The Prophetic Brain: Foretelling Your Future

The act of fortune telling is an ancient practice. Chinese diviners burnt turtle shells and studied the resulting cracks to make a host of predictions, including future crop conditions and weather forecasts, and ancient Greeks read animal entrails in their divinatory practices. While the modern scientific community regards fortune telling as mere hogwash, brain science is starting to use genetic information, environmental conditions, and brain structure to predict an individual’s future actions. Neuroscientists could become the oracles of our era.

One such scientist is Penn professor and neurocriminologist Adrian Raine. In his controversial research, Dr. Raine proposes that the structure of the brain may provide insight into an individual’s propensity to commit a violent crime. In fact, he argues that future criminal offending can be predicted in children as young as three years. In one experiment, Dr. Raine studied 1,800 three-year-old children from the tropical island of Mauritius in the Indian Ocean. In his longitudinal study, he followed subjects for 20 years, noting any criminal convictions. He then compared the criminals with the noncriminals and discovered that the former demonstrated a lack of fear as children.*

Although the findings of Dr. Raine's research are intriguing, the environmental and biological affects on brain and behavior ought to be examined. Child abuse, cigarette smoking and alcohol consumption during pregnancy, and poor nutrition give scientists great predictive power regarding individuals' outcomes. For example, children of moms who smoked tobacco while pregnant were 2-3 times more likely to be violent criminals by age 20, and pregnant women who consumed just 1 drink per week birthed children who were 30% more aggressive than their peers. Poor nutrition during prenatal and postnatal development also leads to greater antisocial behaviors in children.

Additionally, genetics, brain structure and function, and testosterone levels have a tremendous influence on behavior. Using EEG to study the electrical activity of prisoners' brains, Dr. Raine noted that violent criminal offenders demonstrated poor-functioning prefrontal cortexes, the part of the brain associated with the regulation of behavior and emotions. The amygdala, which is responsible for emotions, is also implicated in antisocial tendencies.  For example, sociopaths have been shown to have an amygdala 18% smaller than individuals without sociopathy.

While it is extremely enticing to regard the brain as quasi-prophetic, it is necessary to consider the ethical dilemmas and misguided conclusions that can be drawn from related research. The following questions are helpful in understanding the consequences of such work: Could neuroscience research be used to fuel a eugenics movement? Is it possible to reduce antisocial tendencies in adulthood by enriching the brain in childhood? Are brain structure and function reliable predictive measures? Does brain structure lead to violent behavior, or does a violent lifestyle lead to changes in the brain? Dr. Raine explores some of these concerns and more in Radio Times with Marty Moss-Coane.

*The amygdala is critical in fear conditioning.

The Curious Case of the Phantom Penis

Our investigation of the phantom penis begins with Mirabelle, a twenty-five-year-old woman born without arms but who nonetheless experiences phantom limb syndrome. Phantom limb syndrome is the sensation of a limb that is not physically present due to a hard-wired body map in the brain that persists after an amputation or congenital defect. Dr. V.S. Ramachandran of UC San Diego has conducted extensive research on phantom limb syndrome, and he describes Mirabelle in his book, Phantoms in the Brain. In one encounter between Mirabelle and Dr. Ramachandran, Mirabelle states that she has experienced phantom limb sensations since childhood. This is not unlike female-to-male transsexual men, individuals who were born female but identify as male (also known as gender dysphoria). Many trans men report experiencing vivid phantom penis sensations, suggesting that they have a hard-wired male body map in their brains that is incongruous with their physical female bodies.

In 2007, Dr. Ramachandran set out to learn more about phantom penis sensations in trans men. What he learned was surprising.  After interviewing 29 trans men, he learned that 18 of the 29 subjects experienced phantom penis sensations prior to sexual reassignment surgery. Two of the trans men interviewed reported that the sensations began after starting testosterone therapy, while most reported that the sensations began in childhood. In an ABC interview, Dr. Ramachandran stated that the trans men provide precise descriptions regarding the length of their phantom penises, which side their phantom penises lean, and the angle between their pubic bones and their phantom penises. Phantom penis sensations are commonly experienced in cisgender men, men who were born male and identify as male, without penises as well. Approximately 58% of cisgender men who have had their penises removed due to accident or disease experience phantom penis sensations, including phantom erections and phantom orgasms. However, they're not the only ones capable of experiencing such sensations. That is to say that trans men with phantom penises also experience phantom erections, both during arousal and in some non-erotic situations.

