Just a short note to let everyone know that Neurorexia is in the process of moving to a new host (with a face change)! If odd things happen in the next day or so please drop me a note in the comment section or email me.
And a teaser :p
Like most junkies, I struggle to come up with excuses to justify my addiction. Lucky for me, increasing evidence is supporting my semi-hourly coffee habit: caffeine, the world’s favourite drug, not only keeps you awake and alert, but may also boost your memory.
Perhaps in an effort to excuse their own coffee addiction, many research groups have studied whether caffeine enhances memory. The results, unfortunately, are highly mixed. One study, for example, found that 200mg of caffeine – roughly the amount in two cups of drip coffee – consumed before a memory-taxing game enhanced working memory, the ability to flexibly maintain and manipulate information in your head to solve a problem. The catch? Only if you’re an extrovert. In a separate cohort of volunteers, 75mg of caffeine (roughly that in a cup of espresso) taken together with glucose on an empty stomach helped stabilize a new verbal memory. This is called “memory consolidation”, whereby new and unstable memories are moved into semi-permanent storage. However, in that study caffeine by itself had little effect on memory.
One problem with these previous studies is that caffeine was always given prior to learning or testing. This makes interpreting any improvements in performance difficult: is caffeine directly boosting memory or is it enhancing performance indirectly through increasing attention, vigilance and/or processing speed, thus giving the appearance of memory gain?
D Borota et al. Post-study caffeine administration enhances memory consolidation in humans. Nature Neuroscience, published online Jan 12, 2014. doi:10.1038/nn.3623
To get to the bottom of this, researchers from University of California, Irvine* decided to see how caffeine consumed after learning affects memory consolidation. They recruited 160 uncaffeinated adults, a rare breed that drank less than 5 cups of coffee per week and showed no traces of caffeine or its metabolites in their saliva prior to the experiment. In fact, average caffeine intake of most of these “caffeine naïve” people lingered around 70mg a week, coming mostly from chocolate and soda rather than coffee per se. (*The research described in this post was done at Johns Hopkins before the lead author moved to UC Irvine)
The volunteers first looked at a series of images of various objects, such as a saxophone, a sea horse or a basket, and categorized them as either an indoor or outdoor object. Upon completing the task, they immediately popped a pill containing either 200mg of caffeine or a placebo and left the lab.
A day later, the volunteers returned. By now all traces of caffeine and its metabolites had washed out of their system; they were stone-cold sober. The researchers then showed them a new series of pictures, instructing them to identify whether they had previously seen the picture (“old”) or if it was new. To make things harder, researchers sneaked in several pictures extremely similar those shown before. For example, instead of the old picture of a svelte sea horse arching its back, they now presented a “lure” picture of the animal hunched over. This type of “pattern separation” task is considered to reflect memory consolidation to a deeper degree than simple recognition.
Regardless of caffeine intake, both groups had no trouble identifying the old and new pictures. However, as shown below, the caffeinated group outperformed their peers in picking out the lure, with a higher propensity of calling them out as “similar” rather than “old” (though the effect was small and barely reached significance, more on that later). In other words, caffeine seemed to help them retain minute details present in the original pictures. A similar boost in performance was seen when researchers repeated the experiment with 300mg of caffeine (~1 cup more than before), but the advantage disappeared when they dropped the dose down to 100mg. Remember that caffeine was administered after viewing the photos, hence the drug was not increasing attention to detail during the learning process.
However, not everyone metabolizes the same 200mg caffeine pill to the same degree. When researchers accounted for individual differences in caffeine absorption and metabolism, they found that participants who broke down the largest amount of caffeine performed worse than those who metabolized slightly less. In other words, there is a sweet spot for caffeine’s memory enhancing powers – go either under or over and you loose that edge.
Finally, what if you waited too long after learning, only to remember to chug that Starbucks mocha the day after? In a separate study, researchers allowed 24hrs for volunteers to consolidate the memory of the initial picture stack before giving them the same caffeine pill, just one hour before the test. This time it didn’t work – these volunteers mixed up similar and old pictures just like the placebo control group. Whatever caffeine is doing, it has to be done during consolidation.
Researchers aren’t quite sure how caffeine induces memory gain, but they have a few ideas. The image discrimination task used here engages the hippocampus, a key brain area involved in learning and memory. It expresses high amounts of the caffeine receptor (adenosine A1 receptor) in its CA2 subregion, thus allowing caffeine to tweak (strengthen?) its function in memory consolidation. Caffeine can also indirectly boost the level of norepinephrine, a neurotransmitter that helps you lay down a memory for good.
While exciting, this study cannot end the debate on whether caffeine improves memory. The effect sizes were small, with some only scraping significance – that is, researchers were only barely able to say with some confidence that the effect is real. This doesn’t reflect the quality of the research, but most likely represents individual variance among the volunteers: different gene variants for faster caffeine metabolism, BMI, basal metabolic rate, oral contraceptives and so on. It would also be interesting to see if caffeine boosts memory reconsolidation: when you retrieve a memory, it temporarily becomes labile. Can coffee help the memory restablize?
Unfortunately, we don’t known if caffeine-induced memory gain applies to caffeine junkies like me. But to quote the lead author: one needs to do the experiment with habitual drinkers to find out, but my guess is that it’s why we’re so awesome!
Many thanks to the principal investigator @mike_yassa for patiently answering my questions over Twitter. You can check out our full conversation in my timeline.
