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Clearing the wires
by Ann Brock

Imagine not being able to button your shirt, pour a cup of coffee or hold a pen. You try to brush your teeth, but instead smear toothpaste on your face. You have muscle stiffness or a twitching that cannot be controlled, or maybe your left leg swings uncontrollably in wide circles. You’re virtually dependent on a caregiver because life is no longer normal. You can’t sleep, and pain and muscle spasms have a bulldog grip.

You are one of about a million people in the United States who suffers from Parkinson’s disease. There is no cure, and medicine can only do so much to alleviate the symptoms of the disease. That’s when you desperately hope that somewhere on the planet there are researchers who are determined to find something to make it all better.

Dr. Charles Blaha
Dr. Charles Blaha's research may dramatically ease symptoms of those who suffer from Parkinson's disease.

There are, and one of them is a professor of behavioral neuroscience in the College of Arts and Sciences’ Department of Psychology at the University of Memphis. Dr. Charles Blaha has spent much of his life studying the neural systems of the brain. While getting his undergraduate degree at the University of California at Santa Barbara in the 1970s, he became interested in a new science called physiological psychology, which eventually evolved into behavioral neuroscience, a study of the neurochemistry, neurophysiology and neuroanatomy of the brain and their functional relationships to normal and abnormal behavior.

“We knew virtually nothing about how the brain works, but with the advent of molecular biology, genetics, pharmacology and anatomy in the 1970s and 1980s, all the tools were developed that made it possible to understand and investigate brain function at levels that were never possible before,” Blaha says.

In the 1970s, the technique of measuring dopamine had been used for about 30 years and was done mainly in a beaker. It was going from beaker to brain that gave Blaha the springboard that led to his current work in neurological diseases such as Parkinson’s and psychiatric disorders like schizophrenia, autism and drug addictions. He says, “In the chemistry department at the University of California at Santa Barbara in 1976, I conducted my first recording of neurotransmitters in the living brain using a new technique called in vivo electrochemistry, and I haven’t looked back since.”

Parkinson’s disease was first named in “An Essay on the Shaking Palsy,” published in 1817 by a London physician named James Parkinson, but has probably existed for thousands of years. The disease is associated with the loss of dopamine-producing nerve cells in the midbrain, which is likely to be a combination of environmental, genetic and biologic factors. Parkinson’s patients have lost up to 80 percent or more of these cells by the time symptoms appear.

Blaha is on a quest to improve an existing treatment for Parkinson’s that is used somewhat blindly. Deep Brain Stimulation (DBS), an established therapy for neurological disorders, was first developed in France in 1987 and evolved out of surgeries in which doctors used heat probes to burn and permanently damage small regions of the brain. Although the procedure is now performed in such a way that no longer harms brain tissue, it is done without the necessary neurochemical feedback to assure precision and promote effectiveness.

Currently, a three-part system is used in DBS. A stimulating electrode is implanted in a specific region of the brain, and a wire from this electrode snakes under the skin to a pacemaker-like stimulator device implanted in the chest under the clavicle bone. An external hand-held device is then used to transmit a stimulation program to the pacemaker under the skin using radio frequencies. Surgeons aim the electrode toward the subthalamic nucleus and dopamine neuronal fibers called axons in the brain and hope they hit the right spot. “They’ll increase or decrease the stimulation intensity or frequency and do everything they can to get the best therapeutic effect after implantation of the electrode, but if they’re not in the right place to begin with, no amount of fiddling is going to give them a better response,” Blaha says.

Conceptual Drawing
Conceptual drawing of wireless transmission of neurochemical data from the newly developed dual neurochemical sensor (dopamine and glutamate) and stimulating electrode positioned in the subthalamic nucleus of a Parkinson’s patient.
The brain surface implantable CMOS chip (wireless control) replaces the bulky pulse generator (wired control)
and enables simultaneous brain stimulation and neurochemical recordings that can be wirelessly transmitted
to the outside world for diagnostic purposes.

