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Deep brain stimulation therapies benefit from graphene fiber electrodes
(Nanowerk Spotlight) The electrical stimulation of neural tissues forms the basis of current and emerging neural prostheses and therapies that can help alleviate symptoms like the intrusive tremors associated with Parkinson's disease. Deep brain stimulation (DBS) is an effective treatment for many neurological disorders, but despite its widespread utilization the underlying mechanisms and downstream effects of DBS remain poorly understood.
One major issue to understand the therapeutic mechanism of DBS is to map the wide variety of brain responses at both the local and global levels.
"Simultaneous DBS and functional magnetic resonance imaging – fMRI; a powerful tool for mapping brain spatial activation patterns on a whole-brain scale – could provide us with valuable insights into brain functionS and connectivity patterns, as well as modulatory effects and therapeutic mechanisms of functional electrical stimulation in various neurological disorders," Xiaojie Duan, an Associate Professor in the Department of Biomedical Engineering, College of Engineering, at Peking University, tells Nanowerk. "However, the artifacts induced by conventional DBS electrodes prevent the full mapping of the brain activation pattern."
Conventional DBS metal electrodes, such as those made from PtIr, which is the material most commonly used in clinical settings, elicit strong magnetic field interference and produce significant artifacts, which obstructs functional mapping of a large volume of brain tissues surrounding the electrodes. This prevents researchers from obtaining full activation patterns when using fMRI to study the neuromodulatory effects of DBS.
Duan and her collaborators aimed to develop a technique, which provides full brain activation maps under DBS, to illustrate the neuromodulatory effects and help to reveal the mechanism of DBS.
They now report in Nature Communications ("Full activation pattern mapping by simultaneous deep brain stimulation and fMRI with graphene fiber electrodes") the development of a highly MRI-compatible graphene fiber electrode that enables full activation pattern mapping by fMRI under DBS.
These full maps provide comprehensive pictures of how DBS modulates the brain and are important to reveal the neuromodulatory effects of DBS therapies.
Besides showing little-to-no artifacts in various anatomical and functional MRI images, the graphene fiber electrodes exhibit high charge-injection-capacity and stimulation stability, which is important for DBS electrodes.
A schematic drawing of the DBS–fMRI study using graphene fiber bipolar microelectrodes
A schematic drawing of the DBS–fMRI study using graphene fiber bipolar microelectrodes. (Reprinted with permission from Springer Nature)
"The utilization of graphene fiber electrodes in DBS made the full activation pattern mapping possible," says Duan. "We detected the blood-oxygenation-level-dependent (BOLD) responses, which is a signal indicating the activation of the brain in multiple cortical and subcortical regions. The BOLD responses of some of these regions were not previously detectable with traditional metal electrodes due to their large artifact."
The team's platform can serve as a powerful tool for translational research investigating the neuromodulatory effects and therapeutic mechanisms of DBS therapies.
"With further development and careful safety evaluation, the graphene fiber electrode technology could even potentially be used on patients as DBS electrodes," Duan points out. "Combined with MRI, this enables predicting the clinical effects and optimizing the clinical outcome of DBS therapies."
The researchers note that DBS-fMRI studies with the graphene fiber electrode technology are widely applicable to other targets or neurological circuits. Consequently, they plan to use the graphene fiber electrodes on DBS-fMRI studies of other disorders, particularly on treatment-resistant depression.
The team is hopeful that full brain activation pattern mapping under DBS with the graphene fiber electrodes at different targets and with varied stimulation frequency and strength could provide important insights for developing effective DBS therapies to treat depression.
Whereas the current study used anesthetized animals for fMRI mapping, the difference in physiological states between normal (awake) and fMRI (anesthetized) might limit the detection of all potential neural correlates of the DBS therapeutic effect. For future studies, applications of awake animal fMRI would be beneficial to provide more detailed clues of circuitry mechanisms of DBS therapies.
"To improve the DBS-fMRI studies, we first need to solve the difference in physiological states between awake and anesthetized," Duan concludes. "In addition, another challenge we need to overcome is how to improve the stimulation selectivity of DBS and long-term stability. We also are working on improving electrode design and materials."
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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