r Spatial Heterogeneity in Language Lateralization r [Binder et al., 1996; Desmond et al., 1995], was mainly con- cerned with demonstrating the concordance between fMRI LI values and well-established clinical tools such as the Wada test. However, this historical approach is still moti- vating further investigation into how the consistency between laterality indices from fMRI and Wada can be fur- ther improved (e.g., see [Arora et al., 2009; Lee et al., 2008; Rutten and Ramsey, 2010; Suarez et al., 2009; Wellmer et al., 2008]), despite the fact that a total agreement between Wada and fMRI assessments may never be reached because they are measuring different things (see critical review in [Rutten and Ramsey, 2010]). In the context of using fMRI for preoperative assess- ments, we suggest that a shift needs to be made in the way fMRI is presented and implemented in the clinical set- ting. The rich source of information provided by fMRI needs to be preserved rather than over-simpliﬁed into lat- erality indices that can be misleading rather than helpful. This perspective is in accordance with the recent attempts to integrate fMRI maps into clinical navigation systems which assist clinicians in making optimal decisions during surgery (e.g., [Ganslandt et al., 2009; Rutten et al., 2003; Sankar and Cosgrove, 2009; Wurn et al., 2008]). As recently stressed, neurosurgeons are more comfortable with inter- preting fMRI results when shown in a navigation system. This approach provides high spatial deﬁnition (e.g., [Yoo et al., 2004]) which can be especially helpful in deﬁning the extent of the surgical exposure [Wurn et al., 2008]. A shift from fMRI based language LI to fMRI based lan- guage mapping for preoperative investigations would be beneﬁcial for the whole ﬁeld of clinical fMRI. Neverthe- less, to pursue this perspective, and to address previous criticisms of the clinical interpretation of fMRI maps [Bell and Racine, 2009; Desmond and Chen, 2002; Giussani et al., 2010; Matthews et al., 2006; Robinson, 2004], further investigations are required to: (i) establish reliable ways of differentiating indispensable regions from less critical regions [Paolicchi, 2008; Rutten and Ramsey, 2010], (ii) minimize the occurrence of false negatives in the presence of abnormal neuronal or hemodynamic responses (e.g., [Jayakar et al., 2002; Westerveld et al., 1999]), and (iii) characterize variability across subjects that may confound the deﬁnition of normative functional responses [Seghier et al., 2008a]. This will necessitate standardization of fMRI protocols (tasks and analyses), and their validation in dif- ferent clinical populations [Allen and Fong, 2008; Binder et al., 2008; Rutten et al., 2002]. CONCLUSION In summary, our ﬁndings highlight the limitations of interpreting laterality indices, irrespective of whether later- alization is assessed with fMRI or the WADA test. From a nonclinical theoretical perspective, the interpretation of global LI needs to consider the relative contribution of the left and right hemispheres as well as between subject dis- sociations in regional lateralization. Future work is also required to further our understanding of how laterality changes: with the underlying anatomy (e.g., [Josse et al., 2008, 2009]), with genetic variables (e.g., [van Rijn et al., 2008]); and following brain damage [Crosson et al., 2009; Hertz-Pannier et al., 2002]. Speciﬁcally, the implications of our ﬁndings need to be tested in patients with variable focal or nonfocal damage. This will allow the impact of damage on laterality to be assessed while considering the relative contribution of the ipsilesional and contralesional regions. Extensive postsurgical language testing would also allow the presurgical conclusions to be evaluated in a systematic way so that the contribution of both fMRI maps and laterality values can be better understood. From a clinical perspective, our ﬁndings highlight the need for fMRI evaluation of language function because this will provide precision in the spatial localization of lan- guage areas. More speciﬁcally, we suggest that presurgical language assessments with fMRI should not rely solely on laterality indices but should focus on individual regions, at the site of the intended surgery, and consider the contri- bution of the right and left hemisphere independently. ACKNOWLEDGMENTS The authors thank their three radiographers (Amanda Brennan, Janice Glensman, and David Bradbury) as well as Clare Shakeshaft, Laura Stewart, and Tom Schoﬁeld for their help with fMRI data collection, Caroline Ellis for her help with data analysis, and Hwee Ling Lee and Sue Rams- den for their valuable help setting up the fMRI database. REFERENCES Abou-Khalil B (2007): Methods for determination of language dominance: The Wada test and proposed noninvasive alterna- tives. Curr Neurol Neurosci Rep 7:483–490. Allen MD, Fong AK (2008). Clinical application of standardized cognitive assessment using fMRI. II. Verbal ﬂuency. Behav Neurol 20:141–152. Arora J, Pugh K, Westerveld M, Spencer S, Spencer DD, Todd Constable R (2009): Language lateralization in epilepsy patients: fMRI validated with the Wada procedure. Epilepsia 50:2225–2241. Ashburner J, Friston KJ (2005): Uniﬁed segmentation. Neuroimage 26:839–851. 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