The NIH/NIGMS
Center for Integrative Biomedical Computing

Collaborating Investigators: Alvaro Pascual-Leone, MD, PhD, Michael Fox, MD, PhD, Mark Halko, PhD, Moushin Shafi, MD, Brad Manor PhD
Institution: Beth Israel Deaconess Medical Center and Harvard Medical School

Dr. Pascual-Leone, is the director of the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center. He and his collaborators carry out extensive research and clinical studies in the application of all types of transcranial neuromodulation to the treatment of neuropsychiatric disorders such as depression and schizophrenia, epilepsy, and chronic pain as well as studies of mechanisms and effects of stimulation on both normal and disease populations. The other investigators listed are either already actively involved with CIBC (Drs. Fox and Halko) or are in the initial planning stages of projects (Drs. Shafi and Manor). The primary interaction for this DBP is with the Simulation & Estimation TR&D, in the areas of effective algorithms for broad and flexible simulation and optimization of transcranial modulation, fast model building for simulation in population studies, and quantification of uncertainty in simulations and optimizations. In addition the BrainStimulator package, in an initial form, is already being used by Dr. Halko and this DBP is a primary driver of its development. However, we also anticipate significant interaction with the Visualization TR&D in the area of uncertainty visualization, an essential advance in order for uncertainty quantification to be of use to our DBP collaborators. Finally, in our effort to streamline model building while keeping error and uncertainty within acceptable levels, we have employed shape modeling and shape statistical methods developed under the Image and Geometric Analysis TR&D.

There are many practitioners adopting transcranial modulation methods around the world, but there are very few studies establishing mechanisms, limits, and best practices for control of current deposition in realistic geometries, and a striking paucity of clear mechanisms of action or effective dose. At the same time, there are only modest numbers of published studies using computational methods to predict, and even fewer to optimize, current deposition with transcranial technologies. Validation remains a huge problem, as does the availability of effective, efficient, usable, open source, and well supported software tools to study these problems from a computational point of view. Useful progress in all these realms can only come from a close partnership between leading clinicians and scientists in the field of applied neuromodulation and a strong algorithm, modeling, and software center such as CIBC. Our key innovation, then, is truly this research collaboration itself. The innovative products of that collaboration will include modeling and optimization tools that are tested and validated in a diverse set of stimulation scenarios, the ability to carry out such computational studies on more significant population scales, the provision of modeling tools with usable controls to clinical and research practitioners, quantification and visualization of the uncertainty associated with computational predictions, and increased understanding of the contribution of stimulation parameters and bioelectric anatomy and function to the broader questions of mechanism and dose. In our discussions with Dr. Pascual-Leone, he has underlined to us his belief that only through innovation in effective modeling methods can progress be made at a sufficiently rapid rate towards these longer-term goals. Moreover, because we freely distribute and actively disseminate and support our software, and in light of our established relationships with the other DBPs and collaborators in the Neuromodulation and Brain Source Localization Research Cluster, our work has a broad impact across the country and the world among the rapidly growing community in transcranial neuromodulation research and treatment.