Closed-Loop DBS Program
This program, led by Dr. Andrew Krystal who works closely with Dr. Edward Chang and Dr. Katherine Scangos, builds upon prior work led by Dr. Chang in patients with epilepsy who had iEEG electrodes implanted for the purposes of evaluating them for possible epilepsy surgery. The team developed a model of the pattern of iEEG activity that best differentiates the epilepsy patients on the basis of the presence of major depressive disorder. This model and the results of intracranial EEG stimulus response (both behavioral and iEEG) experiments carried out with the epilepsy patients formed the basis for the core Center circuit-targeted, personalized, intracranial closed loop DBS project. This project includes 3 phases for each subject: 1) an up to 10 day exploratory period where an iEEG model is developed for identifying the circuit-dysfunction linked to the target depressed state in each subject and stimulus-response mapping is carried out both of which are used to develop a personalized, closed loop (stimulation only occurs when the iEEG model indicates that the target state is present and when stimulation occurs it both improves symptoms and normalizes the iEEG pattern) treatment paradigm for that subject; 2) an up to 1 year period of treatment optimization in which the paradigm developed in Phase 1 is implemented in an implanted device and the algorithm for guiding treatment is fine-tuned to optimize response; and 3) a double-blind sham-controlled trial of the circuit-targeted, personalized, closed-loop DBS therapy.
Basic Science Program
Complementing the Closed Loop DBS clinical research program are projects being carried out in four basic science laboratories aimed at carrying out studies in animals that would advance the capacity to deliver circuit-targeted intracranial closed loop DBS in humans and also provide an opportunity to back-translate to animal studies findings emerging from the human work. An example of this is building on iEEG biomarkers found to be linked to specific depression symptom dimensions in humans by providing a greater characterization of circuitry, cell types, and activity patterns in animals than is possible in humans. Principal investigators of the participating laboratories include Vikaas Sohal, MD, PhD and Mazen Kheirbek, PhD of UCSF and Karl Deisseroth, MD, PhD and Robert Malenka, MD, PhD of Stanford University.
Late-Life Depression Program
This program supports two primary projects. The first is a collaboration with the UCSF Memory and Aging Center led by Dr. Bruce Miller, working with Dr. Scott Mackin and Dr. Andrew Krystal, which seeks to test the hypothesis that depression is sometimes the initial presenting symptom of a dementia and the specific phenotype of the depression is determined by the type of dementia present and the specific circuits affected by the dementia in each individual. The second is an effort aimed at assessing the relationship between depression and key proteins that are believed to play a role in some types of dementias by accumulating in the brain (e.g. Beta-Amyloid, Tau). This project is evaluating the extent to which depression may affect the accumulation of these proteins as measured by positron emission tomography (PET scanning) as a possible mechanism by which depression may interact with dementias.
Dolby Center Programs:
Translational Psychedelic Research Program: https://psychedelics.ucsf.edu
Memory and Aging Center: https://memory.ucsf.edu/
Chang Lab: http://changlab.ucsf.edu/
Late Life Depression Lab: https://latelifedepression.ucsf.edu/
Sohal Lab: https://sohallab.ucsf.edu/
Kheirbek Lab: http://kheirbeklab.org/
Cognition, Affect, and Neurodevelopment in Youth (CANDY) Lab: https://candylab.ucsf.edu
Child and Adolescent Behavioral Sleep Medicine Program: https://kidssleep.ucsf.edu