Several years ago, neurosurgeon Dr. Kendall Lee in the department of functional stereotatic neurosurgery at the Mayo Clinic in Rochester, Minn., was using DBS to treat Parkinson’s patients, as well as those suffering dystonia and essential tremor. Like many other neurosurgeons, he was aware that when certain electrical stimuli were delivered to the subthalamic nucleus, many of the symptoms of Parkinson’s disappeared, but he did not know why or how it worked. So he began searching the Internet for someone whose expertise would enhance and complement his own. Blaha says, “He called me in 2004 when I had just arrived at the University of Memphis. When I told him that I had stimulated the subthalamic nucleus, an area they target for Parkinson’s, and that I had routinely recorded dopamine with those types of stimulation, he got extremely excited and asked me to send him some of the data.”

That incident served as a catalyst to both deciding to combine their efforts into developing a new kind of methodology that would improve DBS by using neurochemical feedback, in essence the development of a “smart” DBS system.

Blaha and Lee partnered to invent a stimulating and recording device coupled to a new type of brain implantable electrode that combined stimulating contacts with neurochemical sensors that yielded them a patent. This patent was licensed for $1.5 million by Advanced Neuromodulation Systems (ANS), a St. Jude Children’s Research Hospital medical-device company located in Plano, Texas. The electrode will give neurochemical signals that can be monitored during implantation to tell the surgeon if it’s in the right place and will also give signals after it’s implanted to increase or decrease stimulation.

Blaha and Lee have formed a DBS consortium, which includes members in the division of engineering and technology services at the Mayo Clinic and in the departments of electrical engineering and biological sciences at Case Western Reserve University and Illinois State University. The research group of Dr. Zahn-Hee Cho (inventor of Positron Emission Tomography, PET) of the Neuroscience Research Institute in Seoul, South Korea, has recently joined the consortium. Members of the consortium are working together to take the existing system to the next level of sophistication. Via a weekly conference call and periodic meetings, they are fine-tuning the design and implementation of these new DBS devices. They are working on such details as optimum stimulation parameters, what areas of the brain to stimulate and the kind of neurochemical signals that can be used for feedback control of the stimulator.

The consortium is working on replacing the bulky three-part system with wireless technology. Blaha says, “What we’ve done is to reduce it to a microchip about two millimeters in diameter, which will sit on top of your head on the surface of the skull. It will be connected to the implanted electrode, but there won’t be any wires that go down the neck and nothing implanted in the chest.” A prototype of this device has been manufactured and is ready for testing.

The implantation of electrodes into Parkinson’s patients is not a cure, but a way of markedly easing symptoms in order to make living with the disease bearable. For at least 150,000 patients, it could mean being relatively free of tremor, uncontrollable twitching, muscle stiffness, slow movement and pain.

At present, DBS is performed on patients who have used therapeutic drugs a long time, and the side effects have become unwarranted. “We want to change that,” Blaha says. “We want to push this technique towards more of an early phase rather than half way towards the eventual demise from the disease. In this sense we’re talking about people in stage three who have a pronounced gait and a significant disability.”

DBS has other potential uses such as with psychiatric disorders, including depression and obsessive-compulsive disorder.

“We’re looking at advancing this technology not only to help neurological patients, but also psychiatric patients,” Blaha says. “This is just the beginning. It is just the tip of the iceberg.”

Blaha’s route to Memphis was a circuitous one. After earning his PhD at the University of Oregon, he went to the University of British Columbia in Vancouver, Canada, where he had a joint position in the departments of psychiatry and psychology as a Medical Research Council of Canada Research Scholar. He was there 11 years before becoming an associate professor of psychology at Macquarie University in Sydney, Australia. At a Society for Neuroscience meeting in 2003, Blaha met a U of M professor, Dr. Guy Mittleman, who persuaded him to apply for a faculty position here. He applied, got the job and then packed up his laboratory at Macquarie, his family and household and moved all to Memphis in January of 2004.

Money and recognition are inconsequential to Blaha — he’s on a mission. “I’m doing this because I enjoy it, and because it has value to me,” Blaha says. “Money gives me the facilities, personnel and means to do research and do more of it.”

He invests long hours in his research, arriving at the University about 7 a.m.

“I get up in the morning, and I want to go to work,” he says. “They have to drag me out of here at night.”

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