Impaired target detection in schizophrenia and the ventral attentional network: Findings from a joint event-related potential-functional MRI analysis

Abstract

Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrated event-related potentials (ERP) and fMRI to examine the contributions of the ventral (salience) and dorsal (sustained) attention networks to this dysfunctional neural activation. Twenty-one schizophrenia patients and 22 healthy controls were assessed in separate sessions with ERP and fMRI during a visual oddball task. Visual P100, N100, and P300 ERP waveforms and fMRI activation were assessed. A joint independent components analysis (jICA) on the ERP and fMRI data were conducted. Patients exhibited reduced P300, but not P100 or N100, amplitudes to targets and reduced fMRI neural activation in both dorsal and ventral attentional networks compared with controls. However, the jICA revealed that the P300 was linked specifically to activation in the ventral (salience) network, including anterior cingulate, anterior insula, and temporal parietal junction, with patients exhibiting significantly lower activation. The P100 and N100 were linked to activation in the dorsal (sustained) network, with no group differences in level of activation. This joint analysis approach revealed the nature of target detection deficits that were not discernable by either imaging methodology alone, highlighting the utility of a multimodal fMRI and ERP approach to understand attentional network deficits in schizophrenia.

Keywords: ERP; Joint ICA; Oddball; Salience network; fMRI.

Fig. S1

Whole brain analysis for the target vs. baseline contrast in healthy controls (red, left) and schizophrenia patients (blue, right). Reported activations were thresholded at p < .01, uncorrected for multiple comparisons, with an extent threshold of 36 contiguous voxels, corresponding to a false-positive discovery rate of < 5% across the whole brain.

Fig. S2

Event-related potentials (ERPs) to for P100 and N100, pooled over electrodes P5, P7, PO7, P6, P8, and PO8, and corresponding topographical maps to target stimuli in healthy controls (left) and schizophrenia patients (right). ERP waveforms in black = target, red = nontarget.

Fig. S3

Results from the fMRI/ERP jICA analysis for the sensory components. A) Average ERP waveforms for controls (yellow) and patients (pink) overlaid onto the temporal aspect of the identified joint component for controls (blue) and patients (green). B) 2D rendering of the spatial aspect of the joint component. Activation can be seen in inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, and postcentral gyrus, areas included in the dorsal network.

Fig. 1

Brain regions showing greater activity to target stimuli in healthy controls compared with schizophrenia patients. A) Crosshairs corresponding to anterior cingulate cortex on coordinates shown. B) Crosshairs corresponding to right lateral occipital cortex on coordinates shown. Reported activations were thresholded at p < .01, uncorrected for multiple comparisons, with an extent threshold of 36 contiguous voxels, corresponding to a false-positive discovery rate of <5% across the whole brain.

Fig. 2

A) Event-related potentials (ERPs) at electrode Pz and corresponding topographical maps in healthy controls (left) and schizophrenia patients (right). ERPs waveforms in black = target, red = nontarget. B) Statistical cluster plot depicting running t-tests comparing ERP amplitudes to targets in the healthy control group vs. schizophrenia patient group. Significant effects exceeding an alpha level of 0.01, lasting for a minimum of 20 ms (10 data points at 500 Hz), are shown. The color bar depicts the direction of the difference, with green colors representing no significant difference. Time, plotted on the x-axis, between −50 to +500 ms is shown. The y-axis depicts regions of electrodes, moving from frontal (F) electrodes at the bottom of the axis to frontocentral (FC), central (C), central-parietal (CP), parietal (P), parietal-occipital (PO), and occipital (O) at the top of the axis.

Fig. 3

Results from the fMRI/ERP jICA analysis at electrode Pz, showing the joint component with a significantly different loading parameter (p < 0.05) for controls vs. patients. A) Average ERP waveforms for controls (yellow) and patients (pink) overlaid onto the temporal aspect of the identified joint component for controls (blue) and patients (green). B) 2D rendering of the spatial aspect of the joint component for controls (red), patients (blue), and areas of group overlap (green). Crosshairs centered on left insula on MNI coordinates as shown. C) 3D rendering of the spatial component. Arrows point to activation in anterior cingulate cortex (ACC), anterior insula (AI), and temporo-parietal junction (TPJ) and motor cortex.