Forget the stair master, brown fat is where the burn is at

There has been a flurry of articles recently about the rise in research on brown adipose tissue (BAT), endogenous body fat that contains higher levels of mitochondria and is used to help keep the body warm. Until only three years ago, this holy grail of body tissues, “good” fat that burns significantly more calories and can help rid the body of “bad” fat, was thought to exist only in rodents, where it was more commonly seen in the young and in thinner animals. However, BAT has also been seen in human infants, important in helping to keep newborns warm, as they can not shiver to create body heat. BAT was thought to gradually disappear as individuals aged, but it is now believed that adults can retain small levels of their brown fat from childhood, with thinner individuals maintaining more, and that exercise can aid in this retention

How BAT promoted weight loss was not understood until recently. Researchers from Canada shed light on this process using PET-CT scans to identify the metabolic processes involved in BAT. Published this month in the Journal of Clinical Investigation, researchers subjected participants to acute cold exposure by placing them in a special liquid thermo-controlled suit at a temperature of 18 degrees Celsius (64 degrees Fahrenheit) for 90 minutes. During the course of this exposure, brown fat in the upper back experienced a significant increase in cell metabolism while working to keep the body warm, a process dubbed “cold-induced nonshivering thermogenesis”. Researchers hypothesized that this increase in BAT metabolism was initially fueled by elevations in extracellular glucose and fatty acid uptake, but that when these levels were depleted the tissue began drawing on stores of intracellular triglycerides, meaning that BAT was burning off lipid reserves during cold exposure.

As such, total energy expenditure of participants increased during the study by a whopping 80%, resulting in an average burn of an additional 250 calories. Curiously, there was no significant interaction between the amount of brown fat an individual had and caloric expenditure despite a wide variability in BAT levels, though this could be due to the small study sample size, involving only six participants. There was an interaction between BAT and thermogenesis though, with the added increase in metabolism helping to keep an individual warmer longer, and the more brown fat a participant had, the longer and colder conditions he or she could stand before starting to shiver.

A second study on brown fat looked at a more elusive type whose production is promoted through exercise. Published this month in the journal Nature, researchers at the Dana-Farber Cancer Institute discovered a new hormone, christened irisin, that seems to help transform white fat into brown fat. This production is dependent upon the transcriptional co-activator PGC1-α, a protein found in muscle tissue that is generated during exercise and involved in metabolism, cell genesis, and protection against muscle atrophy.

Knowing its vast beneficial effects, scientists bred mice to have elevated levels of PGC1-α to determine its influence on BAT and energy expenditure. Although the increase in protein had no effect on either brown or typical white adipose tissue, there were effects in a special type of subcutaneous white fat that is more susceptible to “browning”. This process involves increases in levels of the protein UCP1, which is highly active in brown fat cells and is involved in thermogenesis. These same effects also seem to occur following a regular exercise program in mice, facilitated by changes in mRNA expression induced by increases in PGC1-α and subsequent protein production.

Through several elaborate experiments, researchers were able to narrow down the proteins to those affected by the gene expression of FNDC5, including the newly discovered irisin. Irisin is significantly elevated in both mice and humans after exercise, and appears to be the key ingredient in the expression of UCP1 in the transition from white to brown fat. Direct injections of the protein resulted in increased levels of UCP1 in subcutaneous white fat, as well as subsequent increases in metabolism and small decreases in body weight in obese mice 10 days after exposure.

While both of these studies are still in their infancy, their potential implications for future research are very exciting. In the mean time though, if you want to lose weight try going for a run, the benefits may be twofold. Alternatively, if you’re too lazy to work out you could try sitting outside in the cold for a while.*

*Please note, I do not actually recommend this as a safe or valid weight loss plan.

A predisposition for drug addiction? Shared traits between stimulant dependents and their siblings

An exciting new study published in Science this week attempts to answer the chicken-or-egg question pervasive in drug addiction research of, “Which comes first, drug use or brain abnormalities?” Dr. Karen Ersche from the University of Cambridge* approaches this question with a new perspective, investigating the biological siblings of dependent drug users. And as is the case with most seemingly dichotomous questions in science, the answer is: both.

