BrainBlog

The origins of empathy?

2012-01-10T13:14:00.006-05:00

Neuroscience is uniquely suited to investigate the biological underpinnings of the features and traits that make us human, including morality, complex emotions and higher-order cognition. However, as we continually learn more about our behaviour and its origins, one unavoidable and startling possibility is frequently made clear; many quintessentially 'human' characteristics may not be unique to ourselves. One recent example is empathy, the experience of feeling and understanding the state of another agent. Empathy may cause one to respond altruistically; for example, to relieve the suffering or discomfort of another in unfortunate circumstances. Biologists have found evidence of altruistic behaviour across the animal kingdom, presumably due to evolutionary pressures favouring those behaviours that promote species survival and not due to active cognition. However, recent studies have raised the startling possibility that the experience of empathy may be older (evolutionarily) than we think, that we may not be alone in our understanding of the states of others, and that our own understanding of the mental states of animals may be even more primitive than we hold them to be.

Some of the recent evidence suggesting that rodents may have the capacity for empathy comes from pain research here at McGill. Mice in the presence of another mouse in pain are more sensitive to pain themselves, but only if the mouse is familiar (a 'roommate', essentially), and not if the alternate mouse is unfamiliar. To put it another way, if a mouse sees a 'friend' in pain, their understanding (such as it is) of the familiar mouse's experience can affect their own perception of pain, as part of a phenomenon termed “emotional contagion” that is believed to be a precursor to empathic behaviour.

A brand-new study has potentially added some exciting insight to the issue of empathy precursors in animals. A team from the University of Chicago developed a novel method of examining empathy-related behaviour, in which one rat is held in a restraining device that can be released by another rat. After learning how to open the restraining cage, the freely-moving rat chose to free its restrained companion, but not empty restrainers or those containing a toy rat. Notably, female rats seemed to show more altruistic behaviour than males. In a subsequent experiment, this team showed that if a second restrainer containing chocolate was placed alongside a trapped rat, the free rat was equally likely to initially open the chocolate restrainer (and enjoy the chocolate alone) or to open the rat restrainer and share the chocolate, suggesting that freeing the trapped companion is as motivating to the rat as a tasty treat. The authors of this study suggest that these results indicate empathy on the part of the freely-moving rat, in that it is highly motivated to rescue a companion animal that it perceives as distressed, even when doing so costs the rat resources (in terms of sharing the chocolate).

However, is this really the case? In the scant time since this article was published, alternative explanations for the rats' behaviour have arisen. One possibility is that the freely-moving rat becomes distressed by the trapped rat (either by their vocal cries, a released scent, or another signal), and the free rat is opening the restrainer to extinguish these cues and reduce its own distress, as opposed to 'helping' the other rat. Supporting this hypothesis, the animals emitted more frequent 'alarm calls' when an animal was trapped, explaining why the free animals were more motivated to open only those cages containing a trapped companion. This would not be empathic behaviour, as the freely-moving rat is merely acting to reduce its own distress, rather than altruistically 'rescuing' the trapped rat. In addition, the evolutionary advantages of empathic experiences in rodents are unclear.

So the animal empathy issue, new as it is, remains somewhat murky. It seems that rodents possess the capacity for emotional contagion, a primitive precursor for actual empathy. The more recent research raises the possibility for empathy underlying altruistic behaviour in rats, although the evidence so far is insufficient to conclude that this is the case. However, these studies provide clear research directions for future studies investigating the origins of our own uniquely human condition. We already know that human infants display empathy- and morality-related behaviour, as well as a basic understanding of the mental experiences of others (“theory of mind”), as early as one to two years of age. Taken together, these avenues of research bring us closer to understanding the evolutionary and developmental origins of those traits that make us human, to whatever extent we can say they remain uniquely ours.

[Adapted from a post originally posted here.]

Concussion repercussions

2011-03-16T16:17:00.003-04:00

I went to a Montreal Canadiens game last week, with the Bruins as the visiting team. The atmosphere in the Bell Center was festive, as the Habs went up 4-0 in the first two periods. The mood shifted drastically, however, as a Canadiens forward was checked into the stanchion between the benches and fell to the ice, unconscious.

The now-infamous hit by Zdeno Chara on Max Pacioretty resulted in a serious concussion, as well as a fractured C4 vertebra. Amid the controversy regarding the hit and whether further disciplinary action should be brought against Chara, the incident brings the seriousness of concussion injuries back into the public eye.

A concussion is a form of traumatic brain injury, in which a sudden impact causes the brain to compress against the inside of the skull, resulting in a temporary loss of brain function. The majority of concussions do not result in loss of consciousness. Roughly 1% percent of the population will suffer from a concussion at some point, although this statistic is likely an underrepresentation of the true prevalence. We used to view concussions as relatively minor events, but some disturbing recent studies have shown that they can have serious consequences.

Common side effects of a concussion are headache, nausea, loss of motor coordination, and sensory dysfunction. These usually dissipate without requiring treatment acutely after the injury. However, with post-concussion syndrome, symptoms may not disappear for months or years, or even at all, and there is currently no treatment except rest.

We are also learning a rapidly increasing amount about the effects of concussion on emotional and cognitive function. Recent studies in National Football League players have shown an association between concussion and depression, as well as memory deficits and general cognitive impairment. Tragically, traumatic sports injuries have even been linked with suicide. These effects have been attributed to chronic traumatic encephalopathy, a degenerative condition in which multiple head injuries lead to aggregate damage to the brain; boxers that are termed ‘punchy’ suffer from one form of CTE.

Pacioretty will hopefully recover from his injuries avoiding these particular issues, although his future career is in doubt. However, the primary issue is that millions of young athletes engage in contact sports on a regular basis, putting developing brains at risk for serious neuropsychological consequences. It is imperative that future research determines how best to mitigate the risk of concussion-related injuries in these vulnerable individuals.

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On a lighter note, this week is Brain Awareness Week, so make sure to attend some of the great events and get involved!

- Ian Mahar
[Adapted from a post originally posted here.]

Human Libido = Mouse Libido?

2011-03-11T11:29:00.003-05:00

(crossposted from The Naive Observer)

No! Right? Maybe some sociobiologists would argue that they obey the same basic rules, but no, not the same. Not so fast though – anyone who has had to defend their mouse research against doubts about its relevance will tell you (a little too earnestly) that there is around 90% similarity between the mouse and human genomes. So in all your faces, non-mouse geneticists.

Many of us use mice and rats as model organisms to study things from a genetic point of view with reasonable hope that info gleaned from rodents will inform our knowledge of human biology and direct “less invasive” research on humans. But there’s no denying that humans and rodents are very different. So where do we draw the line when inferring from rodent studies? This problem is especially relevant in neuroscience, where we are caught trying to bridge the gap between the physical, cellular, genetically influenced brain and the less tangible, socially conditioned mind. What better way to give air to this issue than by juxtaposing the genetics and neural correlates of mouse and human libido?

Last year I reviewed a study that discovered that male mice release a small aphrodesiac molecule (ie pheromone) in their tears. This small molecule, called ESP1, makes female mice more receptive to males’ sexual advances. In other words, female mice are turned on by the smell of tears in their man’s eyes.

So, er… “a friend of a friend” read that study, was thoroughly convinced and, armed with the knowledge that mice and humans are genetically quite similar, took his tears to the bedroom, hoping to turn over a new leaf. Unfortunately he neglected to look at what seemed to be a follow up study in humans in the new year. Turns out female human tears contain a substance that does the exact opposite, decreasing male arousal when the men sniffed paper soaked in tears collected from women. (Is sniffing tears not creepy? What ethics committee approved that?) True enough, the authors only looked at female tears, so maybe there is a human analogue of the male mouse tear aphrodisiac. So, in the interest of being fully honest, guys, if you want to run the risk, you can still have a go at crying. However, it turns out that the friend of a friend shouldn’t have risked it; last I heard he’s lonely and writing a blog or something.

The point is that humans and mice are similar in some instances, and opposites in others. So there is no point. Rest assured that rodents will continue to provide a popular and invaluable model organism well into the future. That means when you see something in the paper to the tune of “Now-Famous Scientists Show Such and Such Will Make Someone Special Horny” or not, before hitting the streets in search of Such and Such, figure out what species the research was done on and make your own tentative judgment.

Reference

Gelstein S, Yeshurun Y, Rozenkrantz L, Shushan S, Frumin I, et al. 2011. Human Tears Contain a Chemosignal. Science 331: 226-30

Synesthesia

2011-02-22T12:03:00.001-05:00

Does your best friend's name taste like macaroni and cheese? Does your favourite song look like a blue bolt of lightning? Is four red? If so, you are most likely a synesthete - a person who experiences the rare neurological condition synesthesia. Synesthesia occurs when a stimulus induces not only the expected percept (perceived representation) but also an involuntary, automatically evoked percept, sometimes in another sensory modality. For example, the most common form of synesthesia is grapheme-colour - where seeing, hearing or thinking of a letter or digit evokes a colour. These associations are highly consistent (e.g. the letter A, will always evoke the colour green), and are present from childhood. For some synesthetes, the concurrent percept is projected into a specific location in space (i.e., right onto the grapheme) - these are called projectors. Associators, on the other hand, see the elicited percepts "in the mind's eye".

