Grant: CIHR Fellowship

Memory loss is a significant aspect of brain diseases, which are the leading cause of disease-related burden worldwide. Despite this, effective treatments for memory loss are lacking, with no FDA or Health Canada-approved drugs available. Pharmaceuticals cannot precisely target the brain regions responsible for memory. In contrast, brain stimulation therapies can target specific brain regions, allowing them to treat symptoms resistant to medication such as tremor, seizures, or depression. Therapeutic brain stimulation requires two key elements: 1) a thorough understanding of the brain circuits responsible for a given symptom, and 2) knowledge of where within those circuits to stimulate. Brain stimulation therapies for memory loss has been variable, partly because it is unclear where the optimal stimulation target is. Convergent causal mapping is a modern technique that has successfully identified optimal stimulation targets for depression, leading to FDA-approved treatments. I propose to apply this method to identify brain stimulation targets for memory loss, working with experts in the field. Preliminary convergent causal mapping analyses suggest that memory symptoms do converge upon a common network, and that there is an optimal memory stimulation target. I will expand upon these preliminary results by analyzing eight datasets, including patients with Alzheimer's disease undergoing fornix DBS, Parkinson's disease patients with subthalamic nucleus DBS, epilepsy patients with thalamic DBS, and individuals with strokes, traumatic brain injuries, hypometabolism, and brain atrophy affecting memory (total n > 1500). By mapping these diverse data sources, I aim to identify common brain networks associated with memory outcomes and pinpoint optimal targets for neuromodulation therapies.