Time-resolved sex differences in language lateralization.

Many clinical, behavioural and brain imaging studies have suggested that language functions are less asymmetrical in women than in men. Sommer and colleagues challenge this view in a recent review on the outcome of 24 functional brain imaging studies (PET, functional MRI or functional transcranial Doppler ultrasound) that looked at possible sex differences in language lateralization. A vote count analysis over all studies revealed a much higher score for those studies that reported no sex differences. In addition, a meta-analysis of the lateralization index in 13 of these studies revealed no statistically significant difference between men and women. The authors concluded that the hypothesis of sex differences in cortical language representation probably has to be rejected at the population level (Sommer et al., 2004). We believe that the hypothesis of subtle, but crucial sex differences in language representation should not be rejected on these grounds, considering the selective sample of studies included in the review. There is one important limiting factor of functional imaging with PET, fMRI or Doppler, namely their weak temporal resolution. Consequently, the studies reviewed by Sommer and colleagues (Sommer et al., 2004) might have identified not only regions that are critical for language processing but also other areas that are activated while subjects solve the task, in particular when the control (subtraction) condition consists of ‘passive’ rest. This issue was discussed in detail in an earlier publication of the same group (Ramsey et al., 2001), in which they propose a combined analysis of several ‘active’ language conditions using so-called conjunction analysis to overcome the problem. In that study, the authors convincingly showed that the latter approach is more reliable for the study of language lateralization and yields a small amount of variance across subjects. Unfortunately, with the exception of one study (Sommer et al., 2003), the reports considered in the meta-analysis did not use this approach. On the contrary, six of the 14 selected studies contrasted activation during a language task with a ‘passive’ control condition (block design). Five of these six studies were among those that did not find sex differences. The limitation in temporal resolution does not apply to brain mapping methods such as the recording of eventrelated potentials (ERPs) or magnetic fields (MEG). Consequently, these methods make it possible to functionally define and temporally restrict the analysis window to the task-relevant processing steps. In the study of language, the functionally relevant time interval would correspond to 170–400 ms after stimulus onset, as many previous studies have reported the critical language-related ERP responses to occur in this window (for reviews see e.g. Khateb et al., 1999; Cohen et al., 2000; Kutas and Federmeier, 2000; van den Brink et al., 2001; Friederici and Kotz, 2003; Cohen and Dehaene, 2004). Sex differences in lateralization of language processing should consequently be most dominant (if not restricted) to this critical period of around 200 ms in length. Indeed, a recent MEG study by Walla and colleagues provides evidence for gender differences in word recognition in exactly this time window, i.e. between 200 and 350 ms (Walla et al., 2001). Beside differences in strengths of activation, topographical differences were found in this time period that were interpreted as reduced asymmetry in females compared with males. The point we want to make is that brain imaging techniques that can be used to reveal functional neuronal activity in a precise, predefined time window may refine our understanding of functional brain asymmetries and should be considered before rejecting the hypothesis of sex differences in language representation. This will be further illustrated with a re-analysis of an ERP data set that has been published in part previously (Ortigue et al., 2004). In contrast to