Finding Mr. Right just got a lot harder

It’s hard being a young woman these days. Chivalry is dying, but many glass ceilings are still firmly in place. We’re supposed to have it all but sacrifice nothing, balancing choosing a career path and a life partner. We can delay having kids by putting our eggs in the freezer next to our vodka, but our similarly aging male partners’ sperm might handicap our chances of having healthy offspring, with higher risks for autism and schizophrenia linked to paternal age.

And now it turns out that hormonal contraception, or The Pill, our revolutionary defense against the inherent misogyny of biology, could be tricking us into choosing the wrong men.

Two studies led by Dr. Craig Roberts from the University of Stirling in Scotland have suggested that taking oral contraception can change your attraction to and preferences for men. In an initial study, Dr. Roberts and his team asked women who were about to go on the pill to rate the attractiveness of a selection of male faces, considering them as both short-term and long-term partners. They were then tested again approximately three months later to see if their preferences had changed. Sure enough, in the second test session women who had started hormonal contraception had significant shifts in their partner preferences, now preferring significantly less masculine-looking faces than they had three months earlier. Conversely, control women who had not started the pill did not differ in their choices from the first session.

In a follow-up study, real couples who had met while the woman was either on or off the pill were assessed for the male partner’s masculinity. This involved complex photo manipulation and judgment of the pictures by outside individuals, who ranked the male faces on features of masculinity. Though these methods are a bit fuzzy and convoluted, the researchers’ results (surprise surprise) matched those of the first study. That is, male partners of women who were already on the pill when they met were judged to be significantly less masculine looking than men whose female partners were not taking hormonal contraception.

Notable masculine features include squarer face-shapes, stronger jawlines and less prominent cheekbones, all of which are typical signifiers of higher levels of testosterone. The authors claim that this shift to preferring less masculine features is perhaps a transition towards subconsciously choosing more faithful or nurturing partners after starting contraception, which can be beneficial for long-term relationship success. However, a major problem with these partner preference shifts is that presumably at some point during a mature, adult, monogamous relationship women go off their contraception, potentially reversing back their partner preferences. This can lead to dissatisfaction in the relationship, female philandering, and some very awkward conversations: ”Sorry honey, you used to do it for me, but now I find you much too feminine for my liking.”

Another major concern is that genetically we are supposed to be drawn towards mates who are more dissimilar to ourselves. This is evolutionarily advantageous, as greater parental genetic variability reduces the likelihood of heritable diseases in the offspring. Basically, your children are less likely to be born with a genetic disorder if you and your partner’s DNA are more different. It has been proposed that some of the shifts in partner preferences after initiating oral contraception are actually towards men who are more genetically similar to you, which can be problematic, but no theories as to why this might be the case.

However, it’s a pretty big stretch to say that preferring men with slightly rounder faces means you’ve undergone a major change in your list of demands for your partner’s personality and genetic makeup (if you happen to have such a list for that). Also, the first study was only performed with 18 women in the experimental condition, which is a pretty tiny population for measuring significant differences in behavior. So the researchers conducted another follow-up experiment to investigate if these effects mapped onto real-world behavior. Researchers tested 2500 women (a much better sample size) in stable relationships who had started dating their partner while they were either on or off the pill, and compared them on several measures of relationship and sexual satisfaction.

Women who had first met their partners while taking oral contraception scored significantly lower on measures of sexual satisfaction and rated themselves less physically attracted to their partners than those women who had met their partners while not on the pill. However, the women taking the pill did have higher overall relationship non-sexual fulfillment and financial stability than those who were off. And in a related twist, women who were on contraception were actually less likely to have separated from their partners than women not on the pill at ‘partner choice’.

