Summary Preserved language function is essential to quality of life. For patients with a brain tumor near putative language cortex, neurosurgeons may use functional magnetic resonance imaging (fMRI) presurgical language mapping to assess and mitigate the risks of surgery-induced permanent language deficits. Critical barriers to clinical deployment of presurgical fMRI are that 1) The validity of conventional fMRI is contingent on the patient’s ability to perform precisely timed phonological and semantic tasks. But up to 50% of patients assigned to fMRI have language or other cognitive deficits that affect task performance and may invalidate the mapping. 2) Expertise in administering language tasks is insufficient in many clinical settings. To tackle these challenges, we propose a single-group clinical trial to test movie fMRI (in which subjects watch short movie clips while being scanned) as a novel diagnostic intervention for language mapping in neurosurgical patients. Our primary hypothesis is that movie-watching relative to task-based and resting-state fMRI can provide comprehensive language mapping in a greater number of neurosurgical patients, especially those with language deficits. Compared to conventional fMRI language mapping tasks, movie-watching is predicted to engage more completely the neural networks supporting language in real life. Movie-watching also improves subject compliance in fMRI scanning. Our preliminary results demonstrate reduced in-scanner head motion, higher mapping sensitivity in receptive language areas, and overall higher language mapping specificity, of movie versus conventional task fMRI, in brain tumor patients undergoing presurgical language mapping (n=34). In this project, Aim 1 will evaluate in individuals with stroke-induced aphasia (n=80) and healthy controls (n=40), the comprehension and expression elicited by movie-watching versus conventional paradigms, as a function of language impairment. We predict that language performance will be comparable, and in most individuals with aphasia superior, for movie-watching relative to the other paradigms. Aim 2 will assess in neurologically-healthy subjects (n=40), the quality of movie fMRI language mapping as a function of movie clip, and relative to conventional paradigms, using indices of language localization sensitivity and specificity, hemispheric lateralization, and proximity to language white- matter tracts. We predict that for clips inducing the most sensitive and specific synchronized fMRI activation, movie-fMRI will produce better language mapping quality indices than the other paradigms. Aim 3 will similarly evaluate movie-fMRI in neurosurgical patients with frontal or temporoparietal gliomas (n=80), as a function of baseline language function, against the gold standard intra-operative electrocortical stimulation language mapping, and relative to post-operative language outcome. We predict that movie-fMRI will produce better language mapping in a large proportion of patients, especially those with language deficits. Study materials will be publicly released, including optimal movie clips for certain language deficits and fMRI analysis routines.

Narrative The goal of this clinical trial is to improve current functional magnetic resonance imaging (fMRI) language mapping practices for diagnostic neurosurgical planning, including for patients with pre-existing language deficits. The movie-watching language mapping test that will be developed uses naturalistic stimuli predicted to engage more completely the neural networks supporting language in real life. Our goal is to test and publicly share a novel method of comprehensive language mapping which is applicable in more neurosurgical patients, especially those with language deficits.