Starting up

We’ve all had (or think we’ve had) that million dollar idea. But how do you turn that idea into a reality?

In my new piece for Science Careers, I interview two budding entrepreneurs who are taking their ideas out of the lab and into industry. While the odds aren’t necessarily in their favor (75% of all startups fail), they both say that the learning experience and satisfaction of seeing their ideas come to fruition are worth the struggle.

Read about their process here, starting from the initial idea, to securing intellectual property protection, and the all-important fight to find funding.

Beating the poppy seed defense

During my PhD, one of the research projects I was involved in was a relapse prevention study testing individuals who had previously been addicted to alcohol, cocaine or heroin, but were no longer using any drugs.

One participant who took part in the study — I’ll call him Dave — was a young guy who was dependent on alcohol, but swore up and down he had never abused any drugs. Dave was three weeks into the study and doing well, staying abstinent and remaining cheerful and cooperative throughout the sessions. However, one morning when Dave came in and went through his usual drug screen, he tested positive for heroin, something he claimed (and I believed) he had never taken.

Instead, Dave maintained he had eaten a poppy seed bagel for lunch the day before, which would explain the positive test.

Opiates — like heroin, morphine or opium — are all derived from the poppy seed plant, and it’s not uncommon for poppy seeds to give a false-positive result for opiates on a drug screen. However, it’s also not uncommon for people to falsely plead the poppy seed defense, and there is no way of confirming what form of morphine (heroin or poppy seed) is actually causing the positive screen. Until now.

Researchers from King’s College London have discovered a metabolite of heroin that only exists in the synthetic form of the drug and can be reliably tested for using a urine screen. This means that instead of screening for all types of opiates, doctors and researchers can now test for only the presence of heroin in the body.

Notably, the test would also not come back positive for any prescription painkillers, which is simultaneously an advantage and a disadvantage of the new screen. For those who are legitimately prescribed the medications, there would be no more concerns over having a suspicious positive result. However, the tests would also not be able to identify the more than 12 million Americans who are using these drugs without a prescription. This is especially problematic as prescription painkillers have quickly surpassed all other types of drugs as the most common form of overdose, totaling more deaths in 2010 than cocaine and heroin combined, and prescription painkiller overdose has now become the leading cause of death by injury in the U.S.

The new test is still under investigation and isn’t perfectly refined (only 16 of the 22 known current heroin users tested positive for the metabolite in the study — meaning it has a detection rate of only about 75%), but it is a promising new avenue for researchers and medical screeners to more accurately identify the presence of heroin.

As for Dave, he successfully completed the study without any other events, and he never ate another poppy seed before a session again.

Do you have an addictive personality?

You’ll have to bear with me if this is a bit of a self-indulgent post, but I have some exciting news, Brain Study-ers: I’ve officially submitted my dissertation for a PhD in psychology!

In light of this – the culmination of three years of blood, sweat, tears and an exorbitant amount of caffeine – I thought I’d write this week on part of my thesis work (I promise to do my best to keep the jargon out of it!)

One of the biggest questions in addiction research is why do some people become dependent on drugs, while others are able to use in moderation? Certainly some of the risk lies in the addictive potential of the substances themselves, but still the vast majority of individuals who have used drugs never become dependent on them. This then leads to the question, is there really such a thing as an “addictive personality”, and what puts someone at a greater risk for addiction if they do choose to try drugs?

We believe that there are three crucial traits that comprise much of the risk of developing a dependency on drugs: sensation-seeking, impulsivity and compulsivity.

Sensation-seeking is the tendency to seek out new experiences, be they traveling to exotic countries, trying new foods or having an adrenaline junkie’s interest in extreme sports. These people are more likely to first try psychoactive drugs, experimenting with different sensations and experiences.

Conversely, impulsivity is acting without considering the consequences of your actions. This is often equated with having poor self-control – eating that slice of chocolate cake in the fridge even though you’re on a diet, or staying out late drinking when you have to be at work the next day.

