New, carbon-based neural probe provides a robust, multimodal platform for better understanding the brain

Wayne Gillam

The CSNE has engineered a new, all glassy carbon neural probe capable of electrically stimulating and recording from neurons in the brain while simultaneously detecting dopamine, a neurotransmitter involved in debilitating neurological conditions such as Parkinson’s disease.

Researchers at the Center for Sensorimotor Neural Engineering (CSNE) have been developing sophisticated ways to interface with the brain for several years now. In their quest to invent new and better tools to connect with neurons and increase our fundamental understanding of how the brain operates, they have engineered technologies such as glassy carbon electrodes at San Diego State University (SDSU), multi-functional fibers at the Massachusetts Institute for Technology (MIT) and the Neurochip at the University of Washington (UW).

Now, through a multi-institutional effort between CSNE members at SDSU and the UW, researchers have developed and presented a new type of glassy carbon neural probe in Nature Scientific Reports. This probe is sturdy enough be implanted for long periods of time, and it can electrically stimulate and record from neurons while simultaneously detecting the release of the neurotransmitter, dopamine, at extremely low levels in the brain.

The high-resolution, real-time dopamine detection capability makes it an ideal research and clinical platform

-Sam Kassegne, CSNE Deputy Faculty Director at SDSU

“The high-resolution, real-time dopamine detection capability makes it an ideal research and clinical platform,” said Sam Kassegne, a senior author of the study and director of the NanoFab at SDSU, where fabrication of the neural probe took place. “For example, being able to record both electrical and neurotransmitter signals in real-time will allow investigation of correlation between the two signals. Questions such as, ‘What will be the optimum electrical stimulation that can help normalize the concentration of neurotransmitters at the neural synapse?’ can be explored and the answers used to help improve patient outcomes in clinical applications related to this technology.”

Finding ways to normalize the amounts of neurotransmitters between synapses in the brain is important to the medical community. Scientists have known for years that neurotransmitters, such as dopamine and serotonin, play critical roles in brain function. Dopamine, in particular, is crucial to central nervous system functions such as movement, pleasure, attention, mood and motivation. Low dopamine levels have been linked to several debilitating neurological conditions including depression, schizophrenia and Parkinson’s disease, so the ability to detect and gauge this neurotransmitter’s impact on brain function in precise, measurable ways holds profound implications for improving treatments of these conditions in the future.

“The brain is the biggest, uncharted frontier in terms of our understanding, and this probe is a significant step forward in letting us measure one of the most critical processes in the brain, which is neurotransmitter regulation,” said Chet Moritz, CSNE co-director and a senior author of the study. “Being able to detect and measure dopamine in real-time, whether it’s for basic neuroscience understanding or to cure a certain disease is a significant step forward.”

A unique design yields unique capabilities

Kassenge’s lab has been evolving carbon-based microelectrode arrays for some time now, and slowly building the electrode’s ability to detect neurotransmitters, but this is the first neural probe made entirely out of glassy carbon, which means there are no areas of mechanical or electrical weakness where metal contacts carbon. Earlier versions of Kassenge’s glassy carbon electrodes involved the use of metal wires on top of a glassy carbon substrate, so each point of contact between the glassy carbon and metal wires represented a potential mechanical or electrical failure point. The new, all-carbon design makes this neural probe exceptionally sturdy and capable of lasting for years in the body without failure.

Carbon combines very important properties, such as inertness, capability of interaction with biomolecules and electrochemical stability, which are not simultaneously present in the most commonly-used materials for neural interfaces.

- Elisa Castagnola, CSNE researcher at the SDSU NanoFab

“Carbon combines very important properties, such as inertness, capability of interaction with biomolecules and electrochemical stability, which are not simultaneously present in the most commonly-used materials for neural interfaces,” said Elisa Castagnola, a lead author of the study. “We demonstrated that this new probe has compelling advantages over existing technologies in almost all key metrics from mechanical and electrical properties to electrochemical kinetics, which is quite remarkable for a probe fabricated from a single material without any surface coating.”

The probe’s sturdiness was demonstrated by enduring a record-setting 3.5 billion cycles of bi-phasic charge-balanced pulses over 1,000 hours, and it was proven to be able to detect dopamine down to the miniscule level of 10nM.

“This study will help address medical conditions treated with neural stimulations, such as deep-brain stimulation (DBS), which is used to treat Parkinson’s disease,” said Surabhi Nimbalkar, also a lead author of the study. “The probe’s ability to sustain the 3.5 billion pulses attests to its durability, which could be translated to long-term, real-life medical applications through spinal stimulation for neuromodulation and neuroplasticity.”

Potentially, any disease or medical condition where dopamine plays a key role, such as chronic depression, might be impacted by the capacity this probe has to gather finely-tuned measurements. The knowledge the probe provides could be used by researchers to better understand the disease state and how the brain operates under both healthy and impaired conditions.

“We think that this new multi-functional probe will allow a critical component in the feedback loop in such clinical areas as DBS. For example, currently the feedback component of DBS systems for treating chronic depression relies exclusively on the self-reported feedback of the patient and the judgment of the doctor,” Kassenge explained. “With this probe included in a DBS regimen, we can envision a scenario where this high-resolution, real-time dopamine detection at a synaptic and circuit-level could be made a key parameter in the feedback loop, providing a more reliable and measurable means of guiding the treatment.”

Opening the door to a new class of neural devices

The vision for glassy-carbon electrodes and this new neural probe grew out of conversations between neuroscientists and material engineers at the CSNE. For the study, a team of material scientists and engineers in Kassenge’s lab fabricated the probe in close partnership with another team of researchers at the UW who specialized in neuroscience and rehabilitative medicine. Feedback from the UW research team informed the SDSU fabrication team and vice-versa.

“The two teams strongly interacted for the successful validation of this innovative technology,” Castagnola said. “SDSU was responsible for the development of the probe, as well as for the electrochemical and mechanical characterizations. The UW was responsible for the design and execution of in-vivo (in-life) neural recording experiments. This is an example of how engineers and neuroscientists must interact closely to successfully optimize and validate a new neural technology.”

This study will help address medical conditions treated with neural stimulations, such as deep-brain stimulation (DBS), which is used to treat Parkinson’s disease.

-Surabhi Nimbalkar, CSNE researcher at the SDSU NanoFab

The advance this probe represents is opening the door to a new class of neural devices that are not only interfacing with the brain’s electrical systems, but are capable of detecting and measuring neurotransmitter levels as well. Next steps for the research team include more extensive validation of the technology in-vivo and developing a similar type of electrode for detecting serotonin. Like dopamine, serotonin is involved in and associated with important brain and body functions, but it is also important in the spinal cord, impacting motor function. Over the long-term, moving advanced multimodal probes like these into clinical applications will be an aim for the CSNE.

“We are developing the next generation of neural probes that let us interface bi-directionally with the brain and spinal cord, so we’re not just putting information into the spinal cord or the brain, but we’re able to measure and manipulate the neurotransmitter level and record the output of that activity electrically,” Moritz said. “We want to know what our stimulation is doing to these circuits, and recording neurotransmitter levels is critical for this goal. It will allow us to discover new ways to help the brain and spinal cord heal and recover after injury and then apply that knowledge to improve people’s lives.”

For more information about this study, please contact CSNE Deputy Faculty Director at SDSU, Sam Kassegne.