The relationship between the caudate nucleus-orbitomedial prefrontal cortex connectivity and reactive aggression: A resting-state fMRI study
收稿日期: 2016-07-23 网络出版日期: 2018-06-01
Received: 2016-07-23 Online: 2018-06-01
作者简介 About authors
采用修改后的Taylor攻击范式, 将被试为虚拟对手选择的白噪音的惩罚强度作为反应性攻击的指标, 选取眶部内侧前额叶(Orbitomedial Prefrontal Cortex, OMPFC)作为种子点, 考察静息状态下正常人群OMPFC与其他脑区的连接及其与反应性攻击之间的关系。功能连接结果表明, 左侧OMPFC与右侧角回(Angular gyrus)、左侧OMPFC与双侧尾状核(Caudate nucleus)、右侧OMPFC与右侧尾状核的功能连接与反应性攻击显著负相关。格兰杰因果分析的结果进一步表明, 右侧尾状核到右侧OMPFC的效应连接与反应性攻击呈显著负相关, 尤其是与激发条件下的反应性攻击呈显著负相关。这表明, 静息状态下OMPFC与尾状核的连接与反应性攻击有着密切的关系。
采用修改后的Taylor攻击范式, 将被试为虚拟对手选择的白噪音的惩罚强度作为反应性攻击的指标, 选取眶部内侧前额叶(Orbitomedial Prefrontal Cortex, OMPFC)作为种子点, 考察静息状态下正常人群OMPFC与其他脑区的连接及其与反应性攻击之间的关系。功能连接结果表明, 左侧OMPFC与右侧角回(Angular gyrus)、左侧OMPFC与双侧尾状核(Caudate nucleus)、右侧OMPFC与右侧尾状核的功能连接与反应性攻击显著负相关。格兰杰因果分析的结果进一步表明, 右侧尾状核到右侧OMPFC的效应连接与反应性攻击呈显著负相关, 尤其是与激发条件下的反应性攻击呈显著负相关。这表明, 静息状态下OMPFC与尾状核的连接与反应性攻击有着密切的关系。
Reactive aggression has been widely concerned by researchers because of its serious impact on society, such as violent crimes. Existing neuroimaging studies using patients with high levels of aggression indicated a network of brain regions subserve reactive aggression, including amygdala, caudate nucleus, and orbitofrontal cortex. Furthermore, researchers believed that reduced prefrontal activity along with heightened subcortical activity in the context of provocative stimuli poses an increased risk for reactive aggression. However, evidence for this theory in healthy population is lacking, especially this independently of the experiment task. In this study, the modified TAP was used and the punishment levels selected for the virtual opponents serve as indicator of reactive aggression. Based on the previous researches, Orbitomedial Prefrontal (OMPFC) was selected as the seed to investigate the relationship of reactive aggression and the connectivity between OMPFC and other brain regions using resting state fMRI. Thirty-night undergraduates (mean age = 20.05 ± 0.92 years old) were enrolled in the experiment. The resting state functional magnetic resonance (rs-fMRI) data was acquired using Echo Planar Imaging (EPI) sequence from a 3-T Siemens Magnetom Trio scanner (Siemens Medical, Erlangen, Germany). This scanning acquired 242 volumes with TR = 2 s (lasting 8 min and 8 sec). rs-fMRI data was processed and analyzed using the REST (Resting-State fMRI Data Analysis Toolkit) toolbox to calculate Functional Connectivity (FC) and Granger Causality Analysis (GCA), which reflects the functional and effective connectivity among different areas, respectively. The results of FC indicated that the functional connectivity between the left OMPFC and right angular gyrus, left OMPFC and bilateral caudate nucleus, right OMPFC and right caudate nucleus were significantly correlated with the reactive aggression. Furthermore, the follow-up GCA indicated that the effective connectivity of right caudate nucleus to the right OMPFC was correlated significantly with reactive aggression, especially in the provocative condition. The caudate nucleus plays an important role in flexibly responding to the environment. It is activated in response to reward. When the individuals thought the aggression was valuable and seemed to receive reward after the aggression, the caudate nucleus was also activated. Furthermore, a study combined PET and fMRI and revealed a strong relationship between the caudate nucleus and cortical areas associated with executive functioning (i.e., the function of prefrontal cortex). Another study demonstrated that violent offenders behaved more aggressively and showed significantly higher brain reactivity to provocations within the caudate nucleus, as well as reduced caudate nucleus-prefrontal cortex connectivity. To sum up, these results suggest that the connectivity between OMPFC and caudate nucleus is closely related to reactive aggression. It provides some evidence for further revealing the neural mechanism of reactive aggression, and firstly made a systematic analysis of reactive aggression using resting state functional connectivity and effective connectivity.
