Dormivigilia

Over the past ten days, I have been chillaxing in Fort Myers, Florida and the surrounding area with my mom’s family for the 1st Annual Evanoff (my mom’s maiden name) Extravaganza. The week was booked with numerous festivities beginning as early as 4 AM (four hour travel to Universal Studios) and as late at 2 AM (traveling 20 miles south to a club only to discover that my brother and other male cousins could not enter because they were wearing shorts!!!!!).

These pictures from Universal Studios in Orlando, my high school BFF’s wedding to the person of her dreams since 7th grade (!!!), and Evanoff cuckoo and craziness capture my two week blogging hiatus, which will be no more that is if I don’t travel to the remote land of Costa Rica again…..wishful thinking……

From A Day At Hogwarts, Robyn’s Wedding, and Evanoff Extravanganza, posted by Allison Brager on 7/28/2010 (50 items)

Generated by Facebook Photo Fetcher

First off, I have an excuse for my week long hiatus. My best friend from high school who has been dating her boyfriend since 10th grade (or if you count the years of endless flirtation, then 6th grade) finally got married and had a fabulous, quintessentially Italian Youngstown wedding. Now that the festivities are over and I am in Florida for a family reunion, I happened, ironically enough, to encounter a circadian-related article in Cosmopolitan while waiting in line at the grocery store. Though I haven’t been able to locate a digital copy of the rather inconspicuous graph, Dr. Holly Phillips (MD) reports of a biological rhythm in sexual desire (i.e. horniness).

As represented here, horniness is highest in the morning (no surprise) and at night (also no surprise). Cosmo suggests that during the mid-morning and afternoon when horniness is precipitously dropping that you and your man get a coffee and spend time with the guys/girls (so you’ll miss each other’s presence), respectively.

Three years ago at the Society for Research on Biological Rhythms meeting, I recall seeing a poster with similar data; though I don’t remember which circadian time points the bathypahse and acrophase of sexual performance and sperm quality occur, sadly, sexual performance is out-of-phase with sperm quality, which isn’t good news for baby wanters. Google scholar wasn’t any help either, unfortunately.

I attended Science Cafe Cleveland held at the Great Lakes Brewery, home of Lake Essie, Christmas Ale and the extra-hoppy Commodore Perry tonight. While nursing a Commodore Perry, I listened to two experts on anthropological and psychological influences on teenage eating disorders by Drs. Anderson-Fye (of Case Western) and Jamor (also of Case), respectively. The former does her research in Belize, the latter is a practicing clinical psychologist. While the underlying message of their lecture was that the physiological (genetics, dopamine!!!), psychological (overachievement), and social (the media) influences on the etiology of eating disorders is multi-level and difficult to disentangle (though considerable progress is being made), I did learn about some disturbing case studies and cross cultural disparities regarding body image.

From the clinic:
-One dietitian in attendance recalled a time when she found a girl suffering from bulimia in the bathroom doing jumping jacks while being attached to an IV, which was placed in her arm to rehydrate/re-calorize her after she had previously discovered a method of relieving herself of calories that had intra-gastrically (reverse stomach-pumped) been infused.

From the field:
-Predicting the prevalence of eating disorders is fairly easy (it’s higher) in rapidly developing countries where there is frequent overexposure to American media (Cosmopolitan, America’s Next Top Model) directed towards teenagers.
–> In Fiji, the parents of a suddenly thin child are often chastised by other family members and friends, with this support group attributing a child’s transient thinness to a lack of maternal/paternal care and love, that is until Tyra Banks came to the country and suddenly many Fiji teenagers became (or strived to be) thin. And now its domesticated voodoo.
–> The prevalence of eating disorders is still reduced in Belize because this country, unlike ours, embraces voluptuousness. School girls are often seen arguing whether Coca-Cola (top-heavy) or Fanta (bottom-heavy) bodies are prettier. Regardless, curves are enamored in this culture.

–>One juxtaposing treatment (though highly implausible) for eating disorders is immigrating these patients from their native country with a high prevalence of eating disorders (surprisingly Korea) to an area with a lower prevalence (even more surprisingly, LA!!!!), because their symptoms can shockingly subside!

From the genes:
-Kids are biologically resistant towards eating leafy greens because it wasn’t safe for a three-year old “Lucy” to be grabbing and eating every green leaf, was it?

Though I was displeased with certain generalizations such as the belief that ALL gymnasts suffer from an eating disorder and/or body image distress (I was a gymnast as well as my friend attending), I thought the session was very informative….and the beer was refreshing as usual…..