It is only in the past few decades that research involving synesthesia has flourished. Historically, the condition was regarded with much skepticism. At worst, synesthetes were condemned as mentally ill, and confined to asylums , at best they were considered to be overly imaginative, or liberally metaphorical. In the last two decades innovative, psychometric methods have also been used to empirically demonstrate and stud the existence of synesthesia. Tons of behavioral findings have demonstrated that synesthetic percepts behave like typical sensory percepts in attentional tasks, which established their perceptual reality.

In recent years, the focus has now shifted towards forming an explanatory framework for interpreting the various empirical findings. One difficulty in putting forward a complete framework is that there is a lack of knowledge concerning what is is about a synesthetes brain that is different from someone without synesthesia. For many years, synesthesia has been vaguely attributed to "crossed wires" in the brain. Despite sophisticated brain imaging methods (like fMRI and PET scannin), and substantial progress in neuroanatomy, the underlying mechanisms of synesthesia remain elusive. Several competing theories have emerged, with the main disagreement being whether the pathways implicated in synesthesia are unique to those with the disorder - indicating the presence of a structural brain difference - or if they are present in the normal population - indicating the presence of a functional brain difference. So, the question comes down to: extra wires or altered functioning?

If you're interested, check back for parts two and three, where I'll review some evidence for each of the sides of the debate!

For lots more information on synesthesia, including personal anecdotes, check out: http://www.mixsig.net/.

Hilary D. Duncan

Concordia University

"Parkinson's Disease: Working Towards a Cure" Part 3 -- Towards a Cure

2011-02-21T17:08:00.001-05:00

This is the third post from a three part series written by Andrew Greene, a graduate student at McGill University studying Parkinson's Disease.

Rather than giving a broad, but ultimately superficial overview of modern research in the field of Parkinson's disease I'll try to delve more deeply into one particular line of research that I believe holds great promise. It's important to keep in mind, however, that there are many other exciting avenues presently under investigation around the world that could prove more effective. It's also important to remember that much of the research I'll be discussing is still very new, and the interpretations that myself and others are drawing from it have not yet been firmly established as correct.
     Let's begin by taking a step back and recalling that the movement-related difficulties that afflict those suffering from Parkinson's are largely due to the death of a subset of brain cells (neurons) known as the dopaminergic neurons of the substantia nigra pars compacta. The ultimate goal therefore becomes finding a way to stop these neurons from dying, but to do that we first need to understand why they die. This has proven to be an incredibly difficult question to tackle, and the laboratory in which I'm conducting my research is just one of many around the world that are dedicated to it.
     Particularly puzzling is why these neurons, which I'll call SNc DA neurons for short, succumb when other groups of neurons remain healthy. The obvious answer is that they have intrinsic properties that make them different from other neurons, and this has led many labs to characterize SNc DA neurons in detail to try to find what makes them so special. James Surmeier's lab in Chicago has identified some particularly interesting attributes, which may very well contribute to the SNc DA neurons' selective vulnerability. Foremost among these is the heavy reliance of SNc DA neurons on an unusual type of calcium conductor called an L-type calcium channel. SNc DA neurons take in large amounts of calcium through these channels at regular intervals as part of their normal signaling processes. The problem is that despite calcium's important roles in bone formation and cell signaling it's actually quite toxic when too much of it accumulates within a cell like an SNc DA neuron (don't worry about drinking too much milk though, any excess calcium that you consume is stored in your bones, which makes them stronger and keeps the calcium out of sensitive areas; SNc DA neurons don’t take up so much calcium because the person they’re a part of is imbibing too much of the stuff, it’s simply a normal part of how they function). Because this calcium 'ingestion' is an ordinary part of an SNc DA neuron's second to second activity these neurons are equipped with miniature pumps that pump calcium out before it reaches toxic levels. However, these pumps require a massive amount of energy to power, and thus represent a heavy burden for the SNc DA neuron's metabolism. On top of this, SNc DA neurons each make approximately 370,000 output connections with other neurons, hundreds of times more than what most other neurons of the brain make. These output connections also require a massive amount of energy to maintain and operate, adding to the energetic burden imposed by the calcium pumps.
How is all this energy produced? Cells have internal organs much the way people do, and the organs responsible for using the combination of oxygen and food to produce a cell's energy are called mitochondria. Each cell has many mitochondria that work collectively to meet the cell's energy needs. Because SNc DA neurons have such high energy requirements their mitochondria have to work double time. This is problematic because mitochondria produce toxic chemicals called reactive oxygen species as by-products of their effort to supply the cell with energy. The harder the mitochondria are working the more reactive oxygen species they produce, and these toxic chemicals can go on to damage various elements of the cell, including DNA and the mitochondria themselves. This damage accumulates in SNc DA neurons over a person's lifetime, and can ultimately lead to the neurons' death.
     If SNc DA neurons produce so many toxic molecules you may be wondering why they don't die off in all of us as we age. In fact they do, and what separates a healthy elderly person from someone with Parkinson's disease is how many have died. You can be pretty much symptom-free with up to 80% of your SNc DA neurons gone, but once you lose more than that you start to have serious problems.
    So why do some people lose almost all their SNc DA neurons and get diagnosed with Parkinson's disease while others reach ripe old ages without even getting close to the 80% threshold? The answer to that is almost certainly quite variable. In some cases it appears to be due to exposure to certain toxins that damage mitochondria and/or enhance the production of reactive oxygen species. In other cases the problem lies with inherited mutations that may increase reactive oxygen species production or affect a cell's ability to survive them. In most cases it's probably a little of each.
      Classic examples of the kinds of mutations that can lead to inherited Parkinson's disease are those found in two genes called Parkin and PINK1. The vast majority of genes, including Parkin and PINK1, are encoded in your genomic DNA, which is contained in almost every cell in your body. The DNA itself is essentially just a set of instructions, and generally doesn't take an active part in the functioning of a cell. The instructions encoded in each gene usually allow for the manufacturing of a particular protein, and these proteins are what perform most of a cell's functions. For example, it's now well established that mitochondria produce energy thanks in large part to a collection of proteins that lock together to form a molecular machine known as ATP synthase. ATP synthase acts much like a hydroelectric power plant, except that instead of using the energy from water flow it uses the energy from protons flowing through a small opening in a fatty membrane, which acts as a dam. The flow of protons quite literally spins a miniature turbine contained within ATP synthase, and the energy from the spinning of many of these turbines is used to power the cell.
      The proteins encoded by the Parkin and PINK1 genes are not directly involved in energy production, but what's becoming increasingly clear thanks to a landmark study by Richard Youle's lab in Washington is that they act together to perform a quality control function for mitochondria. As I mentioned earlier, one of the elements of a cell that can become damaged by reactive oxygen species is the mitochondria themselves. When mitochondria are damaged they often become less efficient and wind up producing more reactive oxygen species by-products, which can further damage themselves and the cell. The cell has mechanisms to repair mitochondria, but when mitochondria become so damaged that it's impossible to fix them they have to be eliminated to prevent them from running wild in their reactive oxygen species production. The Parkin and PINK1 proteins are responsible for identifying heavily damaged mitochondria and flagging them for a process called autophagy (literally meaning 'self-eating'), in which the cell destroys the defunct mitochondria and recycles their components.
   This is all well and good, except in people in whom Parkin or PINK1 are mutated. Mutations are errors in the DNA instructions, and they can result in the production of defective proteins. The mutated PINK1 and Parkin proteins that are found in Parkinson's patients are unable to perform the mitochondrial quality control survey undertaken by their healthy counterparts, which causes damaged mitochondria to accumulate. These damaged mitochondria function less efficiently and thus produce more reactive oxygen species by-products, putting more stress on cells. This is particularly detrimental for SNc DA neurons since, as discussed earlier, they are already heavily burdened in this department. Losing mitochondrial quality control processes probably explains at least part of why people with grave mutations in Parkin or PINK1 almost always get Parkinson's disease, usually at an abnormally young age.
    While the molecular and cell biology described so far is interesting in its own right, it also serves a critical role in designing treatments for Parkinson's disease. Since we are beginning to understand what might be killing SNc DA neurons we can identify ways to protect them. Anti-oxidants that soak up reactive oxygen species could be a good start, but there are others. For example, drugs that can enhance the mechanisms that eliminate defunct mitochondria may be able to reduce the production of reactive oxygen species in SNc DA neurons (and other cells) and thus slow the progression of the disease. Another promising therapeutic avenue is forcing SNc DA neurons to stop relying on the L-type calcium channels, thus reducing their energy requirements and corresponding production of reactive oxygen species. This has already been shown to work well in mouse models of Parkinson's disease, and will probably move into clinical trials in the near future.
    As I emphasized in the beginning, what I've described here is only a glimpse of some of the exciting discoveries that are being made in the field of Parkinson's research. There are now many competing theories to explain why SNc DA neurons die in Parkinson's disease, and time may prove one of them to be the most accurate. It seems more likely, however, that several of these theories are correct and there are a multitude of factors that contribute to SNc DA neuron death. The best treatment will thus probably not come in the form of a single drug, but rather a mix of molecules designed to protect SNc DA neurons from the various threats they face over the course of a person's lifetime.

