We thank Erin Douglas, Anna Evans, and Carolyn Bellion for their contributions to participant recruitment and clinical assessment. We also thank Michael Casp, Zoe Englander, Justin Woodlief, and James Carter for their contributions to data collection and analysis, and Robert M. Hamer for consultation on statistical analysis and editing of the manuscript. Finally, we thank the individuals and their families who participated in this study. 
This study was supported by Conte center grant P50 MH064065 from the National Institute of Mental Health. Dr. Hart was supported by T32 HD040127 from the National Institute of Child Health and Human Development.

在这项研究中所使用的研究技术被批准的机构审查委员会杜克大学（IRB）和北卡罗来纳大学 - 教堂山分校。 1.成像任务设计<ol><li>生成呈现稀少目标刺激（圆）的更频繁标准刺激（加扰图像）的序列内的基于事件的行为的任务。的任务的示意图示于图1。出示使用CIGAL软件10的任务。 </li></ol><img alt="图1" src="/files/ftp_upload/51484/51484fig1.jpg" /> 图1.原理任务设计的，这个数字已经被修改哈特等人 20，许可。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/51484/51484fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol style="margin-left: 40px;"><li>选择作为厌恶刺激等和一组从国际情感图片系统数据库（IAPS）中性刺激的。 IAPS图像以反映觉醒和价11的水平在额定1-9。高数值表示较高正价和觉醒。选择一组是年龄相适应的研究组，如蛇，蜘蛛，或其他动物的照片图像。 注意:用于此研究的任务无关的厌恶刺激图像具有3.38（标准差= 1.78）和6.14（标准差= 2.08）的平均觉醒评分的平均价的评价。中性刺激的图像有6.21（SD = 0.26）和3.72（SD = 2.15）的平均觉醒等级的平均价。 </li><li>计划任务脚本，使得图像显示在一个伪随机的顺序为1500毫秒用500毫秒的平均刺激间的时间间隔。现在的目标刺激和任务无关的中性影像不超过频繁每15秒，使每个约4％的刺激。吉tter事件发生时间，以提供更好的分辨率的血流动力学响应函数。 </li></ol><ol start="2"><li>创建8套图像，一个用于每个的8个功能的运行，使得与会者都带有总共40个目标和40的任务无关的中性图像对所有8次操作过程。 </li></ol> 2.参与者设置和扫描<ol><li>招募儿童和青少年的9岁至18岁谁不是健康对照个人或谁在家族性高风险的精神病之间。 <ol><li>确保健康的人没有精神疾病或任何一级的家庭成员有精神疾病。确保家族性风险的参与者都至少有一个一级亲属（父母或兄弟姐妹）患有精神分裂症。不排除他们对其他精神疾病的一级亲属的存在。 </li><li>年龄和性别匹配的健康参与者家族危组参与者秒。 </li></ol></li><li>收购参与者知情同意18岁的未成年人超过，获取家长/监护人知情同意书。此外，收购未成年人参加学习谁写的同意。 </li><li>将在一个模拟的核磁共振成像扫描仪的参与者，以便与环境的熟悉他们。播放扫描仪噪音的录音，让他们完成任务的行为的实践运行，以确保他们了解任务的说明。 </li><li>将在核磁共振成像扫描仪的参与者，并获得必要的脑部扫描定位和/或解剖图像。 </li><li>使用MRI安全的输入框，告诉参与者按下一个按钮，与他们的食指针对所有目标刺激和另一个按钮与中指所有其他刺激。 </li><li>随着功能磁共振成像扫描，收集觉醒和价的参与者的一个子集，在研究中使用的图像的主观评价。该柯伦来自15个控制器和13家族高危T研究获得的评级。 </li></ol> 3.图像采集<ol><li>将参与者分为一个3.0特斯拉的核磁共振成像扫描仪。首先，获取了一组结构图像，包括一个3D共面解剖T1对比度图像使用一个被宠坏的梯度召回收购脉冲序列（TR的:5.16毫秒; TE:2.04毫秒，FOV:24厘米;图像矩阵:256×256;翻转角度:20;像素大小:0.94毫米×0.94毫米×1.9毫米; 68轴位片）。 </li><li>采用梯度回波平面回波成像序列全脑覆盖采集功能成像数据（TR:2000毫秒; TE:27毫秒; FOV:24厘米;图像矩阵:64×64;翻转角度:60;像素大小:3.75毫米×3.75毫米×3.8毫米; 34轴位片），使大脑的活动可以在行为任务的执行过程中进行测量。竞选行为的任务的每次运行该成像序列。每次运行应包括120成像时间点。 </li><li>目前TASK在8个功能运行时，每次持续约4分钟。 </li></ol> 4.分析<ol><li>图像预处理:开放式磁共振成像专家分析工具（技艺）的FSL 12。选择第一个层次的分析和预统计。 <ol><li> 在 "数据"选项卡中，选择输入图像的数量和进入路径每次你要处理的MR图像。设置输出目录。进入总体积，废旧收购的数量，以及TR。 </li><li>在"预统计 "选项卡上，设置动态校正MCFLIRT，空间平滑FWHM为5彩信， 和 " 切片定时校正"，选择"下注大脑提取"和"高通 "时间滤波，但不要选择B0解弯曲（UNESS你有一个梯度场地图）或"我ntensitiy normaization"。12,14。 </li><li> 在 " 注册"选项卡， 选择 "主STRUctural图像"。输入路径主体的头骨剥离T1加权像，用线性正常的搜索与至少6个自由度，选择的标准空间复选框，输入路径MNI图谱的图像，使用正常，线性搜索与12 DOF。 按 GO。 </li><li>排除参与者大于3毫米头部运动在X，Y或Z方向。 </li></ol></li><li> 1级:在一次运行中的任务条件之间的数据进行比较。开放式的壮举。选择"第一级分析"和 " 统计+后统计"。 <ol><li> 在数据选项卡，设置的输入数量，并输入路径到每个MR图像。输入"输出目录"的路径。 进入 " 总卷"，放弃收购的数量，以及TR。 </li><li>在" 统计信息 "选项卡，选择" 使用针对电影预先白化 "复选框16。按"全模式本身TUP"按钮。设置为任务条件的数量"原电动车的数量"。对于每个条件，"从双伽马HRF"卷积 "下拉菜单中选择17,18从基本形状下拉菜单和"自定义（3列格式 ）"，并选择包含任务进度的文本文件。 <ol><li>格式化在3列这个文本文件与对于给定类型的每个"事件"一个条目。第一列应包含的发作时间（以秒计），第二应包含的持续时间（以秒为单位），以及第三应包含该事件的重量。在对比与F检验标签，创建一个对比每个任务的条件，并为每个比较。 </li></ol></li><li>在"后统计"选项卡中， 选择 " 集群"中的" 阈值"下拉菜单中，并设置"Z门槛"和群P牛逼hreshold为2.3和0.05分别为8,19。 </li><li> 在 " 注册"选项卡， 选择 "主结构性形象"，输入路径主体的头骨剥离T1加权像。使用线性正常的搜索与至少6个自由度。 选择 " 标准空间"复选框。输入路径MNI图谱形象。使用正常的，线性的自由度12搜索。按"开始"。 </li></ol></li><li> 2级:比较运行之间的数据为每个任务的条件。开放式的壮举。选择从下拉菜单中选择"更高层次的分析"和"统计+后统计"。 <ol><li>在数据选项卡， 选择 " 输入是低级别FEAT目录 "。设置的输入的数量和输入路径到每个MR图像。输入"输出目录"的路径。 </li><li> 在 " 统计信息"选项卡，将" 混合效应:FLAME1"选择框"固定êffects"，按"模式设置向导"按钮，选择"单组平均"，然后单击"进程"按钮 。 </li><li>在"后统计 "选项卡中， 选择 " 集群"中的" 阈值 "下拉菜单中，并设置"Z 门槛 "和" 群P"门槛为2.3和0.05分别为8,19。按"开始"。 </li></ol></li><li> 3级:比较对象之间的数据在所有运行的每个任务的条件。开放式的壮举。选择从下拉菜单中选择" 更高层次的分析 "和" 统计+后统计 "。 <ol><li>在数据选项卡，选择" 输入是3D从FEAT目录应对图像。"设置的输入数量，并输入路径到每个MR图像。输入"输出目录 "的路径。 </li><li> 在 " 统计"TAB，按"全模式的设置"。设置电动汽车等于组变量和协变量如诊断组，年龄，性别等输入每个受试者的值（输入1 - 输入n）的数目的数目为每个EV。您可以使用"粘贴"窗口，以复制这些值的电子表格。 <ol><li> 在 " 对比与F-测试 "选项卡中，为每个测试变量和每个对比差异（例如，诊断组）添加对比。对于每个测试变量，设定由下的相应的EV选择该列中的值1的对比度。对于每一个相对，设置第一值1和第二为-1。选择"完成"。 </li></ol></li><li>在"后统计 "选项卡中， 选择 " 集群"中的"阈值"下拉菜单中，并设置"Z 门槛 "和 " 群P"门槛为2.3和0.05分别为8,19 </suP&gt;。按"开始"。 </li></ol></li></ol>

