17 In a study examining intensity judgment, patients had an exaggerated amygdala response: positive faces induced right amygdala activation in both groups, while negative faces activated only the

right amygdala in controls and bilaterally in patients.18 Picture categorization (pleasant, unpleasant, neutral) produced less activity in amygdaloid-hippocampal and cortical-basal ganglia- thalamic circuitry in patients.19 The role of limbic response in identification of facial emotions and its relation to symptoms is Inhibitors,research,lifescience,medical illustrated in Figure 4. 20 As can be seen in the middle row, top-down (task-related) limbic activation is diminished in schizophrenia. However, patients showed abnormally increased limbic activation time-locked to the appearance of threat-related facial emotions Inhibitors,research,lifescience,medical of anger and fear. Furthermore, increased amygdala activation for fear was associated in patients both with failure to identify the emotion and with more severe flat affect (Figure). Figure 4. Regions activated for emotion identification task relative to baseline (block analysis) in controls (upper row), patients (middle row), and the controls-patients Inhibitors,research,lifescience,medical contrast (bottom row). No patients-controls contrast survived correction. Significance thresholds … Figure 5. Association between brain activity and

clinical measures. A, Correlations between event-related activation for the 4 emotional expressions in activated regions and severity of clinical ratings for flat affect. B, Scatterplot of

the association between … Studies of emotion processing in schizophrenia vary in methodology and design. Nonetheless, there seems to be considerable convergence of evidence that patients show abnormal Inhibitors,research,lifescience,medical activation in amygdala and associated regions. It also appears that the abnormalities are more pronounced for negatively valenced stimuli, although no further differentiation for specific emotions has Inhibitors,research,lifescience,medical been established. In most studies patients performance was carefully examined and tasks were often constructed so as to minimize performance difference, to avoid confounding of physiologic measures. In all cases where performance was evaluated, it did not explain the difference in activation patterns. However, reduced task-related (top-down) next activation could reflect bottom-up Small Molecule Compound Library interference from abnormally increased amygdala activation related to stimulus valence. Thus, if the task is to identify emotions, sensitivity of the amygdala for specific stimuli may disrupt cortical processes required for categorization and response. Frontotemporal connectivity was examined by considering the pattern of correlations among activation parameters obtained from regions recruited for specific tasks. Controls have high specific connectivity for activation to the top-down task and for bottom-up activation associated with correct responding.