So what’s the take-away from this? Don’t take oral contraception and you’ll have better sex with a more attractive man, but will be more likely to break up with him in the future? Go on the pill and you’ll be dissatisfied sexually by your unattractive mate and your offspring will have genetic disorders, but at least you’ll stay together forever? Maybe. Or maybe being on the pill leads you to choose partners based more on long-term than short-term payouts. Or means that you have different priorities in your partner preferences to begin with. Either way, make the decision wisely, your future children may depend on it.

Nothing to fear but asphyxiation?

Think of the scariest movie you’ve ever seen (for me it’s The Ring). How did you feel when the group of teenagers popped in that video, or the girl climbed out of the TV? When the phone rang and the killer was on the other end? Or when the babysitter was home alone and a shadow passed across the screen? Even though you know it’s just a movie, you still experience that knot in your stomach, pounding heart, sweaty palms and building anxiety that comes with a real stressful or frightening encounter.

These visceral, gut reactions are physiological fear responses our brain and body automatically initiate when in a perceived threatening situation. These experiences are thought to be subserved by the amygdala, an old and deeply rooted part of the brain that is essential in processing emotion, particularly fear. This is partly through connections the amygdala has to the sympathetic nervous system, which controls our basic ‘fight-or-flight’ reactions to danger – preparing us to either stand and fight or flee as fast as we can.

However, some people don’t experience this sensation of fear. Individuals who have undergone damage to the amygdala, either through a stroke or head injury, or from the rare genetic condition Urbach-Wiethe disease, report an inability to feel this emotion. One famous example of this absence is in the patient SM, who reported no feelings of fear when faced with snakes, spiders, horror films or haunted houses. Even after being threatened with a real life knife attack SM had no experience of fear sensations. However, there was one thing that was able to instill in her these feelings of anxiety and terror – asphyxiation.

Researchers at the University of Iowa have been studying SM over the last decade to try to find something, anything, that would scare her. After exhausting all the typical psychological stressors to no avail, they decided to try a physical stressor that can elicit the same reactions. Published last month in Nature Neuroscience, the researchers had SM and two other people with similar amygdala lesions inhale carbon dioxide for several seconds, cutting off their oxygen flow and essentially suffocating them. This experience typically causes panic attacks and fear responses in people, including extreme distress, pounding heart and an immediate desire to escape the situation. All three participants – none of whom had previously experienced fear – had these exact same panicky reactions to the CO2. In fact, when compared with normal healthy individuals, the amygdala patients had significantly greater fear responses, both physically and psychologically, than those with intact amygdalas.

So what’s behind this phenomenon? The researchers believe that these panic reactions are distinct from learned fear responses, such as phobias of snakes or spiders. Instead, there appears to be a unique pathway involved in panic from inherent physiological stressors that passes through the amygdala. In fact, this response may actually be inhibited in the amygdala, as the control participants had less dramatic reactions to the carbon dioxide than the amygdala patients. However, learned fears or perceived outside dangers may rely on the amygdala to integrate these scary sensory situations – such as seeing someone with a gun – as a threat. Thus, those with amygdala lesions do not learn and incorporate the proper fear associations with these triggers, but they do still have the capacity to experience these dramatic panic responses to internal physical stressors.

So the next time you’re watching a scary movie, you could try reminding yourself that it’s not real, or you could try hyperventilating – it may actually reduce your panic (assuming your amygdala is still intact).*

Boo!

*I do not actually recommend this as a fear-coping mechanism.

Weed be better off smoking our parents’ pot

We’ve all heard our parents say it*: “Back in my day, dope was much better than it is now. It wasn’t nearly as strong as what you kids smoke today.”

Like much of the advice our parents give us (like always take out your contacts before you go to bed), this one is also true. The THC (tetrahydrocannabinol – the primary psychoactive compound in cannabis) concentration in marijuana has increased by as much as 12% over the last 30 years. This rise in THC levels is related to increases in the subjective ‘high’ feelings associated with smoking cannabis, like changes in perceptual sensations, contentedness, and increased appetite. However, THC is also linked to many of the negative consequences of cannabis use, including risk for dependence, attentional bias or distraction, impaired memory and cognition, and the potential emergence of psychotic symptoms.