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Dr. Perkins is currently receiving grant support from Janssen, and is a consultant to Dainippon. In the past, Dr. Perkins is or has been on speaker's bureau for Eli Lilly and AstraZeneca. Dr. Perkins has previously received grants from AstraZeneca, Bristol-Myers Squibb, Otsuka, Eli Lilly, Janssen and Pfizer; and consulting and educational fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Glaxo Smith Kline, Forest Labs, Pfizer and Shire. All other authors declare no biomedical financial interests or potential conflict of interest.

The modified emotional oddball paradigm in the current study has been shown to elicit differences in neural recruitment during selective attention and emotional processing in children and adolescents at risk for schizophrenia. While existing paradigms using the emotional oddball task have been used to investigate neural changes in adult populations with psychiatric illness8, the current paradigm may be particularly useful for measurement of vulnerability markers in younger age groups. 
There are several challenges inherent in performing fMRI studies with children and adolescents, including ensuring that the task is appropriate in terms of difficulty and content and in minimizing motion artifacts. Critical steps in the protocol include step 2.2, which requires that participants have a mock scan and practice session prior to the fMRI session. This step is particularly helpful for improving participants&#8217; comfort and data quality. Additionally, the design of the behavioral task is critical to ensure that the task has an appropriate level of difficulty and that the selection of aversive images is appropriate for younger age groups. The current task design was successful in eliciting significant behavioral differences between the aversive and neutral conditions and had a moderate difficulty level for both high-risk and control groups. 
A limitation of this protocol was that the task did not elicit a significant difference in amygdala activation between the aversive and neutral conditions. There was significant amygdala activation during the aversive condition, but the difference was not significant when contrasted with neutral stimuli. This finding is likely due to the selection of children-appropriate stimuli. Future modifications of the task could examine effects of emotional facial expressions, which may produce more robust differences in amygdala activation between emotional and neutral conditions21. 
Other future applications of this technique include applying it to populations of children and adolescents who may be at risk for other psychiatric illnesses that may similarly affect executive and emotional processing. Several other psychiatric conditions, such as bipolar disorder and mood disorders, have been found to be associated with alterations in brain structure and function that reflect endophenotypes, or heritable markers associated with a disease22,23. This suggests the possibility that these intermediate changes in brain structure or function may potentially precede the onset of pathological symptoms in at-risk individuals. The use of the described paradigm in longitudinal studies and with children and adolescents may help to identify relevant endophenotypes for a particular condition to help to refine risk estimates.

Schizophrenia is a neurodevelopmental disorder with a known genetic component1,2 and with symptoms including deficits in both executive and emotional processing3,4. First-degree relatives are thought to be at an increased risk of developing schizophrenia, and have been shown to share some of these same neurocognitive deficits in both cognitive and social-emotional domains5. We therefore expect that brain activity in regions associated with executive and emotional processing may be altered in at-risk family members preceding the onset of clinical symptoms. 
Previous studies have indicated that both adults with schizophrenia and adults at familial high risk show aberrant activity within executive and emotional processing networks; however it remains unclear how these changes come about during development. Demonstrating that these changes occur early in life will be a critical first step in understanding the pathophysiology of the disorder. Therefore, this study utilizes an emotional oddball paradigm during functional MRI (fMRI) scanning in order to measure brain activity during the completion of a task that requires both executive and emotional processing in adolescents who are at risk for developing schizophrenia. Oddball paradigms are frequently used to examine the function of fronto-striate circuitry in schizophrenia6 and in individuals with familial high risk7 by measuring selective attention processes allocated to task-relevant target stimuli. Here, a standard oddball task has been modified to include task-irrelevant aversive and neutral stimuli that have been shown to elicit changes in brain activity in patients with schizophrenia8. 
This paper measures functional differences between healthy adolescents and adolescents at high familial risk for schizophrenia using an emotional oddball task. The task design is similar to that used by Fichtenholtz and colleagues9, but the selection of aversive emotional images has been modified to be appropriate for children between the ages of 9-18. The use of this task during functional MRI allowed for the identification of specific brain regions that showed patterns of hyperactivation and hypoactivation in children and adolescents with FHR for schizophrenia, in addition to age-related changes in neural activity during adolescent development.