Dr. Ersche’s group studied 50 stimulant-dependent individuals, 50 of their healthy, non-dependent biological siblings, and 50 unrelated control volunteers on a barrage of cognitive tests, personality measures, and brain imaging techniques. Throughout the assessments, there was a striking pattern of similar responding between the drug users and their siblings, significantly differing in their results from the control participants. Specifically, drug users and their siblings were both significantly more impaired on the Stop Signal Reaction Time Task (SSRT), a test of inhibitory control that measures how well an individual can stop an ongoing response when triggered. Impulse control and inhibition are traits known to be impaired in drug-dependent individuals, and poor performance on the SSRT has previously been associated with an increased risk for drug abuse. However, these dysfunctions have long been debated as to whether they can be attributed to accumulated years of drug use and its effects on the brain, or are instead a predisposing factor that places an individual at an increased risk for drug dependence. In the current study, sibling participants performed as poorly on the SSRT as drug-dependent individuals, requiring more time to inhibit their actions. This would suggest that poor impulse control is a shared trait that is present in drug-dependent individuals before the onset of abuse. However, impaired inhibition is clearly not a determining variable, as dysfunction in the siblings did not lead to subsequent drug abuse or dependency.

The brains of stimulant users and their siblings were also structured similarly as compared to control volunteers, with an increase in gray matter in limbic and striatal regions such as the amygdala and putamen, areas important in emotion regulation and habit formation. Drug addiction is often seen as a disorder involving dysfunctional habits, and the putamen is implicated in the acquisition of these compulsive behaviors, targeted by an influx of dopamine and commonly a site of subsequent adaptations in the brains of heavy drug users. Additionally, the postcentral gyrus was significantly smaller in both groups as compared to healthy volunteers, indicating further pre-morbid differences.

Finally, white matter tract integrity, the neuron fibers that travel throughout the brain relaying messages from one region to another, were less intact in both the drug users and their siblings, signifying a decrease in brain connectivity in these groups as compared to the control participants. This was particularly evident in the inferior frontal gyrus, a region implicated in impulse control, supporting the findings of impaired self-regulation characteristic of compulsive drug users. Changes in connectivity in this area were also associated with an increase in impulse control dysfunction on the SSRT, with decreases in this region accounting for 6% of the variability in SSRT scores. Additional damage to white matter tracts and gray matter regions were also seen in the stimulant-dependent group, correlating with years of stimulant abuse and suggesting further damage and dysfunction due to chronic drug use itself.

Taken together, the abnormalities in the limbic and striatal regions, which have projections to the frontal cortex, as well as the decrease in frontal cortical volume and impaired connectivity between these key areas, confirms prior research indicating the importance of the cortico-limbic-striatal circuitry in drug dependence. These differences in the brains and behaviors of drug users and their siblings could potentially serve as endophenotypes for the development of drug dependence, characterized as stable inherited traits that are seen in clinical disorders and that can serve as indicators or predictors of pathology, both in patients and in their biological relatives. As such, these abnormalities in key regions for drug addiction could act as biomarkers for an increased risk of dependence.

However, the key question arises as to what protective factors could exist in the siblings to prevent them from trying or developing dependence on drugs. Sharing 50% of their genetic make-up, as well as familial environments growing up, drug-sibling pairs have highly similar brains and behaviors. However, clearly the differences that do exist between these groups are incredibly important. Early drug experimentation may exacerbate the structural abnormalities seen in these individuals, increasing the risk for later dependency, or even creating an epigenetic effect as has been seen in previous studies investigating early cigarette smoking and its link to later drug dependence. Alternatively, protective factors in the siblings could include greater education, outside interests or hobbies growing up, or even an increase in exercise and physical activity.

The question of the path to drug dependency is still very much open, however this study may take us one step closer to finding the answer.

*Disclaimer: I am a member of the Ersche lab at Cambridge, but was not involved in this study.

That Diet Coke isn’t so diet anymore

While everyone is working on their New Year’s resolutions for 2012, either making them or not breaking them, I thought it would be a good time to write about a trio of articles on sugar and artificial sweeteners and their respective health consequences.

