Alterations in Functional Brain Network Structure Induced by Subchronic Phencyclidine (pcp) Treatment Parallel Those Seen in Schizophrenia

Klinefelter (van Rijn et al., 2006a). Difficulties in social adaptation and abnormal brain asymmetries suggest that a genetic mechanism (involving genes on theX chromosome)might affect the development of social cognition in XXY men. Language and emotion are important aspects of social cognition. Reduced or abnormal lateralization of language has been found in Klinefelter's syndrome (Geschwind,1998; van Rijn et al., 2008). Additionally, impairments in emotional prosody perceptionhavebeen reported (vanRijn et al., 2007).Weexpected that lateralization of emotional prosody differed in Klinefelter's syndrome. Therefore, we used fMRI-guided transcranial magnetic stimulation (TMS) to study lateralization effects. Methods: Sevenmenwith Klinefelter's syndrome and seven controls (matched on age, gender and education) performed an emotional prosody task during fMRI-scanning. In this task, subjects attended to the affective (happy, sad, angry or anxious) intonation and had to ignore the neutral semantic content of the sentences. We used fMRIguided TMS (with BrainVoyager neuronavigation) to reduce excitability of areas thatwere active during emotional prosody processing in the MR scanner (left and right superior temporal gyrus). TMS was performed for 20 minutes on 1 Hz. After stimulation, the subjects performed the emotional prosody task again. In addition, a baseline measurement without TMS was included. Results were analyzed with repeated measures analysis of variance (ANOVA). Results: Klinefelter patients showed a trend to react slower than controls (p=0.12). They also showed longer reaction times on the angry condition after stimulation of the right superior gyrus (p=0.05), whereas controls reacted faster. No other effects of TMS reached significance. Discussion: Menwith Klinefelter's syndrome respondedmore slowly to sentences with an angry intonation in the emotional prosody task after right STG stimulation, whereas controls responded faster. The emotion angry is hypothesized to be primarily processed by the left hemisphere. Thus, the involvement of the right STG in anger prosody processing in Klinefelter patients suggests a switch in lateralization. The faster responses in the healthy group for this emotion might be due to callosal disinhibition of the left hemishere by the right hemisphere TMS. As fMRI studies have suggested similar patterns of aberrant lateralization in Klinefelter syndrome and schizophrenia, our results may have implications for understanding schizophrenia.