Dynamic Alterations of Amplitude of Low-Frequency Fluctuations in Patients With Drug-Naïve First-Episode Early Onset Schizophrenia

Abstract

Abnormalities in static neural activity have been widely reported in early onset schizophrenia (EOS). However, dynamic brain activity alterations over time in EOS are unclear. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by EOS. A total of 78 drug-naïve first-episode patients with EOS and 90 healthy controls (HCs) were enrolled in this study. Dynamic amplitude of low-frequency fluctuations (dALFF) was performed to examine the abnormal time-varying local neural activity in EOS. Furthermore, we investigated the relationships between abnormalities in dALFF variability and clinical characteristics in EOS patients. Compared to HCs, EOS patients showed significantly decreased dALFF variability in the bilateral precuneus, right superior marginal gyrus, right post-central gyrus and increased dALFF in the right middle temporal gyrus (MTG). Moreover, increased dALFF variability in MTG was negatively associated with negative symptoms in EOS. Our findings reveal increased dynamic local neural activity in higher order networks of the cortex, suggesting that enhanced spontaneous brain activity may be a predominant neural marker for brain maturation. In addition, decreased dALFF variability in the default mode network (DMN) and limbic system may reflect unusually dynamic neural activity. This dysfunctional brain activity could distinguish between patients and HCs and deepen our understanding of the pathophysiological mechanisms of EOS.

Keywords: default mode network; dynamic amplitude of low-frequency fluctuations; early onset schizophrenia; middle temporal gyrus; variability.

FIGURE 1

Pattern of dALFF variability in early onset schizophrenia (EOS) patients and healthy controls (HCs). EOS patients and HCs exhibited significant differences in the spatial distribution of dALFF variability. dALFF, dynamic amplitude of low-frequency fluctuations; HCs, healthy controls; EOS, early onset schizophrenia; L, left; R, right.

FIGURE 2

Brain region differences in dALFF variability in EOS compared to HCs. (A) EOS showed increased dALFF variability in the right middle temporal gyrus (MTG) (winter color) and decreased dALFF variability in the bilateral precuneus, right supramarginal gyrus and post-central gyrus compared to HCs (warm color) (GRF corrected; p < 0.005; cluster level, p < 0.05; minimum clusters size of 20 voxels). (B) The graph exhibiting the ROI-wise post hoc comparison results. *p < 0.01, uncorrected; ***p < 0.0001, Bonferroni correction.

FIGURE 3

Relationship between dALFF variability and clinical symptoms. Increased dALFF variability of the right MTG was negatively correlated with PANSS negative scores of patients with EOS (p < 0.05, uncorrected).