Borota D, Murray E, Keceli G, Chang A, Watabe JM, Ly M, Toscano JP, & Yassa MA (2014). Post-study caffeine administration enhances memory consolidation in humans. Nature neuroscience PMID: 24413697
As 2013 grinds to an end, the internet fills with reminiscence of the year’s top stories and moments. I, for one, especially can’t resist ruminating about the past, especially when packaged in a brain-tickling, “top n” list form. Without further ado, here is my Top 10 list of the year: Science Stories I Wish I’d Blogged About.
Bonus. A List of Reasons Why Our Brains Love Lists. By Maria Konnikova.
To start off, why are we drawn to lists anyway? Is it due to the clean, structured organization that helps us navigate the material efficiently? Or is it more a product of our current “bite-sized” information culture? Maria has the answers.
10. Can we lessen the effects of fearful memories while we sleep?
Spontaneous activation of memories during sleep is generally thought to strengthen them. However, when researchers in Northwestern University repeatedly brought up a recently learned fear memory in their sleeping participants by presenting a fear-associated odour, the participants showed a smaller fear reaction to the odour after they awoke. According to the researchers, this is the first time emotional memories have been successfully manipulated in humans.
9. Men and women’s brains are wired differently. Is THAT why men can read maps better (or so the cliché goes)?
Here‘s one cover of the study that would let you believe that (gasp) it is indeed so!
Here are a few level-headed analyses that tackle the nitty-gritty of the study and how its conclusions got blown out of proportion. The bottom line? Brain scans don’t tell us anything about behaviour. Here’s the original paper for reference.
Are men better wired to read maps or is it a tired cliché? By Tom Strafford.
Men, Women and Big PNAS Papers. By Neuroskeptic.
Getting in a Tangle Over Men’s and Women’s Brain Wiring. By Christian Jarrett.
You know how you are what your grandpa ate? Epigenetics offers an answer to how our interactions with the environment can influence the expression of our and our offspring’s DNA. However there is little evidence that stress and fear can directly change the germline, so that offsprings inherit the fear memory (or something akin to it) of their parents. (There was this interesting report earlier in the year on how cocaine-addicted sires lead to cocaine-resistant male pups through a purely epigentic means, though I remain skeptical.)
Virginia Hughes broke this story at the 2013 Society for Neuroscience conference. Since then, it has garnered plenty of attention from media and neuroscientists alike, with opinions from “deep scepticism” to “awe-inspiring”. Here’s the original paper if you’d like all the juicy details.
Ketamine, the clubbing sweatheart and horse tranquillizer, is now being repurposed as a fast-acting antidepressant; this is perhaps THE most breakthrough new treatment for depression in the last 50 years. In this 3-part series, Gary Stix explains the uprising of grassroots ketamine prescriptions, big pharma interest in the drug and how ketamine is directly the development of next-generation antidepressants.
6. Computer Game-Playing Shown to Improve Multitasking Skills. By Allison Abbott.
Rejoice, gamers of 2013! Not only has the year given us PS4 and Xbox One, this study from Nature has also given us an excuse to game (uh, or not): in subjects aged 60-85, playing a 3-D race car-driving video game reduced cognitive decline compared to those who didn’t.
Commercial companies have claimed for years that brain-training games help improve cognition; yet whether their games actually work is hotly debated (I’m looking at you, Luminosity!). In this new study, researchers from UCSF show that a game carefully tailored to a specific cognitive deficit can be useful, even months later. Unfortunately this doesn’t mean any ole’ video game will do. Shame.
5. 23andme versus the FDA.
I’m sure by now you’ve heard about the fight of the year.
David Dobbs has a full page of links over the 23andme and FDA food fight. What’s the big deal? Why did the FDA issue a cease and desist order? Is it simply a clash of cultures between the company and government department? Or are we selling out our own genetic data to the next-generation Google, and should we fear the services the company offers?
Why do we sleep? Reasons range from learning and memory, metabolism and body-weight regulation, physiology, digestion, everything. A study this year proposes that sleep has another function: nightly cleaning, in which the cerebral spinal fluid washes a day’s worth of brain waste down the sewers. That is, if you’re a rat.
3. Death by sugar? by Scicurious.
With fat making a come-back, sugar and/or carbs are the devil this year. This study in Nature Communications says yes: when mice consumed a diet that has an equivalent amount of sugar to that of many people in the US, the animals’ health and reproductive ability declines.
However, as Scicurious astutely asked, can we really directly translate conclusions derived from mice to humans? Is sugar really that evil?
Here is another article on the topic by Ferris Jabr that’s well worth a read.
2. False memories implanted in mouse’s brain by linking portions of two real memories together. Wow. Just, wow.
False memory planted in mouse’s brain. By Alok Jha
This is one paper I REALLY wish I had the time to cover when it first came out. An MIT group artificially connected the memory of a safe box and the memory of a footshock in another box to generate a new hybrid memory. This is not “implanting” a de novo memory – that is, researchers didn’t use electrical stimulation (or something similar) to generate a memory from scratch. The study also can’t tell us how false memories are generated biologically in our brains (ie linking imagined material to actual memories), but the study is genuinely fascinating all the same.
1. Knockout blow for PKMzeta, the long-term memory molecule.
In a nutshell, previous studies have identified a single protein called PKMzeta that helps maintain long-term memory. Unlike other kinases (a type of protein involved in many cellular processes, including memory) PKMzeta is always active, and seems to help sustain the strengthening of connections between neurons during memory formation. Inhibit PKMzeta, and the memory’s gone.