This “Get Some Sleep” PSA made by students of Dr. Matt Walker at UC Berkeley, who studies the importance of sleep and napping for retaining memories and liberating space in the hippocampus for more memories, was presented at this year’s Sleep Research Society Trainee Day.

Be a good Lego and get 9 hours of sleep.

Given my recent trend of late Neury Thursday posts perhaps Thursday should no longer be the designated day for ABrag’s featured Journal of Neuroscience article of the week….but it can’t be Friday because that’s Fungi Friday and Weird Science Friday, so “Thursday” it is for now…..

In this week’s Journal of Neuroscience Eli and UCLA researchers have used a really cool mouse model to dissociate between sex chromosomal and gonadal influences on alcohol-seeking (” I want”) and full-blown addiction (“I need”).

Sex disparities in alcohol consumption and risk of addiction exist in both animal and human models; in rodents, females drink more as shown in this graph from my own research, which secondarily explains why I solely use males; 1) females have odd, unstable circadian rhythms in addition to 2) unstable, daily drinking caused, of course, by estrus.

In humans, males are at a greater risk of alcohol addiction (possibly due to testosterone influences which hope to be elucidated here…..and are more likely to boss someone around at the bar like this T-juiced guy…..).

In this study, the researchers used a ffour core genome model, which ultimately produced a chromosomal male with nads (XYM),  a chromosomal female with nads (XXM), a chromosomal female with a poon (XXF), and achromosomal male with a poon (XYF).

Using lever pressing as a model of goal-directed alcohol seeking (Yagger bombs!) and habit-forming behavior with alcohol-seeking being classified a mouse learning to press a lever a set amount within a specific time interval for alcohol vs habit-forming behavior where the mouse continuously and impatiently pressed a lever, expecting alcohol and forgetting (or unlearning) the protocol (much like we repeatedly bang the Coke button of a pop machine 100x before realizing that the machine is out of Coke) . As shown here, chromosomal males independent of whether they had a poon or a pen more often engaged in habit-forming behavior (incessant lever pressing vs. specific, timed presses). In contrast, chromosomal females consumed more alcohol, confirming previous data that females drink more.

We can draw two critical conclusions from this fabulous research design: 1) sex chromosomes exert a larger influence on habit-forming behavior that can eventually lead to full-blown addiction in addiction to gating drinking amounts; 2) contrary to previous hypothesis, basic reproductive endocrinology (secretion of T and E) have less of an influence on alcohol-related behaviors and addiction. I certainly believe such elucidation will encourage earlier sought treatment for alcoholism, particularly in males that have an extensive family history of alcoholism.

Barker JM, Torregrossa MM, Arnold AP, & Taylor JR (2010). Dissociation of genetic and hormonal influences on sex differences in alcoholism-related behaviors. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (27), 9140-4 PMID: 20610747

Many of you may remember this lousy foul from the US vs Slovenia match.

Though I initially “jumped to conclusions” and assumed that it resulted from a hefty Slovenian bribe, a recent article in PLOS suggests the call may have resulted from a subconscious bias in reaction time and faulty conclusions of left and right directional movements.

UPenn researchers recruited soccer-knowledgeable fans to view still-frame replays from the English Priemership League (think David Beckham). This league was chosen because aside from David Beckham, many Americans are unfamiliar with the players and teams of this league in addition to limited television viewing within the US. This would reduce the chances of the participants recalling the final outcome of such a play and increase the chances of “unbiasing” directional bias. Kudos to these researchers for taking on the arduous task of blurring out players names and numbers on their jersey’s with Photoshop to eradicate further recall  (many of you are aware of my precipitous hatred for this program!).

Overall, these researchers found that Americans (i.e. individuals who read left to right) react quicker to events that unfold towards the right vs the left. Paradoxically, due to a slower reaction time to left-oriented POVs, participants were more likely to call (or catch) a foul.

I do find it interesting that despite having a slower reaction time to left directional play, fouls are more easily recognized and/or called on the left vs right side. Perhaps this ~100 ms reaction time delay to a left vs right directional play that is unfolding creates a “negativity bias” in that we assume the worst since we aren’t there to witness it….er react quickly enough  (just like we assume that the Slovenian government paid the referees because we weren’t personally there to see if money was slipped from one hand to another….humans love gossip!!!!!!)? Or perhaps the awkwardness of looking right to left causes us to fixate on the left-moving player longer, which leads us to more likely see suspicious activity? This is in contrast to the comfortability of looking left to right, much like reading which involves little fixation on the right-most word and a subsequent rapid transition to the next line. Do we view right directional plays similarly?

