fMRI assessment of language lateralization: an objective approach

Language lateralization based on functional magnetic resonance imaging (fMRI) is often used in clinical neurological settings. Currently, interpretation of the distribution, pattern and extent of language activation can be heavily dependent on the chosen statistical threshold. The aim of the present study was to 1) test the robustness of adaptive thresholding of fMRI data to yield a fixed number of active voxels, and to 2) develop a largely threshold-independent method of assessing when individual patients have statistically atypical language lateralization. Simulated data and real fMRI data in 34 healthy controls and 4 selected epilepsy patients performing a verbal fluency language fMRI task were used. Dependence of laterality on the thresholding method is demonstrated for simulated and real data. Simulated data were used to test the hypothesis that thresholding based upon a fixed number of active voxels would yield a laterality index that was more stable across a range of signal strengths (study power) compared to thresholding at a fixed p value. This stability allowed development of a method comparing an individual to a group of controls across a wide range of thresholds, providing a robust indication of atypical lateralization that is more objective than conventional methods. Thirty healthy controls were used as normative data for the threshold-independent method, and the remaining subjects were used as illustrative examples. The method could also be used more generally to assess relative regional distribution of activity in other neuroimaging paradigms (for example, one could apply it to the assessment of lateralization of activation in a memory task, or to the assessment of anterior-posterior distribution rather than laterality).