Reactive aggression has been widely concerned by researchers because of its serious impact on society, such as violent crimes. Existing neuroimaging studies using patients with high levels of aggression indicated a network of brain regions subserve reactive aggression, including amygdala, caudate nucleus, and orbitofrontal cortex. Furthermore, researchers believed that reduced prefrontal activity along with heightened subcortical activity in the context of provocative stimuli poses an increased risk for reactive aggression. However, evidence for this theory in healthy population is lacking, especially this independently of the experiment task.
In this study, the modified TAP was used and the punishment levels selected for the virtual opponents serve as indicator of reactive aggression. Based on the previous researches, Orbitomedial Prefrontal (OMPFC) was selected as the seed to investigate the relationship of reactive aggression and the connectivity between OMPFC and other brain regions using resting state fMRI. Thirty-night undergraduates (mean age = 20.05 ± 0.92 years old) were enrolled in the experiment. The resting state functional magnetic resonance (rs-fMRI) data was acquired using Echo Planar Imaging (EPI) sequence from a 3-T Siemens Magnetom Trio scanner (Siemens Medical, Erlangen, Germany). This scanning acquired 242 volumes with TR = 2 s (lasting 8 min and 8 sec). rs-fMRI data was processed and analyzed using the REST (Resting-State fMRI Data Analysis Toolkit) toolbox to calculate Functional Connectivity (FC) and Granger Causality Analysis (GCA), which reflects the functional and effective connectivity among different areas, respectively. The results of FC indicated that the functional connectivity between the left OMPFC and right angular gyrus, left OMPFC and bilateral caudate nucleus, right OMPFC and right caudate nucleus were significantly correlated with the reactive aggression. Furthermore, the follow-up GCA indicated that the effective connectivity of right caudate nucleus to the right OMPFC was correlated significantly with reactive aggression, especially in the provocative condition.
The caudate nucleus plays an important role in flexibly responding to the environment. It is activated in response to reward. When the individuals thought the aggression was valuable and seemed to receive reward after the aggression, the caudate nucleus was also activated. Furthermore, a study combined PET and fMRI and revealed a strong relationship between the caudate nucleus and cortical areas associated with executive functioning (i.e., the function of prefrontal cortex). Another study demonstrated that violent offenders behaved more aggressively and showed significantly higher brain reactivity to provocations within the caudate nucleus, as well as reduced caudate nucleus-prefrontal cortex connectivity. To sum up, these results suggest that the connectivity between OMPFC and caudate nucleus is closely related to reactive aggression. It provides some evidence for further revealing the neural mechanism of reactive aggression, and firstly made a systematic analysis of reactive aggression using resting state functional connectivity and effective connectivity.
江琦, 侯璐璐, 邱江, 李长燃, 王焕贞.
JIANG Qi, HOU Lulu, QIU Jiang, LI Changran, WANG Huanzhen.