These results spurred HUGH interest in the “memory molecule”, often with references to Eternal Sunshine of the Spotless Mind. However, things went for a downward spiral at the 2012 Society for Neuroscience conference, when researchers presented the first evidence that mice without PKMzeta had no impairments in LTP (long-term potentiation, widely considered a cellular mechanism for learning and memory) could still form memories. The two groups published their findings in early January 2013 in Nature (here and here).
These observations don’t necessarily mean that PKMzeta is not a memory molecule – it very well could be one of the MANY memory-associated proteins. Given the redundancy that often comes with evolution, it’s hard to believe that one particular molecule would be the sole guardian of our memories. The question remains whether PKMzeta is a MAJOR player, but overall, the debate is a cautionary tale against putting one molecule on the pedestal. So if (or when) you see another article with the headline “erasing a bad memory”, remember there’re plenty of other players in memory that you haven’t been told about.
The morning before Christmas eve, I’m sitting here in the dining room munching happily on the bits and pieces of what’s left of our gingerbread house that was only erected to its full glory the night before. I have not consumed this amount of carbohydrates in over a year.
Inside, a few species of my extensive gut microbe community are screaming bloody murder.
When you eat, you’re not only feeding your own fleshy vessel, but also the 100 trillion of microbugs that thrive in your intestines. Hardly “along for the ride”, these bugs not only help us digest foodstuff, ferment carbohydrates and proteins but also heavily impact our metabolism and general health. Depending on their composition, they tweak our risk of cardiovascular diseases, Type II diabetes and may even cause obesity in humans. There’s tantalizing evidence that their reach extends to the brain, influencing mood, anxiety and cognition in mice.
However, the gut microbiota* is a fluid, ever-changing beast. In one previous study, researchers transplanted gut-free mice with fresh or frozen human poop to inoculate them with a microbiome of known composition. When researchers switched these mice’s plant-based diet to a high-fat, high-sugar one, the structure of the established microbiome changed within a single day: some species dwindled in number, while others exploded onto the intestinal stage, bringing with them their particular metabolic tricks. (*The word “microbiome” refers to the set of genes in the gut bugs).
Similar diet-induced changes have been found in humans. When babies are weaned from their mothers’ milk and switch to solid food, their gut bug community simultaneously go through tumultuous changes. The gut bugs of African hunter-gatherers vastly differ from those in people grown on a Western diet. But these changes take weeks, even lifetimes. Just how fast can the microbiome adapt and change to a new diet?
In a new study, researchers recruited ten volunteers and put them on two drastically different extreme diets for 5 days – as you can see below, the plant-based diet was rich in grains, fruits and vegetables (high-carb and high-fibre), while the animal-based diet consisted of meats, eggs and cheeses (high-fat, high-protein and low/no-fibre). Each day, the volunteers handed in a poop sample for the researchers to monitor.
In general, the animal-based diet had a greater impact on gut flora than the plant-based one. It significantly increased the diversity of gut flora, enriching 22 species whilst decreasing the fibre-intake associated Prevotella in a life-long vegetarian on this meaty diet. The plant-based diet, on the other hand, only increased the abundance of 3 species, mostly those associated with carbohydrate fermentation.
Many of the changes made sense. An animal-based diet enriched putrefactive microbes, shifting carbohydrate fermentation into amino acid digestion, thus helping the body break down the onslaught of heaps animal protein. Several strains of immigrant bacteria – particularly those used for cheese- and sausage-making –settled down and made themselves comfortable in the native gut flora community. The meat-heavy diet also triggered microbes to activate pathways that degrade cancer-causing compounds found in charred meats, and enhanced the synthesis of vitamins.
On the other hand, several strains of potentially health-negative bacteria also multiplied in the meat-eaters. On a high-fat diet, we excrete more bile – a bitter fluid that may ruin a good fish dish – to deal with the digestion of fat. Bile is toxic to many gutbugs, but not to the mighty Bilophila (“bile-loving”) wadsworthia – a bile-resistant bacterium stimulated by saturated fats in milk that may cause intestinal inflammation, at least in mice. The high-fat content in the animal-based diet also triggered increased levels of microbe-produced DCA, which is previously linked to liver cancer in mice. However, as of now there’s no evidence that these risks also apply to people, and researchers caution against making health-related judgments (although some can’t resist the temptation).
On the whole, plant- and animal-based diets induced changes in host microbiome gene structure that resembled those of herbivorous and carnivorous mammals within a few days. Furthermore, the volunteer’s microbiome reversed back to their previous composition only 2 days after the end of the experiment. Researchers believe we might be looking at a fast-forwarded movie of millions of years of co-evolution between humans and their microbugs: when animal food sources fell scarce, our ancestors were forced to switch to a plant-heavy diet; a flexible gut-bug community could quickly and appropriately shift their repertoire and function to help digestion, thus increasing the flexibility of human diets and chances of survival.
Thus, when you gobble down the vast selection of Christmas dishes this year, remember to thank the flexibility of your gut flora for your diverse digestive powers. And remember that we can’t say one diet is better than the other for our microbiota; the take-home message is that they are incredible flexible, more so than we previously thought. In the end, it still comes down to the age-old wisdom: you are what you eat.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, & Turnbaugh PJ (2013). Diet rapidly and reproducibly alters the human gut microbiome. Nature PMID: 24336217
What’s Christmas without a bottle of good wine, a snifter (or two) of peaty Ardburg and a few raunchy family tales that, upon awakening the next morning with a pulsing head and stone-cold sober realization, constitute as Too Much Information that you wish had never graced your ears?
