In the addiction treatment lab at West Virginia University, Prof. Ali Razai shows his patient pictures of lines of cocaine, of syringes, of people under the influence. “What do you feel when you see this picture?” he asks. “And now you feel differently?”
Questioning a patient is not an unusual matter, but with Razai’s specific patient, nothing is normal at that moment, not even for a drug addict. His skull is open, and Razai tickles all kinds of brain areas with an electrode. He is trying to find the exact point that will “turn off” his addiction.
Razai, head of the Rockefeller Institute for Neuroscience at West Virginia University, is considered one of the leaders in the field of brain surgery. He was the pioneer in the implantation of electrodes in the brain for the treatment of mental and brain disorders. Treatments of this type have been very successful in patients with epilepsy and Parkinson’s, and are now considered a treatment option or at least tested as such in a variety of conditions.
In diseases such as Parkinson’s and epilepsy, the treatment area is well characterized, but today brain imaging is also used in less understood diseases, such as depression, OCD (obsessive compulsive syndrome), Alzheimer’s, post-traumatic syndrome or addiction. The use of brain stimulation to treat addiction began experimentally only a few years ago.
Razai’s patient is expected to leave the clinic when he no longer feels the same level of urge for the drug. “The desire for the addictive substance decreases dramatically within ten minutes, and the effect survives months after the treatment,” says Razai in an interview with Globes.
The structure of the brain changes
Addiction, Razai says, does not begin as a problem of the brain (see box) but as a behavioral problem, but gradually it becomes a brain problem: “When you take drugs, and especially opioids, which are our biggest problem in West Virginia, there is an area of the brain, central to the reward system ( nucleus accumbens), which begins to secrete too much dopamine – the same substance that signals to us that our behavior is satisfactory and we should repeat it.”
In a healthy brain, dopamine is secreted in response to food, water when we are thirsty, sex, but also drugs. Today it is accepted in the science of addictions to say that all addictions eventually lead to an imbalance in dopamine.
Razai’s patients are heavy addicts for whom no other treatment has helped, and they see a change in this area of the brain. “The area is different in terms of its physical structure and metabolically, meaning its energy consumption, and also in terms of the passage of electrical signals in it,” he says. This means that there is conclusive evidence that addiction has indeed become a problem of the brain.
“The brain becomes sensitive to dopamine, it needs it more. This is a biological change in the reward area. The brain constantly signals that it needs more and more dopamine. We lower the activity of this area using ultrasound, so that it ‘screams’ less. At the same time, we improve the activity of the frontal lobes, which give more control and help the patient deal with the urge to take drugs.”
recreate the network
The idea to treat addictions with this technology first arose following changes that occurred in Parkinson’s patients. Dopamine-secreting cells are also involved in this disease, but in areas of the brain that are responsible for controlling movement. Despite these differences, in some people who came for Parkinson’s treatment and happened to also suffer from OCD or addiction, improvement was observed in all of these conditions. This is not the only example of the cross effect on different diseases. The research literature documents, for example, a woman who received treatment for OCD and “along the way” lost weight and quit smoking, “without trying at all” according to her. Because of the small number of patients treated with this method, even today, many of the articles published on the subject are actually case studies of treating one person. Nevertheless, the information is starting to accumulate.
In the past, neuroscientists focused on the challenge of mapping the brain and identifying areas of activity such as language processing, music processing, understanding emotions and so on. However, in recent years, neurology is increasingly embracing the understanding that the brain is a collection of networks that are involved in each other, in a way that makes it difficult to separate them.
So, how can a single point stimulus change such a complex event as addiction?
“It is true that many networks in the brain are involved in addiction. We believe that these networks lose their ability to control, and this is the problem of addiction. We actually use the electrical energy of the electrodes or the ultrasound energy to re-create the correct network.
“By stimulating the control points, with a millimeter precision, we can make the entire network, which is spread over the entire brain, operate in a less chaotic manner.”
If the problem is in the area of reward and in the end all addictions are governed by dopamine, why does an addicted person want a very specific thing and not anything rewarding? It seems as if every reward is converted in the brain into a “currency” of dopamine.
“That’s exactly what addiction is. The same reward area connects to the drug and disconnects from other things. When we complete our intervention, patients tell us that they have returned to enjoying life. Before they had no pleasure, but from the drugs. While the decrease in craving comes immediately, the part of resuming the enjoyment of life It takes much longer and requires all the work around – from the psychologist, welfare and the community. It takes years for the brain to change back completely.”
Johnny Cash on batteries
But sometimes brain stimulation leads to rapid changes, even in what gives people pleasure. In an article published in 2014 in the journal Frontiers in Behavioral Neuroscience, it was reported about a man, “Mr. B”, who at the age of 46 underwent surgery to implant a brain pacemaker to treat his obsessive-compulsive syndrome. The treatment was successful, and Mr. B was generally less obsessive and much happier, but the treatment had a strange side effect: he became a fanatical consumer of Johnny Cash’s music – music he had never listened to before. Suddenly, in a fit of rage, he purchased the entire Cash discography, stopped listening to the music he had heard before, and claimed that for every event in his life he fits a relevant song by Cash in his mind.
