Hey, Wake Up, It’s Brain Awareness Week

Your brain doesn’t come with an instruction manual.

The Dana Foundation’s annual Brain Awareness Week (BAW), March 10-16, seems particularly appropriate and useful this time around, after a year in which brain-based disease models of human behaviors came under fire from social scientists and neuroscientists alike.

A recent analysis of the coverage of neuroscience in the popular press showed that the number of news articles using the terms "neuroscience" or "neuroscientist" had increased by a factor of 30 between 1985 and 2009. Moreover, the NIH's massive Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, designed to speed up our understanding of the neural workings of the human brain in the years ahead, is in progress.

Brain Awareness Week, which takes place each year during the third week of March, is the global campaign to increase public awareness about the progress and benefits of brain research. The Federation of European Neuroscience Societies (FENS) administers a BAW grants program for European partners.

During the week, campaign partners around the world organize activities to educate their communities about the brain and brain research. A product of the Dana Alliance for Brain Initiatives, Brain Awareness Week “unites the efforts of partner organizations worldwide in a celebration of the brain for people of all ages. Activities are limited only by the organizers’ imaginations and include open days at neuroscience labs; exhibitions about the brain; lectures on brain-related topics; social media campaigns; displays at libraries and community centers; classroom workshops; and more.”

In league with hundreds of governmental and private partner institutions around the world, BAW’s enormous calendar of events testifies to the success of this outreach. The week kicks off with an interview with Kelley Remole, Ph.D., the director of neuroscience outreach at Columbia University and the co-president of the Greater NYC Chapter of the Society for Neuroscience. 

Here you will find a pile of publications and resources.

And here is a bunch of downloadable brain stuff for kids.

Six Writers Who Battled the Bottle

Book review.

In The Trip to Echo Spring: On Writers and Drinking, author Olivia Laing’s stated goal is “to know why writers drink, and what effect this stew of spirits has had upon the body of literature itself.” To which I can only say, best of luck. The goal is impossibly ambitious; the book itself a bit digressive and loosely organized. But Laing has harvested a satisfying litany of literary anecdotes related to drinking, and throws out a few of her own.

The writers she submits to scrutiny are F. Scott Fitzgerald, Ernest Hemingway, Tennessee Williams, John Cheever, John Berryman, and Raymond Carver—all of them unambiguously alcoholic and, for most of their lives, resolutely in denial. Only two of them—Carver and Cheever—attained some measure of sobriety in their later lives. Fitzgerald died of a heart attack at 44, Hemingway and Berryman committed suicide, and Tennessee Williams either choked on a bottle cap or died of an overdose of pills. If any of that sounds deliciously romantic, than this is a book you need to read. “People don’t like to talk about alcohol,” Laing flatly states. “They don’t like to think about it, except in the most superficial of ways. They don’t like to examine the damage it does and I don’t blame them.”

Start with John Cheever, author of The Wapshot Chronicle, Bullet Park, The Falconer, and short stories, including “The Swimmer,” which begins: “It was one of those mid-summer Sundays when everyone sits around saying, ‘I drank too much last night.’”

“I cannot remember my meanness,” Cheever wrote poignantly, “because my recollections are damaged by alcohol.” It may have been literally true. Cheever suffered from aphasia, hallucinations, and seizures.  On the basis of a CAT scan from 1975, Laing makes the argument that Cheever suffered from diffuse cerebral atrophy, and possible Korsakoff syndrome, a neurological disorder seen almost exclusively in alcoholics.

Tennessee Williams, Pulitzer Prize-winning author of plays such as A Streetcar Named Desire and The Night of the Iguana, also suffered a litany of medical problems directly related to alcohol, including peripheral neuritis in his feet. “Of course I would love to believe the good doctor,” Williams wrote, “but I don’t quite believe him.”

The title of Laing’s book comes from Tennessee Williams’s Cat on a Hot Tin Roof, in which Brick, the alcoholic son, frequently takes “a little short trip to Echo Spring,” referring to the liquor cabinet containing his favorite brain of bourbon. But awareness has a way of creeping in around the edges. In an early story that foreshadowed the play, the character of Brick says, “A man that drinks is two people, one grabbing the bottle, the other one fighting him off it, not one but two people fighting each other to get control of a bottle.” 