If you’re like me, however, you’re probably in too much misery to care about what your 65-year-old-aunt-did-in-that-summer-30-years-ago. Despite its long history and frequent occurrence, hangovers remain enigmatic monsters that haunt those reckless enough to seek the dew of the gods with no reservation. The symptoms appear AFTER the alcohol is eliminated from the body, and (against popular belief) may not be a direct result of dehydration.
Physiological causes aside, perhaps it’s more useful to figure out what type of booze precipitates the worst hangovers all else equal. One common rumour is that dark-coloured alcohols – think bourbons, dark rum and scotch – give more of a punch than their paler counterparts.
Alcohol by itself is colorless. The colour of unadulterated alcoholic beverages comes from congeners – chemicals other than ethanol that seep into the final product due to the fermentation and aging process. They are complex organic molecules with toxic effects, including acetaldehyde (metabolite of ethanol that gives the “Asian glow”), tannins (astringent-tasting molecules found in red wines) and even methanol. That’s not the say they’re BAD – bourbon contains 37 times more of these flavorful molecules than vodka, which gives them their distinctive taste. Nevertheless, congeners are thought to make hangovers worse. A study in 2009 put this theory to the test, pitting Wild Turkey bourbon against Absolute vodka.
Researchers recruited 95 college-aged, non-alcoholic participants and invited them for two wine-and-dine sessions in the lab. One of the nights they got either bourbon or vodka mixed with coke to mask the taste, the other night they got coke-mixed tonic water as a non-alcoholic control bevarage. After ensuring the participants were indeed intoxicated, researchers put them to bed. Since alcohol negatively affects the quality and duration of sleep, researchers monitored the participants’ sleep architecture. The next morning, the team measured the intensity of the participant’s hangovers with a symptom-based scale and tested the subject’s cognitive function with 2 tasks that required sustained attention and reaction time.
Sure enough, bourbon caused a worse self-reported hangover than vodka in both men and women. Alcohol consumption also made it more difficult to fall asleep for women and decreased sleep efficacy in both sexes, which led to poorer performance on the cognitive tasks. However, although bourbon made the subjects FEEL crappier, its effects on sleep and next-day brain function were no worse than that of vodka.
These results seem to suggest that alcohol is alcohol, regardless of what type you drink. Bourbons may make you suffer more the next morning, but as coke can hardly mask the spicy bite of Wild Turkey, placebo effects could have skewed the participant’s subjective hangover ratings. But the data is hard to extrapolate. Most of the participants were caucasian (79%); since many asians lack the aldehyde dehydrogenase enzyme that helps break down acetylaldehyde – a toxic metabolite of ethanol and a common congener – it’s likely that asians may find bourbon more intolerable than vodka. Furthermore, the amount of alcohol consumed in this study was just enough to reliably induce a hangover – it’s hard to say how well results hold if you drink more. After all, even for congeners the dose makes the poison.
In line with this, a survey in 2006 among Dutch college students after drinking beer, wine or liquors showed that it takes fewer high-congener drinks to get a hangover and a worse one at that (see graph below). Unfortunately as surveys are hardly strictly controlled and rely on self-reporting, so take these “naturalistic” results as you will. Personally, I think I’ll keep embracing the dark side.
Finally, one special case in hangovers is the notorious red wine headache. Although red wine is lower in alcohol content than spirits, it’s especially high in histamines, tannins, flavonoids and sugar (especially the cheaper reds), all of which along with alcohol makes a perfect hangover stew. Add to the fact that wine glasses are much larger in size than shot or tall glasses, and that people tend to pour more into wider glasses and when they’re holding the glass, it’s perhaps not so surprising that a classy family night with wine can still feel like a night out clubbing the morning after.
Ultimately, you’re probably going to keep drinking your drink-of-choice no matter what science says. But maybe stick to lighter quality booze at family gatherings just in case. It just might make your boxing day shopping a little easier.
Rohsenow DJ, Howland J, Arnedt JT, Almeida AB, Greece J, Minsky S, Kempler CS, & Sales S (2010). Intoxication with bourbon versus vodka: effects on hangover, sleep, and next-day neurocognitive performance in young adults. Alcoholism, clinical and experimental research, 34 (3), 509-18 PMID: 20028364
As Christmas approaches like a freight train I, like many, scramble to buy last minute gifts and prepare myself to gorge on feasts and booze and laughter(?) – all part of a joyous(??) family gathering. In last effort to procrastinate until the very end, I present to you this short series of posts on various and totally random holiday-related themes. Enjoy!
Sings: Petri dish sterilizing near an open fire, lab rats nipping on my shoe, data woes cried by grad students, and PIs dressed like You-Know-Who! Ok, this might’ve gotten a laugh out of grad students. Anyone? I’ll show myself out.
Laughter permeates holiday gatherings. Dubbed “grooming at a distance”, laughter is thought to establish and maintain bonds between individual primates of all sorts. Like yawning, the mere sound of laughter often triggers giggling fits in others in a contagion-like manner. Within four-tenths of a second after exposure, electrical activity spreads out through areas involved in cognition, emotion, sensation and movement; this triggers facial contortions, spasmodic breathing and bodily convulsions as we involuntarily emit a series of curious vocalizations, ready to infect another.
