BACKGROUND Prefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia. OBJECTIVE /Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity. METHODS We enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition. RESULTS Of the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p=0.0157; max z-score=4.7) and neighboring BA46 (p=0.019; max z-score=4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p=0.02; max z-score=3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p=0.004). CONCLUSIONS Subjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.

中文翻译：

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未经治疗的精神分裂症患者的半球间连接性降低和皮质兴奋性增加：前额叶交错 TMS fMRI 研究

背景精神分裂症的前额叶异常一直来自静息状态和认知神经影像学研究。然而，这些相关发现需要通过组合成像/刺激方法进行因果验证。迄今为止，还没有交错的经颅磁刺激和功能磁共振成像研究 (TMS fMRI) 探测到精神分裂症中假定的前额叶皮层异常。目的/假设：我们假设精神分裂症患者在刺激部位 (BA9) 会表现出显着的过度兴奋和半球间功能连接性降低。方法 我们招募了 19 名未接受药物治疗的精神分裂症受试者和 22 名对照组。所有受试者都使用带有 SENSE 线圈的 3T MRI 扫描仪进行脑成像。他们还接受了一次 TMS fMRI 会议，包括运动阈值 (rMT) 测定、结构成像和参数 TMS fMRI 协议，其中 0、80、100 和 120% rMT 的 10Hz 三重脉冲。扫描涉及为双边前额叶皮层图像采集优化的表面 MR 线圈。结果 在最初登记的 41 名受试者中，8 名患有精神分裂症的受试者和 11 名对照者符合最终数据分析的全部标准。在相同的 TMS 强度下，患有精神分裂症的受试者在左侧 BA9（p=0.0157；最大 z-score=4.7）和相邻 BA46（p=0.019；最大 z-score=4.47）中表现出过度兴奋。通过增加右侧 BA9 的激活，对照显示左侧 BA9 和右侧 BA9 之间更多的对侧功能连接（p = 0.02；最大 z 分数 = 3.4）。精神分裂症受试者的 GM 密度与标准化的前额叶与运动皮层的比例（S-BA9/S-MC）的颅骨与皮质比值（S-BA9/S-MC）的标准化正相关（r = 0.83，p = 0.004）。结论 与对照组相比，精神分裂症患者左侧 BA9 表现出过度兴奋和半球间功能连接受损。交错 TMS fMRI 是研究精神分裂症前额叶功能障碍的有前途的工具。