In 2014, Kari Hoffman and her team were awarded a team grant to investigate the use of deep brain stimulation (DBS) as a potential treatment method to improve the function of the memory circuits impaired in AD and TLE. The multidisciplinary team consisted of leaders in DBS and imaging, biomedical engineers in brain-machine stimulation interfaces, and clinician scientists who are all using complementary approaches to investigate memory function. DBS, which has been around for over 50 years, involves the implantation of a neurostimulation device that sends electrical impulses to specific regions of the brain. Although it has been successfully used to treat symptoms of Parkinson’s disease, the exact mechanisms of therapeutic action are not completely understood. Understanding the mechanisms involved in DBS would contribute significantly to advancing our knowledge of normal and pathological memory processes, of DBS technology and of protocols for clinical trials. The goal of this project was to answer the questions – how do the neurons in the memory circuit work? and consequently can this process be altered or improved by DBS in cases where memory is impaired?
Through testing in preclinical animal models and analysis of epilepsy and AD-fDBS patient data, the team was able to advance the research towards clinical-trial-ready stimulation protocols to modulate memory circuits. They found two stimulation frequencies that appear to modulate memory function. They also developed a roadmap of structural changes in the brain that occur with stimulation, for use in ongoing patient research and future clinical trials. Team member Taufik Valiente is currently refining the stimulation approach for use in epilepsy patients and Andres Lozano is continuing the work that has resulted from this grant, using the protocols that were developed in AD patient studies using DBS. The work from the Chakravarty lab also resulted in some interesting potential sex differences which will warrant further research into the role of sex in memory function and treatment.