Alternatively, CBD (cannabidiol – one of the other major chemicals in cannabis that works by increasing endogenous cannabinoid levels in the brain) is associated with the anxiolytic or anti-anxiety effects of marijuana. Additionally, it is thought to act as a protective factor against many of the negative effects the drug can have, including the development of abuse, cognitive impairments, and even psychotic symptoms.

Unfortunately, in addition to the high levels of THC seen in today’s cannabis, there is also a significant depletion of CBD. ’Skunk’, as it is referred to by users and dealers alike, is the strain of this new high-THC, low-CBD cannabis that is flooding the marijuana market. And it is this drug that is thought to be at the root of the increase in cannabis dependence diagnoses seen over the last decade.

Recent changes in policy and public perception of the risks associated with cannabis have also resulted in an increase in use, particularly among adolescents and young adults, with roughly 50% of high school students reporting having used the drug at some point in their lives. However, despite a previous belief that cannabis was not addictive, there has also been a substantial increase in the number of users seeking treatment for dependence, and nearly 11% of current users qualify as addicted. Skunk smokers in particular are more likely to experience cravings for the drug, go through their stash in shorter amounts of time, and have greater attentional bias to cannabis cues.

Professor Val Curran’s group from University College London has been leading the charge on research into the effects of cannabis use, comparing recreational and chronic smokers, and studying the varying effects different strains of cannabis have on the brain. Her group is particularly interested in comparing skunk to THC-CBD strains, and they have discovered much of the evidence for the protective effects CBD has against the development of psychosis and dependence. CBD’s action upon the endogenous cannabinoid anandamide seems to be behind the reduction in psychotic experiences in regular smokers, and CBD has even been looked at as a potential treatment for schizophrenia, reducing psychotic symptoms as effectively as some of the anti-psychotic drugs currently prescribed. THC-CBD users also show less distraction to marijuana stimuli than skunk smokers, and they report significantly reduced feelings of craving. There were also no differences in the subjective intoxication effects of smoking either skunk or THC-CBD, indicating it does not alter the psychoactive properties of the drug.

So the question is, where has all the CBD gone? Modern day growing methods using indoor marijuana farms have greatly decreased the risk of detection for cannabis producers by circumventing the need to import cannabis internationally. Cannabis greenhouses also guarantee a more reliable crop, as they are not dependent on changes in weather patterns. However, the 24-hour lighting used in these farms results in an inadvertent destruction of the CBD levels in the plant. Thus, these new strains not only have increased potency with higher THC contents, they also have reduced protective factors against the drug’s negative effects. In the producers’ eyes, these are just additional economic advantages to growing on an indoor farm, as more dependent users who go through the drug more quickly will result in more cannabis being sold.

These changes in potency raise interesting questions regarding the recent legalization of recreational and medicinal marijuana use in some states. Most pressingly, where and how is this cannabis being produced? And what are the differing levels of THC and CBD present in it? Also, would it be possible to better control cannabis production to avoid its addictive or psychotic-inducing effects? And should we start to think about prescribing CBD to patients currently suffering from THC dependence?

While the developments in cannabis policy may potentially reduce the harm caused to individuals from incarceration or criminal records for minor possession, in terms of the potential psychological effects caused by the drug, it appears we’d be better off smoking our parents’ pot.

*Apologies to my parents, who have never actually uttered the above phrase.

**Title pun credit to Claire Gillan.

SFN ’12: Vulnerabilities for drug addiction

For anybody who’s in New Orleans for SFN this week, come by room 273 at 1pm today to learn about vulnerabilities for drug addiction. It’s an excellent nanosymposium set up by the fantastic Dr. Jenn Murray covering both human and preclincial studies into risk factors for addiction. The talks will include investigations into the classic predictive traits of impulsivity, anxiety and novelty-seeking, and they’ll also delve into environmental risk factors for addiction, such as maternal care and environmental stimulation.