Brains need love too

2011-02-14T22:06:00.003-05:00

I recently saw the new ad campaign from the institute where I work (the Douglas Institute), ‘Brains need love too’. Seeing as the campaign touches on brain awareness-related topics (including the brain's involvement in psychiatric illness), as well as today being Valentine’s Day, I thought it deserved sharing. The video is extremely open-ended, with the actual message of the campaign open to the interpretation of the viewer, at least until they visit the campaign’s web site. Here are the initial interpretations I took away from it:

- Psychiatric conditions are neurobiologically based, as implied with the opening shots of brains labelled by psychiatric diagnosis. I’m assuming the reasoning behind this is that it has traditionally been believed that stigma against mental illness could be ameliorated in the general public if it was more widely known that mental illness is fundamentally due to the structure and function of the brain itself, as opposed to any personal weakness of afflicted persons themselves. Although it’s noble to attempt to combat stigma by replacing popular misconceptions with fact, however, recent studies showing that stigma against mental illness persists even in the face of improvement of the public’s understanding of the origins of mental illness sadly cast doubt on the effectiveness of this particular strategy.

- People are more than their labels, another anti-stigma message. Outside of its labelled container, the brain reveals it’s capable of experiencing life just like anyone else.

- Take care of your brain, not meant as an anti-stigma message but more of a suggestion that all of our brains, well, ‘need love too’. Speaking of which, Brain Awareness Week is coming up in the near future, so get involved if you need some spring brain-awareness-lovin’. I’m assuming the figurative message here is to be aware that your brain needs care, if not by skateboarding and psychedelic brain-tossing, then by nutrition, exercise, mental stimulation, paying attention to your mental and emotional functioning, and not-sniffing-glue-or-opening-doors-with-your-head-or-something. They’re pretty vague on this one.

Overall, it’s charming and cute, and I like the bold approach of using real (albeit calf) brains up-close and bloody to show that something that may seem disquieting to us (in this case, a bloody brain) is capable of experiencing cognition, emotions and the world around us. Similarly, although mental illness can be disquieting to those with a stigma against it, psychiatric patients are fully capable of these same experiences. Also, regarding the brain images, I feel obligated to point out that we’re talking about something we’ve all got, which is processing this sentence right now within your own head, and while you don’t necessarily have to realize how cool that is, you should at least try to get over your squeamishness over the look of your own brain. It is, after all, what ‘you’ really look like.

It’s a bit difficult to determine the overarching message of the campaign from the 62-second ad alone; it does seem to be necessary to go to the campaign website for clarification, where there’s a slightly vague description urging people to take care of their brains and, more usefully, a list of diverse resources for information on the brain as well as psychiatric disorders and treatment. However, despite this it’s a well-produced and genuinely endearing ad. So go love your brain.

-Ian Mahar

(Adapted from a post previously appearing here)

"Memory, Aging and Alzheimer's: When forgetting too much becomes a problem"

2011-02-14T18:44:00.002-05:00

Although our brains produce new neurons throughout our lives, their overall number peaks in our early twenties and then gradually declines as we age. Certain forms of memory tend to get worse with age as a consequence. Episodic memory in particular is often weaker in the elderly, making it more difficult to remember where a car was parked, or what time a friend was supposed to arrive for dinner. The good news is that other types of memory such as semantic (remembering general facts and concepts) and procedural (remembering how to do something) memories remain robust in most people well into their later years.

Unfortunately this is not the case for people suffering from an increasingly well-known disorder called Alzheimer’s disease, which severely impairs normal memory. Alzheimer’s is the most common example of a spectrum of disorders known as neurodegenerative diseases, all of which cause neurons to die off more rapidly than they would with normal aging. The prevalence of Alzheimer’s increases dramatically with age, rising from just 3% in those aged 65-74 to almost 50% among those 85 years and older.

Currently available treatments tend to focus on minimizing the symptoms of Alzheimer’s by compensating for the loss of neurons. Some of these therapies can be helpful, but scientists have not yet found a ‘cure’ for Alzheimer’s, i.e. a treatment that would actually slow or halt the neuronal loss. This is because it’s still not entirely clear why neurons die in Alzheimer’s, although thousands of laboratories across the world are bringing us closer to the answer every day. We can hope that several of the many promising therapeutic avenues currently under investigation by scientists in Montreal and elsewhere will one day provide an effective means of combating the disease for both present and future generations. (Andrew Greene, McGill University)

All are welcome to join us on Wednesday, February 23rd, at 7:00 pm at La Sala Rossa (4848 boul. St-Laurent, Montreal, QC, H2T 1R6) for an evening of questions and answers, as we discuss memory and aging with world-class experts Andrea Leblanc, Ph.D., Serge Gauthier, M.D., F.R.C.P.C., and Judes Poirier, Ph.D., C.Q. Refreshments will be provided. This is a free event! We hope to see you there!

for more information: http://sfn-montreal.ca/baw/cafe/

http://www.facebook.com/#!/event.php?eid=183243215043955

hosted by BAW Montreal as part of our 2011 Brain Awareness Week public events.

Thank you to our sponsors .

*** Our popular Science Cafés offer the public the opportunity to meet and discuss various topics in Neuroscience in an informal setting. These Cafés feature a Question & Answer with three to four guest panelists who are experts in their fields, snacks and entertainment. Our Cafés are always free thanks to our sponsors. ***

Monogamous cheaters

2011-01-12T22:59:00.003-05:00

In my previous post I wrote about vasopressin and oxytocin, so-called “love molecules” that promote attachment and pair-bonding in voles and humans. These molecules act on receptors found in the dopamine-reward system to enhance the dopamine “pleasure” response thereby re-enforcing monogamous activities. However, socially monogamous voles, like humans, are prone to “mistakes” or “slip-ups” with males and females frequency engaging in uncommitted sexual behaviors. Indeed, using genetic testing of offspring, researchers have found that many of the species first thought to be “monogamous” like birds and gibbons actually participate in extra-pair copulations. It’s now more exciting to find a species that is actually sexually monogamous (such as the recent discovery of a monogamous frog). Evolutionarily speaking this is not surprising; we want to get it on with as many people as possible to pass on our genes and increase genetic diversity, while at the same time having enough resources to take care of our young. Therefore, it is possible that two competing systems co-evolved in humans: one that promotes monogamy (vasopressin, oxytocin and others) and another previously uncharacterized system that promotes sleeping around with as many people as possible. This predicts that our tendencies towards infidelity and sexual promiscuity could also be genetically encoded.

Is unfaithfulness really all in the genes? A new study published recently in PLoS ONE suggests that it might be, at least in part. The authors linked a certain variant of the dopamine D4 receptor gene to the propensity towards one-night stands (but not the actual number) and the number of sexual partners in those that were unfaithful (but not to unfaithfulness per se, although there was a trend towards significance). Interestingly, people with this variant have less dopamine D4 receptors in the reward centers of the brain and these receptors show less binding to dopamine, suggesting that these individuals might need more dopamine floating around to reach the same feel-good mood. It’s not a surprise then, that this variant has also been associated with a slew of other behaviors that increase dopamine release including addictions, risky behavior and novelty-seeking.

So, what does this mean? The authors are careful to point out that the dopamine D4 receptor gene should not be labeled the “cheating gene” or the “promiscuity gene” (although it already has) since having the variant does not necessarily mean that you will sleep around or be unfaithful. Many other genetic, environmental (alcohol) and cultural influences are likely to play into an individual’s decision to sleep around or cheat. In addition, the variant may be associated with a third confounding variable like being more honest about sexual behavior, more attractive, etc. Or it may simply be associated with risky behavior and novelty-seeking, increasing the likelihood of wanting uncommitted sex.

For now, I’d hold off on sending your significant other for genetic testing.

Part 3 of 3: Stress and the Aging Brain

2011-01-03T23:21:00.004-05:00

Perhaps where we see the most extensive effects of stress on the brain is in adulthood and into older age. In rats, it has been discovered that acute and chronic stress can have very different effects. An acute stressor (ie. something that only lasts for a short period of time) actually enhances learning and memory, up to a certain point, beyond which too much stress causes performance to deteriorate again. A state of chronic stress, however, has been shown to have very negative effects on the brain. Specifically, in rats, chronic stress has been associated with a shrunken hippocampus, specifically because dendrites in the hippocampal neurons begin to die off. These rats also perform more poorly on memory tasks, especially those involving spatial memory.