A piece published in New York Times magazine several months ago raised the alarm on the extreme health detriments of our sugar habits. Author Gary Taubes cited Dr. Robert Lustwig, a researcher in pediatric obesity and hormone deficiencies, as promoting the idea that sugar, not fat, is the main cause for the dramatic rise in type 2 diabetes, hypertension and other “western diet” diseases seen in the last 30 years. These particular detriments stem from the way our bodies metabolize fructose (which makes up half of the refined sugar molecule sucrose), as opposed to pure glucose, which makes up the other half and is found in foods such as potatoes and white bread.

Glucose is metabolized by all cells in the body, whereas fructose is primarily processed by the liver. If the liver cannot adequately break down the sugar (both fructose and glucose) it receives into energy, it is converted into fat. This is more likely to occur if the liver becomes overloaded by the fructose in sucrose solutions, such as in high fructose corn syrup which has a greater concentration of fructose to glucose. The more and faster the body receives the fructose the more likely this is to happen. Therefore, drinking a sugary beverage, such as soda or even fruit juice, results in an even greater spike in fructose as it reaches the liver much more quickly. These drinks place a greater strain on the body than a raw piece of fruit, a “pure” form of fructose, which contains fiber and is digested much more slowly. This failure to break down sugar and the subsequent rise in liver fat is believed to be at the root of insulin resistance, the main underlying deficiency in metabolic disorders such as type 2 diabetes and heart disease.

It is undeniable that as our sugar consumption increases, so do our rates of obesity, diabetes and heart disease. Currently the average American consumes roughly 90 pounds of added sugar a year, and recently non-sugar sweeteners have been proposed as an alternative to sugar and high-fructose corn syrup to help reduce these rates. However two studies from the University of Texas: San Antonio presented at the American Diabetes Association’s Scientific Sessions suggest that these changes might not provide any real benefit.

The first, a longitudinal health study, measured participants’ waist circumference over a ten-year period. They discovered that diet soda drinkers had an almost 70% increase in waist circumference over this time, and those who reported drinking more than two diet soft drinks every day had waist circumference increases 500% greater than individuals who did not consume any diet drinks. These results remained even after controlling for variables such as starting circumference, diabetes, age, sex, smoking status, physical activity levels, and neighborhood of residence.

The second study assessed the effect of aspartame on a high fat diet in mice. One group received food chow with added corn oil and aspartame, the other just the additional corn oil. The group that consumed the extra aspartame had significantly higher glucose levels, but similar insulin levels than the mice who only received the high fat diet. This signifies severe consequences of a fake sweetener diet on diabetes, as blood sugar levels were elevated but insulin (which lowers blood sugar) was not compensatorily raised. This suggests that diet sodas and other foods made with fake sugar could actually lead to an increased risk for developing type 2 diabetes compared to a high fat diet alone.

So if anyone is still looking for a resolution this New Year, perhaps try cutting back on your soda consumption, both regular and diet. Your liver will thank you.

Salivating for stocking stuffers

In the spirit of this season of holy consumption, I thought it appropriate to write about an article released earlier this year in the Journal of Consumer Research on salivating over material goods. Author David Gal, an economist at Northwestern University, proposes that when we covet an item, be it ice cream or an iPhone, we literally drool over it. He hypothesizes that this response mechanism is induced by our reward system, with desired material items stimulating the same pathways and neural regions as the hunger for food or other natural reinforcers do. This includes the striatum, amygdala and hypothalamus, areas involved in reward responses and homeostatic mechanisms such as hunger and satiety. Activation of these areas in response to salient stimuli signals that these items are rewarding and could be important for survival. Supporting this claim, in previous research the mesolimbic dopamine reward pathway is seen to light up in a similar manner for luxury items and sports cars, which are secondary learned reinforcers, as for natural incentives such as food and drugs.

