Very few experiments have used fMRI to study neuro-cognitive effects of testosterone in the normal population, and most look at variation in females (see Celec et al., 2015 for a recent review). Results are mixed and generally related to emotional and/or spatial processing that was not the focus of the current study. No controlled studies exist on the effect of testosterone treatment on cognitive abilities in adult KS, but the effects of testosterone treatment on cognition in the normal population have been limited (Warren et al., 2008) and no effects are seen in elderly hypogonadal patients (Holland et al., 2011). Thus, should there be an effect of testosterone deficiency and testosterone treatment in KS, then we would expect it to be primarily at the physiological level, e.g. through a link to hematocrit levels (Levin et al., 2001). The differences between KS and Controls in this experiment are, however, not likely to be due to testosterone as we found no difference in testosterone levels across the two groups due to the presence of both testosterone treated and untreated KS participants. Also, we did not see any correlation between testosterone level and BOLDresponse in neither KS nor Controls. Previously we have found no differences in neither global nor local brain volumes between testosterone treated and untreated KS (Skakkebæk et al., 2014b). In general, no one has yet been able to establish a role for testosterone in the cerebral phenotype of KS.

Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation