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Researchers use unique case to unearth the workings of the brain

by Dawn Brazell | News Center | April 29, 2014


NeuroPaceResearchers glad to see patient being helped by novel treatment that involves deep brain stimulation in two different areas of his brain - the subthalmic nucleus and the nucleus accumbens - to create an "electric cloud."
 
Emma Vought 

Operating on patients’ brains on a daily basis, neurosurgeon Istvan Takacs, M.D., can be hard to impress.

When he talks of an unusual case at the Medical University of South Carolina, though, there’s wonder in his eyes. The case involves a patient who has four electrodes in his brain to create “an electric cloud” to treat his obsessive compulsive disorder and Parkinson’s disease.

“It rocks to be a neurosurgeon when you get to do things like this,” he said of his collaboration with interventional psychiatrists at MUSC. Traditionally, psychiatrists and neurosurgeons have approached the treatment of the brain from polar-opposite perspectives.

Dr. Takacs MUSC 
Dr. Istvan Takacs 

“You traditionally think of psychiatrists as talkers or medicators. These psychiatrists are all beyond that,” he said of the brain stimulation techniques that are transforming the field and creating powerful, new therapeutic partnerships. “The more input you get from more people, it can only be good. When you get to work with people who chose to work in a completely different field of medicine, and then you spend decades of your lives learning things in different directions, and here we are. We are in this thing together for the same ultimate purpose.”

Nolan R. Williams, M.D., agrees. Williams is chief resident of Combined Neurology and Psychiatry, and is the patient’s interventional psychiatrist.

“There were probably 15 psychiatrists and neurologists and neurosurgeons packed into Dr. Takacs’ office planning the surgery. Everybody was equally excited, and everybody knows their role in all of it and respects one another for each other’s role,” he said. “That tells us a lot about how medicine is moving in general to a much more collaborative mentality.”

It’s a shift patients, such as this one with the bilateral DBS implant, need. The patient has experienced depression for most of his life that medications have failed to treat adequately. Several rounds of electroconvulsive therapy also have failed to relieve his symptoms. In his 50s, the patient faced a new challenge: Parkinson’s disease. He agreed to have deep brain stimulation treatment, with two electrodes placed in his subthalamic nucleus. When the procedure brought him relief from his Parkinson’s symptoms, he wondered if it also could treat his lifelong obsessive compulsive disorder (OCD) that has been so intense it compelled him to check the garbage, retrace his footsteps and feel hopelessly depressed.

Takacs, Williams and colleagues thought it was worth a try since implanting the second set of electrodes would offer a unique opportunity to see how the bilateral electrodes would interact, especially given the placement into the patient’s nucleus accumbens or reward circuitry portion of the brain. Beyond treating his OCD, the hope was this also could relieve the man’s depression and apathy, symptoms often seen in patients with Parkinson’s disease.

In July 2013, he received his second set of electrodes. Interventional psychiatrists have been adjusting his electrode settings through a “brain pacemaker” that is implanted in the chest and monitoring his reactions and progress. It takes months to see what effect treatment will have. Williams said the patient is no longer having suicidal thoughts, his levels of depression and apathy have improved and the severity of his OCD has lessened. “He is doing much better. He went from compulsively calling the office daily to now checking in only during his scheduled visits. He states that his mood is better and he has been able to find joy in his life again.” 

New Paradigm

Takacs said he’s glad to see the growth in the field of interventional psychiatry.

“It’s a whole new paradigm that’s been adopted. It’s very rare to have a psychiatry department and a neurosurgery department in sync where there’s an agreement that, on a carefully selected subgroup of patients, invasive procedures are OK and helpful and move both the patient’s lives and science forward. It is not something that exists in very many places, not in the United States and not worldwide.”

Dr. Nolan Williams 
Dr. Nolan Williams 

Williams said the strength of MUSC’s brain stimulation research and lab is one reason MUSC is offering a new interventional psychiatry fellowship. It is for residents and psychiatrists who want to have an additional year of training in the wide variety of both invasive and non-invasive brain stimulation technologies that now are available, some of which have been pioneered at MUSC. MUSC also has a curriculum within the residency program called the interventional psychiatry track.

Attracted by a field that is fertile ground for the next leap in what psychiatric treatment can offer, Williams said the interventional fellowship program will expose trainees to all the latest brain stimulation technologies, teaching them how to use them so they will be able to push the field forward and reach patients who unfortunately have been unresponsive to traditional treatments.

“What we’re trying to say is that we still have a couch and a prescription pad, but we have other types of technologies including brain stimulators that we’re using to treat various psychiatric disorders. This is not to replace talk therapies or medications, but it’s an augmentation for people who are not responding to traditional treatments.”

It’s also a shift in how the brain is viewed – how it is an electro-chemical organ.

“We’re looking at the electricity primarily, the circuits and how the circuits behave. There are ways to directly and focally intervene on those circuits. We’re interested in making sure that we educate doctors, psychiatrists and the public on these types of technologies to let them know where the current state is, and where we’re going. We’re interested in people collaborating and synergizing to evolve these technologies to help people. We’re trying to help people who are barely living or dying.”

Electric Conversations

Inside the three-pound gray mass that is the brain, there is a rhythm of electrical oscillations among the billions of neurons.  When an electrode probe is implanted, it adds to this electrical conversation going on among the cells. Takacs said DBS is an invasive procedure not to be done on a massive scale, but for certain carefully-chosen cases, it has advantages. One is the current can be directed, unlike systemic medications that may cause side effects. And, it’s reversible, Takacs said.