Additionally, few trans men experience phantom breast sensations after undergoing a mastectomy in comparison to cisgender women. Between 33% and 53% of cisgender women who have had their breasts removed due to cancer experience phantom breast sensations, while only 3 of the 29 trans men interviewed experience phantom breast sensations following chest surgery. A similar finding was found in male-to-female transsexual women who have undergone sexual reassignment surgery. While their penises are not removed during the sexual reassignment procedure, some of the penile tissue is removed. That being said, only 30% of trans women experience phantom penis sensations following the removal of penile tissue as opposed to the 58% of cisgender men previously discussed. These findings suggest that gender dysphoria is not solely a product of nurture, as previously believed, but can also be largely attributed to nature.

Click here to read the SF Gate article on Dr. V.S. Ramachandran's study and here to access his research proposal.

Smart Drugs: Penn Professor Martha Farah Speaks to Students about Adderall and Ritalin

How do stimulants work? What is their effect on the body, both long term and short term? In Provost Tower on Wednesday, March 13, Professor Martha Farah answered such questions and led a discussion about the nonmedical use of stimulants, or “smart drugs,” like Ritalin and Adderall. Farah, the Annenberg Professor of Natural Science and Director of the Center for Neuroscience and Society, said that according to data collected in 2001, 7% of students have used a stimulant nonmedically in college. This number has likely increased since then. Some factors that increase the frequency of use by the student body include Ivy League or elite institutions, coastal location and fraternity members. “B” students are more likely to use smart drugs than “A” or “C” students due most likely to a desire to excel without having to sacrifice extracurriculars and other activities. On some campuses, usage rates are as high as 25%.

Many people think of drugs like Adderall and Ritalin as cognitive enhancers but Farah debunked this myth. She explained that their main effect is to keep the user awake and improve his or her attitude. Thus, it is mainly a motivational factor, especially because it improves one’s evaluation of their own work while they are under the influence. These drugs work by directly acting on dopamine neurons, which, due to their role in the reward pathway, also give the user a high. This makes such drugs carry the risk of dependence for nonmedical users. Medical users, like patients with ADHD on the other hand, tend to bear less risk of addiction. In patients with ADHD, Farah said “drug treatment seems to do nothing but help patients.”

It is difficult to study the long term effects of stimulant use but Farah said that for the most part, long-term use is probably fine for medical users. Nonmedical users on the other hand bear the risks associated with self-medicating and dependence. She explained that “1 out of 10 non-medical users of stimulants have symptoms of physical dependence.” Despite advocating for medical Adderall and Ritalin use, she did mention an animal study that showed shorter swim times for adult rats using those drugs long term. This is a sign of decreased psychological health. Such risks are due to the effects of dopamine which include not only focusing attention but possibly schizophrenia and psychosis as well.

Despite knowing much about the different studies done on Ritalin and Adderall use, Farah was unable to come to many concrete conclusions about long term their effects. This is due to many factors including the difficulty of determining who actually has ADHD (“There is no lab test,” Farah said) and the self-selection inherent in experiments on long term stimulant users. The short term effects of dopamine, which is increased in concentration by stimulants, are much easier to determine. One of the main purposes stimulants are used for is to fight off sleep; Farah said this is terrible because sleep deprivation is not only bad for memory consolidation and mood, but it is bad for the immune system and related to cancer as well. Stimulants also have the possible side effects of heart attack, sudden death and psychosis. Farah described the nonmedical use of Adderall and Ritalin as “playing a little bit of a Russian roulette.” With millions of people addicted to a weaker stimulant, caffeine (which acts indirectly on dopamine neurons), where is the line drawn between acceptable and unacceptable stimulant use? What is risk is staying awake worth? Farah, despite being a long time coffee drinker, exclaimed that is much safer to just “get your eight hours of sleep!”