I’ll be presenting first (so be there at 1pm sharp!) on my work on endophenotypes for addiction. This involves studying both dependent drug users and their non-dependent biological siblings, who share 50% of their genes and the same environment growing up, but who never developed any sort of drug or alcohol abuse. I’ll be looking specifically at cognitive control deficits and frontal cortex abnormalities in both of these groups compared to unrelated healthy control volunteers. There are some surprises in the results, so if you’re at SFN come by at 1pm to find out what they are!

I saw the (negative) sign: Problems with fMRI research

I feel the need to bring up an issue in neuroimaging research that has affected me directly, and I fear may apply to others as well.

While in the process of analyzing a large fMRI (functional magnetic resonance imaging) data-set, I made an error when setting up the contrasts. This was the first large independent imaging analysis I had attempted, and I was still learning my way around the software, programming language, and standard imaging parameters. My mistake was not a large one (I switched a 1 and -1 when entering the contrasts), however it resulted in an entirely different, but most importantly, still plausible output, and no one noticed any problems in my results.

Thankfully, the mistake was identified before the work was published, and we have since corrected and checked the analysis (numerous times!) to ensure no other errors were committed. However, it was an alarming experience for a graduate student like myself, just embarking on an exploration of the brain – an incredibly powerful machine that we barely understand, with revolutionary high-powered technology that I barely understand – that such a mistake could be so easily made and the resulting data so thoroughly justified. The areas identified in the analysis were all correct, there was nothing outlandish or even particularly unexpected in my results. But they were wrong.

Functional MRI is a game of location and magnitude. The anatomical analysis, looking for blobs in the brain that light up where we think they should, can be confirmed with pre-clinical animal models, as well as neuropsychology research in patients who have suffered localized brain damage and related loss of function. Areas involved in motor control and memory have been identified in such a manner, and these findings have been validated through imaging studies identifying activation in these same regions during performance of relevant tasks.

The question then remains as to the direction of this activation. Do individuals “over activate” or “under activate” this region? Are patients hyper- or hypo-responding compared to controls? FMRI studies typically compare activation during the target task to a baseline state to assess this directionality. Ideally, you should subtract neural activity levels during a similar but simpler process from the activation that occurs during your target cognitive function, and presumably the resulting difference in activity is the neurocognitive demand of the task.

An increase in activation compared to the baseline state, or compared to another group of participants – i.e. patients vs. controls, is interpreted as greater effort being exerted. This is typically seen as a good thing on cognitive tasks, indicating that the individual is working hard and activating the relevant regions to remember the word or exert self-control. However, if you become expert at these processes you typically exhibit a relative decrease in activation as the task becomes less demanding and requires less cognitive effort to perform. Therefore, if you are hypo-active it could be because you are not exerting enough effort and consequently under-performing on the task compared to those with greater activation. Or, conversely, you could be superior to others in performance, responding more efficiently and not requiring superfluous neural activity.

Essentially, directionality can be justified to validate either hypothesis of relative impairment. Patients are over-active compared to controls? They’re trying too hard, over-compensating for aberrant executive functioning or decreased activation elsewhere. Alternatively, if patients display less activity on a task they must be impaired in this region and under-performing accordingly.

Concerns about the over-interpretation of imaging results are nothing new, and Dr. Daniel Bor, along with a legion of other researchers in the neuroscience community, have tackled this issue far more eloquently and expertly than myself. My own experience, though, has taught me that we need greater accountability for the claims made from imaging studies. Even with an initially incorrect finding that resulted from a technical error, I was able to make a reasonable rationale for our results that was accepted as a plausible finding. FMRI is an invaluable and powerful tool that has opened up the brain like never before. However, there are a lot of mistakes that can be made and a lot of justifications of results that are over-stretched, making claims that can not be validated from the data. And this is assuming there are no errors in the analysis or original research design parameters!

