Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia

Abstract

Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

The power of using functional fMRI on small rodents to study brain pharmacology and disease

“…Interestingly, FC as well as ultra-structural features, defined with diffusion imaging, were significantly decreased in the same regions ( Sekar et al, 2010 ). Similar FC results were reported in a genetic model for schizophrenia ( Song et al, 2015 ).…”

“…Additionally, the effects of new antipsychotic drugs can be tested using the same read-outs, enabling target validation and early assessment of drugs ( Sekar et al, 2010 ; Bifone and Gozzi, 2012 ; Song et al, 2015 ).…”

Disrupted functional connectivity between the periaqueductal gray and other brain regions in a rat model of recurrent headache

“…These T2-weighted images (T2WI) were obtained using a 2D-RARE sequence with the following parameters: TR = 6,200 ms, TEeff = 24 ms, flip angle = 180°, FOV = 35 × 35 mm 2 , matrix size = 256 × 256, slice thickness = 0.3 mm, slice gap = 0 mm, and total scan time = 20 min 37 . Functional images were obtained using a gradient echo-planar imaging (EPI) sequence (TR = 2,000 ms, TE = 27.1 ms, flip angle = 90, slice thickness = 1 mm, slice gap = 0 mm, matrix = 128 × 128), and 150 continuous EPI functional volumes were acquired axially over 13 min 20 s 38 .…”

Influence of EGR3 Transfection on Imaging and Behavior in Rats and Therapeutic Effect of Risperidone in Schizophrenia Model

“…disorders in the risperidone treatment group were also restored to a certain extent. Therefore, the increased activation in the prefrontal lobe cortex and hippocampus might be an indicator that can be used for schizophrenia diagnosis (1). We determined the lower seed-based FC in the olfactory bulb (AOD and GI) and frontal brain areas (M2, S1H1, and DLO) of schizophrenia model rats.…”

“…Schizophrenia is a complex psychiatric disorder that affects approximately one percent of the world's population. Genetic and environmental factors adversely affect neural development, and they are thought to contribute to the pathogenesis of schizophrenia (1). The disease is characterized by 'social brain' disorder and disturbances in functional connectivity (FC) (2).…”