Resting-state fMRI connectivity impairment in schizophrenia and bipolar disorder

Abstract

Background: Schizophrenia and bipolar disorder share aspects of phenomenology and neurobiology and thus may represent a continuum of disease. Few studies have compared connectivity across the brain in these disorders or investigated their functional correlates.

Methods: We used resting-state functional magnetic resonance imaging to evaluate global and regional connectivity in 32 healthy controls, 19 patients with bipolar disorder, and 18 schizophrenia patients. Patients also received comprehensive neuropsychological and clinical assessments. We computed correlation matrices among 266 regions of interest within the brain, with the primary dependent measure being overall global connectivity strength of each region with every other region.

Results: Patients with schizophrenia had significantly lower global connectivity compared with healthy controls, whereas patients with bipolar disorder had global connectivity intermediate to and significantly different from those of patients with schizophrenia and healthy controls. Post hoc analyses revealed that compared with healthy controls, both patient groups had significantly lower connectivity in the paracingulate gyrus and right thalamus. Patients with schizophrenia also had significantly lower connectivity in the temporal occipital fusiform cortex, left caudate nucleus, and left thalamus compared with healthy controls. There were no significant differences among the patient groups in any of these regions. Lower global connectivity among all patients was associated with worse neuropsychological and clinical functioning, but these effects were not specific to any patient group.

Conclusions: These findings are consistent with the hypothesis that schizophrenia and bipolar disorder may represent a continuum of global disconnectivity in the brain but that regional functional specificity may not be evident.

Keywords: bipolar disorder; connectivity; resting-state fMRI; schizophrenia.

Fig. 1.

Connectivity strength differences across the 266 regions of interest.

Fig. 2.

Voxel-wise connectivity strength. Note: When we compared HCs and patients (either SCZ or BD), we found areas where connectivity strength was higher in patients (supplementary table 1), but post hoc analysis in these cases showed that the connectivity strength was closer to 0 (ie, less negative). In a similar manner, the opposite contrasts also revealed areas where patients’ connectivity strength was closer to 0, in very good agreement with the ROI-based calculations and figure 1. Open circles: outliers; data points outside of the quartiles ±1.5 x interquartile range (standard in boxplot with R).

Fig. 3.

Cluster analysis of correlation patterns. Note: In A and B, each row corresponds to an individual and each column to a region. The color-coded values of the rows represent how well that particular region correlates with the caudate nucleus and fusiform gyrus, respectively (s upplementary table 3), which were chosen for illustration given that they demonstrated the most robust group differences in connectivity. The rows of the matrix (ie, the individuals) are already ordered according to the result of the cluster analysis. In C, the horizontal axis represents the strength that the connectivity of an area can separate HCs and patients (t test), while the vertical axis represents the statistical strength that the cluster analysis (chi-square) yields in a certain area.

Fig. 4.

Models to conceptualize disconnectivity.