Addiction in the Spotlight at Neuroscience 2013

Testing treatments for nicotine, heroin, and gambling addiction.

Several addiction studies were among the highlights at last month’s annual meeting of the Society for Neuroscience (SfN) in San Diego. Studies released at the gathering including therapies for nicotine and heroin addiction, as well as some notions about the nature of gambling addiction.

And now, as they say, for the news:

— Transcranial Magnetic Stimulation (rTMS), the controversial technique being tested for everything from depression to dementia, may help some smokers quit or cut down, according to research coming in from Ben Gurion University in Israel. Abraham Zangen and colleagues used repeated high frequency rTMS over the lateral prefrontal cortex and the insula of volunteers. Participants who got the magnetic stimulation quit smoking at six times the rate of the placebo group over a six-month period. Work in this area is limited, but there is some preliminary evidence that some addictions may respond to this form of treatment. azangen@bgu.ac.il

—Speaking of the insula—a site deep in the frontal lobes where neuroscientists believe that self-awareness, cognition, and other acts of consciousness are partially mediated—research now suggests that out-of-control gamblers may be suffering, in part, from an overactive insula. People with damage to the insular region are less prone to both the “near-miss fallacy (where a loss is perceived as “almost” a win) and the “gambler’s fallacy (where a run of luck is “due” to a gambler after a string of losses). The volunteer gamblers played digital gambling games while undergoing functional MRIs. Luke Clark of the University of Cambridge, along with researchers from the University of Iowa and the University of Southern California, uncovered a “specific disruption of both effects” in a study group with insula damage. This ties in with earlier research demonstrating that smokers with insula damage lost interest in their habit. This one remains a puzzler, and further research, that brave cliché’, is needed, especially since disordered, or “pathological” gambling is now classified in the DSM5 as an addiction, not an impulse control disorder.  lc260@cam.ac.uk

—And speaking of stimulation, if you go deep with rat brains, you can stimulate a drug reward area and reduce the motivation for heroin in addicted rats. Deep brain stimulation (DBS), an equally controversial treatment approach, now in use as a treatment for Parkinson’s and other conditions, is a surgical procedure involving the implantation of electrodes in the brain. When Carrie Wade and others at the Scripps Research Institute and Aix-Marseille University in France electrically stimulated the subthalamic nucleus and got addicted rats to take less heroin and become less motivated for the task of bar pressing to receive the drug. Earlier work had demonstrated a similar effect in rats’ motivation for cocaine use. “This research takes a non-drug therapy that is already approved for human use and demonstrates that it may be an option for treating heroin abuse,” Wade said in a prepared statement.  clwade@scripps.edu

—Too much stimulation leads to stress, as we know. And George Koob, recently named the director of the National Institute on Alcohol Abuse and Alcoholism, discussed his work on the ways in which dysregulated stress responses might act as triggers for increased drug use and addiction. Koob focused on the negative reinforcement of stressful emotional states: “The argument here is that excessive use of drugs leads to negative emotional states that drive such drug seeking by activating the brain stress systems with areas of the brain historically known to mediate emotions and includes the stress/fear-mediating amygdala and reward-mediating basal ganglia.” For Koob, “stress can cause addiction and addiction can cause stress.” gkoob@scripps.edu

—Finally, hardcore gamblers show a boost in reward-sensitive brain areas when they win a cash payout, but less activation when presented with rewards involving food or sex. The study features more volunteers playing games inside fMRI machines, and purports to demonstrated that problem gamblers are less motivated by erotic pictures than by monetary gains, “whereas healthy participants were equally fast for both rewards.” This “blunted sensitivity” in heavy gamblers suggests the possibility of a marker for problem gambling, in the form of a distorted sensitivity to reward, said Guillaume Sescousse of Radboud University in The Netherlands, during a mini-symposium at the conference. “It is as if the brain of gamblers interpreted money as a primary reward…. for its own sake, as if it were intrinsically reinforcing.” g.sescousse@fcdonders.ru.nl

Addiction Trajectories: Book Review

Striving for that elusive middle ground.

For a journalist who covers neuroscience, the political and psychoanalytic focus of anthropology sometimes feels like a baffling trip to a foreign land. References to Foucault and Derrida abound, and Freud hovers in the middle distance. The investigative landscape is comprised of socially constructed experiences and environmental processes. Trained to seek out cultural and economic experiences as first causes, many cultural anthropologists have been fighting a rear-guard action against the advances of neuroscience for years now. Which is a shame, because anthropology, importantly, can serve to remind medical scientists of the multi-dimensional nature of addiction. “For psychoactive substances to transform themselves into catalysts for and objects of pleasure and desire,” writes anthropologist Anne M. Lovell, “they must circulate not only through blood, brain, and other body sites but also through social settings.”