I am particularly concerned about the existence of other papers where students and researchers have made similar mistakes to my own, but where the results seem plausible and so are accepted, despite the fact that they are incorrect. I would argue that learning by doing is the best way to truly master a technique, and I can guarantee that I will never make this same mistake again, but there does need to be better oversight, whether internally or externally, during the reporting of methods sections, as well as in the claims made while rationalizing results. Our window into the brain is a limited one, and subtle differences in task parameters, subject eligibility, and researcher bias can greatly influence study results, particularly when using tools sensitive to human error. Providing greater detail in online supplements on the exact methods, parameters, settings, and button presses used to generate an analysis could be one way to ensure greater accountability. Going one step further, opening up data-sets to a public forum after a certain grace period has passed, similar to practices in physics and mathematics disciplines, could engender greater oversight to these processes.

As for the directionality issue, the need to create a “story” with scientific data is a compelling, and I believe very important, aspect of reporting and explaining results. However, I think more of the fMRI literature needs to be based on actual behavioral impairment, rather than just differences in neural activity. Instead of basing papers around aberrant differences in activation, which may be due to statistical (or researcher) error, and developing rationalizing hypotheses to fit these data, analyses and discussions should be centered on differences in behavior and clinical evidence. For example, the search for biomarkers (biological differences in groups at risk for a disorder, often present before they display symptoms) is an important one that could help shed light on pre-clinical pathology. However, you will almost always find subtle differences between groups if you are looking for them, even when there is no overt dysfunction, and so these searches need to be directed by known impairments in the target patient groups. A similar issue has been raised in the medical literature, with high-tech scans revealing abnormalities in the body that do not cause any tangible impairments, but the treatment of which cause more harm than good! Instead of searching for differences in activation levels in the brain, we should be led by dysfunction that results from these changes. Just as psychiatric diagnoses from the DSM-IV are supposed to be directed by symptoms relating to pathology only if they cause significant harm or distress in the individual, speculations made about the results of imaging studies should be influenced by associated impairments in behavior and function, rather than red or blue blobs on the brain.

(Thanks to Dr. Jon Simons for his advice on this post.)

Analytical thinking and religious disbelief: A Dawkinsian tale

Last week Richard Dawkins, evolutionary biologist, out-spoken atheist, and author of The God Gene, announced his support for British education secretary Michael Gove’s proposal to put a King James Bible in every state school in the UK. Dawkins stated that, “I have heard the cynically misanthropic opinion that, without the Bible as a moral compass, people would have no restraint against murder, theft and mayhem. The surest way to disabuse yourself of this pernicious falsehood is to read the Bible itself.”

Dawkins’ tongue-in-cheek support for the measure highlights his proselytism of critical thinking over blind acceptance of the scriptures. This more rational and methodical type of thought is affectionately known as “System 2″ in the neuroeconomics and decision-making literature, and a new study published last month in the journal Science suggests that Dawkins, as an atheist, is not alone in his analytical thinking habits. The other mode of thought, System 1, relies more on instincts and heuristics (quick decision-making tools based on past experiences), and is thought to underlie much of an individual’s conviction in religious beliefs. The stories that make up the dogma of organized religion often require acceptance of supernatural processes that are difficult to rationalize, such as immaculate conception or resurrection. These leaps of faith require a reliance on intuition over analytical rationalization, and as such individuals with strong religious beliefs are thought to have a greater activation of System 1, whereas disbelievers engage System 2 more frequently.