反应性攻击(reactive aggression)是指在被激惹后产生的冲动的、不假思索的指向另一个人并对其造成伤害的行为(Anderson & Bushman, 2002)。由于反应性攻击会造成很大的社会危害, 因而受到社会学、心理学等多学科的广泛关注(Herpertz et al., 2017; McEwen & McEwen, 2017; Fite, Rubens, Preddy, Raine, & Pardini, 2014)。近年来, 研究者试图采用事件相关电位、脑成像等方法对反应性攻击的神经机制进行探讨。已有对具有较高攻击性的病人以及正常人进行的脑成像研究表明, 可能存在一个网络与反应性攻击相关, 这个网络包括杏仁核(Amygdala; McCloskey et al., 2016)、尾状核(Glenn & Yang, 2012)和OMPFC (Beyer, Münte, Göttlich, & Krämer, 2015)。研究者进一步指出降低的前额叶皮层的活动与升高的皮层下脑区的活动(如杏仁核、尾状核) 可能共同导致了反应性攻击的发生(Rosell & Siever, 2015; Siever, 2008; Nelson & Trainor, 2007), 也就是说反应性攻击的产生可能源于前额叶皮层与皮层下脑区的功能连接失调。
已有研究或者根据相关研究(如Coccaro, McCloskey, Fitzgerald, & Phan, 2007), 或者通过对比攻击性较强的病人、罪犯与正常人群的大脑活动差异(如Motzkin, Newman, Kiehl, & Koenigs, 2011)来推论反应性攻击的神经机制, 这些探索虽然为揭示反应性攻击的神经机制起到了重要的启示作用, 但是尚不能提供直接的实证证据加以证实。究其原因, 在于反应性攻击的发生涉及多个心理过程(Bettencourt, Talley, Benjamin, & Valentine, 2006; Ramirez & Andreu, 2006), 这无疑为揭示其神经机制造成了很大的困难。因此, 近年来一些研究者开始尝试运用经典的攻击范式及其变式来探讨反应性攻击的神经机制, 其中, Taylor攻击范式(Taylor Aggression Paradigm, TAP; Taylor, 1967)是应用较为广泛的一种经典的攻击范式(Riva et al., 2017; Liu, Teng, Lan, Zhang, & Yao, 2015)。在经典的Taylor攻击范式中, 主试安排被试与另一个(虚假)对手进行反应时任务的竞赛, 每次竞争中速度快的一方可以为速度慢的一方施加电击(或噪音), 然后根据施加的电压或者噪音强度来判断被试的反应性攻击。已有研究表明, 该范式具有良好的效度(Giancola & Parrott, 2008)。2007年, Krämer, Riba, Richter和Münte进而把Taylor攻击范式中的虚假对手增加为两个, 分别对应激发与非激发条件, 从而可以有效分析激发条件对被试反应性攻击的影响。但是, 综合分析近年来针对正常人群的利用Taylor范式及其变式对反应性攻击的神经机制进行的研究(Beyer, Münte, Erdmann, & Krämer, 2014; Beyer et al., 2015; Krämer, Rib, Richter, & Münte, 2011; Krämer, Jansma, Tempelmann, & Münte, 2007; Lotze, Veit, Anders, & Birbaumer, 2007)可以发现, 这类研究的实验设置都各有不同, 甚至同一个课题组基于研究目的不同也对同一范式做了不同程度的修改, 因此得到的结论各不相同, 并且难以直接进行比较。那么, 是否可以找到一种稳定的指标, 通过找到其与反应性攻击的关系, 进而探讨反应性攻击的神经机制呢?已经较为成熟的静息态功能磁共振技术为我们提供了新的思路。
静息态功能磁共振具有不受实验任务的限制和制约、能够可靠地测量到大脑内在的自发活动等优势(Zuo et al., 2010), 被广泛应用于健康被试与病人的研究中, 以用于发现个体在静息状态下大脑活动情况与某些疾病、特质以及行为的关系(Fulwiler, King, & Zhang, 2012; Wu et al., 2011; Greicius et al., 2007)。功能连接的方法普遍被用来探索脑区之间的联系以及这种联系与某种特定的心理和行为之间的关系(Takeuchi et al., 2012; Zeng et al., 2012; Hahn et al., 2011)。近年来, 该方法在攻击性相关领域也获得了一些有意义的结果, 例如Hoptman等(2010)的研究表明, 比起正常个体, 患有精神分裂症的病人的杏仁核与腹侧前额叶的功能连接降低, 并且功能连接的强度与攻击性呈负相关关系。
