The focus of our research is to contribute to a better understanding of the neural mechanisms involved in learning and memory. Previous studies have identified a system of structures in the medial temporal lobe that is critical for declarative memory, the ability for the conscious recollection of facts and events. This system of structures includes the hippocampus and the surrounding cortical regions. These are the structures that are affected first in Alzheimer's disease, and previous studies have demonstrated that lesions of these structures produce profound memory deficits. Our research focuses on potential mechanisms by which these structures set up new memories and how these structures might work together during memory formation and retrieval. Along with modulations in spiking activity of individual neurons, we are particularly interested in the role of synchronous oscillatory activity across networks of neurons.
Neural Signals for Memory in the Human Brain
In this line of research, we are adapting research approaches from our projects in monkeys to human subjects. While researchers have made great progress in understanding memory through neurophysiological investigations in animals, it is often difficult to directly apply these findings to humans because the behavioral tasks employed are so different. Here, we are using memory task paradigms that can be tested in both monkeys and humans to translate our recent findings regarding the neuronal mechanisms of memory formation in monkeys to the human brain. One way we can accomplish this is by directly recording from electrodes implanted in patients undergoing invasive monitoring as part of their clinical treatment for drug-resistant epilepsy. These studies have the potential to reveal memory mechanisms in the human brain that are homologous to those observed in animals, which should lead to more effective translation of results from basic research to the clinic.
Eye Movements and Memory
As primates, who chiefly get information from the world by looking around, we move our eyes several times a second. Because what we look at determines what we remember, it is perhaps no surprise that neurons in brain structures important for memory, within the hippocampal formation, carry signals locked to eye movement and visual stimuli. For example, neurons can represent visual space by firing selectively when a primate looks at a certain location. Also, neural activity is different between times when eye movement indicates that a thing is remembered, compared to when eye movement indicates it is not remembered. These observations inspire a central question: How do these eye-movement-related representations pertain to the memory function of the hippocampal formation?
Aging and Memory
Both humans and monkeys exhibit cognitive decline during normal aging. Decline is often exhibited as deficits in cognitive flexibility, working memory, and long-term memory. In this project, we are comparing the performance of young and aged monkeys on several memory tasks. During performance of these memory tasks, we are recording electrical signals from both prefrontal and medial temporal areas of the brain. These areas are known to be important for memory and are among the most affected by both normal aging and dementia. Further, through partnership with Pfizer, we are testing several pre-clinical drugs that may help alleviate the symptoms of cognitive aging. Testing these drugs in combination with electrophysiological recordings will allow us to examine how the areas from which we record change under various drug conditions, which will help to reveal the underlying mechanisms involved in aging. These data will aid Pfizer in the development of an eventual treatment for humans. In addition, because monkeys do not develop dementia, our findings will serve as a valuable baseline in studies of pathological aging in humans.