In fact, if you expose a middle-aged rat to high levels of glucocorticoids, it will perform cognitive tasks similar to the way that a rat in old age would perform them, while reducing glucocorticoid levels in an old rat will enhance its performance. So, could chronically high glucocorticoid levels contribute to the cognitive decline (memory and word-finding difficulties) that we know happen as we age? Could they have anything to do with Alzheimer's Disease (AD), a disease characterised by both poor memory and reduced hippocampal volume? The answer so far is that we're still not sure, but more and more evidence is suggesting that there is at least a correlation between chronic stress, a smaller hippocampus and the prevalence of Alzheimer's. In monkeys, higher glucocorticoid levels have also been shown to increase Beta-amyloid in the brain, a protein that's known to be a precursor to the cell death seen in Alzheimer's Disease.

But why is this? If you remember back to my first post about stress and the brain, I said that the hippocampus is one of the main mechanisms by which the HPA axis gets shut down. If you have more and more glucocorticoids, you see hippocampus shrinkage. This means that there's less and less hippocampal tissue to shut down the HPA axis, leading to chronically high glucocorticoid levels and consequently, a chronically shrinking hippocampus. It's a feed-forward mechanism. There's also the neurotoxicity hypothesis, which says that a lifetime of dealing with chronically high glucocorticoid levels may cause the hippocampus to be less able to deal with other aspects of normal aging and therefore its cells are more easily damaged and die off.

Don't panic yet. There's no need to stress out about how your brain is responding to your stressful life. You're not doomed to an ever-dwindling hippocampus. It turns out that if you remove a chronic stressor, dendrites that had previously disappeared are actually able to grow back. Obviously removing every stressor from our lives isn't likely to happen, so there are a few other minor changes that we can make to help us along. Interestingly, one of the few things that we can do in order to grow new neurons (called neurogenesis, a phenomenon that neuroscientists only came to believe in fairly recently) is exercise. Exercise has been shown to especially increase neurons in…wait for it…the hippocampus. How convenient is that? As if we needed another incentive to stick to our 2011 resolution to hit the gym!

Cristina McHenry

Concordia University

Adapted from "Effects of Stress Throughout the Lifespan on the Brain, Behaviour and Cognition" by Sonia Lupien et al. and inspired by Wayne Brake's Neuropharmacology course at Concordia University.

Part 2 of 3: Stress and the Adolescent Brain

2010-12-29T16:48:00.003-05:00

Research is indicating that the adolescent brain is particularly sensitive to the effects of high glucocorticoid levels and therefore to stress as well. During the teenage years, there appear to be high levels of glucocorticoid mRNA (a chemical that comes from DNA and encodes a type of blueprint for the creation of a specific type of protein) in the prefrontal cortex, which is an area that also undergoes development during this time. This suggests that the functions that this part of the brain is responsible for, mainly cognition (reasoning, thinking, planning, sequencing, judgement, etc.) and emotion, are heavily affected by glucocorticoids and therefore by stress. Many forms of psychopathology like depression and anxiety show up in adolescence, often following a period of particularly severe stress. So all of this information is basically another way of saying that teenagers' emotions and decision-making abilities are prone to fluctuate according to any tiny little outside event…which we probably didn't need a neuroscientist to tell us, but now we know why!

Interestingly, although the prefrontal cortex is greatly affected by stress, it seems that the hippocampus is spared in this period. This is likely because the hippocampus finishes developing around 2 years of age. Children who suffered abuse through late childhood and early adolescence did not show a decrease in hippocampal volume in adolescence, although interestingly they do show this decrease later on in adulthood. More to come in my next post about what happens to the stressed brain as we age!

Adapted from "Effects of Stress Throughout the Lifespan on the Brain, Behaviour and Cognition" by Sonia Lupien et al. and inspired by Wayne Brake's Neuropharmacology course at Concordia University.

Cristina McHenry

Concordia University

Stress and the Brain: Part 1 of 3: The Stress Response

2010-12-29T16:13:00.003-05:00

When the brain detects any kind of threat or stress, it sets a coordinated system into motion to counter the stress. This is the stress response, and it involves autonomic, neuroendocrine, metabolic and immune components. One of the most studied stress systems is the HPA (hypothalamic-pituitary-adrenal) axis. To start off this component of the stress response, neurons in the hypothalamus release CRH (corticotrophin releasing hormone). This then causes the pituitary gland to release ACTH (adrenocorticotropic hormone) into the circulatory system. ACTH travels in the blood to the adrenal glands, which sit just above the kidneys, causing them to release glucocorticoids such as cortisol into the circulatory system.

Back in the brain, in an area called the hippocampus, there are receptors for these glucocorticoids, unsurprisingly called glucocorticoid receptors (GRs). Once the stress has disappeared, glucocorticoids are supposed to bind to these receptors, which then function to shut down the hypothalamus, pituitary gland and ultimately the adrenal glands, putting an end to the stress response and returning the body to homeostasis. Unfortunately, this system can go awry with chronic or particularly severe stress.

Prenatal/Infant Stress and the Brain (check out my next 2 posts for Adolescent Stress and the Brain, as well as Stress and the Aging Brain)

When pregnant moms-to-be are stressed, some of their glucocorticoids pass through the placental barrier and reach the fetus. A certain level of glucocorticoids is required for proper nervous system development since they remodel the axons and dendrites of neurons and affect cell survival. However, high levels of glucocorticoids have negative effects on brain development and later functioning. Rats exposed to prenatal glucocorticoids have fewer receptors in the hippocampus later in life. As I said before, these GRs function to shut down the stress response. So if there are fewer GRs present in the hippocampus, the stress response is not shut down as effectively, leading to higher than normal levels of glucocorticoid activity later on (more on why this is important in the section on Stress and the Aging Brain).

Higher prenatal glucocorticoid levels have three main effects on adult behaviour: learning impairments, greater sensitivity to drugs of abuse and increased anxiety and depression. The learning impairments in particular are thought to be caused by the changes in the hippocampus, while drug sensitivity and anxiety/depression are thought to be caused by changes in the amygdala.

In infancy and early childhood, the brain is surprisingly hyposensitive to stress. Certain things can still affect brain development, however. Good parenting actually results in a small decrease in the stress response to everyday occurrences (which is a good thing). However, in cases of extreme deprivation, the HPA axis becomes seriously underactive, possibly due to a downregulation in the pituitary. Basically, the hypothalamus releases so much CRH that the pituitary can't handle it anymore and gives up trying. Remember that a certain level of HPA activity is needed in order for neurons to develop properly. Luckily, this severe reduction in HPA activity can be fixed after a mere 10 weeks of proper care.

Stay tuned for Parts 2 & 3!

Cristina McHenry

Concordia University

Adapted from "Effects of Stress Throughout the Lifespan on the Brain, Behaviour and Cognition" by Sonia Lupien et al. and inspired by Wayne Brake's Neuropharmacology course at Concordia University.

Electricity and the brain

2010-12-19T19:11:00.000-05:00

Part 3 of 3 : Electric currents that create the action potential

The negative voltage of the neuron attracts the positive charges on the outside, but they can not enter the neuron because the neuronal membrane prevents them. That is when another group of proteins steps in. These proteins are sensitive to the voltage of the neuron (voltage-dependent ion channels). They are specific for a single atom, have a structure that reminds us of a tube with a door that opens when a certain potential is reached. Thus, when a neuron receives a stimulus (from the 5 senses or another neuron), there is a fluctuation of the neuron’s resting potential (Figure 4). If a specific potential is reached, the voltage-dependent proteins door opens and lets in the positive charges. This movement of charges is an electrical current that can be measured in amperes, usually on the order of picoampere (10^-12 ampere).

When we think of brain electricity, there are two very important voltage-dependent channels: sodium channels (Na) and potassium channels (K). When the neuron is depolarized so as to achieve a certain potential (threshold potential), these channels open and let their specific atoms (ions) go through (Figure 4). Note that sodium channels have faster kinetics (open faster) than potassium channels ; they will open first, sodium will quickly enter the neuron and there is then an increase of positive charges inside the neuron, up until the sodium channels close. At that time, the voltage in the neuron rises to about 40millivolts (mV). Then the potassium channels come into play. They allow potassium ions to leave the neuron to eliminate the positive charges inside the neuron and allow the neuron to come back to a negative voltage. This very fast sequence of opening and closing is called the action potential. This action potential will develop in the neuron cell body and spread along the axon like a wave in water until it reaches the end where it can communicate with another neuron, allow muscle contraction, allow the release of hormones, etc..

Eric Trudel

McGill University

Electricity and the brain

2010-12-19T19:09:00.000-05:00

Part 2 of 3 : The neuronal membrane and the establishment of neuronal voltage

The "walls" of neurons (neuronal membrane) are composed of special fats that totally separate the interior of the neuron from the outside. If we take these special fats and place them in the tank mentioned above, they will spontaneously form a sphere with a uniform distribution of minerals (those previously dissolved in the aquarium in part 1) inside and outside the sphere (electrically neutral). We then have a draft of a neuron.