Collapsing in a quivering heap, we are left under-the-influence of a deluge of a neuroendocrine cocktail. The amount of epinerphrine, a hormone in the fight-or-flight response plummets, while dopac, a major metabolite of dopamine, shoots up. Laughter also triggers the release of pain-relieving endorphins and growth- and metabolism-boosting growth hormone, which together with other chemicals form somewhat of a panacea for the mind and body. As Robert Burton once astutely wrote in 1621, “Mirth…prorogues life, whets the wit, makes the body young, lively and fit for any manner of employment.”
So where’s the evidence?
British Medical Journal produced a snicker-inducing, tongue-in-cheek report that synthesized findings from 785 papers on the health benefits of laughter. To round things up, they threw in harmful effects for good measure, while discarding papers written by authors with “Laugh” in their last name which where nonetheless “not particularly amusing”. Here’s what they found.
In terms of the psyche, laughter increased tolerance to pain in the lab, but hospital clowns did not reduce distress in children going through minor surgery to any observable extent. Humorous movies had minimal success on serious mental illnesses like schizophrenia, and group-based humor therapy did not particularly benefit late-onset depression in Alzheimer’s disease, though there was some improvement in patient morale and mood. Laughter was associated with life-long satisfaction, but there’s no evidence that one causes the other either way.
More mirthful news comes from laughter’s effect on the body. A 20min funny movie acutely reduced the stiffness of blood vessels and made them more limbre. A sense of humour lowers your risk of heart attack and improved lung function in those with chronic obstructive pulmonary disease, an illness that makes it difficult to breathe. In the latter case the credit goes to hospital clowns, whom apparently until the year of study (2008) were still regarded by some brave souls as non-terrifying entities.
Laughter had no consistent effects on immune functions such as natural killer cells, but sometimes aided the surgical removal of a pouch of pus by bursting it through laughter-generated muscle contractions. Laughter also benefits metabolism: compared to a monotonous lecture that drooled forever on, a comedy show helped control blood sugar levels after a meal. A 15min-bout of genuine laughter burns up to 40 calories, so battling the average 6000-calorie Christmas dinner would requires 37.5hrs of merriment to burn off. Better get those jokes ready.
Finally, if you’re trying to get pregnant through in vitro fertilization (test-tube baby), perhaps consider hiring a clown dressed like a chef de cuisine. In one study, such a clown entertained 110 would-be mothers after embryo transfer for 12-15 minutes with saucy jokes and magic tricks, “a recipe of success” that led to ~16% increase in pregnancy rate compared to the 109 non-clowned controls, adding another win for medicinal clowning.
Unfortunately laughter is not without its pains. Laughter weakens resolve and promotes your preference for certain brands, so keep a skeptic eye on that joke-cracking salesman. A hearty guffaw can cause temporary loss of consciousness, perhaps due to the sudden increase in pressure in the chest cavity that triggers a neural response. Laughing can screw up the electrical activity in the heart causing it to pump irregularly, to the point of cardiac arrest or rupture, giving “dying of laughter” a more sinister undertone.
Laughter can lead to abnormal collection of gas between the lung and chest wall or engorgement of air sacs of the lungs, resulting in labored breathing. The sharp intake of air to initiate laughter can promote inhaling foreign objects, causing you to choke on a small piece of turkey, while frequent exhaling disseminates infection. Laughter may also wreck havoc on your alimentary canal, dislocating the jaw or puncturing the esophagus (your “food-tube”), so maybe eat first and laugh later. You might also want a clear line to the wash(bath)room. Laughter can cause incontinence stemming from involuntary contractions of bladder muscles, which surprisingly may be counteracted by Ritalin.
And finally, uproarious laughter may not be so funny to your brain. Cataplexy, a condition where a person suddenly looses muscle tone, can be triggered by laughter and other salient stimuli, leaving you unceremoniously collapsed under the Christmas tree. That is, unless only one side of you is affected. In one documented case, laughter triggered cataplexy only on the right side of a patient’s body, leaving her presumably capable of continuing laughing on the left side of her face.
Laughter and other pleasurable things may precipitate headaches in the unfortunate, sometimes due to sacs of jello-like material in the third ventricle, a fluid-filled compartment in the brain. Laughter may also be no laughing matter to people with patent foramen ovale (PFO), whom have a hole in the heart that should’ve closed after birth but didn’t. Take this case for example: after 3 minutes of roaring laughter, a PFO patient lost her words (literally) and had a stroke.
This report from BJM obviously shows that laughter is not all beneficial, but it overall carries a low risk of harm in the general population. In terms of cost-benefit analysis a good laugh is still beneficial. Yet, as always, more research calls. As the authors put it:
“It remains to be seen whether, for example, sick jokes make you ill, if dry wit causes dehydration, or jokes in bad taste cause dysgeusia (note: distortion of the sense of taste), and whether our views on comedians stand up to further scrutiny.”
R E Ferner, & J K Aronson (2013). Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis BJM DOI: 10.1136/bmj.f7274
I’m over at #SciAm videos, talking about the (potential) neuroprotective effects of a ketogenic diet. The short clip is based on a blog post The Fat-Fueled Brain I wrote a while back for their Guest Blogs (the article’s older sibling, Brain, living on Ketones can be found here).
