P.3.010 - Imbalance in the deployment of neural resources during visual working memory encoding in schizophrenia as a possible intermediate phenotype

Abstract

Visual working memory (VWM) deficits are a prominent impairment in patients with schizophrenia (SCZ) and are associated with an inefficient encoding process [1] and with neuronal dysfunctions [2]. Both behavioural and neurofunctional impairments can be observed in unaffected first-degree relatives of patients (REL) as well and are thus discussed as a possible intermediate phenotype of the disorder [3,4]. In this study we investigated the characteristics of WM encoding and its neural substrates in SCZ and REL to evaluate their potential role as an intermediate phenotype of the disorder. We examined n = 25 SCZ, n = 22 REL and n = 25 healthy control subjects (CON). All subjects underwent whole brain fMRI scans in a 3 Tesla MR system. During the fMRI scan, a VWM change-detection task was presented, which showed a sample array consisting of 3 red lines of different orientation that should be memorized. After a delay interval of either 100ms, 400ms or 800ms (SOA = stimulus onset asynchrony) a pattern mask was shown, followed by another delay period and a test array. The longer the delay interval until masking, the more durable the VWM representations were expected to be. Response accuracy served as an estimate of the grade of VWM encoding. The behavioural data was analyzed using a two-way univariate ANOVA with repeated measures and post hoc tests. For group statistics of the event-related fMRI data we conducted a random-effects GLM (RFX-GLM) and a subsequent ANOVA with 'group' as a between-subjects factor (3 levels) and 'SOA' as within-subjects factor (3 levels). For behavioural performance in the VWM task we found significant main effects of 'group' (p = 0.026) and 'SOA' (p = 0.013). The longer the SOA interval, the greater the response accuracy across groups (significant linear trend; p = 0.009). Response accuracy was significantly lower in SCZ compared to CON (p = 0.011) and REL (p = 0.041). We observed aberrant neural activation during VWM encoding for both SCZ and REL compared to CON: across SOA conditions SCZ showed widespread neural deactivation, including the DLPFC and precentral gyrus, as well as increased activity of the anterior cingulate. In REL, we observed a shift in neural activation in regard to the length of the SOA interval: at SOA 100 REL showed only decreased activity in the superior frontal gyrus and fusiform gyrus; at SOA 400 we observed decreased activity in the middle frontal gyrus and increased activity in the superior frontal gyrus; and at SOA 800 REL showed only increased activity in the inferior frontal gyrus. The findings indicate that impaired VWM in SCZ may emerge from an insufficient engagement of the functional WM network with concomitant anterior cingulate hyperactivity during encoding. In REL, the shift from decreased to increased activity might reflect a compensatory process: hypoactivity might point towards fundamental neural dysfunctions—at lighter processing demands local hyperactivity might ensure accurate VWM performance. Neural dysfunctions during VWM encoding should thus be considered as a candidate intermediate phenotype of SCZ.