Taking this a step further, the physical outputs of this heightened reward arousal state can include the secretion of saliva, triggered by the sympathetic and parasympathetic nervous systems. Salivation occurs in response to cues for food or water as part of the natural metabolic system, preparing us for mastication and digestion. However, Gal claims that it is also a byproduct of the autonomal arousal system controlled via the hypothalamus, and that salivation can indicate any desired or salient stimulus, whether it be naturally rewarding, such as a member of the opposite sex, or a secondary conditioned reinforcer, like money or material goods.

Gal investigated this theory by presenting 169 undergraduate students with images of either money or mundane items, such as office supplies. While viewing the stimuli, participants were asked to keep cotton dental rolls in their cheeks and under their tongue to measure their saliva output. The weights of these cotton swabs were then compared to baseline measurements taken before the experiment to assess the increase in salivation due to the images presented. A second condition involved priming participants with feelings of either efficacy or helplessness by asking them to recall a time when they had felt either powerful or powerless. Gal hypothesized that money, symbolizing economic control, would be more coveted by those who felt they had little power, making it more desirable and rewarding than to those who deemed that they had greater power at the time of the experiment. Supporting this notion, only participants induced with feelings of powerlessness had significantly increased saliva output in response to the monetary cues. Individuals who felt powerful had no difference in salivatory rates when viewing the money images, nor was there a difference in saliva outputs in either power condition among participants in the control office supply group.

In a second follow-up study, Gal repeated the experiment using coveted luxury items in the place of raw currency. Gal exposed young men to images of sports cars, while also inducing in them the goal of winning a potential mate. He achieved this by presenting some participants with images of attractive women with whom they were to imagine going on a date with, while those in the control condition were to imagine having their hair cut. Men who viewed the sports cars as opposed to the mundane images had greater salivation rates compared to baseline ratings, but only when they had been primed with the goal of mating. The mating prime had no effect on saliva output in the control condition, and viewing the sports cars without the salient goal did not increase salivation rates on its own.

Importantly, increases in saliva production seem to be contingent upon the immediate rewarding value of the goods, only enhancing salivation rates when the presented stimuli were seen to help achieve a recently primed goal. This suggests that the triggering of salivation by reward cues is dependent upon the present desire or need for the item, much like the more visceral feeling of hunger in the presence of food.

So as you are finishing your Christmas wish-list this year, dreaming of drool-worthy duds and mouth-watering machines, perhaps rank your heart’s desire on how quickly they’ll come in handy and how moist your mouth feels afterwards. You’ll be sure to find them more rewarding.

Happy holidays everyone!

(Thanks to Emily Barnet for this article.)

The brain’s social network

Neuroscientists often attempt to attribute various behaviors and traits to certain regions of the brain. These findings make for neat science and great headlines, and while some of these results are little better than phrenology claims, many are highly reliable. The good ones are confirmed and replicated by multiple labs and substantiated using a variety of different methods, such as lesion, animal and human imaging models. For example, we know with relative certainty that much of the occipital lobe is in charge of processing visual information and that the hippocampus is heavily involved in transitioning from short term to long term memory. However, there is much in our behavior and our brains that we still do not understand, and it is highly tempting to simply assign certain sections of the brain to different traits, when in fact the underlying mechanisms are much more complicated. This tendency has become increasingly easy in the past decade with the rise of functional neuroimaging studies, where a region of the brain is seen to “light up” with activity when performing certain types of tasks. Voxel based morphometry (VBM) studies take these investigations a step further, looking at how gray matter volume in our brains correlates to different types of traits and behaviors. Two recent examples of VBM studies have investigated the neural correlates of social networking and extroversion, finding connections between amygdala size (among other regions) and social tendencies.

The first study, out of University College London and published in the Proceedings of the Royal Society Biological Sciences, found that people with more Facebook friends had increased gray matter volume in certain regions of the brain associated with social interactions. The authors of the study had hypothesized that the number of online friends one had could predict the relative brain size of regions important for social networking, particularly those involved in social cognition and mentalizing (the ability to recognize social cues and take another’s perspective). These areas include the fronto-parietal cortical circuit, medial prefrontal cortex and amygdala. However these frontal cortical regions were not identified in the study, and instead the researchers discovered greater volume in the left middle temporal gyrus, right entorhinal cortex and right posterior superior temporal sulcus, as well as the amygdala to a lesser extent. These areas are implicated in social cognition, perception of movement and intention (both physical and social), and autobiographical and associative memory. Based on these findings, the authors speculate that individuals with greater brain volume in these regions are more adept at the skills needed to maintain online socio-personal connections, such as enhanced memory of face-name combinations and awareness of movement of individuals in social circles. However, of these regions only the amygdala was correlated with real life social interactions, and none of the other originally proposed areas were found to correlate with social network size.