It is anthropologists, for example, who have documented that “three-fourths of all state-licensed drug treatment programs in Puerto Rico were faith-based.” This study of faith-based healing in the addiction recovery community forms one chapter of a new volume, Addiction Trajectories, edited by Eugene Raikhel of the University of Chicago and William Garriott of James Madison University.

What anthropologists can do for addiction science is document these sociocultural attributes of addiction. In a chapter on buprenorphine and methadone users in New York City and the five boroughs, Helena Hansen, assistant professor of anthropology and psychiatry at New York University, finds that buprenorphine users live in predominantly white, high-income neighborhoods, tended to have college educations, and get their bupe from a private doctor. However, “others are directed to methadone maintenance programs with requirements for daily attendance, urine drug screens, surveillance, and control,” and there is little overlap between the two recovering populations.

There is a chapter devoted to a punitive form of addiction treatment known in Russia as “narcology,” and another that dwells on the semiotics of meth addiction. There are chapters taking drug counselors to task for their inadequate training and lack of nuanced background. And there is a chapter that views the advent of buprenorphine for heroin addiction as a step backwards, or, at best, a typical step sideways—addictive drugs for addiction, just like the old days when heroin addicts were offered alcohol as a cure.

A chapter by E. Summerson Carr is devoted to the treatment known as motivational interviewing, a technique with which she claims “drug users can talk themselves into sobriety regardless of whether or not they originally believe what they say to be true.” Irrespective of your view on M.I., Carr makes a useful point when she notes that sometimes a client’s refusal to admit drug use, even after a positive drug test, is not because of denial, but because of a logical understanding that their status as credible plaintiffs in legal proceedings could be on the line.

And there is simply no arguing Carr’s central point—while addiction science has been increasingly incorporated within the broad outlines of neuroscientific models, “the project of using talk to treat denial and demonstrate insight remains remarkably consistent” in the treatment practices used by the more than 13,000 outpatient addiction treatment programs across the U.S.

What else can anthropologists bring to the table? An understanding of “the loaded institutional and cultural conditions of clinical assessments, which inevitably and profoundly shape what drug users do and do not say.” Chief among these, Carr writes, is “the distinctly clinical terms of addicted denial, the chief organizing heuristic of mainstream American addiction treatment.”

The gap remains wide between addiction viewed as the neuroscientist’s disease entity, and addiction viewed as the anthropologist’s contingent outcome emerging from specific social settings. It’s easy to see why the attempt at an alliance between anthropologists and neurobiologists is an uphill struggle. Reading Addiction Trajectories, it becomes apparent how frequently the two disciplines are talking past one another. But I like to think there are enough bright and motivated anthropologists and neuroscientists around to forge some manner of middle ground; the elusive third way of viewing addiction, holistically, as a living blend of genetic and environmental influences, sensitive to both, and registering that dual sensitivity in the form of compulsive drug taking. (See, for example, anthropologist Daniel Lende’s recent post.)

The more invigorating contributions in this volume help us to zero in on “the popular representation of drugs as inherently criminogenic,” writes William Garriott, as well as the concomitant “lack of faith in the ability of the criminal justice system—and the state more generally—to address drug problems through the punitive management of the addicted offender population.” It is anthropologists, not neuroscientists, who dwell on the ramifications of this paradox: “The majority of Americans appear committed to fighting a war they feel cannot be won, using a strategy in which they no longer believe.”

The present volume is sometimes inclined to view biology with suspicion, and many of its contributors are quick to point out the hazards of attempting to meld social science and neuroscience. A similar but somewhat less skeptical collection—one that seeks to connect the socioenvironmental influences helping to shape how the biological disorder known as addiction will play out in the real world—was published last year by co-editors Daniel H. Lende and Greg Downey. In The Encultured Brain, Lende and Downey look ahead to a time when field-ready equipment will measure nutritional intake, cortisol levels, prenatal conditions, and brain development in the field. Predicting the future is a fool’s game, but it seems clear that the field of anthropology is aware of, and awake to, the controversial research avenues opened up by advances in contemporary neuroscience.