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			<td class="xl63">3T MRI scanner</td>
			<td class="xl63">GE</td>
			<td class="xl63"></td>
			<td class="xl63">BIAC 3T scanner (replaced)</td>
		</tr>
	</tbody>
</table>

measurement of fronto-limbic activity using an emotional oddball task in children with familial high risk for schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing.

有基于人口统计特征20组无显着差异。行为数据表明，目标探测任务是在困难的9-18岁之间的儿童和青少年适当的水平。在目前的研究中，控制系统正确识别目标（SD = 0.14）82.36％，而家族高危人群正确识别目标（SD = 0.17），76.8％。两个组识别情绪的图像时相比，中性图片精度降低（F（1,40）= 5.63，p值= 0.03）。 成像数据表明，实验条件导致显著激活预期行政和情绪加工过程中被招募的区域。在目标的试验，并在右侧杏仁核，双侧眶额皮层，皮质呈梭形和视觉心病激活见于前额，前尾，孤芳自赏，和后顶叶区域期间两组厌恶试验蒂卡尔区域。表1示出显著活化在每种条件的控制区。 这种模式也引起在控制和有家族高风险的精神分裂症个体之间的激活显著的差异。该家族的高危人群呈下降激活额叶 - 纹状体电路响应目标刺激。控制，与此相反，显示该额中回和岛更大活化。条件之间的组间差异示于表 2和图2，家族性高风险组也表现出不同的年龄有关的激活模式，在响应控制目标和厌恶刺激（图3）相比较。 <img alt="图2" src="/files/ftp_upload/51484/51484fig2.jpg" /> 图组间差异2.激活图。（A）地区的家族高危组（n = 21）表现出比对照（n = 21）的目标处理过程中更大的激活。 CAUD =尾; IFG =额下回; ITG =颞下回。 （二）地区的控制表现出比家族性高危险群更大的激活目标处理过程中。 INS =岛; MFG =额中回; MTG =颞中回。 （C） 地方家族高危人群中厌恶&gt;中性对比激活多于对照组。 COC =环鳃盖骨皮质。 （四）凡在厌恶&gt;中性对比度控制激活超过了家族高风险组区域。 ACC =前扣带皮层; PC =楔前叶。这个数字已经被修改哈特等人20，许可。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/51484/51484fig2large.jpg" target="_blank">请点击此处查看该F的放大版本。</a>igure。 <img alt="图3" src="/files/ftp_upload/51484/51484fig3.jpg" /> 图3的年龄相关组差异激活地图。（A）的区带与年龄目标处理期间更大的正相关性的家族性高风险组比对照组中。 ACC =前扣带皮层; INS =岛; OFC =眶额皮层; TH =丘脑。 （二）地区与年龄对照比家族性高危人群中厌恶&gt;中性反差更大的正相关关系。 IFG =额下回; PostCG =中央后回; PreCG =中央前回。这个数字已经被修改哈特等人20，许可。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/51484/51484fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <table border="0" cellpadding="0" cellspacing="0"> &lt;TBODY&gt; <tr><td> ST1。组内激活疫源地对照组（n = 21） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td colspan="3"> MNI坐标</td><td></td><td></td></tr><tr><td>地区</td><td>半球</td><td> x </td><td> ÿ </td><td> ž </td><td>最大Z值</td><td>最大p值1 </td></tr><tr><td>目标激活（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>额中回/额极</td><td>乙</td><td> -30 </td><td> -2 </td><td> 50 </td><td> 5.57 </td><td> &lt;0.0000001 </td></tr><tr><td>额下回</td><td>乙</td><td> 46 </td><td> 12 </td><td> 32 </td><td> 5.41 </td><td> &lt;0.0000001 </td></tr><tr><td>岛</td><td>乙</td><td> -32 </td><td> 24 </TD&gt; <td> 0 </td><td> 5.4 </td><td> &lt;0.0000001 </td></tr><tr><td>中央前回</td><td>乙</td><td> -40 </td><td> -22 </td><td> 48 </td><td> 5.53 </td><td> &lt;0.0000001 </td></tr><tr><td>丘脑</td><td>乙</td><td> -12 </td><td> -16 </td><td> 12 </td><td> 5.03 </td><td> &lt;0.0000001 </td></tr><tr><td>尾</td><td>乙</td><td> -12 </td><td> 12 </td><td> 4 </td><td> 4.07 </td><td> 0.000003 </td></tr><tr><td>壳</td><td>乙</td><td> 18 </td><td> 8 </td><td> 2 </td><td> 4.27 </td><td> 0.00009 </td></tr><tr><td>前扣带/ Paracingulate回</td><td>乙</td><td> 0 </td><td> 12 </td><td> 46 </td><td> 5.6 </td><td> &lt;0.0000001 </td></tr><tr><td>后扣带回</td><td>乙</td><td> 