Researchers from the University of British Columbia tested this hypothesis of a distinction between religious believers and non-believers in dual-process thinking (System 1 vs. System 2) by carrying out several experiments assessing analytical abilities and religious beliefs in 179 undergraduate students (insert joke about the oxymoron of analytical thinking and undergrads here). The tasks required “an analytical overriding of initial intuitions”, meaning that the first obvious answer to any problem was wrong, and an inhibition of this initial response and critical re-assessment of the problem was required to arrive at the correct answer. Participants then completed three questionnaires asking about religiosity, intuitive and supernatural beliefs. Successful analytical thinking on the cognitive tasks was negatively correlated with all three measures of religious beliefs, such that the ability to over-ride an immediate intuition was associated with greater religious disbelief.

Follow-up studies aimed to assess the directionality of these trends – i.e. whether a lack of religious beliefs led one to think more critically, or if a tendency towards analytical thought resulted in greater disbelief. Researchers attempted to answer this by exposing participants to a series of subtle primes of words and images that were meant to subconsciously evoke connotations of analytical thought, and then asking them about their levels of religious or supernatural beliefs. For example, in one test students were primed with an image of either Rodin’s The Thinker or a control image matched for pose, material and familiarity. During a pilot test, viewing The Thinker was related to an increase in analytical reasoning, and during the experiment seeing it resulted in an increase in self-report levels of religious disbelief as compared to control images.

In the final and most devious manipulation, researchers had participants rank their religious beliefs on a questionnaire presented in either standard font or in a more challenging and difficult-to-read one. Reading in an unusual font, known as perceptual disfluency, requires greater cognitive effort, which the researchers hypothesized would result in increased recruitment of System 2. This would then over-ride any natural inclinations towards System 1 and presumably reduce reliance on intuitions. Sure enough, participants who filled out the difficult-to-read questionnaire rated themselves as being less believing, regardless of previously obtained baseline levels of belief.

The researchers caution against reading too much into these experiments, stating that no estimation on the value of religious beliefs can be interpreted from the findings. Additionally, disbelief could stem equally from a lack of intuition-based thought as an increase in analytical thinking. My main question regarding these findings is just how unaware the participants were to the researchers’ objectives in the study. A psychology experiment, a setting less than welcoming to religious convictions, and particularly one with an emphasis on cognition and critical thinking, may cause individuals to feel sheepish about their beliefs in supernatural phenomena, religious or otherwise, and lead them to under-report their personal levels of faith. Thus the setting of a research laboratory, as well as any expectation bias introduced by the researchers, should be considered as a caveat for the results of this study.

On an unrelated side note, today marks the one year anniversary of Brain Study! A big thank you to all of my readers, be they friends who feel obligated to check in every week or poor unwitting strangers who stumble across the blog through Google searches. Hope everyone’s enjoyed reading this past year as much as I’ve enjoyed writing, and stay tuned for more posts on our brains, bodies and life as a graduate student in science!

If I can’t remember it, it didn’t happen: A susceptibility for alcohol-induced blackouts

As anyone who’s ever taken an Alcohol Edu course (or been 21 in the last decade) knows, consuming too much alcohol can cause memory loss, colloquially known as a “blackout”. This anterograde amnesia stems from an inability of the brain to form new long-term memories and is caused by a disruption in the GABA and NMDA receptors in the prefrontal cortex (PFC) and medial temporal lobes when drinking.

First, for those of you who skipped (or drank) your way through your alcohol education, a brief reminder on the effects of alcohol on the brain. GABA is a primary inhibitory neurotransmitter, acting to decrease the likelihood of a cell’s firing. Alcohol acts as a GABA agonist, elevating levels throughout the brain and therefore diminishing the rates of firing in normal cellular processes. At high levels, alcohol also acts upon glutamate NMDA receptors, one of the main excitatory neurotransmitter systems. Alcohol works as an NMDA antagonist, blocking the NMDA receptors and preventing glutamatergic activation, further inhibiting neuronal functioning. This inhibition particularly occurs in the PFC, medial temporal cortex and the parietal lobe, primary targets of alcohol in the brain. In the hippocampus in particular, an area in the medial temporal cortex crucial to memory formation, this inhibition can result in a disruption of long-term potentiation, a cellular process involved in the consolidation of short-term to long-term memories.

