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

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/