The neuronal membrane contains several proteins that distinguish neurons from all other cells. One group in particular, called pumps or exchangers, transfers one or more atoms to the other side of the membrane (Figure 3). Therefore, if we introduce this group of proteins in the membrane of the example of the aquarium above, one group of proteins will be responsible for removing the sodium atoms inside the neuron, another group will be responsible to concentrate potassium atoms inside the neuron, etc. (Table 1). The net result will be a decrease of positive charges (Na +, Ca2 +) inside the neuron and the inside will be negatively charged, thus forming a potential difference (about -60millivolt) ; this is called the resting potential.

Eric Trudel

McGill University

Sight Recovery and it's Discontents

2010-12-07T20:02:00.001-05:00

Many of us take for granted that we have the ability to see the world around us. Vision is an invaluable sense that leads us to make dozens of behavioural decisions every second. Historically, the fate of individuals blinded since childhood due to accident or congenital diseases were destined to never see again.

Although these procedures are rare, there are methods which can restore their sight. For example, corneal graft transplantation involves removing the cornea from a deceased donor and surgically placing it onto the eye of a blind patient after removing the unusable cornea. Another technique is corneal stem cell transplantation. Limbal stem cells (immature epithelial cells) from healthy corneas are removed and cultured into a new cornea in ex vivo. And now, new research in the field of bioenegineering is investigating the use of synthetic corneas made from complex polymers.
The ability to give someone their sight back is extraordinary. However, regaining vision after decades of blindness may not always be a happy or easy experience. There are two sight recovery cases which demonstrate the powerful effects of vision restoration.

Patient SB has become a famous case study in vision research. He was blind from age 10 months due to complications with a smallpox vaccination. At the age of 52, he received a corneal graft operation to restore his sight. SB thought that vision would be positive and life-altering. However, when his surgical recovery was complete and the bandages came off, he was ultimately "disappointed in what he saw." SB went from being a successful blind person to an unsuccessful sighted individual. Although it is hard to understand if you have not experienced it, vision can be a shocking and confusing blur (no pun intended!).

If you are not accustomed to that level of mental stimulation, the variety of information as well as the sheer quantity of input we get from sight is very overwhelming. Your brain needs to essentially learn to see. Therefore, patients like SB need to be given the proper psychosocial support in order to function and mentally adjust to their drastically different lives. Unfortunately for SB, he did not receive adequate support to help him through this transformation. Within two years of regaining his sight, SB became clinically depressed and died after catching a brief illness. SB was simply not ready to handle his new sensory modality.

This story, greatly contrasts that of patient M.M. who lost his sight due to a chemical accident at the age of 3. When M.M was 43 years old he got a stem cell transplant to restore his sight. M.M very much enjoyed living in the visual world, adapted well and continues to master his new abilities. An important lesson to learn from these two cases is that it takes a long time for the brain to get used to processing this new kind of information. Furthermore, it takes motivation and patience to handle such drastic changes to daily life. More generally speaking, gaining back any sort of key ability (not just vision) is intense and it is not always an easy process to endure. It is important to judge the expectations of the patient as well as provide a solid network of coping strategies in order to facilitate a functional recovery. As scientific research finds new and inventive ways to cure physical disabilities, psychological resources are needed for an effective recovery. It should be seen as essential as the medical procedure itself.

Lisa Kirsch
McGill University

Out of Sight, Out of Mind, but Not Entirely Out of Order: What Cortical Blindness Reveals about Consciousness

2010-12-07T13:55:00.004-05:00

Everybody knows that our thoughts are linked to our brains in some way. We say things like "Use your brain!" to encourage people to think things through, or "Can I pick your brain?" in the hopes of gaining thoughtful insight from a friend. But while we take it for granted that our thoughts – our very consciousness – is a product of our brains, centuries of scientific evidence was collected before this idea worked its way into our everyday language. One of the most fascinating demonstrations of the principle that our brains generate our conscious experience comes from the frontiers of neuropsychology, with a curious syndrome called “blindsight.”

Blindsight is a strange phenomenon - an oxymoron! Surely, there can be no such thing as “blind” sight. How could an individual see and be blind at the same time?

Remarkably, such a phenomenon does exist in a population of individuals who are cortically blind. This form of blindness occurs when there is tissue damage to the main visual area of the brain - the primary visual cortex, or “v1.” V1 lies at the very back of the brain and is fundamental for visual experience. While our eyes receive light signals from the world around us, v1 interprets those signals to generate what we experience as “seeing.” Individuals with cortical blindness have properly functioning eyes, but their v1 is damaged.

For at least a century, doctors knew about cortical blindness, and they assumed that it resulted in the same visual impairment as ordinary blindness – the inability to see. But roughly 35 years ago, it was discovered that cortically blind patients were able to do things that ordinarily blind individuals could not. A series of carefully designed studies in the 1970’s revealed that cortically blind patients were able to point to the location of objects and distinguish between various shapes, all the while claiming that they could not see the objects they were locating or the shapes that they were discriminating! At the time, the discovery transformed the way scientists understood vision and generated much speculation about the nature of consciousness.

Why consciousness?

Blindsight tells us something about consciousness because the syndrome revealed that cortically blind patients are not really blind; they are just unaware of what they see.

We now know that vision is the product of the unified effort of many different brain networks, each specializing in a particular aspect of our visual experience. Like a machine, the brain has many different wires traveling back and forth between different locations. These brain wires (i.e., neurons) carry information that gives rise to specific mental states and behaviors. In our visual brain, some of these networks specialize in recognizing faces; others specialize in recognizing colors, and still others are used for interpreting the lines and curves that comprise letters and familiar objects.

At a more basic level, the visual pathways of the brain can be reduced to two main networks: One pathway connects our eyes to v1, and a second pathway connects our eyes to a region of the brain that controls movement. While the first pathway is fundamental for our visual experience, allowing us to see the rich detail in our environment, the second pathway is more primal, allowing us to respond reflexively to sudden movement even before we are fully aware of what we have seen. This second pathway bypasses v1 and serves a motor, rather than a visual, function. It allows you to flinch in response to something flying in your direction, even if you are not aware of the projectile. It also helps your direct your gaze to something important, like a car moving towards you.

In blindsight, the pathway responsible for visual experience is damaged, but the pathway that coordinates movement in response to objects in our environment is preserved. Thus, although individuals with blindsight cannot see, they can respond reflexively to a sudden movement.

Blindsight provides evidence that the brain is responsible for our conscious experience because damage to the brain tissue of v1 diminishes visual awareness. Individuals with blindsight can still process what they see in important ways. Through the non-visual, reflexive pathway, they can identify the location of objects, avoid obstacles in their path, and direct their gaze to moving objects. What they lack is the awareness of the objects they are locating and the obstacles they are avoiding – it is their very visual consciousness that is impaired as a result of damage to v1, and therefore, v1 is crucial for such consciousness.

-Levi Riven

Female Mice Hot for Guys Who Cry

2010-12-02T15:15:00.003-05:00

Attempts at mixing up love potions go back at least to Tristan and Isolde, but since the discovery of pheromones it has become increasingly clear that many animals have only to look to their armpits - and an assortment of other glands - for an irresistible concoction of their own. Pheromones are small molecules that animals release into the air, and when another animal of the same species detects them, the pheromone will cause a specific social behavior – perhaps most notably, an increase in sexual receptivity. While many people are excited by the prospect of chemicals that might improve their sex lives, pheromones make neuroscientists randy for another reason: they represent an opportunity to dissect how the brain works. As far as we can tell, the brain is a huge network of smaller circuits. This means that to do things like control movement and store memories, the brain relies on circuits of nerve cells that communicate with one another to store info or output some kind of behavior. Presumably, the behavior associated with a pheromone relies on a specific neural circuit that is activated when a pheromone is detected by an animal. So, once a pheromone is isolated, you can use it to search out the neural circuit in the brain that is responsible for the behavior; just spray the chemical into the air and watch for a change in behavior of the animal you are studying. Theoretically, experiments like this may help determine exactly how small sets of nerve cells generate behavior. This is a big deal, because although we think small circuits run the brain, we know surprisingly little about the details of how these circuits are wired up.

This summer, a Japanese group in pursuit of a circuit to call their own published a study examining the role of a potential pheromone called ESP1 in sexual behavior of female mice. ESP1 has a quirk, though: it is released in the tears of male mice. Although tears and sex may seem an unlikely pairing to us humans, previous results suggested that ESP1 might be a sex pheromone. Besides, it would be the smell of the tears, not the look of them, causing the excitement. Banking on this, the group characterized ESP1, the proteins that detect it (its receptor) and the nerve cells that use this receptor to tell whether ESP1 is present in the air. By sticking electrodes up a female mouse’s nose, they found that ESP1 sprayed in the surroundings causes electrical responses in neurons of the vomeronasal organ - long thought to be solely responsible for pheromone detection. This organ contains a number of small populations of neurons that respond very specifically to single pheromone types. The group confirmed that ESP1 was indeed responsible for the electrical activity by testing mice whose ESP1 receptors were non-functional. As expected, females without functioning receptors showed no activity in their vomeronasal organ when exposed to ESP1.