然而, 上述研究均是采用相关分析的方法考察脑区之间的协同工作, 还不能反映脑区之间信息的输入输出方向等关系。因此, 有研究者进一步认为广义的功能连接应该分为(狭义的)功能连接(Functional Connectivity, FC)与效应连接(Effective Connectivity, EC)。关于效应连接的分析中, 格兰杰因果分析(Granger Causality Analysis, GCA)受到研究者们的广泛关注和青睐。它主要是利用多重线性回归的方法考察某个脑区在过去某一时间点的活动是否可以反映现在另外一个脑区的活动情况, 可以揭示脑区之间单向的因果关系(Hamilton, Chen, Thomason, Schwartz, & Gotlib, 2011; Chen, Hamilton, Thomason, Gotlib, & Saad, 2009)。
Coccaro, Sripada, Yanowitch和Phan (2011)基于以往研究指出, OMPFC与反应性攻击密切相关。OMPFC能对攻击冲动进行有效调控, Pietrini, Guazzelli, Basso, Jaffe和Grafman (2000)给被试呈现一系列的场景要求被试抑制或者表达对侵犯者的攻击, 结果显示当被试抑制攻击冲动时, OMPFC激活程度增强。而OMPFC损伤的病人不能对敌意反应进行调节(Koenigs & Tranel, 2007), 脾气变得暴躁(Damasio, Grabowski, Frank, Galaburda, & Damasio, 1994)。OMPFC还与社会情绪信息加工相关, Beyer等(2015)的研究通过在TAP范式的决策阶段之前增加面孔(愤怒或者中性), 来考察愤怒在反应性攻击中的作用, 结果显示呈现愤怒面孔时, OMPFC的激活程度与反应性攻击负相关显著, 这表明OMPFC对社会情绪信息(即, 情绪面孔)的反应可以预测其随后的反应性攻击行为。New等(2007)在比较有边缘人格障碍的个体与正常个体的大脑活动情况时发现, 比起那些有边缘性人格障碍的个体, 正常个体的OMPFC与杏仁核之间的“耦合”更强。此外, 比起正常的个体, 当看到愤怒的面孔时, 患有间歇性爆发障碍的个体(攻击性较强)OMPFC与杏仁核之间的功能连接下降(Coccaro et al., 2007)。da Cunha- Bang等(2017)研究显示, 比起正常人, 暴力罪犯在受到敌意激发后, 反应性攻击更强, 尾状核和杏仁核的激活强度升高, 并且尾状核-前额叶以及杏仁核-前额叶的功能连接降低。以上研究都显示OMPFC与反应性攻击密切相关, 可以对敌意反应以及攻击冲动进行抑制, 并且和杏仁核、尾状核等皮层下脑区的连接也在反应性攻击中起着重要作用。另外, TAP范式由于虚假对手的设置使得被试在实验过程中处于一种“竞争和人际对抗”的背景下(Giancola & Parrott, 2008), 具有较强的社会互动性, 而OMPFC在社会情绪信息加工、情绪性决策方面, 尤其是社会互动背景下发挥重要作用(Rudebeck, Bannerman, & Rushworth, 2008), 因此OMPFC可以作为本研究的种子点。
综上所述, 本研究拟选取OMPFC作为种子点, 首先运用静息态功能连接方法探索眶部内侧前额叶-皮层下脑区的功能连接及其与反应性攻击的关系; 其次, 进一步运用格兰杰因果模型分析探讨静息状态下眶部内侧前额叶-皮层下脑区的效应连接及其与反应性攻击的关系。基于以往的研究结果(da Cunha-Bang et al., 2017; Coccaro et al., 2007; New et al., 2007), 我们假设OMPFC与皮层下脑区(例如, 杏仁核、尾状核)的连接与反应性攻击负相关, 即当OMPFC与皮层下脑区的连接较强时, 个体反应性攻击较低; 反之, 当OMPFC与皮层下脑区的连接较弱时, 个体反应性攻击较强。在理论层面, 本研究利用静息态功能磁共振技术的特点避开了任务态功能磁共振研究因受任务设置不同而导致的结论分歧的不足, 直接为前额叶皮层-皮层下脑区功能连接与反应性攻击的关系研究提供了新的实证证据, 为全面揭示反应性攻击的神经机制提供了重要的基线资料。在实践层面, 本研究可以为针对高反应性攻击倾向个体在认知神经层面的预测和诊断提供理论指导。