Regardless, it would be interesting if this study was replicated to compare cross-cultural differences in directional bias, particularly with societies that read right to left like Hebrew, Arabic, Chinese, and Japanese. Then perhaps this information can be adopted by FIFA to balance cultural -specific POV and ensure a fairer game.

Kranjec A, Lehet M, Bromberger B, Chatterjee A (2010). A Sinister Bias for Calling Fouls in Soccer PLoS One, 5 (7) : 10.1371/journal.pone.0011667

A few months ago, I briefly discussed the emerging field of behavioral epigenetics, when one of KSU’s job candidates and a cited author in last week’s Science review of behavioral epigenetics, presented data on DNA methylation, resulting from physical abuse, and serving as a predictor of suicide. While I support epigenetic research as it may provide more tangible treatments if not cures for banes of human existence, including cancer and Alzheimer’s and reduce the stigmatization of child, drug, and domestic abuse, I do agree that we can’t be too quick to jump to conclusions; if we dissect the etymology of epigenetics with “epi” meaning outer (think of a tip of an iceberg) and “genetics” being more of a rhetorical element, even the translation means outer genetics or if we metaphorically compare epigenetics to an iceberg, environmental modulation of the genetic molecular machinery has roughly 10% of an influence with the other 90% attributed to gene and neuroendocrine interactions. Though this may be a crude analogy, certainly not one expressed in the The Seductive Allure of Behavioral Epigenetics, many interviewees in the Science review would agree.

But if you want to anyways….

Miller, G. (2010). The Seductive Allure of Behavioral Epigenetics Science, 329 (5987), 24-27 DOI: 10.1126/science.329.5987.24

First, I apologize for the tardiness of last week’s Neury Thursday, but I was too busy enjoying the long patriotic weekend doing this: Slip N Slide!!! It was like time travel back to 2nd grade before helicopter parents and neighborhood lawsuits.

Speaking of related tardiness, last week’s Journal of Neuroscience featured an article illustrating dopaminergic and amygdalar influences on impulsivity assessed through differences in the subjective value of sooner-smaller or later-larger monetary rewards between dopaminergically-medicated and unmedicated subjects. Using mathematical modeling, fMRI, dopamine agonists (L-dopa) and antagonists (haloperidol), and a complex, yet compelling experimental design, British neuroscientists revealed that highly upregulated dopaminergic states, induced through L-dopa,increased impulsivity and subsequently decreased amygdalar activity (I want that money now to buy an iPad and not six months from now when I will have more money and knowing that iPads will be 1/2 off because a newer generation will have been birthed by them, and therefore, I can buy two iPads!!!) . It’s almost as if attenuated activation of the amygdala concomitant with impulsivity serves as a protective mechanism against emotional irritability, preventing the opportunity to over-think and realize that the later-larger monetary reward was the better bargain. Very counterintuitive, indeed.

Here is a vibrant schematic (side note: I was disappointed to not see error bars on the graphs given the nuanced experimental design) and a few fMRI images from the paper. Descriptions of the graphs are viewable by dragging the mouse over the picture (which I hope that many of you have figured out by now!)

The broader implication of this research, aside from elucidating neural mechanisms of impulsivity which is a hallmark symptom of many psychiatric disorders, such as ADHD and schizophrenia, and L-dopa-treated Parkinsonian patients, is illustrating the adverse effects of dopamine on decision-making in addition to its pathological contributions to addiction, grandiose delusions, and motor discoordination of restless legs syndrome and Parkinson’s; drug addict researchers know that impulsivity is increasingly common in drug addicts–overlooking monetary, health, and environmental risks to obtain the drug of choice–and that the administration of dopamine pharmacological agents to patients with restless legs syndrome can cause them to engage in addicting behaviors like gambling and online-shopping, drive, and even rape in their sleep (!!!; see previous post). This research, moreover, illustrates the need to reconsider the adverse side effects of many popular pharmacological treatments such as L-dopa, which does alleviate Parkinsonian tremors and generates huge payout for its shareholders, because it may be that dopamine, given the increasing diagnosis of Parkinson’s and subsequent filling of L-dopa prescriptions, has a greater contribution to the economic recession than previously believed….or even considered…….and certainly can facilitate a vicious spiral of economic malaise for the L-dopa-treated Parkinsonian patient.

