Over the past decade, therapy by neurostimulation has become one of the fastest growing areas in the medical-device industry. Neurostimulation uses low levels of electricity to treat medical conditions affecting different parts of the central nervous system. Disorders include chronic pain, Parkinson's disease, essential tremor, paralysis, epilepsy, obesity, and depression. The worldwide market for neurostimulation devices is estimated at $1.5 billion in 2007 and is growing.

Electrical-stimulation products in the neuromodulation business stem from technology developed for pacemakers. The heart beats on low electrical signals which is why hearts can be paced. The brain is made of nerve cells that are electrically excitable, and can similarly be activated by exposure to an electric field.

Deep within the brain

There are multiple networks within the brain that control different behaviors, functions, and sensations. To access some of those networks it's necessary to place the electrodes deep within the brain. The Activa Deep Brain Stimulation (DBS) system from Medtronic, Minneapolis, (medtronic.com) is a neurostimulation system for applications where a target network requires penetrating the brain tissue with a lead. The Activa DBS system was developed to stimulate neural networks associated with movement, specifically for treating tremors, motor symptoms associated with Parkinson's disease, and dystonia. The system is also under exploration to treat epilepsy, obsessive-compulsive disorder, and depression.

“Activa DBS is a tool that allows access to circuits deep within the brain,” says Mark Rise, Distinguished Scientist at Medtronic. “As the neuroscience community continues to unravel how the brain works and which circuits are linked to certain behaviors and which circuits are disrupted or not functioning properly in each disorder, then clinicians can use the tool to modulate that circuit and bring it back into a more normal behavior.”

The Activa DBS system includes electrode leads, connecting wires, and a neurostimulator. The latter, a pacemaker-like device, powers the system. When the battery runs out, minor surgery is required to replace and reconnect the neurostimulator. The neurostimulator, or can, has a titanium shell hermetically sealed to keep out corrosive body fluids. Connector wires, or feedthroughs, plug into the neurostimulator through a header block, without compromising the hermetic seal. The wires are coiled and insulated with a polymer such as urethane or silicone, depending upon the particular product. The electrodes on the main wire are a platinum-irridium alloy.

An implantation begins with an MRI to help the neurosurgeon map the brain with a coordinate system. Using a stereotactic procedure, a lightweight frame is attached to the head after applying a local anesthesia. Because the frame and target area appear in the MRI image, the distance from reference points on the frame to the target can be measured in three dimensions. Surgical instruments attached to the frame are adjusted to the coordinates so surgeons can drive them accurately to targets. “Certain ‘landmarks’ in the brain guide surgeons to the anatomical target, where they place the test probe and record electrical activity,” says Rise.

Based on his experience, the recording, and a general atlas of the brain, the surgeon can test stimulate in the operating room. A test box, or scanner, connects to the lead temporarily to simulate the pulse generator. If symptoms are repressed then the lead is fixed and fully implanted. If not, the position of the lead is slightly adjusted. The extension wires are then tunneled underneath the skin and connected to the implanted neurostimulator. The patient is awake while the lead is passed into the brain but there's no pain associated with the stereotactic procedure.

After the patient has sufficiently healed the device is turned on, and in the case of tremors, the symptoms instantly stop. The device is left on, but patient and doctor can make adjustments. “For instance, one side effect to fully suppressing tremors occasionally limits the ability to speak. So the patient may be given a device that lets them make electrical adjustments. If the patient is working on a hobby like painting, they will want perfect control of their hand. Then later if they are in a conversation, they may switch to a setting that still reduces their tremor, but doesn't affect speech,” says Rise.

Stimulating from the outside

Cortical stimulation refers to stimulation of the cerebral cortex, or the outermost layer of the brain. Unlike deeper targets, the cerebral cortex may be accessed without penetrating the membranes covering the brain. Researchers believe cortical stimulation promotes neuroplasticity (strengthening connections between neurons) and alters neural networks within the brain, leading to an improvement in neurological conditions, such as tinnitus and depression. Northstar Neuroscience, Seattle, (northstarneuro.com) is conducting feasibility trials to investigate the benefits of cortical stimulation in the treatment of these two disorders.

“Tinnitus is the perception of sound when no external source is present,” says Brad Gliner, vice president of research at Northstar. About 2 million people in the U.S. are so seriously debilitated by tinnitus they cannot function on a “normal” day-to-day basis. The Renova-TT cortical stimulation system delivers stimulation to the auditory cortex, the portion of the brain's surface responsible for perceiving sound.

Also in clinical trials is the Renova DT system for treating major depressive disorder. The system delivers stimulation to the prefrontal cortex, the part of the brain's surface associated with behavior and emotion. Major depressive disorder is the most common of all psychiatric disorders, and has a profound impact on individuals, their family's quality of life, and activities of daily living. While depression can be effectively treated in the most patients with medication and psychotherapy, up to 30% of them fail to respond to any treatment.