Time Course Emotional Prosody Figure 1. Reaction times on emotional prosody task during triple-pulse rTMS at different time-point at the right anterior superior temporal gyrus (aSTG, n = 14 subjects), the fronto-parietal operculum (FPO, n = 14 subjects) and at the POz-EEG location (n = 10 subjects) for detection of emotional intonations. A: reaction times for perception of fearful intonations, B: reaction times for perception of sad intonations and C: reaction times for detection of happy intonations. doi:10.1371/journal.pone.0002244.g001 p,.05 and F (1, 9) = 8.9, p,.05 respectively. There was also a main effect of Time F (5, 45) = 21.2, p,.001 and a main effect of Emotion F (2, 18) = 8.6, p,.01 as was found in the anterior superior temporal gyrus versus fronto-parietal operculum analysis. Analyzing the data for separate emotions, revealed a significant effect of Site of stimulation for ‘fear’ F (2, 18) = 4.2, p,.05, and for ‘happiness’ F (2, 18) = 6.5, p,.01, but not for ‘sadness’ F (2, 18) = 2.6, p = 0.10. As can be seen in Table 1, reaction times were shorter for all three emotions in the POz condition, as compared to anterior superior temporal gyrus and fronto-parietal operculum. The interaction between Site of stimulation and Time was significant, F (10, 90) = 1.9, p = .05, with stronger effects of Time in the anterior superior temporal gyrus and fronto-parietal operculum conditions than in the POz condition (see figure 1). There was no interaction between Site of stimulation and Emotion. With regard to accuracy of responses, inclusion of the active control condition did not reveal significant effects of Site of stimulation, indicating that on accuracy measures no differences were found between the Sites. A significant interaction between Emotion and Time was found, paralleling the results for the reaction times analysis, F (10,90) = 5.7, p,.001. This reflects that the time of delivering the triplet of pulses had a different effect depending on which emotion was expressed. Data are presented in table 2. Discussion To our knowledge this is the first study investigating the time course of processing emotional prosody in natural sentences. This study demonstrates that triple-pulse transcranial magnetic stimu- lation (TMS) over the right anterior superior temporal gyrus as well as the right fronto-parietal operculum interferes at critical time points with the process of emotional prosody recognition from spoken sentences. This effect was significantly stronger after TMS over the fronto-parietal operculum and the anterior superior temporal gyrus than in the active control condition, stimulation over the occipital cortex. The most critical time point was at 1300 ms after sentence onset. This effect was apparent for withdrawal, but not for the approach emotion. The strong delay in response times at 1300 ms was found for detection of vocally expressed ‘fear’ and ‘sadness’, but not for ‘happiness’. We did not find a difference between right anterior superior temporal gyrus and right fronto-parietal operculum. Results showed a similar time pattern for both brain areas. Our results are consistent with those of a recent study that targeted a right somatosensory area close to the fronto-parietal operculum but a bit higher, using TMS to investigate the perception of facial emotion expression [26]. Interestingly, this PLoS ONE | www.plosone.org 3 May 2008 | Volume 3 | Issue 5 | e2244