Modulating memory circuits: focal DBS treatments to improve medial temporal lobe function

Project Overview

Two diseases that show very different trajectories have nevertheless led researchers to identify dysfunction in a common brain network. The diseases in question are Alzheimer’s disease, a devastating neurodegenerative disorder, and temporal lobe epilepsy, the most common type of partial-seizure epilepsy, characterized by brief episodes of abnormally synchronous neural activity. The structures implicated in these diseases are focused earliest and most severely in the ‘memory network’: the hippocampus and other regions to which it is connected. This has led independent researchers studying two different diseases, to the same place, using similar tools, in search of treatments. This proposal integrates the expertise of researchers from fundamental and clinical backgrounds, across diseases that target a common brain network. The goal is to modulate the memory network using innovative, focal stimulation methods, to improve network function. Dr. Hoffman and her team will achieve this goal by using novel approaches to a promising therapeutic approach known as ‘deep brain stimulation’ (DBS), that has recently been applied to the treatment of AD and epilepsy. Deep Brain Stimulation (DBS) involves the targeted delivery of patterned electrical stimulation to specific brain regions. DBS is best known for its use in the treatment of debilitating symptoms in movement disorders, including Parkinson’s disease (PD; a neurodegenerative disorder). The therapeutic mechanisms of DBS, and sensitive markers of its efficacy are largely unknown. Understanding the response pathway would be a critical step towards the refinement of DBS delivery to structures in the memory network leading to possible improvements in treatment efficacy. By testing preclinical models and through analysis of epilepsy and AD-fDBS patient data, the team anticipates that their project will shed light on the pathophysiology and progression of both diseases, and point the way to therapeutic refinements in DBS that may lead to better patient care.

Partners and Donors

Krembil Foundation