Why Dogs Are Better Than Doctors

Over the past ten years, myriad groundbreaking and progressive cancer treatments have been implemented in oncology departments everywhere. Whether the treatment involves some sort of chemotherapy, radiation or positive psychological therapy, more and more advances are being made to make sure cancer is detected and attacked as early as possible.

What would at first appear to be completely unrelated to this is that dogs have a fantastic sense of smell [up to one third of a dog's brain is devoted solely to olfactory detection]. In light of this, recent studies have implied that dogs' senses of smell are good enough to sniff out cancer.

This may sound wild and wacky [I admit I had to reread the abstract three times just to make sure I was reading what I thought I was reading], but it's absolutely true. A recent article published in GUT posited that labrador retrievers that smelled the exhaled breath and watery stool samples of colorectal cancer (CRC) patients were able to identify even early cases of CRC extremely accurately.

In the study, Sonoda et al. exposed dogs highly trained in scent detection to the breath and stool samples of both CRC patients and normal, healthy subjects. For exhaled breath, the labradors had a detection sensitivity [compared to regular colonoscopy] of 0.91 and a specificity of 0.99. The sensitivity of the watery stool samples was even higher--0.97, and the specificity was 0.99. These measures were not confounded with inflammatory disease, benign colorectal disease or even current smoking behaviors.

Just one more reason to love animals! [if you need yet another, check out this cute and fuzzy video that has absolutely nothing to do with science]

Full pdf article can be found here.

Jack & Diane & Your Brain

Valentine's Day is tomorrow, y'all. For those of you with significant others, spending exorbitant amounts of money on a mediocre steak and boxed red wine may be in your near future. The rest of us [myself included], however, have slaps in the face from every Hallmark-worthy couple and vomit-inducing bouquet of roses to endure.

Perhaps I'm a little cynical, but can you blame me? Love, a concept so abstract, so complicated, so devoid of scientific foundations, is hard to understand, let alone appreciate as a single college student majoring in neuroscience.

But wait! There's hope.

Acevedo, Aron, Fisher et al. recently published an article in Social Cognitive and Affective Neuroscience titled 'Neural Correlates of Long-term Intense Romantic Love' that investigates where and how love is expressed in the brain.

[Note: the image above is a painting by Greg Dunn titled "Hippocampus" and can be found on his website, here.]

They studied married subjects using fMRI experiments to determine where the brain is activated while the subjects were thinking about their spouses. To control for confounding variables, subjects were also exposed to a long-term acquaintance, a close friend and a stranger while undergoing the fMRI procedures.

The authors observed that areas of the dopamine reward and basal ganglia systems were activated during the subjects' exposure to their spouses. Additionally, the hypothalamus and posterior hippocampus were found to be associated with sexual frequency. Lastly, the study discovered that the caudate, the septum/fornix, the posterior cingulate and the posterior hippocampus were correlated with obsession [creepy].

Alright, so you probably don't have a spare fMRI laying around your house to analyze your girlfriend or boyfriend while he/she watches you. However, these findings add to the growing resources citing that love does, in fact, have a biological basis.

So in the end, I guess love is like a box of chocolates: you never know what you're gonna' get [unless you apply and receive funding from the NIH, perform extensive neuroimaging experiments, analyze the data and most likely lose your significant other in the process]. Happy Valentine's Day!

Research Opportunity

The Siegel lab is looking for pre-med/pre-grad undergraduate research assistants to help out with several ongoing research projects. Our lab investigates electrophysiological, behavioral, and molecular deficits in mouse models of Schizophrenia and Autism. Undergraduates would work under direct supervision of a MD/PhD graduate student or senior post doc and are expected to become highly independent. Time commitment of 10-20 hours/week which can be done for honors thesis, credit, or work study. Undergraduates would be expected to participate in and take lead on publication of work. Potential projects include:

• Developing a behavioral task to assess working memory in mouse models of schizophrenia, followed by drug testing
• Investigation of language lateralization in mice using electrophysiological recordings
• Characterizing electrophyiological activation of amygdalar activity during social behaviors of mice
• Development of auditory EEG tasks in mice to predict deficits observed observed in schizophrenia

Previous mouse work and/or experience with signal processing is helpful. Please send a resume to mgandal@mail.med.upenn.edu.