Williams endured years of psychoanalysis and spent time in mental hospitals. He dutifully kept detailed notebooks: “Two Scotches at bar. 3 drinks in morning. A daiquiri at Dirty Dick’s, 3 glasses of red wine at lunch and 3 of wine at dinner—Also two Seconals so far, and a green tranquilizer whose name I do not know and a yellow one I think is called reserpine or something like that.” Now think of making it through a single day under that load of intoxicants.

F. Scott Fitzgerald, best known for his novel The Great Gatsby, wrote to his editor, Maxwell Perkins, in 1934: “I have drunk too much and that is certainly slowing me up. On the other hand, without drink I do not know whether I could have survived this time.” Laing notes that this ambivalence “could be interpreted as a refusal to see alcohol as a cause rather than a symptom of his troubles,” and in this Fitzgerald was by no means alone. For Fitzgerald, as for many others of the day, being “on the wagon” often meant restricting oneself to beer and the occasional glass of champagne. Fitzgerald, on the wagon at the rate of 30 beers a day, said that “when I swell up I switch to cokes.”

Laing provides us with a litany of these “excuse notes” from her writers: “I drink because it improves my work. I drink because I am too sensitive to live in the world without it. There are hundreds more of these,” she writes. In Ernest Hemingway’s A Moveable Feast, she finds “an example of someone flat-out denying their own disease….” My own personal favorite is Hemingway’s letter in which he claims to be amazed and chagrined that alcohol, something “I could not have lived without many times; or at least would have cared to live without; was a straight poison to Scott instead of a food.”

John Berryman, poet, Pulitzer Prize Winner, National Book Award winner, and author of The Dream Songs, also battled depression and a tendency to fall down stairs, breaking arms, legs, and wrists. He served a stint as a creative writing instructor at the University of Iowa writing program, as would John Cheever and Raymond Carver. He ended up at the University of Minnesota, where he dried out repeatedly at Hazelden and other local clinics. Even Berryman’s most ardent supporters gave up on him. His chairman at the university said of him: “I concluded that the only John one could love was a John with 2 or 3 drinks in him, no more & no less, & such a John could not exist.” Berryman killed himself by jumping off a bridge in Minneapolis.

Let’s let Raymond Carver—poet, short story writer, and legendary drunk— have the last word. In a 1982 poem, he wrote:

And then…something: alcohol—

What you’ve really done

And to someone else, the one

You meant to love from the start.

Addicts and Disease

Commentary.

Former National Institute on Drug Abuse (NIDA) director Alan Leshner has been vilified by many for referring to addiction as a chronic, relapsing “brain disease.” What often goes unmentioned is Leshner’s far more interesting characterization of addiction as the “quintessential biobehavioral disorder.”

Multifactorial illnesses present special challenges to our way of thinking about disease. Addiction and other biopsychosocial disorders often show symptoms at odds with disease, as people generally understand it. For patients and medical professionals alike, questions about the disease aspect of addiction tie into larger fears about the medicalization of human behavior.

These confusions are mostly understandable. Everybody knows what cancer is—a disease of the cells. Schizophrenia? Some kind of brain illness. But addiction? Addiction strikes many people as too much a part of the world, impacted too strongly by environment, culture, behavior, psychology, to qualify. But many diseases have these additional components. In the end, the meaning of addiction matters less than the physiological facts of addiction.

One of the attractions of medical models of addiction is that there is such an extensive set of data supporting that alignment. Specifically, as set down in a famous paper by National Institute of Drug Abuse director Nora Volkow and co-author Joanna Fowler: “Understanding the changes in the brain which occur in the transition from normal to addictive behavior has major implications in public health…. We postulate that intermittent dopaminergic activation of reward circuits secondary to drug self-administration leads to dysfunction of the orbitofrontal cortex via the striato-thalamo-orbitofrontal circuit.” This cascade of events is often referred to as the “hijacking” of the brain by addictive drugs, but nothing is really being hijacked. Rather, the abusive use of drugs changes the brain, and that should come as no surprise, since almost everything we do in the world has the potential of changing the brain in some way. “Why are we so surprised that when you take a poison a thousand times, it makes some changes in your head?” said the former director of a chemical dependency treatment program at the University of Minnesota. “It makes sense that [addictive drugs] change things.”