Graphics credit: http://www.culturalneuroscience.org/

Review: Memoirs of an Addicted Brain

“I’m a drug addict turned neuroscientist.”

What’s it like to swallow 400 milligrams of dextromethorphan hydrobromide, better known as Romilar cough syrup? “Flashes of perception go by like clumps of scenery on either side, while you float along with the slow, irresistible momentum of a dream.” Marc Lewis, a former addict, now a practicing neuroscientist, further muses: “But what was Romilar? It sounded like an ancient kingdom. Would this dark elixir take me to some faraway place? Would it take me into another land? Would it be hard to come back?”

In Memoirs of an Addicted Brain: A Neuroscientist Examines his Former Life on Drugs, Dr. Marc Lewis follows his description of his gateway Romilar drug experience with the neurological basics of the matter: “The problem is that the NMDA receptors in my brain are now clogged with dextromethorphan molecules! The glutamate isn’t getting through. The receptor neurons aren’t firing, or they’re not firing fast enough…. Drugs like DM, ketamine, PCP, angel dust, and those most damaging of substances, glue and gasoline, are called dissociatives, because they do exactly what drugs are supposed to do: they dissociate feeling from reality, meaning from sense—and that’s all they do.”

Speaking of the self-reinforcing cycle “through which calamities of the mind arise from vulnerabilities of the brain,” Lewis argues that dissociatives only produce an absence. As a friend of his puts it with regard to another popular dissociative, “Nitrous oxide doesn’t give you consciousness. It takes it away.” And then, the friend adds: “Just bonk yourself on the head with a baseball bat if you want to lose consciousness.”

Lewis ultimately turns to opioids. “The emotional circuitry of the ventral striatum seems to derive its power from an intimate discourse between opioid liking and dopamine wanting.” In the end, this partnership does more than produce pleasure. It also, Lewis points out, “gets us to work for things.” And by doing that, addictive drugs demonstrate “the fundamental chemistry of learning which really means learning what feels good and how to get more of it. Yet there’s a downside: the slippery slope, the repetition compulsion, that constitutes addiction. In other words, addiction may be a form of learning gone bad. For me, this neurochemical sleight of hand promises much more pain than pleasure in the years to come.”

Lewis does a good job of capturing the feeling of existential despair brought on by uncontrolled addiction: “Contemptible. That’s what I was. Unbelievably stupid, unbelievably irresponsible: selfish, selfish, selfish! But that wasn’t quite it. What described me, what this inner voice accused me of, wasn’t exactly selfish, not exactly weak, but some meridian of self-blame that included both, and also, dirty, disgusting… maybe just BAD.”

How did heroin feel? “I feel relief from that pervasive hiss of wrongness. Every emotional wound, every bruise, every ache in my psyche, the background noise of angst itself, is soaked with a balm of unbelievable potency. There is a ringing stillness. The sense of impending harm, of danger, of attack, both from within and without, is washed away.”

And Lewis provides a memorable summation of the reward system, as dopamine streams from the ventral tegmental area to its targets, “the ventral striatum, where behavior is charged, focused, and released; the orbitofrontal cortex, where it infuses cells devoted to the value of this drug; and the amygdala, whose synapses provide a meeting place for the two most important components of associative memory, imagery and emotion.” In fact, “dopamine-powered desperation can change the brain forever, because its message of intense wanting narrows the field of synaptic change, focusing it like a powerful microscope on one particular reward. Whether in the service of food or heroin, love or gambling, dopamine forms a rut, a line of footprints in the neural flesh.”

And, of course, Lewis relapses, and eventually ends his addictive years in an amphetamine-induced psychosis, committing serial burglaries to fund his habit. “You’d think that getting busted, put on probation, kicked out of graduate school, and enduring a kind of infamy that was agonizing to experience and difficult to hide—all of that, an the need to start life over again—would be enough to get me to stop. It wasn’t.”

Not then, anyway. But Lewis has been clean now for 30 years. “Nobody likes an addict,” he writes. “Not even other addicts.”

If drugs are such feel-good engines, what goes wrong? Something big. “Because when drugs (or booze, sex, or gambling) are nowhere to be found, when the horizon is empty of their promise, the humming motor of the orbitofrontal cortex sputters to a halt. Orbitofrontal cells go dormant and dopamine just stops. Like a religious fundamentalist, the addict’s brain has only two stable states: rapture and disinterest. Addictive drugs convert the brain to recognize only one face of God, to thrill to only one suitor.”  The addict’s world narrows. Dopamine becomes “specialized, stilted, inaccessible through the ordinary pleasures and pursuits of life, but gushing suddenly when anything associated with the drug comes into awareness…. I wish this were just an exercise in biological reductionism, or neuro-scientific chauvinism, but it’s not. It’s the way things really work.”

