Okun’s path was also turned in medical school. Though he majored in history as an undergraduate at Florida State University, he made a late decision to go to med school and become a “black bag doctor,” a general practitioner caring for families and making house calls. “Then I got my first introduction to the brain,” he recalls, “and I said, ‘This is really cool.’”
Twenty years later, his enthusiasm is fresh as he describes his neurological satori. “A lot of people were saying all these pathways and everything are really complicated, and they just wanted to get through the class and get a grade. But to me it made perfect sense. You could localize diseases and networks within the brain and figure out where things were and actually make a difference.” Later, as Okun’s interest in movement disorders grew, he realized he had been exposed to them his whole life. “The Jews have some of the highest incidences of movement disorders,” says Okun, who grew up in a Jewish family in West Palm Beach, Florida. “If you go to temple you see it, a lot of people are blinking, they have tics, they have tremors. One of the reasons I was fascinated by this field is I would look back and remember seeing people shaking and shuffling and thinking to myself, ‘Why is that?’”
He knows the answer to that question now. “There’s an abnormal conversation going on between different regions of the brain,” he explains. DBS interrupts those abnormal conversations. The challenge for Okun and Foote is to identify the tiny spot in each patient’s brain where the electrodes will do the most good, to locate, amid the cacophony of a hundred billion chattering neurons, the specific neural network that is causing the patient’s problem. “Location is everything,” says Okun. “A couple of millimeters in the brain is like the difference between Florida and California.”
Before setting up shop at UF, Okun and Foote both studied with DBS legends. Okun trained at Emory University with neurologist Mahlon DeLong, who pioneered the “brain circuit” approach to understanding and treating movement disorders. (DeLong is one of six 2014 recipients of a $3 million Breakthrough Prize in Life Sciences, created last year by Mark Zuckerberg and other Silicon Valley leaders to recognize major achievements in medical science.) Foote, after completing his residency, went to Grenoble, France, where he worked with Alim-Louis Benabid, who developed DBS as a treatment for Parkinson’s and performed some of the first procedures in the early 1990s. Foote then joined Okun at Emory, where the two continued their DBS training with DeLong and neurologist Jerrold Vitek.
Now, as the two of them try to better understand and manipulate neural circuitry, they are working in what could be called a golden era in brain science. Each week seems to bring news of another advance, like a report in January from England affirming the effectiveness of transcranial magnetic stimulation as a treatment for acute migraine, which followed reports about the successful use of the non-invasive procedure for depression and some symptoms of schizophrenia. And research interest is booming too, as evidenced by the ambitious, multidisciplinary White House BRAIN Initiative. DeLong, after four decades studying the functional organization of the brain and neuromodulation, has never seen anything like it. “The pace of change and discovery is just unprecedented,” he says. “We’re forging really great advances in almost every disorder you look at, for both neurology and psychiatry. And this will pay off.”
Surgeons, as a rule, do not like sharing power. The stereotype of the domineering OR general is rooted in the simple fact that cutting open human bodies is a high-risk business and someone needs to be in charge. Foote, tall and commanding in his scrubs, gladly cuts against this expectation in his collaboration with Okun. He treats the neurologist as an equal partner in the procedure, a co-operator, to be exact, though the neurologist does not scrub in or get near the sterile field that surrounds the opening in the patient’s skull.
Okun, several inches shorter than Foote, is focused and intense in the OR, a forceful presence from the moment he enters, though he doesn’t say much at first. On this day, he is too busy studying the computer screen where Rodney Haning’s MRI is being compared with a brain atlas that Okun, Foote and other UF colleagues created with data from the dissection of dozens of postmortem brains; because every brain is slightly different, matching structures in Haning’s brain with the atlas helps the doctors map their targets. Standing side by side, Okun and Foote discuss their planned approach, pointing to familiar landmarks, which are outlined on the screen in bright red, green, yellow and blue.
When the skull has been opened, Foote slowly feeds a microelectrode on a hair-thin wire down into Haning’s brain. This is not the lead that will be permanently implanted in the brain; rather, it’s a kind of electronic advance scout, a radio receiver that picks up and amplifies the electrical signals of individual brain cells, while canceling out ambient electrical noise. As the probe moves deeper into the brain, the sound of the cells fills the OR, like static from deep space. Okun, who has taken up his position at the patient’s side, manipulates Haning’s left arm and fingers, and strokes his arm, chin and lips, triggering electrical activity in the brain. As he does this, he listens to the screech of individual neurons—their electrical signatures—as they are pierced by the microelectrode. With his trained ear, Okun distinguishes between normal neurons and the abnormal neurons that are causing Haning’s tremor, and he guides Foote to their target, a malfunctioning network of cells located in Haning’s thalamus, near the center of his brain, about four inches down from the hole in the top of his head. “That’s a tremor cell,” he says at one point. “Can you hear it?”
Keeping movement disorder patients awake during DBS procedures makes it possible to track the effects of the surgery in real time. One of the quirks of the treatment is that the operation itself alters brain tissue and interrupts the abnormal signals, reducing the patient’s symptoms before the current is even turned on. (This temporary effect is an echo of past practice; years ago, before DBS, surgeons treated movement disorders by creating tiny lesions in the brain.) Several times over the course of his operation, Haning uses his left hand to draw spirals on a clear plastic clipboard that is held up for him. His first spiral, made before the procedure begins, is jagged, unsteady. His last one is smooth, the work of a tremor-free hand.
As the operation winds down, with the lead in place in Haning’s brain, a pleased Okun tosses Foote a compliment. “Kelly, I don’t know how you did it, but you’re all hand,” he says, referring to the way Foote hit the target area, the circuit that was causing the tremor in Haning’s left hand.
“Imagine that,” Foote replies, deadpan.
DBS isn’t an option for everyone. It offers hope to selected patients who, despite expert medical management, remain disabled by their symptoms. While it usually works, it is hardly a panacea. It’s brain surgery, after all, arguably the most invasive of all invasive procedures. And besides the usual surgery risks, it requires follow-up outpatient surgery every four years to replace the battery pack.
But it has showed itself as an effective and generally safe treatment for many, including Rodney Haning. With those successes, Okun and Foote, like other leaders in the field, are looking beyond movement disorders. That’s why they added the word “neurorestoration” to the name of their UF treatment center, and why they are already performing experimental DBS procedures on patients with obsessive-compulsive disorder, Tourette’s syndrome and Alzheimer’s disease.
Similar DBS research is going on at academic medical centers across the country. DBS has even attracted attention from DARPA, the research arm of the Department of Defense, which is launching a five-year effort specifically targeting four neuropsychiatric conditions—PTSD, major depression, borderline personality disorder and general anxiety disorder—as well as traumatic brain injury, addiction and chronic pain.