This is a K01 application for Monika M. Polczynska, Ph.D., a current junior faculty at the University of California Los Angeles, to become an independent investigator and leader in the field of clinical language mapping. The five-year K01 award will provide Dr. Polczynska with the necessary training in (1) designing and optimizing functional MRI experiments, (2) approaches to analyzing functional connectivity data and (3) the structural analysis of the brain. Environment: Experts in cutting-edge methods in functional and structural neuroimaging, imaging statistics and neurolinguistics will serve as Mentors: Drs. Susan Bookheimer, Martin Monti, David Shattuck and Ariana Anderson, and Consultants: Drs. Tim Behrens, Nina Dronkers and Susan Curtiss. Research and Career Development: Studies in neurosurgical language mapping have primarily focused on language evaluations at a word level and they have ignored the following: (1) a broader neural configuration of language function based on grammar, (2) right hemisphere contributions that could be critical to rehabilitation and (3) network connectivity, treating language regions as isolated units rather than nodes of the network. The objective of the study is to comprehensively identify the language network in surgical candidates with brain tumor by addressing the three gaps. It is hypothesized that applying both grammar tests and standard single- word based tests and using mixed methods (advanced neuroimaging techniques and behavioral tests) will allow for a more comprehensive mapping of the crucial language regions and important connections between them. The proposed study will fulfill three specific aims: (1) Create an optimized fMRI battery of grammar assessment to maximally identify the critical language network in healthy subjects (N=25), (2) Model how a brain tumor affects structural and functional connectivity of the critical language network; subjects: 40 patients with brain tumor neighboring the left inferior frontal gyrus (N=20) and posterior temporo-parietal regions (N=20) and 24 matched controls and (3) Examine the effect of lesions in the frontal versus posterior language areas on structural and functional connectivity within the left and the right hemisphere. The approach is innovative because it will be the first attempt, to our knowledge, to augment our understating of altered connectivity patterns in the brain tumor population, including hyperconnectivity in the RH. The study is significant because it will help establish the crucial functional and structural anatomy of the language network in patients with brain tumors in specific locations. The study will be a fundamental step in advancing the comprehensiveness and depth of pre-surgical language mapping. The proposed research aligns directly with the 2017 NIDCD Strategic Plan to focus on changes in the structure and function of the brain following a pathologic insult that results in language disturbances. Results will support a future R01 focused on the compensatory system and rehabilitation. This research will lay the foundation for Dr. Polczynska's career as a leading expert in clinical language mapping.
Standard language tests as currently used in clinical language mapping generate a risk of suboptimal assessment of the crucial neuroanatomy of the language network in patients with brain tumor. Brain surgeries guided by suboptimal tests may result in significant new language deficits. The proposed research is highly relevant to public health because it will (a) focus on identifying a more comprehensive language network in the left hemisphere along with its connectivity patterns in patients with a brain tumor and (b) contribute to developing critical knowledge that will help prevent human disability.