For the valence ratings (positive, negative and neutral), ANOVA showed a significant effect of valence (F1.23,38 = 335.63, p < 0.001, ). Pairwise comparisons with Bonferroni adjustment showed a significant difference between each valence condition (negative < neutral < positive, p < 0.001). Regarding the percentage of accuracy in the emotional valence categorization task, ANOVA revealed a non-significant effect of valence (F1.32,38 = 3.67, p = 0.06). Another ANOVA was conducted for reaction times during the emotional valence categorization task (positive valence: mean 1237 [SD 182] ms; negative valence: mean 1313 [SD 173] ms; neutral valence: mean 1400 [SD 183] ms) and showed a significant effect of valence (F1.49,38 = 7.98, p = 0.004). Pairwise comparisons demonstrated a significant difference in reaction times only between the positive and neutral valences (p < 0.05), suggesting that MDD patients needed more time to categorize neutral pictures than positive ones.
Results of a picture valance rating task for patients with major depressive disorder
For recognition memory accuracy (index Pr), ANOVA showed a significant effect of valence (F1.28,38 = 10.15, p = 0.002). The results of pairwise comparisons showed a significant difference in recognition memory accuracy only between positive and neutral valence conditions (p = 0.001) and between positive and negative valence conditions (p < 0.001). Thus, MDD patients were significantly less accurate in recognizing positive pictures compared with neutral or negative ones. An ANOVA performed for reaction times during the recognition task (positive valence: mean 1372 [SD 165] ms; negative valence: mean 1408 [SD 146] ms; neutral valence: mean 1288 [SD 169] ms) showed a significant effect of valence (F2,38 = 29.08, p < 0.001). Pairwise comparisons showed significant differences between neutral and negative valence conditions (p < 0.001) and between neutral and positive valence conditions (p < 0.001). Neutral pictures were remembered faster than emotional ones.
Among the 20 patients included in the study of recognition memory accuracy and symptomatic improvement, we found that symptomatic improvement was significantly and positively correlated with Pr-Global (r = 0.53, p = 0.015), Pr-Negative (r = 0.51, p = 0.021) and Pr-Positive (r = 0.49, p = 0.028). No significant difference was found for Pr-Neutral (r = 0.43, p = 0.06).
We initially identified the brain regions involved in the successful encoding of complex pictures. We found significant bilateral activation in the middle occipital gyri (Brodmann areas [BA] 18 and 19), thalami and bilateral precentral gyrus (BA 6). We also found significant activation in the right fusiform gyrus (BA 37), left dorsal anterior cingulate cortex (BA 32), left parahippocampal gyrus (BA 35), right amygdala and left inferior occipital gyrus (BA 19; and ).
Results for the subsequent memory effect analyses*
Brain activity associated with successful encoding of complex pictures (contrast: all pictures hits minus all pictures misses). p < 0.001, uncorrected; 10 voxels was the minimum cluster size.
and summarize the results from the correlation between brain activity during successful encoding of complex pictures and symptomatic improvement. We found 4 clusters in the frontal lobe that were significantly and positively correlated with symptomatic improvement: left superior frontal gyrus (BA 9), left ventromedial prefrontal cortex (BA 10), right rostral ACC (BA 24/32) and right superior frontal gyrus (BA 6). No brain activation was negatively correlated with symptomatic improvement. shows the correlation between rostral ACC activity (contrast estimates for the contrast of all pictures hits v. all pictures misses) and symptomatic improvement. shows the correlation between ventromedial PFC activity and symptomatic improvement.
Fig. 2 Brain regions where activity generated by successful encoding of complex pictures (contrast: all pictures hits minus all pictures misses) was significantly correlated with the symptomatic improvement after 8 weeks of antidepressant treatment. p < (more ...)
Fig. 3 Contrast estimates for the contrast of all pictures hits minus all pictures misses correlated to symptomatic improvement for the peak voxel in the (A) right rostral anterior cingulate cortex (x = 16, y = 30, z = 17) and (B) ventromedial prefrontal cortex (more ...)
