Introduction 1 3 4 7 8 12 1 13 14 15 7 7 16 17 21 Fig. 1 p L y y z z  a b c a c 2  22 23 24 25 26 10 27 28 29 In the present study, we investigated potential sex differences in the activity of the primary auditory region, using different auditory stimuli. Material and methods Subjects Twenty healthy, right-handed volunteers participated in this study (10 males, 10 females). The mean age for men was 23 years (range 20–25) and for women 22 years (range 19–27). All volunteers gave written informed consent according to the Declaration of Helsinki and the Medical Ethics Committee of the University Medical Center Groningen approved the study. None of the subjects had any history of psychiatric or neurological disorders. Prior to the scanning, subjects were tested for their hearing thresholds using standard audiometric measures. All subjects had normal hearing thresholds (<20 dBHL, 0.25–8 kHz), and only small intersubject variations in hearing thresholds were observed. Data acquisition 15 15 15 30 Experimental design 15 Data analysis 31 p 32 http://amide.sourceforge.net/ 33 34 18 20 33 p Results Music versus noise 1 1 Table 1 Overview of brain areas with statistically significant cerebral blood flow changes     Side Region Talairach coordinates Number of voxels t-value x y z Music vs noise Females Right BA 22 61 −6 −1 1,459 7.77   Left BA 22 −51 −10 −1 310 5.02  Males Right BA 41, 42, 22 52 2 −3 3,234 7.87   Left BA 41, 42, 22 −51 −8 0 2,190 7.87 Music vs baseline Females Right BA 41, 42, 22 57 −4 −1 2,750 8.85   Left BA 41, 42, 22 −48 −17 3 1,866 7.97  Males Right BA 41, 42, 22 51 −10 2 2,475 10.36   Left BA 41, 42, 22 −48 −12 1 2,306 8.67 Noise vs baseline Females Right BA 41 46 −21 5 446 6.49   Left BA 41 −40 −23 5 463 6.24  Males No suprathreshold clusters       Baseline vs noise Females No suprathreshold clusters        Males Right BA 9 20 50 29 968 5.20 Baseline vs music Males No suprathreshold clusters        Females No suprathreshold clusters       14 p  52 53 p p 2 2 Table 2 Region of interest analysis of the left and right primary auditory cortex (PAC)   P-value Left PAC Right PAC Music vs noise females 0.005* 0.001*  Males <0.001* <0.001*  Females minus males 0.984 0.992  Males minus females 0.016* 0.008* Music vs baseline females <0.001* <0.001*  Males <0.001* <0.001*  Females minus males 0.721 0.779  Males minus females 0.279 0.221 Noise vs baseline females <0.001* <0.001*  Males 0.016* 0.005*  Females minus males 0.042* 0.034*  Males minus females 0.958 0.966 p Fig. 2 Regional cerebral blood flow relative to the baseline of each group, based on all voxels in the left and right PAC (with a global mean flow of 50 ml/100 g/min). Error bars indicate the 90% confidence interval of the mean across subjects per condition; the confidence interval of the baseline is also given  To determine whether this sex difference can be attributed to the processing of either music or noise, we compared these two stimuli with a baseline without experimental auditory stimulation. Music versus baseline 1 1 2 2 Noise versus baseline p 1 1 p 3 p 2 Fig. 3 p L y z 1  4 1 Fig. 4 p x z  Discussion Our data demonstrate a sex difference in regional cerebral blood flow in the left and right primary auditory cortex (PAC) when comparing auditory processing of music and noise. The PAC was more activated by music than by noise in both men and women. But this difference between the two stimuli was significantly higher in men than in women. To determine whether this sex difference can be attributed to the processing of music, noise, or both, we compared the two stimuli with a baseline of no auditory stimulation. Comparing music with the baseline resulted in extensive activation of the primary and secondary auditory cortex in both sexes, but no significant sex difference was found. On the other hand, a sex difference was detected in the processing of noise, because females activated their PAC significantly more than males. The finding that sex differences in auditory processing can already be detected at the level of the primary cortex is very important, because it is often assumed that sex differences act exclusively upon higher-order cortical areas. 34 17 21 18 20 33 15 18 20 33 2 35 36 37 38 38 39 40 41 43 44 45 46 47 29 48 49 50 50 51 In conclusion, a very significant sexual dichotomy was found in the activation of the PAC with different types of acoustic stimuli (noise and music) together with sex differences in deactivation of prefrontal areas. It is known that the auditory and prefrontal regions are anatomically and functionally linked, and the prefrontal cortex is engaged in auditory attention tasks. Hence, we hypothesize that differences in attention might result in a different involvement of the right prefrontal cortex, which in turn modulates the activation of the PAC. This shows that sex influences brain activity already at the level of primary sensory cortex and that in functional imaging studies on primary sensory cortical areas, sex cannot be ignored.