S68. UNALTERED FRONTAL AND PREFRONTAL BRAIN RESPONSE DURING WORK MEMORY TASKS IN PATIENTS WITH A FIRST EPISODE PSYCHOSIS META-ANALYSIS STUDY

There is extensive evidence that frontal and prefrontal cortex have abnormal functioning in patients with schizophrenia (Weinberger et al., 2001). For example, with functional magnetic resonance imaging (fMRI), multiple studies have shown altered activation during working memory tasks in these patients compared with controls (Adamczyk et al., 2017; Li et al., 2017). While most of the studies have been conducted in patients with chronic illness, whether these findings translate to individuals at the time of presenting with a First Episode Psychosis (FEP) is less well understood (Soldevila-Matias et al., 2018). The main objective of this study was to meta-analyze fMRI studies that have investigated the brain response to working memory tasks in patients with FEP. These data may be helpful to understand neurobiology of the longitudinal course of working memory dysfunction in patients with schizophrenia.

We included 19 studies in patients with FEP. We conducted the analysis using anisotropic effect-size seed-based d mapping (AES-SDM, https://www.sdmproject.com/) (Radua et al., 2014). Firstly, AES-SDM used the coordinates and t-values of the peaks of maximum statistical significance reported in the studies to impute a three-dimensional image of the effect-size of the differences in activation between patients and controls, separately for each study. Specifically, it assigned each voxel an effect size that depended on the spatial covariance with the close peaks, whose effect size is known. Secondly, we created a three-dimensional image of the variance of the effect size, again separately for each study. This step is straightforward because the variance of an effect size only depends on the effect size and the samples sizes. Thirdly, we fitted a standard random-effects meta-analysis separately for each voxel.

Patients with FEP showed hypoactivation of median cingulate cortex mainly Brodmann area 32, (peak 4, 26, 40), left precuneus mainly Brodmann area 7 (peak -12,-64, 58), and left anterior insula mainly Brodmann area 47 (peak -36, 18,-12).

Our results might point that FEP exhibit altered brain response in some relevant cortical regions. Nevertheless, we didn’t find any significant results in prefrontal and frontal areas in FEP, implying that may be abnormalities in patients, which are a product of degenerative process of the disease. Moreover, the small size of sample may be another possible explanation, which implies more heterogeneous results suggesting that there are no significant results in the frontal and prefrontal lobes.

References:

• Adamczyk, P., et al., (2017) ‘Neural circuit of verbal humor comprehension in schizophrenia - an fMRI study’, NeuroImage: Clinical. Vol 15: 525–540.

• Li, T., et al., (2017) ‘Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia’, Schizophrenia bulletin. Vol 43: Pages 436–448

• Radua, J., et al., (2014) Anisotropic kernels for coordinate-based meta-analyses of neuroimaging studies. Frontiers in Psychiatry. 5: p. 13.

• Soldevila Matias, P. et al., (2018) Where is the abnormal brain activity in First Episode Psychosis. Schizophrenia Bulletin. Vol 44; S384.

• Weinberger, D. R., Egan, M. F., Bertolino, A., Callicott, J. H., Mattay, V. S., Lipska, B. K., Berman, K. F. and Goldberg, t. e. (2001) ‘Neurobiology of schizophrenia and the role of atypical antipsychotics prefrontal neurons and the genetics of schizophrenia’, Biological Psychiatry, Vol 50, pp. 825–844.