Fig. 5: Interaction between COMT rs4633, Dysbindin Hap, and sex on brain activity during the N-back task performance.

a Brain multi-slice sections and rendering showing the significant DLPFC activity resulting from the three-way interaction between COMT genotype, Dys Hap, and sex during N-Back task located in the left DLPFC (Brodmann Area 9; MNI coordinates x = −30, y = 32, z = 38; k = 52, Z = 3.49; *p_TFCE-FWE = 0.04). The color bar indicates log₁₀ TFCE scores ranging from 1.3 to 4 as suggested by Smith and Nichols [66]. b Box plots showing the differences between the COMT genotype and Dys Hap groups in the female and male groups assessed by the two-sample t test and corrected for multiple comparisons (k = 6; p_FDR < 0.05). The BOLD estimates extracted from Brodmann Area 9 were significantly higher in COMT^Val/Val females with Dys Hap +/− compared with Dys Hap +/+ (t(27) = 3.37; **p_FDR = 0.008), while COMT^MetCar females with Dys Hap +/− presented lower BOLD estimates compared with Dys Hap +/+ (t(69) = −3.68; **p_FDR = 0.005). Furthermore, females with Dys Hap +/− and COMT^Val/Val presented higher estimates than COMT^MetCar (t(23) = 3.22; **p_FDR = 0.009), as well as females with Dys Hap +/+ and COMT^MetCar presented higher estimates than COMT^Val/Val (t(32) = 3.63; **p_FDR = 0.005). Also, the BOLD estimates extracted from BA9 were different in COMT^Val/Val males with Dys Hap +/− compared with Dys Hap +/+ (t(23) = −3.21; **p_FDR = 0.004) in the opposite direction compared with the female analysis, as well as males with Dys Hap +/− and COMT^Val/Val presented trending lower estimates than COMT^MetCar (t(27) = −2.19; p_FDR = 0.06). Only significant differences corrected for multiple comparisons have been reported in the figure (p_FDR< 0.05). c Scatterplots showing the association between brain activity estimates extracted from left Brodmann Area 9 and behavioral indices from the N-back task, i.e., the efficiency rate and the reaction time (in seconds). General linear models revealed a significant negative association between the reaction time and brain activity estimates extracted from left Brodmann Area 9 in females with the COMT^MetCar and Dys + /− (r = −0.39; p_uncorr = 0.02), while a significant positive association between the reaction time and activity estimates (r = 0.37; p_uncorr = 0.05), and a negative association between the efficiency rate and activity estimates (r = −0.38; p_uncorr = 0.04) were found in males. All regression’s r and nominal p-values are reported in the figure. BOLD Blood Oxygen Level Dependent, BA9 Brodmann Area 9.