Structural and functional connectomes from 27 schizophrenic patients and 27 matched healthy adults

<strong><em>Data Acquisition</em></strong> The cohort consists of a total of 27 healthy participants (age 35 ± 6.8 years) and 27 schizophrenic patients (age 41 ± 9.6), scanned in a 3-Tesla MRI scanner (Trio, Siemens Medical, Germany) using a 32-channel head-coil. The schizophrenic patients are from the Service of General Psychiatry at the Lausanne University Hospital (CHUV). All of them were diagnosed with schizophrenic and schizoaffective disorders after meeting the DSM-IV criteria (American Psychiatric Association (2000): Diagnostic and Statistical Manual of Mental Disorders, 4th ed. DSM-IV-TR. American Psychiatric Pub, Arlington, VA22209, USA). The Diagnostic Interview for Genetic Studies assessment was used to recruits the healthy controls (Preisig et al. 1999). 24 out of the 27 schizophrenics were under medication with mean chlorpromazine equivalent dose (CPZ) of 431 ± 288 mg. The written consent was obtained for all subjects - in accordance with institutional guidelines of the Ethics Committee of Clinical Research of the Faculty of Biology and Medicine, University of Lausanne, Switzerland, #82/14, #382/11, #26.4.2005). All subjects were fully anonymised. The session protocol consisted of (1) a magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence sensitive to white/gray matter contrast (1-mm in-plane resolution, 1.2-mm slice thickness), (2) a Diffusion Spectrum Imaging (DSI) sequence (128 diffusion-weighted volumes and a single b0 volume, maximum b-value 8,000 s/mm², 2.2x2.2x3.0 mm voxel size), and (3) a gradient echo EPI sequence sensitive to BOLD contrast (3.3-mm in-plane resolution and slice thickness with a 0.3-mm gap, TE 30 ms, TR 1,920 ms, resulting in 280 images per participant). During the fMRI scan, participants were not engaged in any overt task, and the scan was treated as eyes-open resting-state fMRI (rs-fMRI). <strong><em>Data Pre-processing </em></strong> Initial signal processing of all MPRAGE, DSI, and rs-fMRI data was performed using the Connectome Mapper pipeline (Daducci et al. 2012). Grey and white matter were segmented from the MPRAGE volume using freesurfer (Desikan<em> </em>et al. 2006) and parcellated into 83 cortical and subcortical areas. The parcels were then further subdivided into 129, 234, 463 and 1015 approximately equally sized parcels according to the Lausanne anatomical atlas following the method proposed by (Cammoun et al. 2012). DSI data were reconstructed following the protocol described by (Wedeen et al. 2005), allowing us to estimate multiple diffusion directions per voxel. The diffusion probability density function was reconstructed as the discrete 3D Fourier transform of the signal modulus. The orientation distribution function (ODF) was calculated as the radial summation of the normalized 3D probability distribution function. Thus, the ODF is defined on a discrete sphere and captures the diffusion intensity in every direction. <strong><em>Structural Connectivity</em></strong> Structural connectivity matrices were estimated for individual participants using deterministic streamline tractography on reconstructed DSI data, initiating 32 streamline propagations per diffusion direction, per white matter voxel (Wedeen et al. 2008). Structural connectivity between pairs of regions was measured in terms of fiber density, defined as the number of streamlines between the two regions, normalized by the average length of the streamlines and average surface area of the two regions (Hagmann et al. 2008). The goal of this normalization was to compensate for the bias toward longer fibers inherent in the tractography procedure, as well as differences in region size. The