The talented Dr. Carin Bondar, host of the series, suffered through the process of piecing my camera-dodging, hair-pulling, face-making video clips together (I’m EXTREMELY camera shy). She has my deepest respect.
SciAm also has a great video series called Instant Egghead that’s worth checking out. Fun – and super random- science info in ~2min clips with great graphics. Here’s an example: why toothpaste makes OJ taste bad.
Pot’s not the best thing for your memory. Yes, I know there are functional potheads who enjoy their greens and get also their work done. Still, it’s hard to ignore the legions of studies that show Δ9-THC consumption impairs spatial learning and working memory – that is, the ability to hold several pieces of information in mind and manipulate them to reach a mental goal.
Yet paradoxically, THC may benefit those with Alzheimer’s disease. Previous research in rats show that the compound breaks down clumps of disease-causing proteins (called β-amyloid plagues) by upregulating a “scissor” enzyme that chops them up. Sweeping out these junk protein plagues decreased the number of dying neurons in the hippocampus, a brain area crucial for learning and memory. THC also has powerful anti-oxidant effects and may protect the integrity of mitochondria – the “power plants” of our cells.
So here’s the dilemma: THC may potentially battle dementia, yet it also naturally impairs memory. In an unexpected turn of events, scientists from Louisiana State University discovered a key protein that mediates THC-caused memory loss, and show in mice that you can have your edibles and eat it too.
The protein in question is COX-2, a crucial player in inflammatory pain – think headaches, muscle pains and fever. Sound familiar? That’s because COX-2 is one of the targets of OTC painkillers such as Asprin and Tylenol (the other one is COX-1). Scientists have previously linked 2-AG, a THC-like substance produced endogenously in the brain, to inhibiting COX-2 signaling. Blocking COX-2 led to problems with memory retention. So naturally, they wondered whether THC impaired memory in the same way.
They found the opposite. As you can see on the left (blue bars), a single injection of THC boosted the level of COX-2 in both neurons and astroglias (“structural” non-neurons that play a role in memory and inflammation) in the hippocampus; the more THC, the more COX-2. This effect went away by 48hrs after the injection, but when the mice went on a weeklong THC binge (1 dose/day), their COX-2 levels remained chronically high cough unregulated (right graph, red bar compared to control black bar). When researchers blocked the THC/endocannabinoid receptor CB1R by either genetically deleting it or using a selective pharmaceutical blocker, the effect went away, showing that THC administration is indeed the cause of COX-2 increase.
Why would endogenous cannabinoids (2-AG) and THC have polar effects? Further molecular sleuthing revealed that it’s all in the messenger: although both 2-AG and THC activated the same receptor, 2-AG recruited Gα as courier, while THC opted for Gβγ. It’s like slapping a different address sticker on two boxes shipped to the same sorting facility; they’re now going different places. Indeed, Gβγ triggered a molecular cascade that activated several proteins previously shown to impair memory.
Naturally, researchers went on to block COX-2. After a week of THC, neurons begin to loose their spines – that is, little protrusions along the dendrite that house proteins necessary for forming and maintaining synapses (compare red bar/THC to black bar/control below). The breakdown of spines caused a decrease in the many proteins and receptors needed for normal excitatory signal transmission. Unsurprisingly, eliminating these channels of communication blunted the response of a cohort of neurons in the hippocampus after electrical stimulation. However, giving a COX-2 selective blocker concurrently with THC rescued all these deficits – structural, molecular and electrical (green bar – the spines are back!).
As for mutant mice that lack COX-2 at birth? They didn’t suffer any of these problems associated with THC. In the case of spines, as you can see above, THC (burgundy bar) had no effects compared to control (blue).
Do any of these “under-the-hood” changes lead to observable behaviour? In a fear-conditioning experiment, researchers trained mice to associate a box with electrical shocks. They then gave some of the mice 7 days of THC with or without a COX-2 inhibitor. When tested 24hrs later – presumably to weed out THC’s effect on anxiety* – stoner mice showed little fear when put back into the box. Those on the multi-drug regime, however, froze in fear. Like their sober peers, they retained and retrieved the fear memory. (The half-life of THC is ~20.1 hrs in mice, so they might have still been high at the time of testing.)
In a spatial memory task, researchers trained mice to find a hidden platform in a big tub of water. After 5 days of training, they then gave a subgroup a single injection of THC 30min before the test, which resulted in these mice taking roughly twice as long to find the platform as the controls. Once again, concurrent COX-2 administration “saved” the memory of the platform location. 24hrs later, after the mice had sobered up, they were tested again – same results.
Amazingly, inhibiting COX-2 did not destroy THC’s ability to wipeout Alzheimer’s-related protein plagues in a mice model of the disease. Treatment with THC once daily for a month, with or without the OTC COX-2 inhibitor Celebrex, significantly decreased the number of protein clumps (green below) and protected hippocampal neurons (blue).
Before you reach for the bottle of aspirin, joint in hand, maybe hold back on the self-medication just yet. For one, it’s hard to extrapolate these findings to humans, there are some interspecies differences in THC metabolism. Second, chronic COX-2 inhibition is linked to serious side effects such as ulcers and heart problems (think Tylenol is safe? Think again). Third, mice with inhibited COX-2 showed didn’t seem as couch-locked as they normally would; so if you’re after that body high, an aspirin would be rather counter-productive.
