UC San Diego

The neural substrate of interactions of working memory (WM) with socio-emotional processing is poorly understood in schizophrenia. This study builds on published papers using a delayed match to sample design to study the interaction of WM load with type of distracter (socially relevant faces vs. socially irrelevant geometric designs [FvG]) presented briefly during the WM maintenance period. Based on previously published findings, we hypothesize: (1) The FvG difference in brain activity in the dorsolateral prefrontal cortex (DLPFC) in the task maintenance period will be largest at the highest WM load. (2) Among schizophrenia/ schizoaffective patients and healthy controls the magnitude of the face vs. geometric design (FvG) contrast in brain activity in the amygdala during the task maintenance period will follow a quadratic pattern across WM load when averaged over face type. (3) Among schizophrenia patients, the magnitude of the FvG contrast in brain activity in the amygdala and DLPFC at the greatest WM load will be correlated with negative symptoms.

Individuals between the ages of 18-55 diagnosed with schizophrenia/schizoaffective disorder (N = 12) and non-psychiatric controls (N = 20) matched with the patients on age, gender, paternal education and paternal socioeconomic status underwent structural and functional magnetic resonance imaging (fMRI). To assess the effect of implicit socioemotional modulation on brain activity during WM, the effect of facial distraction on brain activation was assessed for WM of pseudowords at three syllable loads (1, 2, and 3) across several face valence types and contrasted with the effect of a geometric distracter.

Results: Although patients performed significantly above chance, they were less accurate than controls with no difference in response latency. When the FvG contrast was tested for response latency, we observed a significant quadratic effect of WM load in healthy controls (F[1,19] = 6.108, p = .023, η2 = .24) but a linear effect among patients (F[1,10] = 4.012, p = .073, η2 = .29). Similar patterns were found for response accuracy but were not statistically significant. With regard to neural activity, we found a significant bilateral linear trend of percent signal change on WM load for the FvG contrast in the DLPFC (F[1,19] = 5.818, p = .026, MSE = .077, η2 = .23). among controls, with brain activation to faces greater than activation to designs only at the highest WM load. In the amygdala we observed a significant bilateral quadratic effect of percent signal change on WM load for the FvG contrast in the control group (F[1,19] = 10.423, p = .004, MSE = .121, η2 = .35). We observed a significant difference in neural activation patterns in patients compared to controls in the DLPFC and the amygdala. Specifically, in patients, we observed a quadratic instead of a linear trend in the DLPFC but only in the right hemisphere (hemisphere x quadratic: F[1,11] = 9.362, p = .011, η2 = .40). In the amygdala, the patients displayed a quadratic trend also only in the right hemisphere, (hemisphere x quadratic: F[1,11] = 10.442 p = .008, η2 = .49). In neither controls nor patients did individual differences in the quadratic effect of brain activity in the amygdala correlate with the quadratic effect in response time or accuracy. Although the correlation between the magnitude of the quadratic trend in the right amygdala at the highest WM load with general psychopathology was moderately large in patients, neither this effect nor any other brain activation effects were significantly correlated with psychopathology.

Confirming hypothesis one, controls showed the largest difference in brain activity of the FvG contrast in the DLPFC during the maintenance period at the highest WM load. However, in patients we saw significantly decreased percent signal change in DLPFC at the highest WM load on the FvG contrast in the maintenance period. For hypothesis two we observed a quadratic pattern of WM load on the FvG contrast in the maintenance period for both controls and patients, although this effect was only present in the right hemisphere of patients. Furthermore, contrary to hypothesis 3 we did not observe significant correlations between symptom severity and the magnitude of the FvG contrast in brain activity in the amygdala and DLPFC at the greatest WM load. These results suggest a separate process of social-discrimination is taking place in controls. However, this process appears to be impaired in individuals with schizophrenia. This disruption may be due to poor integration of different brain areas and interhemispheric communication.