8 </td><td> -16 </td><td> 28 </td><td> 5.2 </td><td> &lt;0.0000001 </td></tr><tr><td>高级/颞中回</td> &lt;TD&gt;乙</td><td> 48 </td><td> -46 </td><td> 10 </td><td> 5.88 </td><td> &lt;0.0000001 </td></tr><tr><td>梭形/颞下回</td><td>乙</td><td> -30 </td><td> -50 </td><td> -12 </td><td> 5.64 </td><td> &lt;0.0000001 </td></tr><tr><td>顶上小叶/缘上回/中央后回</td><td>乙</td><td>三十</td><td> -44 </td><td> 44 </td><td> 6 </td><td> &lt;0.0000001 </td></tr><tr><td>外侧枕叶皮层</td><td>乙</td><td> 48 </td><td> -62 </td><td> 12 </td><td> 6.12 </td><td> &lt;0.0000001 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>厌恶&gt;中性活化（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>额下回</td><td>大号</td><td> -44 </td><td> 14 </TD&gt; <td> 14 </td><td> 3.16 </td><td> 0.0004 </td></tr><tr><td>额极/内侧额叶皮质</td><td>乙</td><td> -2 </td><td> 64 </td><td> 0 </td><td> 3.42 </td><td> 0.0005 </td></tr><tr><td>中央后回</td><td>大号</td><td> -62 </td><td> -22 </td><td> 34 </td><td> 3.12 </td><td> 0.0004 </td></tr><tr><td>前扣带皮层</td><td>乙</td><td> -4 </td><td> 34 </td><td> 8 </td><td> 3.27 </td><td> 0.0002 </td></tr><tr><td>后扣带回</td><td>乙</td><td> 0 </td><td> -44 </td><td> 28 </td><td> 3.26 </td><td> 0.0002 </td></tr><tr><td>颞/梭状回</td><td>乙</td><td> -44 </td><td> -44 </td><td> -14 </td><td> 3.03 </td><td> 0.0006 </td></tr><tr><td>角回</td><td>乙</td><td> 46 </td><td> -64 </td><td> 8 </td><td> 3.42 </td><td> 0.0001 </td></tr><tr><td>缘上回</td><td>大号</td><td> -40 </td><td> -56 </td><td> 20 </td><td> 3.59 </td><td> 0.00005 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>厌恶的激活（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>杏仁核</td><td> ř </td><td> 22 </td><td> -4 </td><td> -18 </td><td> 2.86 </td><td> 0.001 </td></tr><tr><td>眶额皮层/岛</td><td>乙</td><td> 36 </td><td> 22 </td><td> -4 </td><td> 4.93 </td><td> &lt;0.0000001 </td></tr><tr><td>额中回</td><td>乙</td><td> 32 </td><td> 4 </td><td> 40 </td><td> 4.7 </td><td> &lt;0.0000001 </td></tr><tr><td>额极</td><td>乙</td><td> -38 </td><td> 36 </td><td> 10 </td><td> 4.95 </td><td> &lt;0.0000001 </td></tr><tr><td>前扣带/paracingulate回</td><td>乙</td><td> 6 </td><td> 16 </td><td> 50 </td><td> 4.85 </td><td> &lt;0.0000001 </td></tr><tr><td>后扣带回</td><td>乙</td><td> 2 </td><td> -28 </td><td> 24 </td><td> 5.88 </td><td> &lt;0.0000001 </td></tr><tr><td>丘脑</td><td>乙</td><td> 18 </td><td> -26 </td><td> 2 </td><td> 5.44 </td><td> &lt;0.0000001 </td></tr><tr><td>中央前回</td><td>乙</td><td> -44 </td><td> 8 </td><td> 34 </td><td> 4.54 </td><td> &lt;0.0000001 </td></tr><tr><td>顶上小叶</td><td>乙</td><td> -20 </td><td> -56 </td><td> 54 </td><td> 6.05 </td><td> &lt;0.0000001 </td></tr><tr><td>外侧枕叶皮层</td><td>乙</td><td> -36 </td><td> -82 </td><td> 4 </td><td> 6.05 </td><td> &lt;0.0000001 </td></tr><tr><td>枕极</td><td>乙</td><td> -16 </td><td> -90 </td><td> 18 </td><td> 5.18 </td&gt; <td> &lt;0.0000001 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> B，双侧</td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td></tr><tr><td> 1报告的 p值未经校正，显著在FDR校正值&lt;0.05 </td></tr></tbody></table> 表1.