As a molecular neuroscientist, I love the detailed characterization of THC-CB1R signalling pathway, but the behaviour data could use some strengthening. Although researchers claimed that the water maze task assessed working memory, the protocol they used looks at normal spatial memory. To specifically probe working memory, they would’ve needed to move the platform to different locations and see how well the mice updated their memory. The results also directly counter those of a previous study, which showed that once the mice learn the location of the platform, THC did not impair the memory. They also didn’t report whether THC mice were simply too stoned to swim (or motivated enough) – tracking total swimming distance and speed at the time of testing would’ve helped .
This study focuses mostly on neurons*; a previous study published in March 2012 showed that THC impairs memory through a type of glia called astrocytes (the non-neuron brain cells); in fact, marijuana impaired working memory only when it was able to bind to the CB1Rs on astrocytes. That study pointed to deregulation of excitatory neurotransmitters as the cause of memory impairment; could COX-2, which is expressed in glia, also have a role?
*Edit: HT to reddit/u/superkuh. The text suggests that the authors of this paper did not consider the role of astroglia; in fact they explicitly did, when they showed that COX-2 upregulation occurred greater in astrocytes than neurons. The authors also showed that the reduction of glutamate (excitatory) receptors was due to COX-2-induced increase in glutamate release from both neurons and glia.
When I was young, the one superpower I craved above all was perfect memory. I’d picture my eyes as camcorder lenses, recording everything that I read, saw and experienced into the Kodak film that was my brain. Anytime I wanted to re-experience something, I’d simply hit a mental “play” button and BAM! The video of my life would play before my eyes, as clear and detailed as the day it was created.
Little did I know that for those with Highly Superior Autobiographical Memory (HSAM), my fantasy was their reality. Researchers from University of California reported the first case of this phenomenal ability in 2007 when a lady dubbed AJ reached out to them – with a desperate plea for help – with the following email (experts):
Dear Dr. McGaugh, As I sit here trying to figure out where to begin explaining why I am writing you and your colleague (LC) I just hope somehow you can help me. I am thirty-four years old and since I was eleven I have had this un-believable ability to recall my past...I can take a date, between 1974 and today, and tell you what day it falls on, what I was doing thatday and if anything of great importance (i.e.: The Challenger Explosion, Tuesday, January 28, 1986) occurred on that day I can describe that to you as well...Whenever I see a date flash on the television (oranywhere else for that matter) I automatically go back to that day and remember where I was, what I was doing, what day it fell on and on and on and on and on. ... Most (people) have called it a gift but I call it a burden. I run my entire life through my head every day and it drives me crazy!!!…
AJ was different than any “memory experts” that the researchers had previously encountered. Her ability seemed completely innate; she did not use little tricks (“mnemonics”), such as mental imagery or story telling to help her remember. Her superior memory only pertained to specific aspects of her own life story and related events; she had trouble learning historical dates and reciting poems. Like your average Joe, she couldn’t remember what each of the 5 keys on her keychain was for. Although specific dates triggered recall in an automatic, “non-stop, uncontrollable and totally exhausting” manner, when asked if she’d talked about a particular date with the researchers in previous interviews, she said she couldn’t remember.
AJ, and the handful of people whom had come forward with HSAM since then, pose a troubling dilemma to memory researchers. Recalling an event is nothing like watching a video recording. Instead, it is an active reconstructive process prone to distortions from misinformation. For example, in labs, researchers have been able to manipulate people into remembering events they’d only previously imagined or trick them into recalling that they’d watched a news video that did not exist. In courts, “corrupt” memory plague eyewitness reports. Elizabeth Loftus, an expert in memory research, had even suggested that planting fake memories in children may be a successful way to modify delinquent behaviour.
Contamination seems like an inevitable part of our memory process, yet common sense suggests that those with HSAM would be spared. Their memories, instead of malleable and fluid, should be etched in stone. But is this really the case?
Researchers from UC Irvine recruited 20 HSAM participants and compared them to 38 age- and sex- matched controls. In the first test, they asked the volunteers to remember a string of related words, such as “light”, “shade” and ”table”. What was missing from the list was the highly similar lure word “lamp”. During the test, when volunteers were asked whether they had seen a particular word in the list, around 70% of the control group (light grey, left graph) falsely remembered seeing the lure. Incredibly, HSAM volunteers (dark grey, left graph) did not fare any better.
Verbal memory is hardly autobiographical. Next, researchers showed the volunteers photos of two separate crimes – a man stealing a wallet and putting it into his jacket pocket, and a man jacking a car with a credit card. Forty minutes after the picture show, volunteers read 50 sentences describing each crime. Unbeknownst to them, 3 sentences included misinformation about minute details, such as “he put the wallet in his pants pocket” or “he used a clothes hanger to break in”. When tested an hour later, the volunteers not only misremembered details but also attributed them to the incorrect source. Astonishingly, those with HSAM were far from immune, generating significantly more false memories than controls.
Again, you may say, the above events did not happen to HSAM individuals themselves. Nor were they particularly disturbing – perhaps volunteers simply didn’t care enough to pay attention to detail? Emotionally charged memories tend to demand attention and stick around for longer than neutral ones; like most people, I have no trouble recalling what I was doing when I first heard of the plane crashes on September 11, 2001 (whether my recall is accurate, however, is another question).
Researchers tapped into this powerful memory. Specifically, they asked what the volunteers remembered about the crash of United Airline Flight 93 with a questionnaire. Hidden in the questions were sprinkles of misinformation and flat-out lies -for example, “a witness had filmed the crash on the ground and the film was subsequently aired”, when no such footage actually existed.
