Research on DBS Mechanisms Leads to Enhanced Devices

by James Cavuoto, editor

Investigators at several research institutions in the U.S. are advancing research into the mechanisms of action of deep brain stimulation. This research is not only helping to improve DBS therapies for different neurological diseases and disorders. It is also leading to the development of new neurotech devices that could be commercialized in the years ahead.

Many recent advances in understanding the mechanisms of action of DBS were discussed during a symposium last month at the Neuroscience 2013 meeting in San Diego, CA chaired by Dennis Glanzman of the National Institutes of Mental Health and Helen Mayberg of Emory University. During the symposium, Kendall Lee of the Mayo Clinic in Rochester, MN described his lab’s research measuring changes in neurotransmitter concentration levels in response to DBS. Lee and his colleagues at Mayo’s neural engineering laboratory have devised a wireless intracranial neurotransmitter concentration sensor that can measure the chemical concentration of dopamine, adenosine, or other agents that oxidize.

Lee’s lab is developing a closed-loop DBS device called Harmoni that combines four WINCS systems and a wireless neuromodulation control system on a 4- by 3.4-mm integrated circuit. An optical link connects the neurochemical sensors to the stimulation unit, and a complex algorithm optimizes stimulation waveforms.

Also at the Neuroscience 2013 symposium, Cameron McIntyre of Case Western Reserve University described his team’s research into patient-specific computational models that benefit from white matter tractography data obtained from diffusion tensor imaging. His team is developing a probabilistic stimulation atlas to predict how axons of passage will respond to applied electric fields. This work will enable clinicians, for example, to change the therapeutic benefit of a DBS device by changing the active contact.

Mayberg gave an update on her research on DBS for psychiatric disorders, noting that “the devil is in the details of individuals.” She noted that the difference between DBS depression patients who got better vs. those who did not was not a function of area Cg25 where the stimulation was applied, but activity remote from the target. In an effort to deconstruct the depression circuit, she used PET imaging in animal studies to develop a probabilistic tractography that elucidates where the current goes. Her team has honed in on projections from Cg25 to medial-frontal area 10 as a potential tract that could mediate mood effect.

In order to help devise new biomarkers for measuring DBS effects, Mayberg argued for the development of new FMRI-compatible devices. She would like to see clinicians be able to predict response in the operating room based on some of this feedback.

The final speaker at the symposium, Benjamin Greenberg from Brown University, shared some of his lab’s findings on DBS of the VC/VS for treatment of OCD. He said that only interneurons show an initial response to DBS and that long-term potentiation occurs primarily on the interneurons.