The second study, just published this week in PLoS ONE, also reports that individuals who are more extroverted show increased volume in the amygdala, as well as in the orbitofrontal cortex (OFC). Researchers from the Netherlands administered the NEO Five Factor personality assessment to 65 individuals to subjectively measure extroversion and neuroticism levels. They also had participants undergo an MRI scan and used VBM analysis to measure the size of certain pre-determined regions of the brain against extroversion scores, including the amygdala, anterior cingulate cortex and OFC. Controlling for age, sex and total gray matter volume, researchers discovered that individuals who scored higher on the extroversion scale had significantly larger amygdala and orbitofrontal cortices, as well as finding a significant correlation between total gray matter volume and extroversion scores.

As stated above, the amygdala is one of the brain’s emotional centers and is important in social interactions, both online and offline. It is crucially implicated in recognizing and processing positive and negative emotions, both in oneself and from the facial expressions of others. The OFC is also commonly associated with emotion regulation, as well as reward valuation and decision-making, mainly through its connections to limbic structures such as the amygdala, striatum and hypothalamus. However, it is not typically linked to social interactions, and the authors speculate that their findings are evidence of the amygdala and OFC’s involvement in a greater sensitivity to positive experiences and social interactions, rather than interpersonal skills themselves.

While the findings from these two studies are intriguing and compliment one another nicely, caution must be taken in the interpretation placed on these results. Correlation analyses state only an association, not a causation, and, as recently brilliantly exhibited by Business Week, these connections can be highly questionable at times. This is particularly true of imaging studies, where investigators can potentially go fishing for regions to attribute their target behaviors to. Interpretations for correlations are quick to come by and rationales for connections in unexpected areas of the brain can be justified all too easily when a publication is on the line. A priori regions of interest are thus crucially important, providing groundings for current explorations based on previous studies and alternative research methods. I am in no way denouncing VBM studies and their value and viability generally, or these studies in particular, however I do caution about the interpretations that can be carelessly made with them. Additionally, in studies like these it is unknown whether the size of the regions predicts the behavior, or whether the brain adapts and grows to incorporate new connections based on the repetition and reinforcement of certain actions. In regards to the studies at hand, their confirmation of the amygdala’s role in social interactions is highly supported, however it is unknown whether the increase in brain size is a predictor of social ability and network size, or whether practice of interpersonal skills helps to foster neurogenesis in these regions.

Impaired adolescent decision-making

I am pleased to announce that my first first-author publication has recently been released online by the journal Developmental Psychology.

The article, on decision-making in children and adolescents, looks at the developmental trajectory of affective decision-making abilities using the Iowa Gambling Task (IGT) in children between the ages of 8 and 17. It compares this type of “hot” executive function with more typical ”colder” cognitive abilities, such as impulse control and working memory. Contrary to the accepted belief that children improve universally on cognitive tasks as they age, we discovered that early adolescents (ages 11-13) are actually more impaired on this task than some of the younger participants, making riskier decisions and failing to learn from their mistakes.

The IGT requires participants to choose between four decks of cards that give out varying amounts of wins and losses. Two of the decks issue low wins but also low losses, resulting in an overall net gain, whereas the other two decks are riskier options, giving high payoffs but also higher losses, making them ultimately disadvantageous. A net score is calculated by subtracting the total number of disadvantageous choices from the total advantageous decisions. Early adolescents had significantly lower mean net scores on the task than older participants, but did not differ from the younger children in their ability. However, the total trajectory of mean scores across all ages resulted in a significant J-shaped curve, signifying a dip in ability in early adolescence.