组内激活疫源地对照组（n = 21）。该表已经被修改哈特等人20，许可。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td>表2组间的激活差异</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td colspan="3"> MNI坐标</td><td></td><td></td></TR&gt; <tr><td></td><td>半球</td><td> x </td><td> ÿ </td><td> ž </td><td>最大Z值</td><td>最大p值1 </td></tr><tr><td>目标</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>家族性高风险&gt;对照组（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>额极</td><td>乙</td><td> 16 </td><td> 76 </td><td> 6 </td><td> 3.52 </td><td> 0.00007 </td></tr><tr><td>额下回</td><td>大号</td><td> -58 </td><td> 16 </td><td> 18 </td><td> 3.37 </td><td> 0.0001 </td></tr><tr><td>尾</td><td>乙</td><td> -14 </td><td> 20 </td><td> 10 </td><td> 3.2 </td><td> 0.0003 </td></tr><tr><td>颞下回</td><td>大号</td><td> -52 </td><td> -44 </td><td> -20 </td><td> 2.94 </td><td> 0.0009 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>控制&gt;家族性高风险（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>额中回/中央前回</td><td> ř </td><td> 48 </td><td> 8 </td><td> 34 </td><td> 3 </td><td> 0.0007 </td></tr><tr><td>额叶皮层厣</td><td>大号</td><td> -46 </td><td> 16 </td><td> -4 </td><td> 2.94 </td><td> 0.0009 </td></tr><tr><td>辅助运动区</td><td> ř </td><td> 18 </td><td> -16 </td><td> 40 </td><td> 3.02 </td><td> 0.0007 </td></tr><tr><td>岛</td><td>大号</td><td> -34 </td><td> -18 </td><td> 4 </td><td> 2.94 </td><td> 0.0009 </td></tr><tr><td>中央前回</td><td>乙</td><td> 10 </td><td> -26 </td><td> 60 </td&gt; <td> 3.29 </td><td> 0.0002 </td></tr><tr><td>中央后回</td><td>乙</td><td> 14 </td><td> -38 </td><td> 54 </td><td> 3.57 </td><td> 0.0001 </td></tr><tr><td>颞上回</td><td> ř </td><td> 54 </td><td> -6 </td><td> -4 </td><td> 3.18 </td><td> 0.0003 </td></tr><tr><td>颞中回</td><td> ř </td><td> 48 </td><td> -46 </td><td> 8 </td><td> 3.65 </td><td> 0.00004 </td></tr><tr><td>楔前叶</td><td> ř </td><td> 2 </td><td> -40 </td><td> 46 </td><td> 2.89 </td><td> 0.001 </td></tr><tr><td>外侧枕叶皮层</td><td>乙</td><td> -20 </td><td> -74 </td><td> 36 </td><td> 3.36 </td><td> 0.0002 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>厌恶 - 中性</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><tD&gt;家族性高风险&gt;对照组（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>中央鳃盖骨皮质</td><td> ř </td><td> 50 </td><td> -2 </td><td> 6 </td><td> 3.01 </td><td> 0.0007 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>控制&gt;家族性高风险（P &lt;0.05，错误发现率修正） </td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>前扣带皮层</td><td>大号</td><td> -6 </td><td> 38 </td><td> 8 </td><td> 2.68 </td><td> 0.002 </td></tr><tr><td>楔前叶</td><td>大号</td><td> -10 </td><td> -54 </td><td> 36 </td><td> 2.7 </td><td> 0.002 </td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> B，双侧</td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td><td rowspan="2"></td></tr><tr><td> 1报告的 p值未经校正，显著在FDR校正值&lt;0.05 </td></tr></tbody></table> 表2组间的激活疫源地的差异，该表已经被修改哈特等人20，许可。

