Numerous variables can affect the assessment of language dominance using presurgical functional magnetic resonance (fMRI) in patients with brain tumors. This work organizes the variables into confounding and modulating factors. Confounding factors give the appearance of changed language dominance. Most confounding factors are fMRI-specific and they can substantially disrupt the evaluation of language dominance. Confounding factors can be divided into two categories: tumor-related and fMRI analysis. The tumor-related confounds further subdivide into tumor characteristics (e.g., tumor grade) and tumor-induced conditions (aphasia). The fMRI analysis confounds represent technical aspects of fMRI methods (e.g., a fixed versus an individual threshold). Modulating factors can modify language dominance without confounding it. They are not fMRI-specific, and they can impact language dominance both in healthy individuals and neurosurgical patients. The effect of most modulating factors on fMRI language dominance is smaller than that of confounding factors. Modulating factors include demographics (e.g., age) and linguistic variables (e.g., early bilingualism). Three cases of brain tumors in the left hemisphere are presented to illustrate how modulating confounding and modulating factors can impact fMRI estimates of language dominance. Distinguishing between confounding and modulating factors can help interpret the results of presurgical language mapping with fMRI.
Keywords: brain tumor; confounds; fMRI; glioma; language; language dominance; laterality index.