Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network

Abstract

Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy volunteers. Healthy volunteers demonstrated correlation between spontaneous low-frequency fluctuations of the BOLD signal in the posterior cingulate and fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions, similar to previous reports. Schizophrenic patients had significantly less correlation between spontaneous slow activity in the posterior cingulate and that in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity of the posterior cingulate was found to vary with both positive and negative symptoms in schizophrenic patients. Because these data suggest significant abnormalities in resting-state neural networks in schizophrenia, further investigations of spontaneous slow fluctuations of the BOLD signal seem warranted in this population.

Fig. 1.

Areas of positive correlation with posterior cingulate (0, −56, 20) in (A) healthy control subjects (N = 17) and (B) subjects with schizophrenia (N = 17), thresholded at P < .001 for visual clarity. (C) Areas in which control subjects showed significantly greater positive correlation with the right posterior cingulate than subjects with schizophrenia, thresholded at P < .005.

Fig. 2.

Areas of negative correlation with right posterior cingulate (0, −56, 20) in (A) healthy control subjects (N = 17) and (B) subjects with schizophrenia (N = 17), thresholded at P < .005. No regions were found to be significantly more correlated with the posterior cingulate in control subjects than in schizophrenic subjects.

Fig. 3.

(A) Areas in which correlation with posterior cingulate (0, −56, 20) in 17 subjects with schizophrenia was positively correlated with degree of positive symptoms, as measured by the SAPS. (B) Areas in which correlation with posterior cingulate (0, −56, 20) in subjects with schizophrenia was negatively correlated with degree of positive symptoms, as measured by the SAPS. Thresholded at P < .005.

Fig. 4.

(A) Areas in which correlation with posterior cingulate (0, −56, 20) in 17 subjects with schizophrenia was positively correlated with degree of negative symptoms, as measured by the SANS. (B) Areas in which correlation with posterior cingulate (0, −56, 20) in subjects with schizophrenia was negatively correlated with degree of negative symptoms, as measured by the SANS. Thresholded at P < .005.