The electrical activity in the ESP1-detecting neurons is likely relayed further into the brain to control sexual behavior by activating a neural circuit. To check this, the group exposed normal females and females with non-functional ESP1 receptors to ESP1, introduced them to male mice and watched the magic unfold. Normally, female mice play hard-to-get, and rightly so: although mouse courtship begins with the suitor chasing his crush around like we all used to do in the school yard, he quickly jumps straight to 3rd base, attempting “anogenital investigation.” He then immediately tries to mount – romance has apparently been dead in the mouse world for quite some time. When the female is finally convinced by his wares she initiates lordosis, a perhaps not unfamiliar backward curvature of the spine, facilitating the entry of the penis into the vagina. Females exposed to ESP1 before males were introduced were almost 5 times more likely to initiate lordosis and allow mating than those not exposed to ESP1, while the mutant females, who had no ESP1-evoked activity in their vomeronasal organs, were no more likely than unexposed females. Although most of these experiments were done by exposing the females to purified ESP1, the researchers also compared female responses to males who had ESP1 naturally in their tears and those who didn’t. The results weren’t quite as strong as with purified ESP1, but males who had ESP1 were more successful in their quest.

Although the exact circuitry involved in the sexual behavior has yet to be studied in depth, one thing is clear: female mice are turned on by the smell of tears in their man’s eyes. I wouldn’t count on crying as a go-to pick up line though; humans do respond physiologically to pheromones, but where in the brain and how we detect them is still a mystery, and anything similar to ESP1 has yet to be found in human tears. For now we should either get the good stuff by mail or keep counting on our armpits. (Two for one: the latter is apparently good for the environment.)

What rodents are telling us about human behavior and autism

2010-12-02T15:11:00.002-05:00

A tales of two voles

Prairie voles are extremely social creatures, preferring to spend the majority of their time with other prairie voles. In contrast, the closely related montane voles are extremely asocial creatures, choosing a solitary lifestyle over one where they’d have to be tied down. Eerily, prairie voles and humans share many other social behaviors: after a male and female prairie vole decide to spend the night together, they fall madly in love (called pair-bonding), move into a shared nest and raise their children together (‘Till death do us part: 75% of prairie voles stay together until one partner dies). Like with humans, affairs are fairly common, jealousy is rampant and some males (>40%) just never settle down (known in the field as “wanderers”). Prairie voles are even known to enjoy an alcoholic drink every once in a while. With these similarities, it’s no wonder the prairie vole has been the model system of choice to study the physiological basis of social behavior, and why the montane vole has served as the perfect “asocial” control.

Researchers have focused much of their attention on the role of two neuropeptide hormones, oxytocin and vasopressin, in mediating these social behaviors. Oxytocin and vasopressin are well-known regulators of peripheral tissues involved in birth, lactation and water homeostasis. However, their receptors (the cell-surface molecules which bind to these hormones and transmit their signals to the inside of cells) are also found scattered throughout the brain. Turns out, these hormones are also released by prairie voles when they “spend the night”, suggesting that these hormones may induce the post-mating behaviors of prairie voles: partner preference, aggression towards intruders and parental care (characteristics of social monogamy… referred to as monogamy for the rest of the article). Indeed, researchers can induce partner preference and aggression in virgin male prairie voles by injecting them with vasopressin and can block these behaviors by blocking the vasopressin receptor during mating. The same can be done in female prairie voles, except with oxytocin and an oxytocin receptor blocker, reflecting gender-specific differences in how these hormones affect social behaviors. Only thing is, montane voles also release oxytocin and vasopressin following mating and giving them additional vasopressin fails to induce monogamy—what then results in the difference in post-mating behaviors seen between prairie and montane voles? Surprisingly, when researchers looked at the brains of montane and prairie voles, they found striking differences in the location of vasopressin and oxytocin receptors. Prairie voles had more receptors in the ventral pallidum and nucleus accumbens, areas associated with reward and reinforcement, whereas montane voles lacked receptors in these areas. Importantly, other monogamous species, such as marmosets and California mice, show a similar distribution of receptors to the prairie voles. These results suggest that monogamous species may perceive social attachments as pleasurable and rewarding, therefore reinforcing these behaviors, whereas these behaviors are not reinforced in non-monogamous species.

Of course, the goal of all these studies is to understand and possibly treat some human behaviors. Autism can be a particularly devastating neurodevelopmental disorder characterized by severe social deficits such as lack of eye contact, empathy and social attachment. It is therefore not surprising that researchers are looking to see whether oxytocin and vasopressin are dysregulated in autistic patients. Indeed, some cases of autism are associated with reduced levels of circulating oxytocin or complete deletion or mutations in the oxytocin or vasopressin receptor genes. Can administration of oxytocin or vasopressin help with the symptoms of autism? Surprisingly, administration of oxytocin to humans increases social behaviors such as eye contact, trust and empathy and reduces social anxiety. Initial trials with oxytocin and high-functioning autistics showed improvements in their ability to make eye contact and other social behaviors. Therefore, although a link between autism and the oxytocin or vasopressin systems is tenuous and much research remains to be done, research on voles may surprisingly hold the key to understanding human social and asocial behaviors.

For more information:
Oxytocin, vasopressin and autism (free full-text): http://rstb.royalsocietypublishing.org/content/361/1476/2187.long

Those binge-drinking voles:
http://www.oregonlive.com/health/index.ssf/2010/07/voles_a_party_animal_sheds_lig.html

Certiorari emptor; on informal routes of public science education

2010-11-27T14:44:00.005-05:00

A recent editorial by Dr. Royce Murray, editor of the journal Analytical Chemistry, has garnered significant attention in its attacks on informal dissemination of scientific information to the general public. Given that public education of science is a relevant topic to this blog, I thought it merited a response here.

The basic premise is that the only trustworthy sources of scientific information that can be given to the general public are peer-reviewed journal articles and a small number of established news sources, the latter of which Dr. Murray correctly admits are faltering. To distill his point further, he doesn't like the rise of scientific blogging.

I readily agree that, "The picture of scientifically grounded innovations feeding progress in science is well established. I firmly believe that this system has served science well and that the scientific literature has provided generally reliable information and vast benefits to society over the centuries to the present and will continue doing so into the future." It's true that this information should reach the public for many reasons, including that it protects the public, reduces stigma and susceptibility to pseudoscience, influences public policy, and fosters a sense of scientific wonder in prospective scientists and non-scientists alike.

However, I reject the premise underlying his statement that, "...editors and reviewers reinforce the meaningfulness of Impact Factors by explicit attention to the reliability of submitted articles; if the Scientific Method has not been adequately followed, then there should be a downwardly adjusted evaluation of impact." This is a misrepresentation of impact factor, the measure of how frequently a journal's articles are cited relative to the number it publishes. Impact factor does not measure the extent to which an article follows the scientific method whatsoever; it is more an index of how novel and important, on average, an article published in a particular journal is likely to be, as assessed by how frequently other scientists refer to it in their own articles. The principles of impact factor, far from applying only to peer-reviewed sources, apply just as accurately to informal sources, in that their quality and novelty determine their audience and are reflected by how frequently they are referred to and discussed.

More importantly, it's false to say that the optimal venue for dissemination of knowledge from scientist to layperson is necessarily a published journal article. Scientific articles are not accessible to the general public, even to those members that actively seek them out; restrictive language and jargon, in tandem with prohibitively high costs for accessing articles, prevent access to anyone aside from university-affiliated experts in the respective fields, which defeats the entire concept of limiting the scientific information available to the public to peer-reviewed articles.

In agreement with Dr. Murray, I'm not a fan of the word 'blogger' or its derivatives, but I fear by his attempted definition that he does not understand the term, in that he assumes their primary motivation is to be "entrepreneurs who sell 'news'". This blatantly overlooks the fact that the vast majority of the population he attempts to describe act not out of personal financial gain but rather out of an altruistic desire to educate, and this is especially true of scientific writers in this medium.

Dr. Murray warns, 'caveat emptor'; let the buyer beware, as communication through informal channels increases the risk of malicious misinformation. I propose an alternate viewpoint. Certiorari emptor; let the consumer of these media be informed. This is the ultimate goal of those who seek to educate regardless of medium.

References:

Murray, R. 2010. Science Blogs and Caveat Emptor. Analytical Chemistry 82: 8755.

- Ian Mahar

(Adapted from an article originally appearing here).