Critics like Fernando Vidal object to a perceived shift from “having a brain” to “being a brain.” He is saying that he cannot see the point of “privileging” the brain as a locus for the study of human behavior. In “Addiction and the Brain-Disease Fallacy,” which appeared in Frontiers in Psychiatry, Sally Satel and Scott Lillienfeld write that “the brain disease model obscure the dimension of choice in addiction, the capacity to respond to incentives, and also the essential fact people use drugs for reasons (as consistent with a self-medication hypothesis).”

An excellent example of the excesses of the anti-brain discussions is an article by Rachel Hammer of Mayo Clinic and colleagues, in the American Journal of Bioethics-Neuroscience. “Many believed that a disease diagnosis diminishes moral judgment while reinforcing the imperative that the sick persons take responsibility for their condition and seek treatment.” But only a few paragraphs later, the authors admit: “Scholars have theorized that addiction-as-disease finds favor among recovering addicts because it provides a narrative that allows the person simultaneously to own and yet disown deviant acts while addicted.” Furthermore: “Addiction reframed as a pathology of the weak-brained (or weak-gened) bears just as must potential for wielding stigma and creating marginalized populations." But again, the risk of this potentially damaging new form of stigma “was not a view held by the majority of our addicted participants…”

And so on. The anti-disease model authors seem not to care that addicted individuals are often immensely helped by, and hugely grateful for, disease conceptions of their disorder, even though Hammer is willing to admit that the disease conception has “benefits for addicts’ internal climates.” In fact, it often helps addicts establish a healthier internal mental climate, in which they can more reasonably contemplate treatment. Historian David Courtwright, writing in BioSocieties, says that the most obvious reason for this conundrum is that “the brain disease model has so far failed to yield much practical therapeutic value.” The disease paradigm has not greatly increased the amount of “actionable etiology” available to medical and public health practitioners. “Clinicians have acquired some drugs, such as Wellbutrin and Chantix for smokers, Campral for alcoholics or buprenorphine for heroin addicts, but no magic bullets.” Physicians and health workers are “stuck in therapeutic limbo,” Courtwright believes.

“If the brain disease model ever yields a pharmacotherapy that curbs craving, or a vaccine that blocks drug euphoria, as some researchers hope,” Courtwright says, “we should expect the rapid medicalization of the field. Under those dramatically cost-effective circumstances, politicians and police would be more willing to surrender authority to physicians.” The drug-abuse field is characterized by, “at best, incomplete and contested medicalization.” That certainly seems to be true. If we are still contesting whether the brain has anything essential to do with addiction, then yes, almost everything about the field remains “incomplete and contested.”

Sociologists Nikolas Rose and Joelle M. Abi-Rached, in their book Neuro, take the field of sociology to task for its “often unarticulated conception of human beings as sense making creatures, shaped by webs of signification that are culturally and historically variable and embedded in social institutions that owe nothing substantial to biology.”

And for those worried about problems with addicts in the legal system, specifically, over issues of free will, genetic determinism, criminal culpability, and the “diseasing” of everything, Rose and Abi-Rached bring good news: “Probabilistic arguments, to the effect that persons of type A, or with condition B, are in general more likely to commit act X, or fail to commit act Y, hold little or no sway in the process of determining guilt.” And this seems unlikely to change in the likely future, despite the growing numbers of books and magazine articles saying that it will.

Opponents of the disease model of addiction and other mental disorders are shocked, absolutely shocked, at the proliferation of “neuro” this and “neuro” that, particularly in the fields of advertising and self-improvement, where neurotrainers and neuroenhancing potions are the talk of the moment. Sociologists claim to see some new and sinister configuration of personhood, where a journalist might just see a pile of cheesy advertising and a bunch of fast-talking science hucksters maneuvering for another shot at the main chance. When has selling snake oil ever been out of fashion?

