Abstract BACKGROUND Awake craniotomy with direct electrical stimulation (DES) is the standard treatment for patients with eloquent area gliomas. Language errors (paraphasias) are detected with DES and they indicate functional boundaries that need to be maintained to preserve quality of life. However, it is not fully clear in which brain locations paraphasias at different linguistic modalities and levels (production, comprehension, reading, writing, phonology, semantics, syntax) occur. MATERIALS AND METHODS A systematic review was conducted. We included 102 studies reporting on specific paraphasias and the corresponding brain locations during awake craniotomy with DES in adult glioma patients. RESULTS First, a wide distribution of brain locations for all paraphasias (n=930) was found, but patterns were observed. Cortically, paraphasias occurred most often in the precentral gyrus (22%), while subcortically, they occurred mainly at the inferior fronto-occipital fascicle (IFOF: 10%). Localization patterns for different paraphasia types and the corresponding language functions were also found: production/articulation (n=393)-precentral gyrus (41%), inferior frontal gyrus (9%), frontal aslant/striatal tract (4%), postcentral gyrus (3%); semantics (n=128)-IFOF (57%), superior temporal gyrus (9%); phonology (n=115)-arcuate fascicle (52%), superior longitudinal fascicle (10%), uncinate fascicle (3%); reading (n=25)-temporal lobe (48%), inferior longitudinal fascicle (32%); syntax (n=15)-inferior frontal gyrus (27%); speech initiation (n=9)-supplementary motor area (33%), frontal aslant tract (22%), frontal striatal tract (22%); writing (n=7)-superior parietal gyrus (71%). Second, 59% of all paraphasias occurred cortically, 40% subcortically and 1% at both levels. CONCLUSION The localization of most paraphasias are consistent with the assumed functionality of those brain locations as presented in the Dutch Linguistic Intraoperative Protocol model. However, new locations for production/articulation, phonology, reading and writing were found. This needs to be taken into consideration for future selection of pre, intra and postoperative language tasks at different language modalities and levels. Additionally, DES should always be applied at the subcortical level as a standard addition to the routine cortical mapping during awake craniotomy. In conclusion, this is the first systematic review on the localization of specific paraphasias during awake craniotomy. Based on the identified language localization patterns, language tasks could be selected more accurately. This could guide, and perhaps improve, pre, intra and postoperative language testing and monitoring, which in turn, may pave the way to a better postoperative language outcome. The possible relation between different intraoperative paraphasias and language outcome has yet to be determined.
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