Electricity and the brain

2010-11-27T13:05:00.001-05:00

Part 1 of 3 : Ions

Most people know that the brain uses electricity to operate. However, what most people do not realize is that the electricity produced by the brain is different from the one produced by batteries or the companies that provide electricity to your home. Indeed, the source of electricity in these examples comes from chemical reactions or from natural resources. This electricity is then routed to your house, for your use, by transfer of electrons between metal atoms that make up the electrical wiring. We can thus define electricity as a movement of electric charges between a potential difference or voltage. However, the brain uses a slightly different system to generate and propagate electricity. Some basic concepts are needed before we can understand how brain cells (neurons) generate electricity in their cell body and propagate it along their axons (Figure 1).

Matter can be divided into basic elements called atoms. Calcium, sodium, potassium and chlorine are examples of atoms. Table salt contains mostly sodium chloride, that is a sodium (Na) and a chloride (Cl) atom. If the two atoms are to be held together, each atom carries a charge (sodium has a positive charge and chloride has a negative charge). Since each atom has an opposite charge, they attract each other, much like the poles of two magnets. However, the forces that attract these two atoms are weak so that when you put the salt in an aquarium filled with water (Figure 2), atoms dissociate to form ions, a positively charged sodium (Na +) and a negatively charged chloride (Cl-). The atoms then diffuse so as to be uniformly distributed in the aquarium. It must be noted that although the atoms of the salt are dissociated and they are charged, the aquarium is electrically neutral (as much positive charges as negative charges).

Adding other specific components in this tank (potassium chloride (K + and Cl-), magnesium chloride (Mg 2 + and 2Cl-), glucose (sugar), calcium chloride (2Cl- and Ca2 +), sodium bicarbonate (Na + and HOCOO-), proteins and oxygen) will result in a uniform distribution of these constituents in the aquarium. We then get a liquid that roughly reconstitutes the fluid that neurons bathe in (cerebral-spinal fluid).

Eric Trudel

Neuroscientific Art

2010-11-25T13:12:00.001-05:00

Exactly where the threshold between Science and the Arts lies can be a touchy subject. Like a lot of dichotomies that were once assumed to be fixed opposites, these days it’s looking more like there is a science - arts continuum. This is particularly valid in the nebulous field of neuroscience, where the overarching goal is to bring together disciplines that study the mind and how it works - like philosophy, sociology, psychology - with fields that study the physical processes that underlie brain function - such as neurobiology, -chemistry and electrophysiology. A word to the wise: before you get into the science/arts debate with someone who studies the mind or brain, resign yourself to accepting them as a scientist - safer to keep your reservations about their place on the spectrum to yourself. (Personally, I think we should all call ourselves artists in keeping with the Latin use of “Art,” meaning skill or craft.)

While the debate rages over what should be included in the realm of “Science,” some scientists are working hard to go the other way. A number of Microscopic Art competitions have sprung up, showcasing beautiful images taken by biologists studying things too small for the human eye to see in all their glory. You may have seen the perennial scanning electron micrographs of pollen in National Geographic, but events like Olympus’ BioScapes and Nikon’s Small World Competition comprise images of many different subjects taken by many types of microscopes (the type of microscope used can drastically change the flavor of the picture). This year’s Olympus Bioscapes competition winners were announced last week, and neuroscientists took 1rst, 3rd and 7th places plus some honorable mentions. Take a look here.

The Incredible Human GPS

2010-11-25T12:44:00.002-05:00

Ever wonder how a cab driver is able to get you from point A to point “who knows where” without using GPS? Its cause his brain is bigger than yours… well… his hippocampus is. The hippocampus is a region in the brain important for long-term memory and spatial navigation. While it was long thought that talents were innate and had to be nurtured at a young age, researchers studying London cab drivers say that an old dog can learn new tricks. London cab drivers have to learn the layout of over 25, 000 streets through 3-4 years of schooling after which only 25% of aspiring cabbies make it out with a London cab certificate to attest to their ability to find their way through the city’s complexly interconnected web of streets. Through Magnetic Resonance Imaging, researchers have determined that London cab drivers have an increase in volume of the back part or posterior part of their hippocampus, indicating that the adult brain is still capable of changing its structure to meet certain demands. This means that talents are not necessarily innate but can also be acquired through repeated application. That’s right. Practice does make perfect.

When compared to non-cab drivers or bus drivers, who follow a simple set route, cab drivers have a larger posterior hippocampus, which grows with years of cab driving experience, demonstrating that the posterior portion of the hippocampus is important for spatial representation of highly complex environments. However there is a catch. While the posterior portion of the hippocampus grows larger with driving experience, the anterior or frontal portion becomes smaller than those of bus drivers and non-cab drivers. This decrease in anterior hippocampal volume has been associated with a decrease in anterograde memory performance, that is, while cab drivers were better at spatial representation they were deficient in acquiring and retaining other new types of information such as directing movements in space as indicated by their lower performance in the Rey-Osterrieth test. This means that when cab drivers were shown a complex line figure and asked to draw it from memory, they were able to recall less than than bus drivers or non-cab drivers.

Cab drivers don't only show that practice makes perfect, they also show that if you don't use it you lose it. Researchers compared the hippocampus of present cab drivers to retired cab drivers and found that the structural changes that occur in full-time taxi drivers are reversed in retired taxi drivers. Furthermore, retired taxi drivers scored less on their ability to navigate around London, however performed better in the Rey-Osterrieth test than full-time cab drivers.

These observations are a testament to the fact that the adult human brain is not static but is quite dynamic, always adapting to our surrounding environment. This has implications in several fields such as education or rehabilitation of patients with cognitive impairments such as autism or even in Parkinson's disease. Researchers at UCL believe that with the right brain exercises we can strengthen those parts of the brain that are deficient or damaged. So those of you who claim to be "too old" to learn anything new, pick up that crossword puzzle, take that class you've been dying to take, start a new hobby and practice, practice, practice!

Michael Tibshirani

McGill University

Head and Shoulders, Knees and Toes...

2010-11-21T21:24:00.001-05:00

Part 1:

If you found out that you were going to lose the use of your arms and legs in the next two years what would you do?

ALS, more commonly known as Lou Gehrig’s disease, is one of the most common neurodegenerative diseases and is characterized by the death of motor neurons. Motor neurons are cells located in the brain and spinal cord that send out long projections and control your muscles, sort of like the electrical wires of the body. If these wires are removed, muscles in your body won’t get the message to move. This means that those diagnosed with ALS experience a progressive paralysis, losing the use of their bodies one part at a time. Every year 1 in 100,000 people are affected by ALS; slowly losing their independence, unable to walk, speak, or even express emotion through facial expression while still fully aware of their surroundings, trapped in a body that won’t listen to them. Eventually, usually within 2-5 years of diagnosis, patients die from respiratory failure because the motor neurons controlling the muscles that help you breathe die as well. This devastating disease can affect anyone. Although the usual onset of ALS is between 40-70 years of age a small proportion of ALS sufferers experienced symptoms, like the great Stephen Hawking, in their early twenties. It is twenty percent more common in men than in women however the incidence is more equal among men and women with increasing age.

The cause of ALS is still a little unclear and is thought to be a multifactorial disease and so research has investigated several disciplines such as inflammation, excitotoxicity and cell-cell communication. While only 10% of ALS cases are familial, meaning the cause can be linked to defects in your genes, 90% of cases are sporadic, however there is a silver lining to this. When we look at nervous tissue taken from ALS patients, the common characteristic we find between both familial and sporadic cases is the presence of protein clusters called aggregates. By studying familial cases and the genes involved in ALS, we can generate models that allow us to investigate the mechanisms behind ALS and what makes motor neurons particularly vulnerable to protein aggregation.

In normal cells, proteins initially come out as a string that must be folded properly to function. When these proteins are misfolded either under cell stress or as part of a disease pathway, they tend to stick to each other and form clumps or aggregates in the cell, which interfere with various cell processes and, if not taken care of, will lead to cell death. Whether protein aggregate formation is the beginning or the end of the pathogenic pathway involved in ALS, it is clear by experimentation that motor neurons don’t like having aggregates in them, and so a lot of ALS research has been focused on trying to understand the role aggregate formation plays in the pathogenesis of ALS. In the next segment we will discuss current research, which explores the cell’s responses to these aggregates and possible explanations why motor neurons specifically show aggregate formation in patients with ALS. Stay tuned!

Michael Tibshirani

McGill University

"Parkinson's Disease: Working Towards a Cure": Part 2-- Current Treatments

2010-11-18T11:14:00.000-05:00

This is the second post from a three part series written by Andrew Greene, a graduate student at McGill University studying Parkinson's Disease.

While a number of worthwhile treatments exist for Parkinson’s, they all target the symptoms rather than the root cause of the disease, the death of substantia nigra neurons. This is because, at least in most cases, we still don’t understand exactly why those neurons die. We’re getting closer every year though, and some of the cutting edge research that’s bringing us towards a cure will be discussed in Part 3. For now we’re limited to symptom-targeting treatments, but as we’ll see below, some of them can be quite effective.