For harm reductionists, addiction is sometimes viewed as a learning disorder. This semantic construction seems to hold out the possibility of learning to drink or use drugs moderately after using them addictively. The fact that some non-alcoholics drink too much and ought to cut back, just as some recreational drug users need to ease up, is certainly a public health issue—but one that is distinct in almost every way from the issue of biochemical addiction. By concentrating on the fuzziest part of the spectrum, where problem drinking merges into alcoholism, we’ve introduced fuzzy thinking with regard to at least some of the existing addiction research base. And that doesn’t help anybody find common ground.

Graphics Credit: http://www.docslide.com/disease-model/

Acamprosate For Alcohol: Why the Research Might Be Wrong

Calcium may be curbing the urge to drink.

“Occasionally,” reads the opening sentence of a commentary published online last month in Neuropsychopharmacology, “a paper comes along that fundamentally challenges what we thought we knew about a drug mechanism.” The drug in question is acamprosate, and the mechanism of action under scrutiny is the drug’s ability to promote abstinence in alcoholics. The author of the unusual commentary is Markus Heilig, Chief of the Laboratory of Clinical and Translational Studies at the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Acamprosate, in use worldwide and currently the most widely prescribed medication for alcohol dependence in the U.S., may work by an entirely different mechanism than scientists have believed on the basis of hundreds of studies over decades. Rainer Spanagel of the Institute of Psychopharmacology at the University of Heidelberg, Germany, led a large research group in revisiting research that he and others had performed on acamprosate ten years earlier. In their article  for Neuropsychopharmacology, Spanagel and coworkers concluded that a sodium salt version of acamprosate was totally ineffective in animal models of alcohol-preferring rats.

“Surprisingly,” they write, “calcium salts produce acamprosate-like effects in three animal models…. We conclude that N-acetylhomotaurinate is a biologically inactive molecule and that the effects of acamprosate described in more than 450 published original investigations and clinical trials and 1.5 million treated patients can possibly be attributed to calcium.”

At present, the Food and Drug Administration (FDA] has approved three drugs for alcoholism— Antabuse, naltrexone, plus acamprosate in 2004. In addition, there is considerable clinical evidence behind the use of four other drugs—topiramate, baclofen, ondansetron, and varenicline. Acamprosate as marketed is the calcium salt of N-acetyl-homotaurinate, a close relative of the amino acid taurine. It has also been found effective in European studies.

What did scientists think acamprosate was doing? Various lines of research had linked acamprosate to glutamate transmission. Changes in glutamate transmission have been directly implicated in active alcoholism. A decade ago, the Spanagel group had decided that acamprosate normalized overactive glutamate systems, and hypothesized that acamprosate was modulating GABA transmission. So it became known as a “functional glutamate antagonist.”  But specific mechanisms have remained elusive ever since.

Now, as Heilig comments, “the reason it has been difficult to pin down the molecular site of acamprosate action may simply be because it does not exist. Instead, the authors propose that the activity attributed to acamprosate has all along reflected actions of the Ca++ it carries.” As the researcher paper explains it: “N-acetylhomotaurinate by itself is not an active psychotropic molecule…. We have to conclude that the proposed glutamate receptor interactions of acamprosate cannot sufficiently explain the anti-relapse action of this drug.” Further work shows that acamprosate doesn’t interact with glutamate binding sites at all.  In other words, calcium appears to be the major active ingredient in acamprosate. Animal studies using calcium chloride or calcium gluconate reduced alcohol intake in animals at rates similar to those seen in acamprosate, the researchers claim.

Subsequently, the researchers revisited the earlier clinical studies, subjected them to secondary analysis, and concluded that “in acamprosate-treated patients positive outcomes are strongly correlated with plasma Ca++ levels. No such correlation exists in placebo-treated patients.” In addition, calcium salts delivered via different carrier drugs replicated the suppression of drinking in the earlier animal findings. 

Where there cues pointing toward calcium? The researchers conclude that “calcium sensitivity of the synapse is important for alcohol tolerance development, calcium given intraventricularly significantly enhances alcohol intoxication in a dose-dependent manner,” and “activity of calcium-dependent ion channels modulate alcohol drinking.”

