Projects
The episodic memory network is a circuit that includes the hippocampus, thalamus, and prefrontal cortex. This network is essential for learning and memory, and damage to this network leads to devastating cognitive disorders. Yet almost 50 years after its initial description, the computational roles of its key nodes remain largely unknown.
This knowledge gap fundamentally limits our ability to treat diseases that affect this circuit. Our research program is designed to fill this gap by pursuing two fundamental and complementary guiding questions:
1. How does the episodic memory network transform experiences into rules and concepts that guide our future behaviour?
To answer this, we aim to determine the precise computational function of each node in the episodic memory circuit during learning and generalization. We hypothesize that knowledge acquired from prior experiences is encoded by populations of neurons across this circuit, which in turn influence choice-related computations in the prefrontal cortex. By performing the simultaneous, large-scale recordings across this entire circuit in primates performing complex VR tasks, we aim to reveal the neural fingerprints of learning, memory, and generalization.
2. How can neuroscience help us design and optimize treatments for devastating disorders of learning and memory?
Our lab directly addresses this challenge by leveraging our experimental platform to understand, test, and optimize therapeutic interventions for cognitive disorders. Our first project, supported by an NINDS K99/R00 award, focuses on fornix deep brain stimulation (DBS-f)—a promising treatment for Alzheimer’s disease currently in Phase III clinical trials. The mechanism of this therapy is not known. We will combine DBS-f with our large-scale recording platform to provide a mechanistic, circuit-level explanation for its effects, with the long-term goal of optimizing its clinical application.
Our Approach
We believe that fundamental discovery and translational progress must drive each other forward. We operate at the nexus of basic and clinical neuroscience to tackle one of the most pressing challenges in biology: understanding the “episodic memory network” that governs cognition in both health and disease.
To achieve our goals, we have built a powerful experimental platform that integrates three key elements:
- Rich, Dynamic Behavior: We design immersive virtual reality (VR) tasks that allow us to study complex, naturalistic behaviors like learning, decision-making, and generalization in non-human primates.
- Large-Scale Neurophysiology: Using custom, patented technology, we record simultaneously from hundreds to thousands of neurons across interconnected cortical and subcortical brain regions, capturing a circuit-level view of cognition in real-time.
- Computational Neuroscience: We apply advanced theoretical and computational frameworks to our data, building models that connect the geometry of neural representations to the nuances of behavior.
This synergistic approach allows us to make mechanistic inferences about brain function and, in turn, provides a direct avenue to test and optimize therapies for disorders like Alzheimer’s disease and related dementias.
Some other present and past projects include:
