Thursday, March 15, 2012

Scientific Cafe 2012: Brain Myths

Last night was BAW's first Scientific Café of 2012, with the topic being "Brain Myths," a topic that I've written about before, and the discussion of which I feel is crucial in dispelling popular misconceptions regarding the brain and its functions as well as being particularly suited to the Café’s general audience.

The guest speakers were Dr. Ed Ruthazer (McGill; Montreal Neurological Institute), Dr. Natasha Rajah (McGill; Douglas Institute), Dr. Michael Fehlings (University of Toronto), and Dr. David Ragsdale (McGill; MNI). I'll provide a quick recap of the topics covered by each of the guests along with some of my own comments.

Dr. Ruthazer focused primarily on experience and perception, and how these originate within the brain. Recent advances in technology have allowed us to make incredible leaps in our understanding of perception; in particular, it's possible to reconstruct one's visual experience using imaging techniques, albeit with (currently) limited accuracy and resolution. As technology advances, it will increasingly become possible to reconstruct one's experiences through analysis of brain activity. Future technology may also lead to a complicated (but fascinating) ethical and philosophical issue: if consciousness is an epiphenomenon of brain activity, and we eventually become capable of producing sophisticated artificial 'brains', what are the consequences of producing artificial intelligence and sentience that mimics or rivals our own?

Dr. Rajah focused on myths related to memory. One common misconception is that our brains act as 'recorders' that faithfully encode events for subsequent accurate retrieval. However, work from Dr. Elizabeth Loftus and others has shown that our own memories are in fact rather fallible, in that memories can be modulated or even (in some cases) inserted, with the manipulated individual confident that their adulterated memories are both accurate and their own. In fact, stating that we believe something reinforces that belief, leading to false confidence in a fallible memory if it is declared often enough. Similarly, repressed memories are controversial in this field, with the general consensus being that traumatic events would normally be remembered to some extent, and that repressed memories are likely to be false memories. Finally, myths regarding memory loss in popular media can be misleading, as common misconceptions regarding amnesia are produced from inaccurate fiction.

Dr. Fehlings lamented the fact that there are very few examples of clinical neuroscientists or neurosurgeons in popular fiction (with Dr. Frankenstein, or his younger Mel Brooks equivalent, as rare examples). In the scientific world, however, we are rapidly gaining an understanding of brain regeneration and repair following injury. One example he mentioned is adult neurogenesis, which I've previously written about here, as well as the therapeutic potential of implanted neural stem cells. In closing, he stressed the importance of translational research, in which new insight into brain repair and regeneration gleaned from basic science is applied at a clinical level to patients of neurotrauma.

Finally, Dr. Ragsdale focused on more philosophical concerns related to neuroscience. In particular, if the mind is an epiphenomenon of brain activity, what is the mechanism by which this occurs? If our consciousness is a product of deterministic forces (i.e. underlying neurobiology and its features), do we actually have free will? One experiment exploring the latter described how the neural activity underlying a voluntary action actually precedes the conscious decision to perform the action by roughly a half-second. So if our brains are making our decisions for us, is free will an illusion? He concluded with the importance of creative thinking in neuroscience research, in that our understanding of our brain is still very incomplete, and so there is still lots of room for wild new ideas about the brain to lead to insight about ourselves.

If you couldn't make it to the event, I hope this provided a rough explanation of the type of topics covered. I would definitely recommend checking out any future Science Cafés, as they're stimulating and worthwhile events that make complicated topics accessible to a general audience.

Tuesday, January 10, 2012

The origins of empathy?

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.]

Wednesday, March 16, 2011

Concussion repercussions

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.


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.]

Friday, March 11, 2011

Human Libido = Mouse Libido?

(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.


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

Tuesday, February 22, 2011


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:
Hilary D. Duncan
Concordia University

Monday, February 21, 2011

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

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.

Monday, February 14, 2011

Brains need love too

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)