Interestingly, in the late 50s and early 60s, there was a brief period of interest in calcium therapy for the treatment of alcoholism. In 1964, the Journal of Psychology ran an article titled “Intensive Calcium Therapy as an Initial Approach to the Psychotherapeutic Relationship in the Rehabilitation of the Compulsive Drinker.” Now it appears possible that a daily dose of acamprosate is effective for some abstinent alcoholics because it raises calcium plasma levels. Calcium supplements may be in for a round of intensive clinical testing if these findings hold up.

The authors now call for “ambitious randomized controlled clinical trials,” to directly compare “other means of the Ca++ delivery as an approach to treat alcohol addiction. Data in support of a therapeutic role of calcium would open fascinating clinical possibilities.”  Indeed it would.

Spanagel R., Vengeliene V., Jandeleit B., Fischer W.N., Grindstaff K., Zhang X., Gallop M.A., Krstew E.V., Lawrence A.J. & Kiefer F.  (2013). Acamprosate Produces Its Anti-Relapse Effects Via Calcium, Neuropsychopharmacology, 39 (4) 783-791. DOI: 10.1038/npp.2013.264

Narco-Deforestation Accelerates Loss of Biodiversity

In Central America, drug policies become conservation policies.

The Central American isthmus exploded into prominence as a drug trafficking corridor in 2006, when pressure on Mexican cartels pushed smuggling operations to the south and into the remote forest frontiers of Honduras, Guatemala, and Nicaragua. Since then, vigorous interdiction programs have pushed traffickers into ever more remote zones, back and forth from country to country, bringing money, manpower, and greater opportunities for deforestation.

Kendra McSweeney of the Department of Geography at Ohio State University and co-workers dug into the recent comprehensive report by the Organization of American States (OAS), titled The Drug Problem in the Americas, and wrote up their findings in a recent contribution to Science's Policy Forum. They found that “mounting evidence suggests that the trafficking of drugs (principally cocaine) has become a crucial—and overlooked—accelerant of forest loss in the isthmus.” (See graph above, representing forest clearings in Eastern Honduras.)

In the Caribbean lowlands area known as the Mesoamerican Biological Corridor, and in protected rural regions like Laguna del Tigre National Park in Guatemala and the Rio Platano Biosphere Reserve in Honduras (now listed as “in danger” by UNESCO due to forest loss), there is no shortage of reasons why deforestation in Central American is increasing. Among the causes are weak or corrupt government agencies, climate change, poverty, illegal logging, ill-advised development, and rampant agribusiness expansion. However, what has been called the “compounding pressure” of drug trafficking on biodiverse forestlands and associated rural communities is making things worse. The report in Science documented that an unprecedented flow of cocaine into Central America “coincided with a period of extensive forest loss” as narco-traffickers purchase large ranches in “contested rural landscapes.”

What are the active causal connections between drug trafficking and deforestation? The researchers identified three interrelated mechanisms “by which forest loss follows the establishment of a drug transit hub.”

1. Drug traffickers cut down forests to establish secret roads and aircraft landing strips.

2. Drug money amps up the pressure on weakly governed frontier areas, resulting in “narco-capitalized” land speculators and timber harvesting operations. In the process, local small landowners get priced out, even though the conversion of forests to farmlands is illegal in protected areas.

3. Drug trafficking organizations are themselves drawn into local forest-to-agriculture development plans like pastures and oil-palm plantations. Buying up and developing land is a preferred method of laundering drug money. These vague “narco-estates” monopolize land use in some territories and serve as cover for expanded smuggling operations.

What could mitigate this form of additional pressure on tropical deforestation? The researchers suggest that the heart of the problem is the traditional emphasis on supply-side policies, such as interdiction and crop eradication on foreign soil. “Analysts have long noted that eradication policies often push coca (and opium poppy and marijuana) growers into ever more ecologically sensitive zones, with substantial environmental impacts.”

The authors of the Science article view all of this as something to be added to “the long list of negative unintended consequences borne by poor countries as a result of the overwhelming emphasis on supply-side drug reduction policies…. Recognizing the ecological costs of drug trafficking in transit countries would improve full-cost pricing analyses of the drug policy scenarios explored by the OAS.”