Alcohol’s effect on the PFC also impacts memory ability, as short-term memories are maintained there while they are being worked on or rehearsed. However, when attention shifts to a new stimulus this memory must be consolidated into a more stable long-term version via cellular activity in the hippocampus, or else it will be discarded and forgotten. Alcohol’s inhibition of the PFC via its effects on GABA and glutamate can disrupt the maintenance of these short-term memories, decreasing the likelihood of consolidation and preservation. The dampening of firing in the PFC is also attributed to the behavioral disinhibition that so commonly succeeds alcohol consumption, as the PFC can no longer inhibit or control impulses as well.

Now, on to the exciting bit! In individuals who regularly experience alcohol-induced memory loss, or a blackout, it is the contextual memory that seems to be most impaired. This refers to the details surrounding an experience, such as where, when and with whom the event occurred. However, blackouts seem to affect some drinkers more than others, and are not necessarily determined by the amount of alcohol that an individual consumes. Simply put, you either blackout when drinking large amounts of alcohol or you do not.

Published online this week in Alcoholism: Clinical and Experimental Research, psychologists from the University of California, San Diego and the University of Texas, Austin have recently confirmed this urban drinking legend by testing 24 regular binge drinkers, 12 of whom admitted to blacking out on a regular basis, reporting on average two blackouts per month, and 12 who drank comparable amounts of alcohol but declared no memory problems when drinking. Both groups were matched on their typical alcohol consumption, averaging 3 drinking days per week and consuming 4-5 drinks at a time on a typical day when drinking. Both groups also had comparable binge tendencies, consuming 10 or more drinks on occasion over the previous 3 months.

Participants were tested on a contextual memory task using functional magnetic resonance imaging (fMRI) both when sober and after drinking to a blood alcohol content of .08, the legal limit in the United States, typically 3 drinks for a male and 2 for females. During both the sober and intoxicated trials, participants performed equally well in their behavioral scores, recalling similar amounts of information regardless of their blackout group status. Groups also did not differ in their response times on the task during either condition, however both groups recalled significantly fewer trials when intoxicated and were significantly slower than when sober.

In the imaging analysis, there were no differences in activation levels between the groups during either encoding or retrieval for the sober condition of the task. However, when intoxicated, both groups demonstrated significantly less activation in the right frontopolar PFC during retrieval. The blackout group also had significantly less activation during both the encoding and recall portions of the experiment after consuming moderate amounts of alcohol as compared to the non-blackout group. Specifically, participants with a history of blacking out showed less activation in the left frontopolar PFC during encoding, and decreased activity in the right posterior parietal cortex and the bilateral dorsolateral PFC during retrieval as compared to their non-blackout contemporaries. This fronto-parietal network is implicated in attentional maintenance and inhibition, as well as working memory and executive control, suggesting that there could be greater difficulties in these skills in the blackout group when drinking.

The researchers speculate that the decrease in activity in the frontal pole during intoxication is indicative of an alcohol-induced impairment in executive functioning in both groups, particularly in regards to working memory and cognitive maintenance. The additional decrease in activation in the fronto-parietal network seen in the blackout group also suggests a greater disability in executive functioning and memory maintenance in these individuals when drinking. However, it is notable that there were not any significant behavioral differences between the two groups in total memory recall, particularly during the intoxication condition.

While it is reassuring that there were no impairments in either group during the sober condition, the drinking results do seem to suggest that there may be underlying problems with memory and executive functioning in those individuals with a proclivity for forgetting, which could emerge after more chronic drinking behaviors. Why some people are predisposed towards these additional memory impairments is still unclear, but there does seem to be something different in the brains of those who blackout regularly that is not just dependent on the amount of alcohol they drink.

(Insert poor taste joke about drinking away your memory problems here.)

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.

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.