Watch this Scientific Journal Video about Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia at JoVE.com

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR).&#160;FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

的额边缘活度测量在儿童使用情绪穿着或行为古怪的任务与家族性高风险的精神分裂症

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with ...

measurement-fronto-limbic-activity-using-an-emotional-oddball-task

Nanyang Technological University

Research

JoVE Journal

Behavior

8.8K 次观看.  University of North Carolina at Chapel Hill School of Medicine. This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR). FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

视频: Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

评估和高危新生儿的评价:新生儿重症监护病房的网络神经行为量表

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant.  The NICU Network Neurobehavioral Scale ...

科研

行为学

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&#239;ve Adolescents at High Risk for Psychosis

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of impaired neuromodulation of dopamine in fronto-striatal pathways. The traditional methods for identifying movement abnormalities include observer-based reports and force stability gauges. The drawbacks of these methods are long training times for raters, experimenter bias, large site differences in instrumental apparatus, and suboptimal reliability. Taking these drawbacks into account has guided the development of better&#160;standardized and more efficient procedures to examine movement abnormalities through handwriting analysis software and tablet. Individuals at&#160;risk for psychosis showed significantly more dysfluent pen movements (a proximal measure for dyskinesia) in a handwriting task. Handwriting kinematics offers a great advance over previous methods of assessing dyskinesia, which could clearly be beneficial for understanding the etiology of psychosis.

Handwriting analysis software significantly improves upon existing instruments measuring movement disorders. Individuals at&#160;risk for psychosis and healthy controls completed handwriting tasks to test for dyskinesia. Results suggest that youth at&#160;risk for psychosis exhibit dyskinesia and that handwriting analysis could significantly contribute to wider dissemination of early identification efforts

笔迹分析显示抗精神病药朴素青少年自发运动障碍的高风险精神病

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of ...

Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess children&#39;s cortical processing of light touch, speech sounds and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing children discomfort. To accomplish this we developed a dual channel, time and strength calibrated air puff stimulator that allows both tactile stimulation and sham control. We combined this with the use of event-related potential methodology to allow for high temporal resolution of signals from the primary and secondary somatosensory cortices as well as higher order processing. This methodology also allowed us to measure a multisensory response to auditory-tactile stimulation.

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess infants and children&#39;s cortical processing of light touch, speech sounds, and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing discomfort in vulnerable patients.

皮质听觉，触觉加工的残疾儿童定量评价

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology ...

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.&#160;
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how&#160;EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.&#160;

In recent years, there has been increasing interest in estimating the cortical sources of scalp measured electrical activity for cognitive neuroscience experiments. This article describes how high density EEG is acquired and how recordings are processed for cortical source estimation in children from the age of 2 years at the London Baby Lab.

高密度的脑电图记录在儿童的皮质来源分析

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aim to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of &#8220;to-be-suppressed&#8221; thoughts (&#8220;popping&#8221; back into conscious awareness) with a button press. During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.

We aim to identify the neural correlates underlying sustained and transient thought suppression, and thought re-emergence in controls, at-risk and depressed individuals. Activation was greatest for controls compared to the at-risk and the depressed group in the dorsolateral prefrontal cortex during thought suppression and anterior cingulate cortex during thought re-emergence.

设计的功能磁共振成像研究与实现研究思想抑制在年轻妇女，以及在风险，为抑郁症

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the ...

Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor learning and execution is of critical importance in order to understand the principles and processes that underlie motor function. Here we present a paradigm to study movement acquisition within a daily session of training (within-session) representing the fast learning component and primary acquisition as well as skilled motor learning over several training sessions (between-session) representing the slow learning component and consolidation of the learned task. This behavioral paradigm increases the degree of difficulty and complexity of the motor skill task due to two features: First, the animal realigns its body prior to each pellet retrieval forcing renewed orientation and preventing movement execution from the same angle. Second, pellets are grasped from a vertical post that matches the diameter of the pellet and is placed in front of the cage. This requires a precise grasp for successful pellet retrieval and thus prevents simple pulling of the pellet towards the animal. In combination with novel genetics, imaging and electrophysiological technologies, this behavioral method will aid to understand the morphological, anatomical and molecular underpinnings of motor learning and memory.

A paradigm is presented to analyze the acquisition of a high-precision skilled forelimb reaching task in rats.

收购高精度熟练的前肢到达任务大鼠

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor ...

Measuring Delay Discounting in Humans Using an Adjusting Amount Task

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. Delay discounting tasks are used to identify indifference points, which reflect equal preference for two dichotomous reward alternatives differing in both delay and magnitude. Indifference points are key to assessing the shape of a delay-discounting gradient because they allow us to isolate the effect of delay on value. For example, if at a 1 week delay and a maximum of $1,000, the indifference point is at $700 we know that, for that participant, a 1-week delay corresponds to a 30% reduction in value. This video outlines an adjusting amount delay-discounting task that identifies indifference points relatively quickly and is inexpensive and easy to administer. Once data have been collected, non-linear regression techniques are typically used to generate discounting curves. The steepness of the discounting curve reflects the degree of impulsive choice of a group or individual. These techniques have been used with a wide range of commodities and have identified populations that are relatively impulsive. For example, people with substance abuse problems discount delayed rewards more steeply than control participants. Although degree of discounting varies as a function of the commodity examined, discounting of one commodity correlates with discounting of other commodities, which suggests that discounting may be a persistent pattern of behavior1.

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. We outline a computer-based delay discounting task that is easy to implement and allows for the quantification of the degree of delay discounting in human participants.

测量延迟贴现在人类使用的调量任务

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. Delay discounting tasks ...

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The difference shows that people are affected by the emotional content conveyed by the carrier words even though they are irrelevant to the color-naming task at hand. The ESE has been widely deployed with patient populations, as well as with non-selected populations, because the emotion words can be selected to match the tested pathology. The ESE is a powerful tool, yet it is vulnerable to various threats to its validity. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them. The most prevalent threat to the validity of existing ESE studies is sustained effects and habituation wrought about by repeated exposure to emotion stimuli. Consequently, the order of exposure to emotion and neutral stimuli is of utmost importance. We show that in the standard design, only one specific order produces the ESE.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than those of neutral words. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them.

情绪Stroop任务:评估下暴露的认知表现的情感内容

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The ...

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug&#39;s pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task&#160;battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.

Human pain models are valuable tools used to assess the analgesic potential of novel compounds and predict their clinical efficacy, especially when used in an integrated manner. Although implementation of these models is complex, with proper execution, the pain models described in this protocol can provide predictive and reliable results.

确定疼痛的检测和容忍阈值使用集成的，多模式疼痛任务电池

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug&#39;s pharmacology and identify ...

A Novel Method for Involving Women of Color at High Risk for Preterm Birth in Research Priority Setting

Involvement of patients and the public is now recognized to be essential for the good conduct of research. Patient and public involvement in research priority setting and funding decisions is only beginning to be recognized as important, and methods for doing so are nascent. This protocol describes the Research Prioritization by Affected Communities (RPAC) protocol and findings from its use with women at high socio-demographic risk for preterm birth. The goal was to directly involve these women in identifying and prioritizing their unanswered questions about pregnancy, birth and neonatal care, and treatment so that their views could be included in research priority setting by funders and researchers. The RPAC protocol may be used to meaningfully involve under-represented groups at high-risk for specific health problems, or those who face disproportionate burden of disease, in research strategy and funding priority setting.

This manuscript describes the Research Prioritization by Affected Communities (RPAC) protocol and findings from its use with women at risk for preterm birth. Using the protocol, women identified and prioritized their unanswered questions about pregnancy, birth and neonatal care aimed at influencing research priority setting by funders and researchers.

一种新的方法, 让孕妇在研究中优先考虑早产高危因素

Involvement of patients and the public is now recognized to be essential for the good conduct of research. Patient and public involvement in research ...