The contrast of positive pictures hits minus positive pictures misses revealed significant activation in the left middle occipital gyrus (peak voxel: x = −56, y = −70, z = 4, BA 37, t = 6.38, cluster size = 2298), right inferior temporal gyrus (x = 50, y = −68, z = 10, BA 37, t = 5.02, cluster size = 2548), left superior frontal gyrus (x = −22, y = 14, z = 44, BA 8, t = 5.96, cluster size = 341) and left VMPFC (x = −12, y = 50, z = −10, BA 10, t = 4.11, cluster size = 42). For the contrast of negative pictures hits minus negative pictures misses, we found significant activation in the right fusiform gyrus (x = 46, y = −64, z = −14, BA 19, t = 6.00, cluster size = 307), left inferior occipital gyrus (x = −40, y = −86, z = 4, t = 5.76, BA 19, cluster size = 354), left middle occipital gyrus (x = −26, y = −96, z = 6, BA 18, t = 4.90, cluster size = 170), right hippocampus (x = 36, y = −26, z = −10, t = 5.01, cluster size = 65) and left rostral ACC (x = −20, y = 40, z = 4, BA 32, t = 4.32, cluster size = 36).
The contrast of neutral pictures hits minus neutral misses revealed significant activation in the bilateral precentral gyri (right: x = 40, y = 2, z = 36, BA 6, t = 4.56, cluster size = 95; left: x = −54, y = −6, z = 30, BA 6, t = 4.38, cluster size = 68) and bilateral insula (right: x = 52, y = −20, z = 16, BA 41, t = 3.67, cluster size = 106; left: x = −38, y = −2, z = 14, BA 41, t = 4.21, cluster size = 83).
The paired t test for SME positive minus SME neutral showed significant activation in the right middle temporal gyrus (BA 37), left middle and superior occipital gyri (BA 19), right superior frontal gyrus (BA 8), bilateral ventromedial PFC (BA 10) and right fusiform gyrus (BA 37). This contrast identified brain regions that were significantly involved in successful encoding of positive versus neutral pictures. The brain regions significantly involved in successful encoding of negative versus neutral pictures included the right hippocampus, left superior parietal lobule (BA 7) and left middle occipital gyrus (BA 18; ).
The multiple regression analysis that included rostral ACC activity as an independent variable revealed a significant model explaining the symptomatic improvement following an 8-week citalopram treatment (F1,15 = 13.61, p = 0.002, adjusted R2 = 0.40). The only significant variable included in this model was rostral ACC activity. No other variable significantly explained symptomatic improvement. The multiple regression analysis that included ventromedial PFC activity as an independent variable showed a significant model explaining symptomatic improvement (F4,15 = 12.95, p < 0.001, adjusted R2 = 0.72). Significant variables included in this model were ventromedial activity (R2 variation = 0.47 and standardized β = 0.57, p = 0.001), the HAM-D baseline (R2 variation = 0.14, standardized β = 0.38, p = 0.007), Pr-Global (R2 variation = 0.23, standardized β = 0.40, p = 0.011) and sex (R2 variation = 0.03, standardized β = −0.28, p = 0.042).
Finally, among the 20 participants, rostral ACC activity (contrast estimates extracted from the contrast all pictures hits v. misses) was significantly correlated with memory accuracy for all pictures combined (Pr-Global: r = 0.53, p = 0.017), as well as for positive pictures (Pr-Positive: r = 0.52, p = 0.018) and negative pictures (Pr-Negative: r = 0.46, p = 0.040). The results were nonsignificant for the neutral pictures (Pr-Neutral: r = 0.43, p = 0.06). Interestingly, ventromedial PFC activity (contrast estimates extracted from the contrast all pictures hits vs. all pictures misses) was only significantly correlated to memory accuracy for the positive pictures (Pr-Positive: r = 0.49, p = 0.029). There was no significant correlation between ventromedial PFC activity and memory accuracy for all pictures combined (Pr-Global: r = 0.41, p = 0.07), negative pictures (P-Negative: r = 0.35, p = 0.13) or neutral pictures (P-Neutral: r = 0.27, p = 0.24).