“Whatever you use it for, whether it’s for a psychiatric application or a movement disorder, it’s a reversible procedure. You don’t destroy anything, so if something doesn’t work, then you can tone it down. You can switch the electrode contacts. You can change the shape, size and scope of the electric cloud that you’ve created around your target structure. Under proper and experienced supervision, it allows you to explore these things.”

For the bilateral DBS patient, the treatment opens a window into how the brain’s circuitry does work. Since this has never been done before, doctors will have to find out if the simultaneous stimulation of several target structures is better than the selective stimulation of a few, and how it all will interact, he said.

“Will one device interfere with the other device and, if it does, will it interfere in a negative way or in a positive way? Our hopes have been that either the two devices will not interfere with one another or that they will interfere with one another in a synergistic way. One is a turbo charger for the other. This is a long-term project where you first start to tweak his OCD electrode settings to try to optimize that and then you try to create some cross talk between his Parkinson’s implants and his OCD implants. “

Takacs said it’s well-known DBS can be effective in treating a movement disorder such as Parkinson’s disease, however, electro-neuromodulation gets much more complicated when talking about treatment-resistant depression or other emotional states.

 Monet
Courtesy National Gallery of Art, Washington
 Claude Monet - The Japanese Footbridge

“Walking straight is a very primitive or simple thing, but your general state of mind - if you’re going to be happy or if you’re going to be sad - it’s probably a sum of a lot of different functions. It’s just like a Monet painting. If you look at it from far away, it looks like a sailboat, but if you go close up, it looks like a bunch of dots, so the gestalt of the whole is made up of a lot of inputs. To have just one electrode somewhere and hope that that will color the expression of your whole mind, to think that there is one single switchboard to happiness, to curing depression, I think that is a vain hope to have because we are more complicated as thought machines than that.”

Researchers are exploring if there may be ways to create some sort of triangulation between electrodes that are fairly distant from one another to generate a larger amount of input, he said. 

Selecting the reward circuitry area in the brain as a target for OCD opens new research territory. The thought is that the stimulation will give the patient relief from the anxiety that is being felt if he doesn’t get to perform the repetitive task, he said, “What does the repetitive action do for you? It gives you brief relief. By going to the reward circuit and trying to keep that stimulated - and in a sense we don’t even know if you’re stimulating the reward circuit or if we’re inhibiting a feedback loop that turns off the reward circuit - we are messing with the reward circuit in some way.”

Williams said there’s wide interest in the current bilateral DBS case since it’s thought that some patients with Parkinson’s disease also may have dysfunction in the rewards circuitry. “So this is a really unique and exciting case because not only does he have two sets of stimulators for two sets of diseases, but he’s also the first Parkinson’s patient in the world to have a deep brain stimulation electrode in the rewards circuitry.”

Reducing Stigma

Seventy percent of Parkinson’s patients have depression at some point in the course of the disease and having depression prior to Parkinson’s makes them 2-3 times more likely to develop Parkinson’s disease, Williams said.

“We also know that depression is the most disabling part of Parkinson’s. If you survey Parkinson’s patients, they’ll say that depression is the thing that is the most disabling of all of their symptoms. We don’t have a crystal ball to tell the future, but we’re really monitoring a lot of things closely, certainly monitoring the obsessive compulsive disorder, which was the primary reason for the implantation, but also other things like his mood and his Parkinson’s-related apathy.”

Williams said he’s been glad to see the patient’s mood and anxiety improve. “This could be a really exciting time if he’s able to maintain those gains.”

  
Dr. Baron Short 

It’s an exciting time in more than one way, said Baron Short, M.D., clinical director of MUSC’s Brain Stimulation Services, part of the Department of Psychiatry & Behavioral Sciences. MUSC’s brain stimulation services include a wide array of treatments: Electroconvulsive therapy, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation and epidural cortical stimulation that are being used successfully for a variety of treatment-resistant disorders.

“We’re trying to be advocates for other people with various psychiatric disorders and say that these are conditions that people are not causing,” Short said. “There are conditions related to how their brain and body are functioning and there are some similar modalities that we already are using for other disorders, in this case, various neurological diseases such as Parkinson’s that may be effective for psychiatric disorders. It’s ironically playing a role of reintegrating psychiatry with the rest of medicine.”

Revolutionizing the view in psychiatry of how circuit-based certain types of suffering or certain types of disorders can be, brain stimulation techniques can be used to focally intervene on those circuits. “We’re not as focused on medication that has an effect throughout the body on multiple organ systems,” he said. “There’s more of a focus of trying to find changes in the brain through neuroimaging, through understanding how the brain is behaving with certain disease states and then directly intervening.”

That type of paradigm shift will help reduce the stigma of mental illness in many ways, a change psychiatrists and colleagues welcome.

“It’s hard to make an argument that these things aren’t problems within the brain when you can put an electrode in the brain, stimulate in a specific targeted area in the brain and then the symptom goes away,” Williams said. “That’s a very powerful statement for saying that these are truly brain-based disorders, and there shouldn’t be any more stigma about having obsessive compulsive disorder than having something like Parkinson’s disease or suffering a stroke. We feel that these are very similar conditions in the sense that they’re all happening in the brain.”

It’s also making other doctors, such as neurosurgeons, take note. Takacs said the field of neuroscience is taking a giant leap forward because of the powerful partnership developing between neurosurgeons and interventional psychiatrists.

“Here at MUSC, we have the neurosurgical expertise to get patients wherever they need to go inside the head, and we have members of the psychiatry department, such as Mark George, who are distinguished in having pioneered these newer neuromodulation type of procedures. It’s an exciting place to be.”


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