Webler Ryan D, Hamady Carmen, Molnar Chris, Johnson Kevin, Bonilha Leo, Anderson Berry S, Bruin Claartje, Bohning Daryl E, George Mark S, Nahas Ziad
University of Minnesota, Department of Psychology, USA.
American University of Beirut, Department of Psychiatry, USA.
Brain Stimul. 2020 Sep-Oct;13(5):1467-1475. doi: 10.1016/j.brs.2020.06.017. Epub 2020 Jun 23.
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.
/Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity.
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 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition.
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).
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.
精神分裂症患者前额叶异常一直出现在静息态和认知神经影像学研究中。然而，这些相关性发现需要通过联合成像/刺激方法进行因果验证。迄今为止，尚无交叉经颅磁刺激与功能磁共振成像研究（TMS-fMRI）探究精神分裂症患者前额叶皮质是否存在异常。
目的/假设：我们假设精神分裂症患者在刺激部位（BA9）会表现出明显的兴奋性过高，且半球间功能连接降低。
我们招募了19名未服药的精神分裂症患者和22名对照者。所有受试者均使用配备SENSE线圈的3T MRI扫描仪进行脑成像。他们还接受了一次TMS-fMRI检查，包括运动阈值（rMT）测定、结构成像，以及在0、80、100和120% rMT下施加10Hz三联脉冲的参数化TMS-fMRI方案。扫描使用了针对双侧前额叶皮质图像采集优化的表面MR线圈。
在最初招募的41名受试者中，8名精神分裂症患者和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，精神分裂症患者在左侧BA9（p = 0.0157；最大z值= 4.7）和邻近的BA46（p = 0.019；最大z值= 4.47）表现出兴奋性过高。对照者通过右侧BA9激活增加，在左侧BA9和右侧BA9之间表现出更多的对侧功能连接（p = 0.02；最大z值= 3.4）。精神分裂症患者的灰质密度与相应距离的前额叶与运动皮质归一化比值（S-BA9/S-MC）呈正相关（r = 0.83，p = 0.004）。
与对照者相比，精神分裂症患者在左侧BA9表现出兴奋性过高，且半球间功能连接受损。交叉TMS-fMRI是研究精神分裂症前额叶功能障碍的一种有前景的工具。