While impulsivity and sensation-seeking can be similar, and not infrequently overlap, they are not synonymous, and it is possible to have one without the other. For example, in research we conducted on the biological siblings of dependent drug users, the siblings showed elevated levels of impulsivity and poor self-control similar to that of their dependent brothers and sisters, but normal levels of sensation-seeking that were on par with unrelated healthy control individuals. This led us to hypothesize that the siblings shared a similar heightened risk for dependence, and might have succumbed to addiction had they started taking drugs, but that they were crucially protected against ever initiating substance use, perhaps due to their less risk-seeking nature.

The final component in the risk for addiction is compulsivity. This is the tendency to continue performing a behavior even in the face of negative consequences. The most classic example of this is someone with OCD, or obsessive-compulsive disorder, who feels compelled to check that the door is locked over and over again every time they leave the house, even though it makes them late for work. These compulsions can loosely be thought of as bad habits, and some people form these habits more easily than others. In drug users, this compulsive nature is expressed in their continued use of the substance, even though it may have cost them their job, family, friends and health.

People who are high in sensation-seeking may be more likely to try drugs, searching for that new exciting experience, but if they are low in impulsivity they may only use a couple of times, or only when they are fairly certain there is a small risk for negative consequences. Similarly, if you have a low tendency for forming habits then you most likely have a more limited risk for developing compulsive behaviors and continuing an action even if it is no longer pleasurable, or you’ve experienced negative outcomes as a result of it.

Exemplifying this, another participant group we studied were recreational users of cocaine. These are individuals who are able to take drugs occasionally without becoming dependent on them. These recreational users had similarly high levels of sensation-seeking as the dependent users, but did not show any increase in impulsivity, nor did they differ from controls in their self-control abilities. They also had low levels of compulsivity, supporting the fact that they are able to use drugs occasionally but without having it spiral out of control or becoming a habit.

We can test for these traits using standard questionnaires, or with cognitive-behavioral tests, which can also be administered in an fMRI scanner to get an idea of what is going on in the brain during these processes. Behaviorally, sensation-seeing roughly equates to a heightened interest in reward, while impulsivity can be seen as having problems with self-control. As mentioned above, compulsivity is a greater susceptibility to the development of habits.

In the brain, poor self-control is most commonly associated with a decrease in prefrontal cortex control – the “executive” center of the brain. Reflecting this, stimulant-dependent individuals and their non-dependent siblings both showed decreases in prefrontal cortex volume, as well as impairments on a cognitive control task. Conversely, recreational cocaine users actually had an increase in PFC volume and behaved no differently from controls on a similar task. Thus, it appears that there are underlying neural correlates to some of these personality traits.

It is important to remember that we all have flashes of these behaviors in differing amounts, and it is only in extremely high levels that these characteristics put you at a greater risk for dependence. Also, crucially it is not just one trait that does it, but having all three together. Most notably though, neuroscience is not fatalistic, and just because you might have an increased risk for a condition through various personality traits, it does not mean your behavior is out of your control.

Oh, and I’ll be going by Dr. D from now on.

—

Ersche, KE et al., Abnormal brain structure implicated in stimulant drug addiction. Science 335(6068): 601-604 (2012).

Ersche, KE et al., Distinctive personality traits and neural correlates associated with stimulant drug use versus familial risk of stimulant dependence. Biological Psychiatry 74(2): 137-144 (2013).

Smith, DG et al., Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.Translational Psychiatry 3(5): e257 (2013).

Smith DG, et al., Enhanced orbitofrontal cortex function and lack of attentional bias to cocaine cues in recreational stimulant users.Biological Psychiatry Epub ahead of print (2013).

Beating the odds of addiction

An article I wrote for The Psychologist magazine based on my thesis research investigating risk and protective factors in drug dependence was published online this week.

This work all stems from a question I (and countless others in the field) have of why some people are able to use illicit drugs without becoming dependent, while others seem to quickly succumb to addiction.

While we’re still far from answering this question definitively, my lab at Cambridge, headed by Dr. Karen Ersche, has some theories on why this might be the case.

For example, it appears that there are underlying traits, like impulsivity, compulsivity and sensation-seeking, that can put someone at a greater risk for developing drug dependence. Some of these traits also correspond to differences in brain structure and function, such as smaller frontal cortex volume potentially making it harder for people to stop or inhibit a behavior.