We speculate that this curvilinear trajectory is due to the varying developmental schedules of different regions of the brain, particularly the striatum (involved in reward processing) and the prefrontal cortex, which is responsible for more inhibitory control. Structures in the basal ganglia typically develop earlier in adolescence,  whereas the prefrontal cortex is not fully matured until the early 20s. This earlier development of the striatum could lead adolescents to place undue emphasis on the initially high reward, but ultimately disadvantageous options in the IGT. Coupled with the delayed development of the prefrontal cortex, this group could also lack the necessary inhibitory control to offset this reward-driven urge. Supporting this theory, other imaging studies investigating developing cognitive ability have shown adolescents to disproportionately recruit from subcortical regions, particularly the basal ganglia, on tasks involving monetary rewards.

Conversely, younger children performed neither overtly advantageously nor disadvantageously on the task, choosing between the decks more randomly. This could be due to an earlier neurodevelopmental stage, before the striatum and other limbic regions had fully developed, making them less sensitive to the risky high reward options. Also supporting this J-shape trajectory theory, older adolescents performed the most advantageously on the task, improving their performance and successfully inhibiting the urge to make impulsive choices. This improvement presumably correlates with the continued maturation of their prefrontal cortices, as these inhibitory abilities come on-line.

Notably, all other cognitive tasks administered during the course of testing improved linearly across age, demonstrating that affective decision-making is a unique process that taps into the limbic regions, rather than just relying on the cortical cognitive network.

Importantly, these results are not implying that all adolescents are impulsive risk-seekers doomed to make lasting poor decisions. We all go through these stages of neurodevelopment and the vast majority of us emerge from adolescence relatively unscathed. Also, as this was not an imaging study the neural correlates of the abnormal decision-making development is speculative. However, this study does provide an interesting glimpse into how we develop in our affective decision-making tendencies and how they change as we mature.

Mental and physical exercise: Alternatives to dopamine treatment in Parkinson’s disease

A variety of studies have arisen recently touting unconventional methods for treating Parkinson’s disease. Parkinson’s is caused by damage to the neurons in the substantia nigra (SN), a region of the basal ganglia that is responsible for creating much of the brain’s dopmaine. Dopamine is an essential neurotransmitter in a variety of behavioral and motivational mechanisms, often implicated in reward and addiction, however it is also a key component of the motor system. Feedback loops from the cortex to the basal ganglia circulate information about whether to initiate or inhibit a movement, and these cicuits are greased by dopamine, activating the excitatory loop and suppressing the inhibitory one. However, without adequate dopamine the system comes to a stalemate, making the initiation of movement much more difficult and causing the hesitation, trembling, and inertia characteristic of Parkinson’s.

Common treatments for Parkinson’s include flooding the brain with dopamine agonists or the dopamine precursor L-DOPA. This helps to boost dopamine levels in the brain, causing the remaining healthy SN neurons to produce and fire greater amounts of the neurochemical, attempting to make up for the deficit from the impairment of the other cells. However there are currently no treatments to prevent the progressive cell death in the SN, and in advanced stages it is difficult to compensate for the abundant cell loss. Excess “artificial” dopamine in the brain can also result in the downregulation of other dopamine producing and receiving cells, the brain adjusting to the new flood of dopamine by reducing its endogenous production and receptor sensitivity in an attempts to return to a dopaminergic homeostasis. Additionally, it is impossible to localize dopamine agonists to the motor regions of the brain, meaning that many Parkinson’s patients treated with dopamine come to display symptoms similar to those seen in impulse control disorders, which are also commonly rooted in a widespread dysregulated dopamine system. These can include the development of compulsive gambling and shopping problems, sexually deviant behavior, and drug addiction.

Given the obvious shortcomings in the current treatment options, the need for alternative therapies for Parkinson’s is widely acknowledged. Two labs taking on this problem have recently published results on alternative treatments that do not involve pharmacological challenge and instead target a patient’s motor efficacy, one increasing the patient’s control and the other withdrawing it.

