Altered brain dynamics of facial emotion processing in schizophrenia: a combined EEG/fMRI study

Abstract

Facial stimuli are relevant social cues for humans and essential signals for adequate social interaction. Impairments in face processing are well-documented in schizophrenia and linked to symptomatology, yet the underlying neural dynamics remain unclear. Here, we investigated the processing and underlying neural temporal dynamics of task-irrelevant emotional face stimuli using combined EEG/fMRI in 14 individuals with schizophrenia and 14 matched healthy controls. Specifically, fMRI-informed region-of-interests were subjected to EEG-Dynamic Causal Modeling (DCM) analyses. Among six fMRI-informed EEG-DCM models, alterations in effective connectivity emerged between the primary visual cortex (V1) and the left occipital fusiform gyrus (lOFG). Specifically, individuals with schizophrenia showed enhanced backward connectivity from the lOFG to V1 for stimuli preceded by fearful (but not happy or neutral) faces. Connectivity strength was strongly correlated with self-reported difficulties in comprehending, processing, or articulating emotions (as assessed by the Toronto Alexithymia Scale-20) in individuals with schizophrenia but not in healthy controls. Enhanced backward connectivity from the lOFG to V1 potentially indicates heightened attention towards fearful surroundings and a propensity to assign salience to these stimuli in individuals with schizophrenia. The link to TAS-20 scores indicates that this neural deficit has real-world implications for how individuals with schizophrenia perceive and relate to their emotions and the external world, potentially contributing to the social and cognitive difficulties observed in the disorder.

Fig. 1. Task schematic.

Each trial commenced with the display of a fixation cross, indicating the position of the upcoming target and facilitating gaze fixation. After 500 ms, a facial crowd stimulus was introduced (for 300 ms), followed by the replacement of the fixation cross with a target face, presenting the crowd-target combination for 500 ms. A subsequent blank screen (450 ms) was included to prevent any overlap between response-related movement and the signal of interest. Following this, a response screen was presented for 3500 ms.

Fig. 2. Schematic of the analysis pipeline.

Step 1: Whole-brain fMRI analysis: We conducted an unimodal flexible factorial whole-brain analysis, examining the main effect of the task condition (F-contrast). This revealed regions significantly activated by the experimental paradigm, thresholded at p < 0.001 with cluster-level correction at k = 34, corresponding to a cluster-level FWE of p < 0.05. Step 2: Coordinate Extraction: We extracted MNI coordinates of these activated regions, excluding the cerebellum. Step 3: Network Node Definition for DCM Analysis: Using the extracted coordinates, we defined nodes for the cortical network in Dynamic Causal Modeling (DCM) analysis. Six model structures were created, incorporating combinations of forward, backward, and bilateral connections among the four brain regions identified in the whole-brain fMRI analysis. Step 4: Bayesian Model Selection (BMS): We applied BMS to identify the best-fitting model. The results showed that Model 6 provided the best fit among the six competing candidates.

Fig. 3. Behavioral responses to target emotions.

a Correct identifications and b duration until first response for the three different target emotions stratified by group (healthy controls/individuals with schizophrenia). Error bars indicate standard error of the mean.

Fig. 4

P1 and N170 ERPs in response to target faces (following crowds) for healthy controls (HCs) and individuals with schizophrenia (ISZ).

Fig. 5. Connectivity results.

a Functional connectivity strength of the backward connection between the left occipital fusiform gyrus (lOFG) and the V1 of model 6 for each condition (target after fearful, target after happy, and target after neutral stimuli) and group (healthy controls and individuals with schizophrenia). Error bars indicate standard error of the mean. b, c Pearson correlations between connectivity strength between the lOFG and V1 and the Toronto Alexithymia Scale (TAS)-20 and duration until first response, respectively, for individuals with schizophrenia and healthy controls. Shaded area represents 95% confidence intervals.