As you can see in the graph above, later in an interview, roughly ~20% of HSAM participants (D left, dark grey) said they had seen the footage compared to 29% of controls (D left, light grey). The percentages were roughly the same if the fabricated video was mentioned off-hand by researchers during the interview (not shown). Even more mind-boggling is this: in the HSAM participants, those tested at top 50% for autobiographical memory accuracy performed worst; in fact, they were just as bad as the controls (D right, high PEQ=better autobiographical memory on initial test). The participants weren’t reporting vague feelings of “having seen the video” either; when probed further, they gave elaborate details:
Interviewer: OK, Can you tell me what you remember about the footage? HSAM: Uh, I saw it going down. I didn’t see all of it. I saw a lot of it going down uh, on air. Interviewer: Ok, do you remember how long the video is? HSAM: Just a few seconds. It wasn’t long. It just seemed like some- thing was falling out of the sky. It was probably was really fast, but I was just, you know, kind of stunned by watching it you know, go down. Interviewer: Ok, so now is the last question, I would like for you tell me how well you can remember having seen the video on the scale from 1 to 10, where 1 means no memory at all and 10 means a very clear memory? HSAM: I’d say about 7.
So here’s the conundrum: we have a cohort of people with astonishingly accurate and detailed autobiographical memory, whom nevertheless are susceptible to misinformation and false memories. Perhaps, you may have already pointed out, it’s due to the small sample size. While certainly a problem in most studies, here researchers have consistently found false memories in HSAM individuals, thus proving the point that fallible memory is (somewhat) inescapable. In other words, increasing sample size would not reduce misremembering to zero percent and thus would not disprove their conclusion (it may help tease apart differences between low- and high- performing HSAMs though). The results would have been more difficult to interpret if they had not found false memories in those with HSAM.
The second problem is that the crash of United 93 is semiautobiographical in nature. The volunteers witnessed the event vicariously through multimedia rather than experienced them first-hand. Previous experiments with AJ, our first identified HSAM individual, showed that while “she could quickly, reliably and accurately tell what she was doing on a given date, she couldn’t recall specific events from a videotape the month before”. In other words, her –and presumably, other HSAMs- extraordinary memory are selective. Here the researchers show they could “implant” a fake factoid 11 years after the fact, and some HSAM individuals would incorporate the memory into their original set of memories of the crash. What I would love to know is whether researchers could distort the volunteers’ own experience of the event. That is, whether they can alter an existing autobiographical memory rather than introduce a new one.
If HSAM individual have these common flaws, how are they still capable of remembering trivial details from a decade ago down to a tee? Researchers think it’s because very little misinformation is generally introduced in their daily lives. “No one comes up to them and says March 2nd, 2001 was a Monday not a Friday,” said one researcher to National Geographic. I’m not so sure that’s true – I know every time I go down memory lane with my friends we recall things differently; misinformation abounds. Our personal accounts end up influencing each other’s memory of the event.
Regardless, HSAM is in and of itself a fascinating phenomenon. Along with many other studies that investigated memory distortion in people with typical memory, this paper suggest that fallible memory reconstruction (reactivation and reconsolidation) is a basic and widespread part of human memory, a global phenomenon deeply routed in our neurobiology. No one, not even those with superhuman memory, is spared. But who knows, maybe discoveries of future “memory experts” will prove this wrong.
Patihis L, Frenda SJ, Leport AK, Petersen N, Nichols RM, Stark CE, McGaugh JL, & Loftus EF (2013). False memories in highly superior autobiographical memory individuals. Proceedings of the National Academy of Sciences of the United States of America PMID: 24248358
Think back to that moment when you first heard your favorite song. What about it made you stop in your tracks? Was it the incessant buildup, soaring high, filling you with a sense of elation? The flirty high notes, light as wings, bringing a bounce in your step? Or the rumbling base drop, furiously cascading, sending shiver after shiver down your spine?
Music has always had a special place in my heart. Like many, I use it as an emotional outlet and a painkiller for physical aches. During one of my longer runs a while back I distinctively remember a sense of elation as a drum & bass piece with the perfect BPM came on. I matched my foot strikes to the beat, closed my eyes and ran in a state of pure euphoria. (It helped that I was one of the only people on a flat, spacious wall that hugged the ocean. I must’ve looked high.)
Since that run I’ve been musing over our relationship with music. Across the globe people describe intense pleasure from listening to music, grooving to music, exercising to music. What lies at the core of this abstract euphoria? What is it about our perception that allows us to experience all three in unison?
I hope to answer these questions with my new piece up at Scientific American MIND. It is science writing based on peer-reviewed literature; but it’s also my personal ode to music.
If you have a moment please check it out, and let me know what you think!
Edit: Beau Sievers, one of the authors of the study, kindly provided feedback on Twitter. She pointed out “The SciAm piece could be misread as saying Kreung music has no tuning, timbre, or scales—they do, they are just not Western. Kreung mem music does have clear notes in it, articulated to evoke insect sounds—very ‘buzzy’ but still musical. Thanks for the very nice writeup!”
Hope this helped to clarify things!
Kudos to Virginia Hughes at National Geographic blogs (Phenomena: Only Human) for directing me to the cited studies. She has previously written about them individually on her blog. Her writing is FANTASTIC – if you’re not a reader yet, I highly recommend her work.