本研究随机选取了43名健康右利手在校大学生, 其中男性19名, 女性23名, 年龄18~22岁(20.05 ± 0.92)。所有被试视力或者校正视力正常, 无色盲, 无精神疾病史和手术外伤史。本实验通过了西南大学脑成像中心伦理委员会批准, 与所有被试签订了知情同意书, 并在实验结束后给予一定的报酬。
本研究采取了被广泛使用的Taylor攻击范式(Taylor Aggression Paradigm, TAP), 行为学数据采集实验采用E-prime 2.0进行。图1呈现了单个试次的流程, 首先在屏幕上出现一个时间为8 s的注视点“+”, 然后屏幕上会出现此次的竞争对手(1号或者2号), 在此过程中, 被试需要通过按键做出为1~8的强度的噪音惩罚的选择
需要注意的是, 在整个实验过程中并没有真正的两位对手与被试共同完成竞争反应时任务, 所有的反馈都是电脑按如下参数进行设置的结果：对手1总是做出强度为1~4的选择, 平均为2.0, 为非激发条件; 对手2总是做出5~8的选择, 平均为6.5, 为激发条件。为了使实验更具有真实性, 将实验分为3个run进行, 每个run中包括20个trials, 被试成功的次数占一半。为了增加反馈结果的真实性, 我们参考以往研究(Maren, 2001), 对反馈结果的出现做了如下设置：在第一个run, 被试与1号对手的竞争中胜利3次, 失败7次, 被试与2号对手的竞争中胜利7次, 失败3次; 在第二个run, 被试与1号对手的竞争中胜利5次, 失败5次, 被试与2号对手的竞争中胜利5次, 失败5次; 在第三个run, 被试与1号对手的竞争中胜利7次, 失败3次, 被试与2号对手的竞争中胜利3次, 失败7次, 即随着实验的进行, 被试受到的惩罚越来越大。
被试进入实验室后, 首先签署知情同意书。然后由主试介绍实验程序, 被试在扫描室外完成练习实验, 确保被试了解指导语并且能正确做出反应, 然后由扫描员将其送入扫描室, 依次进行静息态、任务态和结构像的扫描
MRI数据采集使用西门子3.0T磁共振扫描仪(Siemens Medical, 德国), 被试的头部使用MRI兼容的泡沫垫固定以减少头动。扫描前, 让被试更换实验室专用服装, 以避免衣服上的金属物体对被试安全和成像质量的影响, 同时取下被试佩戴的金属首饰或者假牙等。在结构像和静息态扫描的过程中, 都要求被试睁开眼睛看屏幕上的注视点, 保持头部不要发生移动, 不要想特殊的事情。
T1加权结构像使用磁化准备快递采集梯度回波序列(magnetization-prepared rapid acquisition gradient echo, MPRAGE)采集, 具体扫描参数为：重复时间(repetition time, TR) = 2600 ms, 回波时间(echo time, TE) = 3.02 ms, 反转角(flip angle) = 8°, 层厚(slice thickness) = 1.0 mm, 矩阵(matrix) = 256 × 256, 体素大小(voxel size) = 1 mm × 1 mm × 1 mm, 扫描176层覆盖全脑。
静息态数据使用EPI (gradient-echo planar imaging, EPI)序列采集, 具体扫描参数为：重复时间(repetition time, TR) = 2000 ms, 回波时间(echo time, TE) = 30 ms, 反转角(flip angle) = 90°, 层厚(slice thickness) = 3 mm, 层间距(slice gap) = 1 mm, 矩阵(matrix) = 64 × 64, 体素大小(voxel size) = 3.4 mm × 3.4 mm × 4 mm, 层数(slices) = 32, 扫描时间为8分钟零4秒, 共获得242个时间点的图像。
为了检验激发条件实验操作的有效性, 将两种条件下被试为对手选择的惩罚强度进行配对样本t检验, 然后将被试选择的惩罚等级的平均数作为被试反应性攻击的指标。
利用REST (Song et al., 2011)的工具包下的FC工具计算OMPFC与全脑的功能连接(voxel-wise), 之后使用SPM8的多元回归(multiple regression)模型分析方法计算OMPFC与全脑的功能连接(voxel- wise)与反应性攻击相关的脑区, 其中被试的性别、年龄作为协变量回归掉。接下来, 将上一步中显著的区域保存为ROI, 利用REST工具包下的FC工具计算双侧OMPFC与这些ROI的FC值(ROI-wise), 计算FC值与反应性攻击的Pearson相关系数; 最后, 利用REST工具包下的GCA工具计算这些ROI与OMPFC的GCA值(ROI-wise), 计算GCA值与反应性攻击的Pearson相关系数。
