Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

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In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.

It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the hippocampus has been challenged by recent studies. This study was undertaken to assess the effect of lesions in different parts of the left hemisphere, lesions present during language acquisition, on language lateralization. We investigated 84 adult patients with drug-resistant focal epilepsy with structural lesions and 45 healthy control subjects with an established functional MRI language paradigm. Out of the 84 patients 43 had left hippocampal sclerosis, 13 a left frontal lobe lesion and 28 a left temporal-lateral lesion. All these lesions were likely to have been present during the first years of life during language acquisition. To assess the lateralization of cerebral language representation globally as well as regionally, we calculated lateralization indices derived from activations in four regions of interest (i.e. global, inferior frontal, temporo-parietal and remaining prefrontal). Patients with left hippocampal sclerosis showed less left lateralized language representations than all other groups of subjects (P < 0.005). This effect was independent of the factor of region, indicating that language lateralization was generally affected by a left hippocampal sclerosis. Patients with left frontal lobe or temporal-lateral lesions displayed the same left lateralization of language-related activations as the control subjects. Thus, the hippocampus seems to play an important role in the establishment of language dominance. Possible underlying mechanisms are discussed.

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