Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach

Abstract

Recent research suggests that the cerebral correlates of cognitive deficits in schizophrenia are nested in the activity of widespread, inter-regional networks rather than being restricted to any specific brain location. One of the networks that have received focus lately is the default mode network. Parts of this network have been reported as hyper-activated in schizophrenia patients (SZ) during rest and during task performance compared to healthy controls (HC), although other parts have been found to be hypo-activated. In contrast to this network, task-positive networks have been reported as hypo-activated compared in SZ during task performance. However, the results are mixed, with, e.g., the dorsolateral prefrontal cortex showing both hyper- and hypo-activation in SZ. In this study we were interested in signal increase and decrease differences between a group of SZ and HC in cortical networks, assuming that the regulatory dynamics of alternating task-positive and task-negative neuronal processes are aberrant in SZ. We compared 31 SZ to age- and gender-matched HC, and used fMRI and independent component analysis (ICA) in order to identify relevant networks. We selected the independent components (ICs) with the largest signal intensity increases (STG, insula, supplementary motor cortex, anterior cingulate cortex, and MTG) and decreases (fusiform gyri, occipital lobe, PFC, cingulate, precuneus, and angular gyrus) in response to a dichotic auditory cognitive task. These ICs were then tested for group differences. Our findings showed deficient up-regulation of the executive network and a corresponding deficit in the down-regulation of the anterior default mode, or effort network during task performance in SZ when compared with HC. These findings may indicate a deficit in the dynamics of alternating task-dependent and task-independent neuronal processes in SZ. The results may cast new light on the mechanisms underlying cognitive deficits in schizophrenia, and may be of relevance for diagnostics and new treatments.

Keywords: ICA; brain activation; cognitive processing; default mode network; dichotic listening; executive network; fMRI; schizophrenia.

Figure 1

The figure displays each components spatial extension (FWE correction, p < 0.01, cluster extension of 10 voxels). Below each component are corresponding time-courses, the ON-OFF block difference expressed as positive signal change, co-registration effects shown as standard error of the mean in both groups and last the ON-OFF block activation difference visualized between the two groups. The schizophrenia patients (SZ) are visualized with the thicker black line, whereas the healthy controls (HC) have the thinner black line in the figure. The red color represents the activation situation (ON), whereas the blue color visualizes the de-activation (OFF).

Figure 2

Shows the anomalies in the distributions of the two significant correlations, IC3 auditive component (AUD2) with the sum total of positive symptoms and the IC4 visual component (VIS) with the hallucination symptom, from Table 5.