Pine A, Shiner T, Seymour B, & Dolan RJ (2010). Dopamine, time, and impulsivity in humans. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (26), 8888-96 PMID: 20592211

Last week, I blogged about my lab mate’s upcoming publication in Alcoholism: Clinical and Experimental Research. This week, I am attending the Research Society on Alcoholism meeting held in San Antonio (same place, same weather), and have already discovered that finding natural, alternative, non-pharmacological treatments, such as exercise, to reduce risk in individuals with a family history and/or to treat alcohol abuse is being pursued by many other labs. In a symposium clevely titled “Exercising some control on alcohol’s effects on the brain” an estrogenic group of researchers (girl power!) described their most recent, exciting results illustrating that exercise in rodents (via access to a running wheel) not only reduces alcohol consumption, but additionally elicits neuromodulation in a similar manner to alcohol; altering tyrosine hydroxylase kinetics, which syntheizes dopamine, in the ventral tegmental area–a major reward center of the brain–and protein expression within the nucleus accumbens–the other major reward area to which the ventral tegmental area projects too. Though their findings are still not conclusive, given that exercise’s rescuing effects varies in mouse strains, it’s promising, nonetheless, since many of the current alcohol abstinent medications aren’t effective (see previous post).

I didn’t have an opportunity to visit most of the poster’s yesterday because I was presenting my own (RSA 2010), but I also learned about a really cool technique for characterizing real-time dopamine release; fast action voltammetry in which an electrode is implanted into a region of interest and  detects changes in current in response to neurotransmitter release.

Even cooler experimental techniques utilized and presented in posters at the conference, include optogenetics; briefly the insertion of light-sensitive receptors into brain regions and neurons of interest can manipulate the activity of the neurons and even behavior as shown here!!!

A few days ago, my first, first author paper was finally published in Alcoholism: Clinical and Experimental Research. After spending years working on the project, months writing and re-writing the paper, and another few months swearing at Adobe Photoshop for its stubborness, the journey has been captured in eight pages. Here, I describe the results, relying on my schematics of which most of my family will do as well.

First, I wanted to characterize circadian alcohol consumption (how much and what time of the day does drinking occur) in our wild-type mouse strain, which have a moderate preference for alcohol and therefore, requires little training to get them to drink. To do this, I implanted the animals with a probe in their circadian clock that could reliably measure alcohol uptake and the time of uptake within the clock.

As shown, most of the drinking occurred soon after the animals woke up (bloody marys!!) and right before bedtime (gin and tonics!!!) with sometimes, a drinking bout here and there in the middle of the sleeping period (left over bloody marys or gin and tonics!!!).

Once I had an idea of their circadian alcohol consumption, I then presented the animals with a light pulse during their nocturnal activity period, knowing that this pulse would delay their subsequent sleep/wake rhythms  (i.e. they would reliably wake up 1.5-2 hrs later the following few days).

Here, we see that daily, chronic alcohol consumption and its withdrawal reduced the animal’s responsiveness to this light cue, with the effect being more pronounced in animals consuming the more concentrated alcohol solution.

Finally, I conducted a few long-term (13 months ) behavioral experiments addressing the effects of alcohol on their general circadian behavioral rhythms under a more natural environmental schedule (these animals are burrowers and don’t see sunlight across all hours of the day), yet unusual laboratory schedule. To do this, I began with a regular laboratory schedule of 12 hours of light and dark followed by the more natural environmental schedule of 23.99 hours of constant dark with a 1 min light pulse presented in the middle of the animals usual rest period. This type of schedule would force the animals to re-entrain their behavioral rhythms towards the light pulse and therefore , I could assess if alcohol would affect this rate of re-entrainment. It didn’t as shown here, but it definitely disrupted daily circadian locomotor rhythms by reducing the amount of activity across the nocturnal activity period (perhaps to drunk to move)?

What’s the significance of this research? First, it demonstrates that alcohol and its withdrawal directly disrupts circadian physiology which in the long-term may drive alcohol addiction; eliciting  difficulty falling asleep, resulting in a reliance on alcohol as a hypnotic,and a subsequent alcohol-disruption of sleep, leading to more alcohol consumption to fall asleep the following night. Second, it illustrates how robust the circadian clock is across species given that alcohol elicits similar impairing circadian effects as reported via self-reports in humans. This indicates that murine and other rodent models are ideal for investigating the neural mechanisms of alcohol dispruption on the mammalian circadian clock and developing novel chronotherapeutic (manipulating sleep/wake schedules, perhaps even functionality of the circadian clock itself) for the treatment of alcoholism.

Brager AJ, Ruby CL, Prosser RA, & Glass JD (2010). Chronic Ethanol Disrupts Circadian Photic Entrainment and Daily Locomotor Activity in the Mouse. Alcoholism, clinical and experimental research PMID: 20477766