In Part 1 we saw that the major symptoms of Parkinson’s disease are caused by the death of neurons that emit a chemical called dopamine. It’s not surprising then, that the gold standard in Parkinson’s treatment is the administration of dopamine supplements. Unfortunately dopamine taken by mouth does not reach the brain, but scientists have circumvented this problem by using a chemical called Levodopa, or L-dopa for short. L-dopa is a natural molecule found in both animals and plants. In humans and other animals, L-dopa taken by mouth can easily reach the brain, where it is converted into dopamine. Supplementing a patient’s brain with dopamine in this manner allows them to move much more readily than they could without treatment, but there are side effects. Whereas the brain administers dopamine to itself in a carefully regulated manner, the levels of dopamine produced from L-dopa are much less finely tuned. A frequent side effect of the treatment is ‘too much movement,’ with patients making involuntary movements such as writhing or jerking. Fortunately these can usually be minimized by reducing the L-dopa dose.

When medications aren't cutting it, eligible patients can opt for various types of surgery. Like the currently available medications, the surgeries do little to block the root cause of the disease, but they can be very effective in eliminating many of the more debilitating symptoms. An increasingly common option is the implantation of a deep brain stimulation device. Somewhat counter intuitively, the net effect of the deep brain stimulation used to treat Parkinson’s is actually to block the neural activity in a certain section of the brain. This effectively inhibits the indirect pathway, which, as mentioned in Part 1, is involved in inhibiting movement and is overactive in Parkinson’s disease. Deep brain stimulation is effective against symptoms such as rigidity and slowness of movement, and is less prone to causing involuntary movements than L-dopa is. Unfortunately it’s expensive and demands a tremendous amount of expertise in medical imaging, surgery, neurophysiology, and postoperative management, thus limiting its widespread availability. Moreover, because neither deep brain stimulation nor L-dopa treatment target the cause of Parkinson’s, neurons continue to die as the disease progresses. This means that symptoms that don’t respond to the above therapies, such as cognitive problems and frequent falls, continue to worsen. For this reason, Parkinson’s disease remains an active field of research in neuroscience.

Stay tuned for Part 3: Towards a Cure. Coming soon!

New neurons and a new therapeutic target

2010-10-24T12:15:00.003-04:00

The recent discovery that the human brain produces new neurons throughout life has led us to re-evaluate how we think about our brains and their plasticity, as well as examine potential new targets for psychiatric treatment.

In the narrow space between your ears, a roughly three-pound lump of tissue (composed mostly of water) contains everything that makes you who you are. Your brain is responsible for all of your memories, emotions, actions and aspirations. The human brain is also the source of all of our joy and misery, and understanding its workings offers hope for the amelioration of psychiatric suffering and, possibly, greater potential for happiness and enjoyment of life. However, one difficulty in dealing with the complexity of psychiatric disorders is that frequently multiple theories arise to help explain the origin or cause of any particular condition.

Depression is one example of this; there are many hypotheses attempting to explain this debilitating condition that affects more than 120 million people worldwide. One of the most widely-known theories is the 'monoaminergic theory' of depression, which focuses on neurotransmitters (chemicals used by neurons for communication) like serotonin. However, in this article I will try to give a brief review of a more recent theory, the 'neurogenic theory' of depression.

Up until relatively recently, it was believed that the brain stopped producing new neurons after development; as the famous neuroscientist Santiago Ramon y Cajal said around a century ago, "In the adult centers, the nerve paths are something fixed, and immutable: everything may die, nothing may be regenerated". However, the creation of new neurons in the mature brain, a process known as 'adult neurogenesis', was confirmed relatively recently in humans.

But there are some mysterious aspects to this phenomenon. For one thing, there initially seems to be only two clearly neurogenic areas in the brain; the olfactory bulb, and the dentate gyrus of the hippocampus. There's some early evidence to suggest other parts of the brain may be neurogenic as well, but even in these areas, the number of new cells produced seems to be limited at best. So this raises some questions; why just these few areas in particular, and not others? And what is the function of these new cells?

Although adult neurogenesis is still a relatively new discovery, it's become something of a hot topic in neuroscience, so we have some preliminary answers to the questions I just posed. For one thing, these new neurons seem to have special properties, in that immature neurons seem more 'plastic' or flexible in their firing responses than other cells. We also have some hints at their function, particularly with hippocampal neurogenesis; it's been shown to be involved in learning and memory and, most importantly for this entry, has been associated with emotional functioning.

This brings us back to the neurogenic theory of depression, an idea that essentially states that if the rate of production of these new 'special' neurons decreases, depressive symptoms may appear or be increased in severity, whereas increases in the rate of adult hippocampal neurogenesis can reduce the severity or appearance of depressive symptoms. Although this idea is only a few years old, there's some evidence supporting it. For one thing, factors that seem to make depression worse, such as stress, also decrease hippocampal neurogenesis, and factors that have been shown to improve depressive symptoms, such as antidepressant drugs and electroconvulsive treatment, also increase hippocampal neurogenesis. Human depressed patients also show decreased volume of the hippocampus. In addition, the delay between starting antidepressant medication and the amelioration of depressive symptoms, roughly four to six weeks, closely mirrors the time necessary for newly-proliferated cells spurred by this medicine to develop into functional neurons. And finally, experiments using animal models have shown that factors that increase neurogenesis also induce antidepressant behaviour.

So the neurogenic theory of depression, although it's still a relatively new idea, has the potential to offer exciting insight into depression and other psychiatric conditions, including treatment applications; if increasing the rate of neurogenesis can improve depression and depressive symptoms, then we can potentially develop new medications and treatments aimed specifically at increasing adult neurogenesis.

It's important to keep in mind that a lot of the theories scientists have developed concerning psychiatric illness are still preliminary, and a lot of important research is still needed before we can provide the definitive answers patients and their families are desperate to hear. However, the silver lining is that we're constantly getting closer to finding those answers, and offering hope to those searching for it.

- Ian Mahar

[Adapted from an article initially published here]

"Parkinson's Disease: Working Towards a Cure": Part 1-- The Basics

2010-10-17T15:47:00.001-04:00

This is the first post from a three part series written by Andrew Greene, a graduate student at McGill University studying Parkinson's Disease.

James Parkinson was a British apothecary-surgeon best known for his medical report entitled "An Essay on the Shaking Palsy." Published in 1817, it was a detailed description of the disorder that would one day be known as Parkinson's disease. The disease can bring on a variety of symptoms, many of which we're only just beginning to appreciate, but the best understood are the movement related effects. Typical symptoms include tremors of the limbs and difficulties performing movements, especially ones that have multiple parts, such as reaching out to a cup, grabbing it, and bringing it to your lips. There is presently no cure for Parkinson's disease, but there are a number of treatments available to at least temporarily alleviate the symptoms, and these will be discussed in detail in part 2.
Despite the fact that Parkinson's disease is primarily a movement disorder, the muscles themselves generally remain healthy. It's actually a part of the brain involved in coordinating movement that has traditionally been said to be most prominently affected by the disease. This part of the brain is called the substantia nigra, which means black substance, referring to its characteristic dark colour compared to surrounding brain regions. The substantia nigra is located near the center of the brain and contains neurons that secrete a chemical called dopamine. Dopamine is a type of neurotransmitter, which are a class of chemicals that neurons emit in order to communicate with each other.
Dopamine is best known for its role in the brain's reward system, in which it's used to provide feelings of pleasure and enjoyment in response to things such as food, sex, and certain drugs. However, dopamine released by the substantia nigra also plays a critical role in modulating the activity of the striatum, a brain region that is essential in planning and coordinating movements. The striatum is the origin of two neural pathways that exert opposite effects on movement. The first of these is the so called direct pathway, which is thought to facilitate and reinforce intended movements. The second is the indirect pathway, which is thought to be responsible for inhibiting unwanted or inappropriate motion. Dopamine released by the substantia nigra helps maintain a balance between these two pathways by increasing the activity of the former and decreasing the activity of the latter.
In Parkinson's disease the dopamine-emitting neurons of the substantia nigra die off, which tips the delicate balance between the direct and indirect pathways. The result is too much activity in the indirect, motion-inhibiting pathway and too little in the direct, motion-facilitating pathway, which ultimately makes it exceedingly difficult for a patient to move. Why dopamine-emitting neurons of the substantia nigra die in Parkinson's disease is not known, though research over the last few decades has gone a long way towards solving the mystery, as we'll see in Part 3. Uncovering the reasons for their death is the first step in learning how to stop these neurons from dying, leading to better treatments and hopefully even a cure.

Stay tuned for Part 2: Current Treatments and Part 3: Towards a Cure. Coming soon!

Welcome to the BAWMontreal Brain Blog!

2010-10-04T18:13:00.000-04:00

Hi!

Thanks for clicking on the Blog link on the BAW Montreal website! This blog will deal with current and interesting research in the field of neuroscience, written in an easily readable and understandable way. Several university students from across Montreal will be blogging about their research and other topics throughout the year. Stay tuned for the first post! Coming soon!