Disrupted functional connectivity affects resting state based language lateralization

Pre-operative assessment of language localization and lateralization is critical to preserving brain function after lesion or epileptogenic tissue resection. Task fMRI (t-fMRI) has been extensively and reliably used to this end, but resting state fMRI (rs-fMRI) is emerging as an alternative pre-operative brain mapping method that is independent of a patient's ability to comply with a task. We sought to evaluate if language lateralization obtained from rs-fMRI can replace standard assessment using t-fMRI. In a group of 43 patients scheduled for pre-operative fMRI brain mapping and 17 healthy controls, we found that existing methods of determining rs-fMRI lateralization by considering interhemispheric and intrahemispheric functional connectivity are inadequate compared to t-fMRI when applied to the language network. We determined that this was attributable to widespread but nuanced disturbances in the functional connectivity of the language network in patients. We found changes in interhemispheric and intrahemispheric functional connectivity that were dependent on lesion location, and particularly impacted patients with lesions in the left temporal lobe. We then tested whether a simpler measure of functional connectivity to the language network has a better relation to t-fMRI based language lateralization. Remarkably, we found that functional connectivity between the language network and the frontal pole, and superior frontal gyrus, as well as the supramarginal gyrus, significantly correlated to task based language lateralization indices in both patients and healthy controls. These findings are consistent with prior work with epilepsy patients, and provide a framework for evaluating language lateralization at rest.