McSweeney K., Nielsen E.A., Taylor M.J., Wrathall D.J., Pearson Z., Wang O. & Plumb S.T. (2014). Drug Policy as Conservation Policy: Narco-Deforestation, Science, 343 (6170) 489-490. DOI: 10.1126/science.1244082

The Anthropology of Addiction

Can we ever integrate neuroscience and social science?

Bielefeld, Germany—
The last in a series of posts about a recent conference, Neuroplasticity in Substance Addiction and Recovery: From Genes to Culture and Back Again.  The conference, held at the Center for Interdisciplinary Research (ZiF)  at Bielefeld University, drew neuroscientists, historians, psychologists, philosophers, and even a freelance science journalist or two, coming in from Germany, the U.S., The Netherlands, the UK, Finland, France, Italy, Australia, and elsewhere. The organizing idea was to focus on how changes in the brain impact addiction and recovery, and what that says about the interaction of genes and culture. The conference co-organizers were Jason Clark and Saskia Nagel of the Institute of Cognitive Science at the University of Osnabrück, Germany.   Part One is here.   Part Two is here.  Part Three is here.


The disciplines of psychiatry and neurology are being brought intellectually closer to each other. One can foresee the day in the not-too-distance future when resident physicians in both disciplines will share a common year of training, comparable to the year of residency training in internal medicine for physicians who go on to specialize in widely different areas.
— Eric Kandel, In Search of Memory

Anthropology is arguably a perfect discipline within which to connect the two often-conflicting facets of addiction—its fundamental neuroarchitecture, and the socioenvironmental influences that shape this basic biological endowment. In The Encultured Brain, published by MIT Press, co-editors Daniel H. Lende and Greg Downey make an articulate call for a merger of interests, in an attempt to combine laboratory research with anthropological fieldwork. The term “neuroanthropology,” meant to denote this combination of anthropology and brain science, was evidently coined by Stephen Jay Gould. A number of thinkers have dipped into this arena over the years, including Melvin Konner, Sarah Hrdy, Norman Cousins, Robert Sapolsky, and Antonio Damasio. The term gained a more solid foothold when Lende and Downey began their Neuroanthropology blog, now at PLOS blogs. 

The term has the advantage of meaning exactly what it says: an integrative approach to the complicated matter of how our genetic endowment is influenced by our cultural endowment. Or vice versa, if you prefer. Here, from the introductory chapter, is the short definition of neuroanthropology: “Forms of enculturation, social norms, training regimens, ritual, language, and patterns of experience shape how our brains work and are structured…. Without material change in the brain, learning, memory, maturation, and even trauma could not happen…. Through systematic change in the nervous system, the human body learns to orchestrate itself. Cultural concepts and meanings become neurological anatomy.” From the point of view of actual study, there is no choice but to join these two when possible—a task make more difficult by the rampant “biophilia” found among anthropologists and sociologists, as well as the countering notion among biologists that anthropology does not make the cut as a “real” science.

Co-author Daniel Lende, an associate professor in the Department of Anthropology at the University of South Florida, was one of the presenters at the Bielenfeld conference. Lende did his Ph.D. work on adolescent substance abuse in Bogota, Colombia, and told the group that years of research “showed me that addiction is profoundly neuranthropological.” Lende told the audience that the “combination of neuroscience and ethnography revealed that addiction is a problem of involvement, not just of pleasure or of self.”

 This approach calls for applying a critical eye to strictly brain-based explanations that ignore both environmental influence and biochemical individuality. And it opens up the possibility that anthropologists may be incorporating neuroimaging technology into their working tool kit. While the neuroanthropology movement has been mostly a product of the anthropology side thus far, Lende said. But increasingly, cognitive scientists are joining in.

“As neuroanthropologists, we’re not trying to solve problems in the lab or in the clinic, but rather to take the results of that sort of work, and look at what’s happening to those brains in the wild,” Lende said.

Repeated patterning comes from social environments, he said. “We have to deal with how cultural practices and developmental experiences can shape and mold the brain, and how that has an effect on the production of human variation, not just sets of beliefs you can take on and put off.”  The cultural practice of skull shaping, for example, is “impossible to understand without taking into account both the cultural practices that drive it, and the early plasticity in bone formation that allows it biologically.”