Photo Credit: http://ebookstore.sony.com/

What is Brain Awareness Week?

Celebrate your sentience March 12-18.

Gather ‘round, children, and the Dana Foundation will tell you an amazing tale about… the You Man Brain…

Well, that is, the HUMAN brain—and the many ways of increasing understanding and awareness of this little three-pound marvel. Officially the brainchild of the Dana Alliance for Brain Initiatives in New York and the European Dana Alliance for the Brain, “Brain Awareness Week (BAW) is the global campaign to increase public awareness of the progress and benefits of brain research,” according to the BAW website.  

Founded in 1996, Brain Awareness Week is designed to unite partner organizations around the world “in a week-long celebration of the brain.” Partners include universities, hospitals, schools, government agencies, and service organizations. Partner organizations come up with creative and innovative community activities to educate people of all ages “about the brain and the promise of brain research.” For example, on Wednesday the Dana Alliance is sponsoring a “brain bee” at The Rockefeller University in New York City, where students from 21 area high schools will go head-to-head on their knowledge of neuroscience.

To see the full list of partnerships, from 41 countries, go HERE. For a list of events planned for the week, take a look HERE.  Events include open houses at neuroscience laboratories, special brain exhibitions at museums, displays and lectures at community centers, and workshops in the classroom.

If you’re feeling cocky, you can test your brain with several challenges at http://www.testmybrain.org/

Sadly, none of this hoopla will necessarily solve certain perennial brain conundrums, such as:

--If you can’t change your mind, how do you know you have one?

--Is that hole in a man’s penis really there to get oxygen to his brain?

--How can we believe that the brain is the most important organ, when the brain is the organ telling us that?

And finally, the one that keeps me awake at night:

-- How did the scarecrow know he didn't have a brain?

An Interview with Neuroscientist Jon Simons

Brain scans, iPhone love, and state-dependent memory.

(Third post in the “Five-Question Interview” series.)

Brain scans have put cognitive neuroscience on the map. They have become a key part of addiction studies as well. In fact, brain scans have put neuroscience on the front page, due to the controversies they have engendered. Cognitive neuroscientist Jon Simons, a lecturer in the Department of Experimental Psychology at the University of Cambridge, UK, and principal investigator at the University’s Memory Laboratory, is attempting to expand our understanding of the specific regions of the brain involved in human memory. His research involves functional neuroimaging of healthy volunteers and examining the effects of neurological and psychiatric disorders, and normal aging, on memory abilities.

Dr. Simons obtained his PhD at the MRC Cognition and Brain Sciences Unit in Cambridge, and from there moved to a post-doctoral position at Harvard University. He returned to the UK and took up a research fellowship at University College London before returning to Cambridge. He was recently senior author on a thought-provoking paper published in the Journal of Neuroscience about a brain structure variation that might explain why some people in the general population are better than others at distinguishing real events from those they imagined or were told about. We asked Dr. Simons to help straighten out some of the confusion over scanning data, and to be the third guest in our “Five-Question Interview” series.

1. PET and fMRI scans have stirred up a good deal of debate and heated argument lately. While brain scans have been used to extend our understanding of crucial functions like memory and reward, they’ve also been used to “prove” that we’re addicted to our iPhones. Some scientists put almost no faith in them at all. What’s going on?

Neuroimaging methods like fMRI have certainly become quite common in the media over recent years. Unfortunately, not all the media coverage does the kind of job we might wish in explaining the methods and findings and, importantly, the limitations and caveats that need to be considered when interpreting the data. You mention the recent New York Times op-ed in which it was claimed that people “literally love their iPhones,” on the basis that viewing an iPhone was associated with fMRI activity in a brain region previously linked with “love and compassion.” Unfortunately, the same brain area has also been linked with negative emotions like disgust, as well as many other cognitive functions, seriously undermining the claims in the New York Times story. It may turn out to be true that our feelings about iPhones reflect love, or perhaps more likely a kind of dopamine-driven addiction response, but such simplistic analyses as the one the NYT gave such prominence are unlikely to help with understanding that.