If you’re interested in reading more, a full link to the article is here (the magazine kindly made it available open access). So please check it out, and as always I welcome any questions or feedback!

It’s official…

Well folks, I’ve finally been made legitimate.

No, I haven’t received my doctorate yet (that won’t be happening for awhile!) Instead my rogue bastardized blogging days are over – I’ve been made an official Nature Publishing Group blogger, writing for the Nature Education site Scitable. I’ll be blogging on all things brain and biology on the psychology group blog, Mind Read, with the fantastic Jordan Gaines of Gaines, on Brains. We’ll be posting weekly on the latest nerdy neuro papers and fascinating psychological phenomena – think similar Brain Study content but now on a legitimate platform.

As always though, Brain Study is dearest to my blogging heart, and I’ll be sure to post Mind Read pieces here, as well as trying out slightly “edgier” content perhaps not suitable for the corporate science blogosphere.

My first post is on one of my personal favorite topics, synesthesia, exploring Hearing, Touching and Tasting in Color. A sneak-peek with some insight into my own form is below:

I don’t know about you, but to me Wednesday is sun-shiney yellow. Tuesday is hunter green, Thursday purple-ish blue and Friday a deep red. Monday is white, a blank slate and a chance for a new week, whereas Saturday is sparkly black. Sunday is gray, the depressing slouch towards the beginning of the work-week, but also a convenient mix of Saturday and Monday.

This color-word association is not a figment of my imagination or an indication that I’m going crazy, but is instead a recognized neuropsychological phenomenon called synesthesia.

So please check out the new site, and let me know what you think!

New blog on the block

So I have a confession to make: I’ve been cheating on this blog. I’ve taken up with a new writing endeavor, a hot inter-disciplinary thing, and today is the day we go public with our (current) affairs.

A group of highly talented graduate students at King’s College in Cambridge have launched a new web magazine today, and I’m honored to be a part of it. The first issue tackles everything from US national security and the CIA to the uprising of artists in Germany over state funding cuts. I’ve even contributed my own article, which dedicated Brain Study followers might recognize as the mutant off-spring of a piece I posted last year on ‘pathologizing the norm‘. It’s been beefed up and fleshed out as I attempt to tackle some of the proposed changes in the upcoming DSM-V, slated to be published later this year.

Here’s a brief teaser for the article, Pathologising the Norm: The spread of mental illness, to pique your interest:

One in four of us will struggle with a mental illness this year, the most common being depression and anxiety. The upcoming publication of the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM) will expand the list of psychiatric classifications, further increasing the number of people who meet criteria for disorder. But will this increase in diagnoses really mean more people are getting the help they need? And to what extent are we pathologising normal human behaviours, reactions and mood swings?

So please check out the full piece, and the rest of the magazine, at King’s Review, and let me know what you think!

And don’t worry, Brain Study will always be my first blogging love.

More sexism in science

Following on my post the other week on Gender bias on both sides of scientific research, I want to draw attention to an incident that occurred at the annual Society for Neuroscience meeting last week in New Orleans. SFN is by far the largest neuroscience event every year, drawing over 30,000 attendees to come and revel in nerdy neuro madness for a week (think of it as a music festival for science geeks). With so many talks, poster sessions and symposiums, not to mention the sheer number of people, the conference can be overwhelming. But it is also overwhelmingly positive and exciting, allowing you the opportunity to check out new research, get new ideas, forge new relationships and collaborations, and, if you’re lucky, even meet your academic super-star crush (I’m looking at you David Eagleman).