The first, published in the Journal of Neuroscience, suggests that self-regulation of brain activity facilitated by real-time fMRI feedback can increase brain activation and decrease Parkinson’s symptoms. Focusing on the supplementary motor region, an area of cortex that has direct connections with basal ganglia pathways and that is commonly shown to have diminished activity in Parkinson’s, researchers at the University of Cardiff had patients mentally activate this region using motor imagery while in the fMRI scanner. Patients in the experiment group received direct feedback on their activation levels during the trials via a thermometer display, whereas those in the control group did not have any indication of their success at mentally activating the area. The patients who received the real-time feedback were able to activate the supplementary motor region to a greater extent than those who did not, successfully upregulating this area as well as other brain regions associated with the motor system. They also significantly improved their ability on a motor function test and a subjective assessment of Parkinson’s symptoms, whereas control participants did not. Researchers speculate that this increase in activity and subsequent improvement in symptoms is due to a greater excitation of compensatory motor pathways, strengthening these connections and facilitating the activity of the under-utilized basal ganglia circuitry.

The second method, published in Exercise and Sport Sciences Reviews, takes an alternative approach, deliberately taking the control out of the hands (0r legs) of the participants. Researchers at the Cleveland Clinic in Ohio are investigating the idea that forced exercise, with exertion levels out of the patient’s control, can be more effective in treating Parkinson’s symptoms than voluntary physical activity. Led by Dr. Jay Alberts, researchers had patients ride on the back of tandem bicycles where the energy output was set at 50% higher than the patients’ comfortable self-selected effort levels. After eight weeks at the greater energy expenditure, patients had a significant decrease in tremors and other motor symptoms, which lasted for approximately one month after treatment was stopped. Additionally, the benefits seen were not just a result of localized increased muscle tone or coordination as has been the case in previous studies investigating the effects of exercise in Parkinson’s. Instead participants showed improvements in movement throughout the body, as well as increased neural activity during MRI scans of the basal ganglia and cortex. Researchers are as yet unsure of the basis for these improvements, though the emotional and cognitive benefits of exercise are widely known. In an interview with the New York Times, Dr. Alberts speculated that the effects could stem from the release of stress hormones during exercise, which can trigger the neurochemical systems and are more active during forced or very high intensity activities than comfortable voluntary levels of exertion.

While these studies are still only addressing the symptoms rather than the root of the problem, they do provide new evidence for treatment options beyond the standard fair. Importantly, neither of these methods comes with any of the adverse side effects of dopaminergic treatments, which can severely undermine the efficacy and quality of life improvements for patients with Parkinson’s disease. Further research is of course always needed, and certainly these methods would need to be used in tandem with current drug therapies, but these studies present an interesting alternative to complete reliance on pharmacological medication to treat the symptoms of neurological disorders.

Time warp: Subjective time duration

I got to attend a talk by the dynamic neuroscientist Dr. David Eagleman at the Society for Neuroscience meeting this week, who spoke on temporal expansion and compression (i.e. the subjective speeding up and slowing down of time in our minds) and its possible neural underpinnings. The gist of Dr. Eagleman’s research is that unexpected events seem to last longer (the “oddball effect”), whereas repetitive occurrences seem to speed up and go faster. The classic example of this is when an object is presented to you several times in sequence, you begin to think that the presentation has been sped up. However, if a novel object is introduced it seems to be presented for longer (13% longer to be exact) than the anticipated stimulus.

The initial hypothesis for this phenomenon was that greater attention is paid to these surprising events than the expected ones. However if this were the case, strong salient or attention-grabbing images, such as violent or emotional pictures, should seem to last even longer than unexpected neutral images, as they garner even more attention. However this is not the case, with novel affective images subjectively lasting just as long as novel household items.

Instead the answer seems to lie in a perceptual compression rather than expansion of time, with the repeated images appearing to speed up as they become expected. This is thought to be rooted in an increase in neural efficiency for these events, the neurons and pathways becoming faster and more effective at firing for the expected event, leaving the brain greater capacity to process new information that cannot be predicted in this manner. This is paralleled in the EEG literature where conditioned anticipated events do not elicit the same amplitude of firing from cells that they once did. However, when a novel stimulus is introduced there is an expectation violation, which results in a greater magnitude of neuronal firing in the brain again. This then results in the event seeming longer, or rather no longer being temporally compressed as it had become.

