Tuesday, January 28, 2014

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.

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