However, I think it’s a mistake to confuse the media representation of fMRI research with the field itself. Many researchers design very careful fMRI experiments in which factors of interest are varied while others are controlled, and resulting patterns of brain activity are analysed with statistical caution and interpreted in the light of a broad range of previous findings. This is the kind of work that is moving the field forward, but, like most good science, it is not particularly sexy, and the researchers involved are less keen to make the kinds of extravagant claims that get you into the New York Times. In my view, it’s up to all of us—scientists and journalists—to make sure that the public get to hear more about the good fMRI work, and less about silly iPhone love stories.

2. Is there a specific role for functional neuroimaging in the diagnosis and treatment of addiction?

This isn’t really my area, but I know from talking with colleagues that neuroimaging has certainly contributed to understanding the neurobiology of addiction. For example, a great deal is known about the brain networks and neurotransmitter systems implicated in impulsivity, compulsions, reward processing and other cognitive functions that are relevant to addiction disorders. Such knowledge is obviously very important for informing clinical practice. Whether neuroimaging can also play a role in diagnosis and treatment is, as far as I can tell, less clear. Making accurate diagnoses in an individual on the basis of neuroimaging data requires characterisation of the specific patterns of brain activity exhibited by that individual, which is difficult to achieve. Similar problems afflict attempts to assess the success of different treatments. However, as imaging technology develops and statistical methods are refined, it may be that neuroimaging will be able to offer new insights that contribute to effective diagnosis and treatment.


3. Please explain the basics of state-dependent memory as it relates to alcohol, using your famous example about remembering Brad Pitt’s or Angelina Jolie’s phone number.

Ha! Glad if the example I used has proven memorable. The basic idea of state-dependent memory is that your recollection of a previous event is likely to be better if you’re in the same physiological state as you were when the event occurred. So, to use alcohol as an example, if you’re at a party and happen to drunkenly strike up conversation with Angelina Jolie (or Brad Pitt, if you prefer) and, bowled over by your charm and witty repartee, she tells you her phone number, you may well not remember it when you wake up sober the next morning. However, the evidence from many state-dependent memory studies suggests that you would have a better chance of recalling the number if you got drunk again. The effect doesn’t just apply to alcohol: any physiological state, any emotion we’re feeling, in fact any aspect of the context we’re in when we try to remember, which was also there when we previously experienced an event, will improve our memory for that event. This was described as the ‘encoding specificity principle’ by a great memory researcher, Endel Tulving.

4. Some researchers maintain that mental illness and addiction to drugs and alcohol are not, properly speaking, diseases at all. What’s your stance on the continual battles over the “disease model” of addiction and other disorders like depression?

There are both advantages and disadvantages to the “disease model” of cognitive disorders. For some people, it might be helpful to receive a clinical disease diagnosis and, perhaps, an idea of the therapeutic interventions through which they might go about “recovering” from their condition. Among the disadvantages are that labelling people as “addicts”, for example, can stigmatise those struggling with dependence and might lead to them avoiding responsibility for changing their addictive behaviour because they see diseases as requiring expert intervention. It’s a difficult area, and I can see both sides of the debate.

5. You’ve done neuroscience at Cambridge in the U.K., and at Harvard in the U.S. Is science conducted differently in the two countries?

My experience was that science in the US at that time (in 2000-2001) was different from in the UK. There seemed to be many more opportunities to get involved in interesting projects and to gain access to advanced technical equipment like fMRI scanners than was the case in the UK then. I also noted a difference in the willingness of people who were experts in techniques like fMRI, or in research involving patients with rare brain lesions, to share their expertise and resources in a collaborative way. Fortunately, I’ve found since I’ve been back in the UK a similarly friendly and collaborative environment, particularly in Cambridge now. I think this is partly a result of initiatives to bring researchers together across traditional scientific boundaries, such as Cambridge Neuroscience. However, I think the biggest US/UK difference now is the prevalent feeling that science is valued much more in the US than it is over here. Despite the best efforts of campaigns like Science is Vital, successive UK governments have failed to invest in science to the same degree as other nations, including the US. Particularly in the current financial climate, when significant cuts to science funding have been threatened, this means that morale is low, uncertainty is high, and significant numbers of scientists are deciding to move abroad. I don’t know that I’m ready to join them yet, but if the situation gets much worse, it would have to be something I’d consider.

Photo Credit: http://www.neuroscience.cam.ac.uk