Unfortunately no one is quite certain why increased or decreased cell firing results in this subjective expansion or compression of time, but perhaps we’ll be closer to an answer by next year’s meeting. In the meantime, at least it’s comforting that repetitive (read: potentially boring) events actually seem to go faster than they really are.

SFN 2011

I’m excited to announce that I’m headed to Washington, D.C. today to present my very first poster at Society for Neuroscience!

To all my fellow neuro buffs and brain geeks in attendance, stop by session 192: Dietary influences on obesity mechanisms, Sunday from 10:00-11:00 to say hi and see my poster: Decreased Gray Matter Volume in Overweight and Obese Individuals. It’s got some beautiful brain images and snazzy graphics, and hopefully some cool neuroscience thrown in too.

Also, be sure to check out two of the official SFN blogs, blogs.scientificamerican.com/scicurious and futuredrsciencelady.wordpress.com, for up-to-date posts on all of the neuroscience madness going on this week.

Hope to see many of you there!

Learning from our students

Having just conducted my first round of undergraduate supervisions (similar to an intensive tutoring or teaching assistant session), I have a greater amount of respect for an article published in Science back in June that has been making the rounds in academic discussion forums. In it, researchers conclude from both subjective interviews with students and faculty supervisors, as well as through objective reviews of student research reports, that graduate students who teach or supervise undergraduates come away with better research and analytical skills than those who do not.

This finding is at first counter-intuitive and flies in the face of accepted dogma that students who teach are taken away from their own research and laboratory time, and therefore cannot produce as much or as thorough work as those who do not. However the authors of the report, led by Dr. David Feldon at the University of Virginia, have done a thorough job vetting this claim by objectively assessing graduate students’ research proposals on the quality of their experimental design, hypothesis testability, and general research skills. Based on an empirical set of criteria, the authors of the study determined that students who pursued teaching as well as research assistantships had better research and study design skills than those who did not.

As my fellow graduate students and I can attest, teaching undergraduates takes a significant amount of time, effort, and brain power, all resources that would more preferably be spent (both according to ourselves and our supervisors) on our groundbreaking and earth shattering research. However, in accordance with Dr. Feldon’s report, teaching undergraduates is not without its advantages, though some of the benefits I have experienced are somewhat harder to empirically define.

In a PhD we all too often become absorbed in our own niche research, convinced that it is the most imperative and fascinating topic there is to study. If we did not we would most likely drop out. However, it also means that the articles, discussions, work, patients, and results we see are all geared towards this small facet of our respective subjects, which are at times far away from the more general concerns of the field. Tutoring or supervising undergraduates can bring us back into the larger discussion of our disciplines, reminding us of the history and background that predates our own work. It also provides an opportunity to review some of the seminal papers that we may now take for granted but were groundbreaking at the time of their release. And lastly, it reminds us of information we had learned during our own undergraduate tenures, knowledge and analytical skills that are essential in the wider scope of our fields but that might have been forgotten or discarded in favor of our own passions.

This all happened to me in my first tutoring sessions. I was at first overwhelmed with the information the students were expected to learn and resentful of the distraction from my work. Fortunately, over time I was able to recognize much of the material as familiar and even attempted to provide my own spin on it, combining the fundamentals of the lectures with offshoots from my research. However, it was certainly a humbling reminder of just how much there is I do not know about the brain. I was also impressed by the knowledge and intellect of the students themselves, some of whom I have no doubt are vastly more intelligent than myself. More than anything though, reviewing this material and having to master it all well enough to later disseminate it to others reminded me of just how interesting and exciting some of these topics are, and made me aware of connections in systems pertaining to my own research that I had neglected to make.

While teaching certainly does take up vast quantities of time, it also provides an invaluable medium to refresh us on essential material, to review our field with new eyes, and to make us truly learn the information so that we are later able to provide guidance for others. It is also an important exercise in reminding us of just how little we know, and how seemingly “simple” questions can be far more complex than some of the more nuanced “expert” queries.