慢性氯胺酮依赖者的丘脑皮层功能连接改变

Objective: Previous studies have revealed thalamic abnormalities in schizophrenia.Ketamine, a potent N-methyl-D-aspartate glutamate receptor antagonist, can mimic schizophrenia-like symptoms. In this study, we aimed to address whether the thalamus as a whole shows altered functional connectivity to the cerebral cortex in chronic ketamine users compared to healthy controls. Method: 130 subjects (41 ketamine users and 89control subjects) underwent resting-state functional MRI (fMRI). seed-based functional connectivity analysis,to investigate the specific functional relationships between the cortex and the thalamus, the cortex was partitioned into nonoverlappingsix regions of interest (the prefrontal cortex, motor cortex/supplementary motor area, somatosensory cortex, temporal cortex, posterior parietal cortex, and occipital cortex).Mean BOLD time series were extracted for each region of interest (ROI) and entered into a seed-based functional connectivity analysis. Results: We found that the ketamine use group showed significantly less connectivity between the thalamus and the cortical regionsofinterest, including the prefrontal cortex, the motor cortex /supplementary motor area, and the posterior parietal cortex. However, no increased thalamic connectivity was observed for the ketamine users compared with control subjects.The functional connectivity between the posterior parietal area and the right lateral dorsal nucleus was significantly correlated to individual ketamine craving score (p<0.05, corrected). Conclusions: This study provides first evidence for abnormal thalamocortical connectivity of resting state brain activity in chronic ketamine users. Our datafurther support a disruption model of the thalamocortical network and are consistent with a disconnection hypothesis of schizophrenia, and emphasize the functional importance of the thalamus in the pathophysiology of schizophrenia.Further understanding of glutamatergic mechanisms in schizophrenia may facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of this complex disease.?????