However, one conference-goer decided that the quality of the researchers wasn’t quite up to his standards. Dr. Dario Maestripieri of the University of Chicago complained on Facebook that the cosmetic caliber of the female attendees was lacking this year, stating “there are…an unusually high concentration of unattractive women [at the conference]. The super model types are completely absent.” The comment, originally discovered and posted by Drug Monkey on his blog, went on to ask, “Are unattractive women particularly attracted to neuroscience? Are beautiful women particularly uninterested in the brain?”, and considerately topped it off with, “No offense to anyone…”

Fortunately many people did take offense to Maestripieri’s comments, including Dr. Janet Stemwedel who posted an eloquent rebuttal on Scientopia, which I highly recommend. Maestripieri’s overt sexism demeans female scientists, belittling them and insinuating that their value is only measured by their looks, not their research, intelligence or contributions to the field. And keep in mind that this comment was made at a professional scientific conference, where the emphasis should especially be on one’s intellect and creativity, not on beauty or breasts. The response to Maestripieri’s comments has been overwhelmingly negative, and a Wikipedia page about him has even been updated to mention the controversy. However, others still think his behavior was acceptable, writing it off as a joke and telling people to not take it so seriously. This is particularly problematic given the underlying gender bias we know to still exist in science. If we accept overt and covert discrimination against women in science we all lose out, not just women who are dissuaded from the field because of it, but everyone who might have benefited from their future work.

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!

Gender bias on both sides of scientific research

A disturbing new study from researchers at Yale University was released this week in PNAS, reporting that gender bias is still pervasive in science and the workplace. An identical application for a laboratory manager position was given to 127 senior faculty members at a number of research universities, the only difference being that half of the applications contained a male name, while in the other half the applicant’s name was female. Across the board supervisors (male and female alike) ranked the ‘male’ application as more competent, more hireable, and stated that they would be more willing to supervise this candidate. Even more striking was the pay gap that existed between the recommended wages for the male and female applicants, a difference of roughly $3,700 starting salary. This is representative of the reported 23% average earnings difference between men and women in the workplace.

Despite efforts for equal opportunity and the eradication of sexism from science, this study clearly demonstrates that there are significant lingering differences in the perception of male and female applicants and their competence based solely on gender. These findings are particularly disturbing as the job was for an entry-level research position, suggesting that there is a bias against women even trying to get their foot in the door in science. The gender disparity in tenure-track professorships has previously been explained with similar rationales as those used to justify the dearth of women in executive suite positions in finance or industry, namely differences in life choices or a lingering male-domination from previous generations. However, now there is clear evidence that women are discriminated against from the start of their careers, making it far more likely that they will drop out of the profession, and thus perpetuating the gender imbalance in science, particularly at the higher end of the career ladder.

Gender bias in science isn’t just present in a lack of professional opportunities; women are frequently excluded from being subjects in research studies, particularly those involving the brain or behavioral traits. Women can be ‘difficult’ subjects as anatomically our brains differ in size from males, and hormonal fluctuations can affect chemical reactions to pharmaceutical challenges used in experiments. Instead of pursuing and exploring these differences though, females subjects are often omitted from both human and animal research. Results from male participants are then applied to females post-hoc, however this method is far from perfect as these very differences in behavioral and biological performance make extrapolations imprecise and potentially invalid.

For example, a study published earlier this year in Alcoholism: Clinical and Experimental Research reported on the differing effects of heavy alcohol consumption and recovery on the brain in men and women. Females appear to be more sensitive to the neurotoxic effects of alcohol on the brain, particularly in the frontal lobe, with a greater proportionate reduction in white matter volume than men with every additional drink. Conversely, male alcoholics show a greater decrease in volume in the corpus callosum (neuron tracts that connect the left and right hemispheres) related to the duration of heavy drinking. Fortunately, abstaining from alcohol was linked to recovery of white matter in both genders, with longer periods of abstinence associated with greater recovery in each region. However, men did not exhibit this trend with less than one year of sobriety, while women experienced neurogenesis only within the first year. While these distinctions between women and men are subtle ones, they are significant and could be related to differences in behavioral ability or possible treatment outcomes.

Ignoring female subjects in research studies biases results and can hinder progress in the advancement of clinical treatments. Similarly, dissuading or not adequately supporting women in their own research endeavors undoubtedly handicaps scientific progress by limiting the intellectual pool of talent. Reports of women being naturally ‘bad’ in science or mathematics have been overwhelming refuted and lingering prejudices, even unintentional ones, hurt not only the individual but the field of science as a whole.

(Thanks to Adam Levy and Ruth Watkinson for the gender bias article.)

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 with 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.)