Culture, said Dr. Lende, “can bring different elements into one package. It doesn’t have to be the biology side that does all the work. You can take the cultural strands and knit them into something really unusual that you wouldn’t necessarily see in the world. With cultural tools, we are using are brain in ways not necessarily built into it from the start.”

But attending to all of this requires thinking of neural plasticity in novel ways, Lende said. “Hardwiring isn’t quite as hard as we once thought. The lifespan of these circuits set early in life isn’t what we thought.” The brain can use sensory input in ways we don’t yet understand. Lende pointed to “significant recovery from stroke, which was not viewed as possible a couple of decades ago.”

“You have to be critical both of the neuroscience and some of its limitations, and also the anthropologists, who are sometimes saying, ‘it’s got to be all sociocultural.’ That’s not always a good explanation for something as complex as addiction.”

Lende believes that anthropology needs to pursue the impact of “biological embedding, or how experiences get under the skin” to alter human biological and developmental processes. “You can have differential vulnerabilities to biological embedding, coupled with differential environmental vulnerability.”

Dr. Lende points to the well documented clinical finding that exercise enhances neuroplasticity. “And exercising has been shown in various labs to reduce craving,” he said. “What’s important from my community-based orientation is, what sort of interventions or strategies can we have that are low cost and be used in non-professional settings. Can we motivate people to do it? What are the barriers?”

 Subjective experience is hard to get at, but that’s a problem anthropologists think about all the time. “I asked the kids in Columbia, if your drug use were a place, Lende said, “ then what sort of place would that be? Kids who’d never tried drugs didn’t get the question, but a kid with heavy cigarette use who had just quit, and who had recovered recently from using too much cocaine and crack, looked at his fingers, referring to cigarettes, and said, ‘a world in there? No. But with cocaine, yes.”

Going Deep: Surgery For Addiction?

Controversial DBS technique shows early promise for Parkinson’s, Tourette’s.

Bielefeld, Germany—

The third in an irregular series of posts about a recent conference, Neuroplasticity in Substance Addiction and Recovery: From Genes to Culture and Back Again. The conference, held at the Center for Interdisciplinary Research (ZiF) at Bielefeld University, drew neuroscientists, historians, psychologists, philosophers, and even a freelance science journalist or two, coming in from Germany, the U.S., The Netherlands, the UK, Finland, France, Italy, Australia, and elsewhere. The organizing idea was to focus on how changes in the brain impact addiction and recovery, and what that says about the interaction of genes and culture. The conference co-organizers were Jason Clark and Saskia Nagel of the Institute of Cognitive Science at the University of Osnabrück, Germany.  Part One is here.  Part Two is here.

All addictive drugs increase the production of dopamine in the nucleus accumbens, as do other highly pleasurable activities. Part of the medial forebrain bundle (MFB), which mediates punishment and reward, the nucleus accumbens is the ultimate target for the dopamine released by the ingestion of cocaine, for example. The nucleus accumbens is a very old and evolutionarily well-preserved structure in the brain. If you remove large slices of the nucleus accumbens, or knock it out entirely, animals no longer want addictive drugs.

This is essentially the same pathway that regulates our food and water-seeking behavior. By directly or indirectly influencing the molecules of pleasure, alcohol and other drugs trigger key neurochemical events that are central to our feelings of both reward and disappointment. In this sense, the reward pathway is a route to both pleasure and pain. Studies of the nucleus accumbens have demonstrated abnormal firing rates in scanned addicts who were deep into episodes of craving. The craving for a reward denied causes dopamine levels in the nucleus accumbens to crash dramatically, as they do when users go off drugs.

During his presentation in Bielefeld, “Stimulating the Addictive Brain,” Dr. Jens Kuhn of the University Hospital of Cologne walked the audience through an explanation of one of the most controversial addiction treatment options of all, known as deep brain stimulation. For those unfamiliar with DBS, this surgical procedure uses implanted brain electrodes and a subdermal set of wires connected to a small power source to directly stimulate a designated area of the brain via electric current.  Deep brain stimulation (DBS) is becoming an established treatment option for some movement disorders, in particular Parkinson’s disease. It is also being investigated for obsessive–compulsive disorder, major depression, and Tourette’s syndrome.

