Detecting Brain Chemicals

Deep brain stimulation (DBS), in which implanted electrodes deliver electric jolts to the brain, has shown great promise in treating neurological disorders: it is already approved to treat Parkinson’s disease and is being tested to treat severe depression, obsessive-compulsive disorder, traumatic brain injury, and other ailments. But despite its success, little is known about how DBS works. Scientists at the Mayo Clinic and other institutions have developed a new device that can detect neurotransmitters quickly and locally in the brain, which they hope will help make DBS more effective and shed light on how it works.

Patients undergoing DBS are surgically implanted with an electrode, which is connected to a stimulator implanted under the skin. The electrode delivers a tightly controlled series of electrical pulses to a specific part of the brain, but the physiological changes that it triggers are not well understood. Scientists theorize that these jolts either activate sluggish or diseased neural circuits, or interfere with abnormal electrical messages. Many of the parameters of the treatment, such as the place that the electrode is inserted and the magnitude and frequency of the electrical signals that it emits, have been optimized by trial and error.

“There is no standard technique by which we can sample the brain regions in patients as we’re implanting the deep brain stimulation systems,” says Ali Rezai, director of the Center for Neurological Restoration at the Cleveland Clinic, who was not involved in the current study but performs DBS procedures. “In the future, this [device] may be a way of helping improve DBS surgeries and guiding us for improving the outcome of these patients.”

The new device, developed by scientists at the Mayo Clinic Neural Engineering laboratory,consists of a sensor electrode that can be implanted along with the DBS electrode and detects the concentration of chemical messengers, called neurotransmitters, that are released from neurons. The sensor is attached to an external controller, which analyzes the signals and wirelessly sends the data to a remote laptop for further analysis. “This is a powerful device that, in real time, can do the analysis of neurotransmitter changes in the brain,” says Kendall Lee, director of the Mayo Clinic Neural Engineering laboratory, who directs the work.

The researchers are focusing first on Parkinson’s disease, which is characterized by damage to neurons that produce the neurotransmitter dopamine. “We think that deep brain stimulation could be treating symptoms of Parkinson’s disease, at least in part, by activating surviving dopamine neurons,” says Paul Garris, a professor of neurobiology at Illinois State University, who works on the project. “We want to take this surgical procedure to the next step and use the chemical recording to fine-tune the position of the stimulating electrode to release the most robust dopamine.”

So far, the researchers have tested the device in animals and are now working on making similar dopamine sensors appropriate for human use. They ultimately hope to combine the stimulating and sensor electrodes into a single implantable electrode with separate regions for chemical recording and electrical stimulation. “Our long-term goal is to expand the usefulness of new DBS devices in the treatment of a range of neuropsychiatric disorders,” says Charles Blaha, a professor of experimental psychology at the University of Memphis, who is leading the animal work on electrically evoked neurotransmitter release.

Aside from improving the surgery, a device that measures neurotransmitters directly in the brain could shed light on exactly how DBS works and help doctors better understand the intricacies of the brain. “The ability … to detect neurotransmitter changes in the brain will help us understand the mechanisms by which the stimulation works, and help us understand the disease process better,” says Rezai. However, he cautions that the technology needs to be further developed for use in humans.

One concern is that adding additional probes into the brain could result in tearing of the brain tissue. Steven Schiff, a pediatric neurosurgeon and director of the Penn State Center for Neural Engineering, adds that the value of chemical information from neurotransmitters should be demonstrated, to see if it would improve electrode placement and the outcome from DBS. However, he says that using electrodes to measure neurotransmitters “is extremely exciting for the future. You cannot measure these analytes from traditional electrical recordings, and thus very important variables from the functioning of the nervous system go unobserved otherwise.”