Nanthia Suthana is working to become fluent in the “language of the brain.” She does not study linguistics but rather that electrical patterns that the brain uses to communicate. She and her team at UCLA seek to alter these patterns by externally stimulating brain cells with electricity – testing its effects on cognition and memory in particular.
In new work she presented at the CNS annual meeting in Boston in March, Suthana described how the results of brain stimulation vary depending on the track of nerve fibers targeted – perhaps helping to explain mixed results researchers have had in brain stimulation research. Working on epilepsy patients who have electrodes implanted in their brains already to help locate and control seizures, Suthana’s team found that stimulating a particular stretch of the brain’s white matter in the entorhinal cortex boosted memory performance. Stimulating the same region’s gray matter, however, appeared to impair memory. These differences can amount of just millimeter-size differences in electrode placement.
CNS spoke with Suthana about this recent work and the broader field of stimulation, including new directions in wireless technology and virtual reality (VR).
CNS: What first got you interested brain stimulation?
Suthana: Two things have always fascinated me: first, the findings from the early Penfield stimulation studies where electrical stimulation delivered directly to the human brain during awake neurosurgery would evoke vivid experiences and memories; and second the fact that a high-frequency burst of stimulation – known as theta burst stimulation – could induce an enlarged response – known as long-term potentiation (LTP) – in brain tissue that is maintained and “remembered” for hours or even days later.
We still do not fully understand how and why these phenomena occur but can now systematically test some of these things in living humans, and this is exciting. With epilepsy patients who have implanted brain electrodes we can actually deliver the same type of theta-burst stimulation and see if it can improve human memory. Additionally, since the basic “language” of the brain is electrical, the idea that stimulation could modulate brain activity is fascinating and has all sorts of implications for treatment of brain disorders and of understanding how the brain works in general.
CNS: What do you think has been the biggest advancement in the field of brain stimulation in the past 5-10 years?
Suthana: Two things have allowed for huge advancements in the field of brain stimulation in the past 5-10 years. 1) Our ability to understand more precisely the details of the brain’s “electrical language”: Scientists have made huge leaps and bounds in understanding the timing and patterns of electrical activity between brain cells and brain areas. 2) Technical advancements in the way we can simulate the electrical patterns of brain activity using external sources: For instance, the ability to provide a complex, theta burst of stimulation in human patients with very fine microwire electrodes that are the size of a human hair implanted within the brain for clinical treatment is a rare and exciting technological opportunity.
CNS: Were you surprised by your findings on your study of entorhinal white matter and memory improvement?
Suthana: We initially hypothesized that stimulation of the entorhinal white matter would be critical, since decades of findings from animal studies have shown that in the same area, electrical stimulation results in LTP, a phenomenon that is thought to support long-term memory. However, for it to actually show an effect on behavior in humans is still surprising.
What excites me the most about this work is that it is possible from timely technological developments – use of fine microwires to deliver complex stimulation patterns – and clinical opportunity – electrodes already implanted in patients. This opportunity enables future exploration of causal relationships between brain activity and unique human cognitive functions.
CNS: Where are you at with the development of wireless stimulation? How does it work?
Suthana: We can stimulate the brain wirelessly using an FDA approved brain implant that is currently used for treatment of epilepsy. To do this, there is a small device that has to be placed on top of the head near the implanted site, which we can trigger from a distance wirelessly. Additionally, several groups are working on the next-generation of wireless brain implants that will not need the small device that we place on top of the head. So, the future is even more exciting with these types of technological advancements and the consequent research opportunities they will provide.
As neuroscientists, we must constantly push the technological barriers that limit how we do our science and take advantage of any technological advancements developed in other fields.
CNS: Why are you exploring VR for your work?
Suthana: As cognitive neuroscientists, we are ultimately interested in how the human brain processes real world events. However, the real world is highly unpredictable and unstructured. VR provides a more immersive and realistic experience than 2-D computer screens that have been traditionally used to present experiments in laboratory settings. VR also allows for a structured environment where researchers can control when, where, and how things are presented to the participants. VR also provides an ecologically valid medium to test novel cognitive therapies like stimulation to determine real world applicability.
CNS: What do you think are the biggest challenges in the area of brain stimulation over the next decade?
Suthana: How do we optimize stimulation to get maximal benefits, and can these methods be used to treat patients with severe cognitive impairments? The biggest challenges to reach these goals will be 1) technological: we need to create “smarter” devices that can deliver stimulation in a more power efficient and refined manner; and 2) scientific: we need to better understand the precise neural biomarkers that may predict the best times to stimulate and understand the biological consequences of the stimulation on these biomarkers.
CNS: What do you most want people to understand about this work?
Suthana: The brain is complex. Memory is complex. As neuroscientists, we must constantly push the technological barriers that limit how we do our science and take advantage of any technological advancements developed in other fields. In my work, recent advancements made in neuroprosthetics and the virtual reality industry have enabled us to begin to answer never before questions about the human brain. While we may have figured out a few things here, there are so many more questions that are raised. Hard work and exciting times ahead.
CNS: What’s next for you for this line of work?
Suthana: Now that the technology to be able to directly record and stimulate the human brain in freely moving human participants works, we are excited to start exploring our hypothesis about real-world human behaviors. We can start asking all sorts of questions and getting first-in-person data to determine deep brain mechanisms that support real-world human behaviors and how we may be able to restore function through novel neurotechnologies.
CNS: Anything I didn’t ask you about that you’d like to add?
Suthana: We are excited to bring this technology to the cognitive neuroscience community. We hope that others will be able to use these methods to study all sorts of interesting human cognitive functions and expand it even beyond the area of learning and memory.
-Lisa M.P. Munoz