Kuhn and his researchers, the first German group to investigate deep brain stimulation beginning in 2002, started by investigating Tourette’s and OCD. But soon, Kuhn said, it became clear that “valid animal studies show significant induced improvement in cocaine, morphine and alcohol addiction behavior following DBS of the nucleus accumbens…. the few patients who underwent DBS surgery for addiction remained abstinent or had a major reduction of relapses.” 

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.

Dr. Kuhn told the audience that DBS is a “focused neuromodulation procedure to enrich electrical activity” applied to certain brain regions and requiring only “minimally invasive” surgery. In the case of DBS surgery for addiction, which Dr. Kuhn has performed in clinical settings, the target is the nucleus accumbens, which Kuhn called “the key player in the so-called limbic reward loop.”

The problem is that these investigations, while positive in many cases, are small and scattered thus far, and do not represent a systematic investigation of the procedure by the field of neuroscience at large. Not yet, anyway. And maybe not ever. There are very few published studies on human addicts, Kuhn said, “but luckily, the ethical implications of DBS are being more and more discussed.”

Unfortunately, as Kuhn pointed out, “neurosurgical interventions in psychiatric patients raise ethical considerations not only based on the disreputable experiences of the era of psychosurgery.” But that’s a good starting point. The procedure, despite one’s best efforts, conjures up images of “psychosurgery”—prefrontal lobotomies, or early electroconvulsive shock therapy (ECT). It doesn’t help that the likeliest mechanism of action that explains DBS is that high frequency stimulation causes functional lesions at the specific brain sites. From almost every angle, it seems ham-handed and crude—until you see some videos of results, like this one of a Tourette’s patient: Video

Kuhn acknowledged that a number of medical professional believe DBS is a poor choice for addiction, and its use “is premature due to expenses, possible risks and the assumed poor scientific rationale of the method in this field.”  In a letter to the journal Addiction, Adrian Carter and Wayne Hall of the University of Queensland, Australia, noted that some of the positive reports come from China, where scientists have experimented with ablation of portions of the nucleus accumbens and other brain areas. And it seems to work. So, one cure for addiction has been discovered already—but surgically removing chunks of the midbrain isn’t likely to catch on, except as a seminar topic for medical ethicists. Carter and Hall call the evidence base for the safety and efficacy of DBS in addiction “weak,” and argue that “the addition of an expensive neurosurgical treatment that costs of the order of $50,000 will worsen this situation by utilizing scare health resources to treat a very small number of patients with the income to pay for it.”

In a history of “stereotactic lesions” as a treatment for movement disorders, researchers at The George Washington University School of Medicine and Health Sciences reviewed efforts to expand the use of DBS to include specific psychiatric disorders like depression and obsessive-compulsive disorders. Writing in the Journal of Neurosurgery in 2010, they concluded that “addiction and schizophrenia showed the least improvement from surgery. Therefore, pursuing the treatment of these disorders with DBS using the targets in these studies may be ineffective.”

The Neurotech Business Report recently documented that St. Jude Medical, a manufacturer of surgical devices, has shut down its clinical trial of DBS for depression (h/t Vaughan Bell). The company’s website said “The BROADEN (BROdmann Area 25 DEep brain Neuromodulation) Study” has been closed and is no longer enrolling participants. The article suggests that “the complexity of specifying the precise brain circuits involved with major depression” may have been the reason for halting the trial.

Known risks associated with deep brain stimulation placement include: dizziness, infection, loss of balance, and speech or vision problems. In addition, the devices, wires and leads that make up the system, which are all implanted in the brain or under the skin, can break or fail in various ways. DBS can also alter glucose metabolism and food intake in lab rats. Altogether, there are few case reports, and the mechanism of action remains essentially uncharacterized. In the case of addiction, this is one treatment that does not seem ready for prime time. It would be premature to move DBS beyond the clinical trial stage in humans without additional data.

Photo Credit: http://biomed.brown.edu