number of fibers and fiber length were also included in the dataset. For the quantitative measure of structural connectivity, the generalised fractional anisotropy (gFA, Tuch et al. 2004) and average apparent diffusion coefficient (ADC, Sener et al. 2001) were also computed for each tract. <strong><em>Functional Connectivity</em></strong> Functional data were pre-processed using routines designed to facilitate subsequent network exploration (Murphy et al. 2009, Power et al. 2012). The first four time points were excluded from subsequent analysis to allow the time series to stabilize. The signal was linearly detrended and further physiological (white-matter and cerebrospinal fluid regressors) and motion artefacts (three translational and three rotational regressors) confounds were regressed. Then, the signal was spatially smoothed and bandpass-filtered between 0.01-0.1 Hz with Hamming windowed sinc FIR filter. To obtain the brain regions for different atlas scales the signal was linearly registered to the MPRAGE image and averaged within a given region (Jenkinson et al. 2012). Functional matrices were obtained by computing Pearson’s correlation between the individual pairs of regions. All of the above was carried out in subject’s native space (Daducci et al. 2012, Griffa et al. 2017). Brain cortical bert freesurfer rendering for the 5 scales of the Lausanne2008 atlas is available on https://github.com/jvohryzek/bert4lausanne2008.<strong><em>数据采集</em></strong> 本队列共纳入27名健康参与者（年龄35±6.8岁）与27名精神分裂症患者（年龄41±9.6岁），均使用德国西门子医疗（Siemens Medical）3T磁共振成像（Magnetic Resonance Imaging, MRI）扫描仪（型号Trio），搭配32通道头部线圈完成扫描。精神分裂症患者招募自洛桑大学医院（CHUV）普通精神科服务部门。所有受试者均符合《精神障碍诊断与统计手册第四版（DSM-IV-TR）》（美国精神病学会，2000：《Diagnostic and Statistical Manual of Mental Disorders, 4th ed. DSM-IV-TR》，美国精神病学出版社，美国弗吉尼亚州阿灵顿22209）的诊断标准，被确诊为精神分裂症及分裂情感障碍。健康对照受试者通过《遗传研究诊断访谈》进行招募（Preisig等，1999）。27名精神分裂症患者中有24名接受药物治疗，平均氯丙嗪等效剂量（Chlorpromazine Equivalent Dose, CPZ）为431±288mg。所有受试者均签署书面知情同意书，研究符合瑞士洛桑大学生物与医学院临床研究伦理委员会的相关指南（编号#82/14、#382/11、#26.4.2005）。所有受试者信息均已完全匿名化。扫描流程包含以下序列：(1) 磁化准备快速梯度回波（magnetization-prepared rapid acquisition gradient echo, MPRAGE）序列，用于凸显白质/灰质对比度（平面分辨率1mm，层厚1.2mm）；(2) 扩散谱成像（Diffusion Spectrum Imaging, DSI）序列，包含128个扩散加权容积与1个b0容积，最大b值为8000 s/mm²，体素尺寸2.2×2.2×3.0 mm；(3) 对血氧水平依赖（Blood Oxygen Level Dependent, BOLD）对比度敏感的梯度回波平面成像（Echo Planar Imaging, EPI）序列，平面分辨率与层厚均为3.3mm，层间间隙0.3mm，回波时间（TE）30ms，重复时间（TR）1920ms，每位受试者可获得280幅图像。 fMRI扫描期间，受试者未执行任何外显任务，本次扫描视为睁眼静息态功能磁共振成像（resting-state functional Magnetic Resonance Imaging, rs-fMRI）。 <strong><em>数据预处理</em></strong> 所有MPRAGE、DSI及rs-fMRI数据的初始信号处理均采用连接组映射器（Connectome Mapper）流程（Daducci等，2012）完成。使用FreeSurfer软件（Desikan等，2006）从MPRAGE容积中分割灰质与白质，并将其划分为83个皮层及皮层下脑区。根据洛桑解剖学图谱，按照Cammoun等（2012）提出的方法，将上述脑区进一步细分为129、234、463及1015个近似等尺寸的亚区。DSI数据的重建遵循Wedeen等（2005）描述的流程，可实现每个体素内多个扩散方向的估计。扩散概率密度函数通过信号模的离散三维傅里叶变换进行重建。方向分布函数（Orientation Distribution Function, ODF）通过归一化后的三维概率分布函数的径向求和计算得到，因此ODF定义在离散球面之上，可捕捉每个方向上的扩散强度。 <strong><em>结构连接组</em></strong> 针对每位受试者，基于重建后的DSI数据，采用确定性流线型纤维束追踪技术估计结构连接矩阵，每个白质体素的每个扩散方向启动32条流线传播（Wedeen等，2008）。脑区之间的结构连接以纤维密度为衡量指标，定义为两个脑区之间的流线数量，经流线平均长度与两个脑区平均表面积归一化处理（Hagmann等，2008）。该归一化操作旨在补偿纤维束追踪过程中固有的长纤维偏倚，以及脑区尺寸差异带来的影响。数据集同时包含纤维数量与纤维长度信息。对于结构连接的量化指标，还计算了每个纤维束的广义各向异性分数（generalised fractional anisotropy, gFA，Tuch等，2004）与平均表观扩散系数（apparent diffusion coefficient, ADC，Sener等，2001）。 <strong><em>功能连接组</em></strong> 功能数据的预处理采用旨在便于后续网络探索的流程（Murphy等，2009；Power等，2012）。首先剔除前4个时间点，以使时间序列趋于稳定。随后对信号进行线性去趋势处理，并进一步回归生理混淆变量（白质与脑脊液回归因子）及运动伪影混淆变量（3个平移与3个旋转回归因子）。之后对信号进行空间平滑，并使用汉宁窗 sinc FIR滤波器进行0.01~0.1Hz频段的带通滤波。为获取不同图谱尺度下的脑区信号，将信号线性配准至MPRAGE图像，并在指定脑区内取平均（Jenkinson等，2012）。通过计算每对脑区之间的皮尔逊相关系数，得到功能连接矩阵。上述所有操作均在受试者原生空间中完成（Daducci等，2012；Griffa等，2017）。洛桑2008图谱5个尺度的大脑皮层FreeSurfer渲染结果可在https://github.com/jvohryzek/bert4lausanne2008获取。