The team is working with in vivo neurotechnologies to better understand the behavioral and cognitive variables that modulate deep brain activity during freely moving behavior, with an aim of contributing to innovative therapies designed to treat memory disorders in humans.
Understanding brain function and its relation to space and memory in humans requires the study of subjects as they go about their natural behaviors. However, limitations in technology—such as the inability of traditional neuroimaging to record from deep brain structures during physical movement—have hindered progress in this scientific field. Dr. Nanthia Suthana and her team at the University of California Los Angeles (UCLA) set out to break that barrier, leading the first-ever project able to record from medial temporal regions of the brain during freely moving behaviors in humans. This work was made possible through a National Institutes of Health (NIH) BRAIN Initiative grant , as part of the Initiative’s program on Investigative Human Neuroscience.
Dr. Suthana is an Associate Professor of Psychiatry, Neurosurgery, Bioengineering and Psychology at UCLA. She has a diverse methodological background with expertise in human neuroimaging techniques. She completed her graduate training in the UCLA Neuroscience Ph.D. program and postdoctoral training in the Department of Neurosurgery prior to joining the UCLA faculty.
Dr. Suthana also participates in the Research Opportunities in Humans (ROH) Consortium work group, coordinated by staff at the NIH. Members of the ROH Consortium collaborate to identify consensus standards of practice, as well as supplemental opportunities to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community.
Check out the interview below with Dr. Suthana to learn more about her team’s work!
Could you briefly introduce yourself and the team of scientists that significantly contributed to this project?
My name is Nanthia Suthana and I am an Associate Professor at UCLA in the Department of Psychiatry and Biobehavioral Sciences. Our U01 program consists of a multi-disciplinary team of scientists including neuroengineers (Uros Topalovic, Mauricio Vallejo, Sabrina Maoz, and Sonja Hiller), cognitive neuroscientists (Martin Seeber, Matthias Stangl, and Barbara Knowlton), neurologists (Dawn Eliashiv, John Stern, and Vikram Rao), neurosurgeons (Itzhak Fried and Casey Halpern), a statistician (Andy Lin), virtual reality programmers (Daniel Batista and Emi Jenkens-Drake) and industry experts (Nader Shaterian, Tom Tcheng, and Nick Hasulak).
Could you please provide us a brief overview of the central premise of this project, perhaps including the broader context of the neuroscience clinical research that led to this project?
Understanding brain function and its relation to space and memory ultimately requires the study of natural behaviors. Nevertheless, significant methodological challenges arise due to the limitations of conventional neuroimaging techniques in recording from deep brain structures during human physical movement. Our research project is the first to be able to record from medial temporal regions while individuals engage in freely moving behaviors. This breakthrough is made possible by the utilization of wearable intracranial recording platforms combined with behavioral sensors such as motion capture and eye-tracking. The outcomes of our research provide in-depth characterization of the cognitive and behavioral factors that influence deep brain oscillatory activity in humans during spatial navigation and memory processes in free-moving conditions.
What were the major unanswered questions your team hoped to address at the onset of the grant/project?
Our main goal is to understand how behavioral and cognitive factors influence deep brain activity during naturalistic behaviors like spatial navigation and memory. These factors may involve movement variables such as speed, position, saccades, or cognitive aspects like navigational strategies and memory success versus failure. By conducting research in real-life settings, we strive to gain a comprehensive understanding of these processes and explore potential species-specific differences, such as intermittent theta oscillations observed in humans, contrasting with more continuous movement-related theta oscillations seen in rodents, and how these differences relate to memory. To achieve our objectives, we use wearable neural recording platforms to elucidate the neuronal mechanisms underlying human spatial navigation and memory. Additionally, we are committed to sharing our tools with the broader scientific community. By doing so, we hope to catalyze additional studies that go beyond the scope of the proposed project, and lead to further advancements in the field of neuroscience.
The NIH BRAIN Initiative U01 funding opportunity is designed to maximize opportunities to conduct innovative in vivo neuroscience research made available by direct access to brain recording and stimulation from invasive surgical procedures. Could you describe how experiments in this project are performed, and how they differ from projects involving non-invasive recordings?
Due to the limitations in accessing deep brain regions and susceptibility to motion artifacts with non-invasive recordings, we rely on intracranial electroencephalographic (iEEG) recordings from the medial temporal lobe in human participants implanted chronically with depth electrodes for treatment of epilepsy. Given these implants are chronically implanted and thus shielded more so from external noise sources, we are able to record deep brain activity during naturalistic freely-moving behaviors, like spatial navigation tasks. By integrating virtual (and augmented) reality (VR/AR) technologies to control the timing and presentation of stimuli, our studies offer a naturalistic and ecologically valid environment for exploring the neural mechanisms underlying spatial navigation and memory.
This work would not be possible without the invaluable role of volunteers. How do participants engage in the science they are helping to advance? Are there any insights your team would like to share about the engagement of participants in clinical research projects?
Our project depends on the generous participation of volunteers who have indwelling electrodes for seizure treatment and are willing to engage in our research studies on spatial navigation and memory. These dedicated individuals wear on-body behavioral sensors to track motion and eye movements while deep brain activity is recorded during virtual and real-world memory tasks. We are immensely grateful for the invaluable contributions of these volunteers, as our research would not be possible without their willingness to be a part of our studies.
What are some critical new insights into human brain function that this project and your team has facilitated?
We have enabled the first-ever mobile intracranial EEG recordings during both real-world and virtual navigation tasks, leading to several significant discoveries. Notably, we have found that oscillatory activity in the medial temporal lobe is modulated by the proximity to environmental boundaries and the position of another person navigating through the same space. Furthermore, we have recorded hippocampal single-neuron activity during walking in humans for the first time. These findings provide crucial insights into the neural mechanisms underlying spatial navigation and memory and open up new avenues for further exploration in the field of neuroscience.
In addition to the knowledge gained, what are the broader impacts of this project on human health and the development of new therapies for disorders of the human brain?
The findings from our program have the potential to significantly advance the treatment of memory disorders in humans and bridges decades of research across species, providing valuable insights into unique human-specific oscillatory mechanisms within the medial temporal lobe that support real-world spatial navigation and memory.
Science frequently raises as many new questions as it answers. What major research directions does your team envision in your specific area of human neuroscience in the next 5-10 years?
Our vision is to make significant advancements in the miniaturizing of our wearable platforms, enabling the recording of multiple deep brain signals (such as single-neuron and local field potentials from multiple brain regions), along with biophysical data (motion and eye-tracking, heart rate, skin conductance response) and biochemical signals (e.g., epinephrine, cortisol) during spatial navigation. We plan to also share these tools widely to enable comprehensive investigations from our team and others that can investigate the specific mechanisms that underlie a wide range of naturalistic behaviors in humans.
Stay tuned for more research highlights on The BRAIN Blog.