistances after primary exposure.

https://www.youtube.com/watch?v=qGz6tHNNAEo

Although worrisome, Science News Daily emphasizes that Logan states “This doesn’t mean that we should stop using repellents — on the contrary, DEET is a very good repellent, and is still recommended for use in high risk areas. However, we are keeping a close eye on how mosquitoes can overcome the repellent and ways in which we can combat this.”

-Allegra