Sound like any fanatical fan? Maybe, but with an interesting feature: when the batteries in his brain stimulation device run low, his interest in Cash declines, and he goes back to listening to the music of his childhood. The connection is so clear, researchers know they need to replace the batteries when the patient’s interest in the cache declines.
“I know such stories, and they are beautiful stories, which I have not really seen in my experience,” admits Razai. “To date, I have not been able to turn on or off the desire for certain music or to change a patient’s personality dramatically from moment to moment. We do see a gradual change, patients who feel more involved in their lives, their point of view is more positive.”
In the past, Razai raised the possibility that the treatment Mr. B went through reduced his negative thoughts and therefore made room for him to appreciate music in a more complete way, and it happened to be during this time that he encountered Cash. “But I do not rule out the possibility that there will be cases where the stimulus will make a dramatic change,” he said. “This whole field is an ongoing experiment.”
Cash’s story is certainly unusual, but several DBS patients have reported euphoria from the treatment itself. The prevailing attitude in the literature is that this condition, which is too reminiscent of the effects of the drugs themselves or dangerous effects of mania, is to be feared. A phenomenon of addiction to DBS itself is even described in the literature, when a woman who was given the opportunity to control the intensity of the stimulation, preferred to set it on a high intensity and lost interest in any pleasure except that which the device gave her.
Who decides how happy we will be?
But not all patients who report enjoying the device become addicted to it, and then an ethical question arises: assuming that the brain can be stimulated to be happy, without negative consequences, is it really possible and desirable to limit the use of the device? Is the brain stimulation therapist’s job to make the patient as happy as possible or just normal?
One patient even argued about it with the doctors. During the calibration of the device, there was a moment when he felt very happy, but his doctors, contrary to his opinion, chose a lower intensity, in which he was happy “to a normal extent”. In an article published in 2012 in the journal AJOB Neuroscience, the doctors hypothesized that he stopped coming to the clinic because he was angry with them.
Razai prefers not to deal with these questions right now. It concentrates on a specific one-point stimulus that is identified as addictive, and is satisfied with that as long as nothing else is affected. But the way he breaks through could certainly raise these questions in the future.
At the moment this technology is in its infancy. It is still not considered mainstream medicine, and there are fears of a variety of side effects: stimulation of the wrong place in the brain, infection, stimulation of the immune system in the brain, stimulation of other mental disorders, and even cyber attacks on the device in the brain.
Razai believes that brain stimulation, whether it is done with electrodes or ultrasound, often brings the patient back to his true self, especially in cases of treating addicts, where the addiction literally hijacks the patient’s brain and personality.
Patients come to his office who have lost many parts of their lives and may also lose life itself. They have no choice but to try even the most surprising treatment alternatives, hoping that they will help them become mainstream.
The Israeli technology that competes with implants
The brain draining technology also has an Israeli side. In recent years, a possible replacement for stimulation with electrodes has gradually emerged – stimulation of the brain with ultrasound technology. The idea is somewhat similar to a game that children used to play: focusing the light rays on a single point using a magnifying glass, so that only that point will burn. Ultrasound comes from thousands of directions and focuses on a single point of millimeter size, where the stimulation intensity is high. No effect is felt in the rest of the brain, because only one of the thousands of rays passes through each area.
The Sheba Hospital is one of the main research sites for such technology, which is being developed by Insitek. The technology is currently approved for the treatment of Parkinson’s and non-Parkinson’s tremors, and the intention is to use it in many other diseases.
“Focused ultrasound changed the field,” says Dr. Zion Zabili, director of the neurosurgery department at Sheba. “If we use focused ultrasound, we do not need to cut the skull nor all the tissues that are on the way to the tissue we want to operate on. And the effects are immediate.”
Dr. Zion Zibley / Photo: Yossi Cohen
Another Israeli company, Brainsway, already sells its brain stimulation products on the market. It applies the same idea of focusing on one area but does it with the help of magnetic stimulation. The company has registered for marketing a product for the treatment of depression, for the treatment of OCD and for smoking cessation. The last two approvals made her one of the pioneers and innovators in the field. In clinical trials it achieved good results in other disorders.
“The difference between focused ultrasound and magnetic stimulation is the focus deep in the brain,” says Zabili. “The technologies that reach deep into the brain do not reach there in a targeted manner. That is why focused ultrasound is the only technology that shows the same results as the implants.”
Prof. Ali Razai
education: degree in medicine from the University of Southern California and specialized in brain surgery at New York University and the University of Toronto
professional: Founder and director of the Rockefeller Institute for Neuroscience at West Virginia University. Considered one of the leading surgeons in the field of brain stimulation
Something else: Recruited to establish the Rockefeller Institute and deal with the country’s public health problems, primarily opioid addiction