需要注意的是, 由于FC值不符合正态分布, 因此涉及到功能连接的两步, 我们均进行了Fisher-z转换, 并且利用z转化后的值用于进一步的分析。另外, 由于脑成像数据分析过程中存在多重比较而使结果带有误差, 因此在全脑分析中, 使用体素水平p < 0.001, 团块水平p < 0.05(使用FDR进行多重比较校正), 团块大小(cluster sizes) > 20体素作为阈值。
所有行为数据采用SPSS 16.0进行分析。对激发与非激发条件下被试选择的惩罚强度进行配对样本t检验的结果表明, 激发条件下被试为对手选择的惩罚强度显著高于非激发条件下选择的惩罚强度：激发条件：M = 3.91, SD = 1.71, 非激发条件：M = 3.11, SD = 1.49; t(38) = 3.44, p < 0.01, Cohen’ d = 0.55。
将OMPFC与全脑的功能连接进行多元回归分析, 其中性别和年龄作为协变量控制。结果表明, 左侧OMPFC与右侧角回、双侧尾状核以及双侧内侧前额叶的功能连接与反应性攻击相关显著, 右侧OMPFC与右侧尾状核以及右内侧前额叶的功能连接与反应性攻击相关显著, 见表1。由于内侧前额叶不属于皮层下脑区, 因此后续的分析只针对左侧OMPFC与尾状核、角回以及右侧OMPFC与尾状核的功能连接与反应性攻击的关系。
|角回||右||48, -63, 51||51||5.58|
|尾状核||左||-12, 15, 3||30||4.85|
|右||18, -15, 21||27||4.37|
|内侧前额叶||右||33, 48, -6||74||5.66|
|右||51, 30, 33||32||4.95|
|左||-42, 48, 3||88||4.55|
|尾状核||右||12, 0, 15||54||4.41|
|内侧前额叶||右||33, 51, -6||69||5.92|
|右||42, 33, 39||48||4.75|
|左||-36, 45, 3||45||4.32|
注：体素水平p < 0.001, 团块水平p < 0.05 (使用FDR进行多重比较校正), 团块大小(cluster sizes) > 20。
为了考察双侧OMPFC与皮层下脑区的功能连接与反应性攻击的关系, 我们进一步提取上一步中显著的皮层下脑区与OMPFC的功能连接值与反应性攻击做Pearson相关。结果显示, 左侧OMPFC与右侧角回(r = -0.44, p < 0.005, 见图2)、左侧OMPFC与左侧尾状核(r = -0.53, p < 0.001, 见图3)、左侧OMPFC与右侧尾状核(r = -0.59, p < 0.001, 见图4)以及右侧OMPFC与右侧尾状核(r = -0.61, p < 0.001, 见图5)的FC值与反应性攻击均显著负相关, 并且不受激发条件的影响(即各功能连接值与两种激发条件下被试的反应性攻击负相关均显著, p < 0.05)。各功能连接值与反应性攻击的相关矩阵如表2所示。
注：表格中所有的数值均为该行所对应的功能连接值与该列所对应的行为指标的Pearson相关系数, *p < 0.05, **p < 0.01, ***p < 0.001。
由于功能连接反映的是脑区之间的相关关系, 不能反映信息输入输出的方向, 因此我们进一步采用GCA考察脑区之间效应连接的异常与反应性攻击之间的关系。由于ROI水平的GCA分两种情况, 即信息输入和信息输出, 上述4个功能连接一共产生8种因果关系。即左侧OMPFC→左侧尾状核、左侧OMPFC→右侧尾状核、左侧OMPFC→右侧角回、右侧OMPFC→右侧尾状核、左侧尾状核→左侧OMPFC、右侧尾状核→左侧OMPFC、右侧角回→左侧OMPFC以及右侧尾状核→右侧OMPFC。GCA分析的结果显示, 只有右侧尾状核→右侧OMPFC的效应连接与反应性攻击显著负相关(r = -0.36, p < 0.05), 其他效应连接与反应性攻击均不相关(ps > 0.05), 如图6所示。进一步对激发、非激发条件下的反应性攻击与右侧尾状核→右侧OMPFC的GCA值进行相关分析, 结果表明, 右侧尾状核→右侧OMPFC与激发条件下的反应性攻击显著负相关(r = -0.33, p < 0.05), 而与非激发条件下的反应性攻击相关不显著(r = -0.31, p > 0.05)。效应连接值与反应性攻击的相关矩阵如表3所示, 散点图如图6所示。
注：表格中所有的数值均为该行所对应的效应连接值与该列所对应的行为指标的Pearson相关系数, *p < 0.05, **p < 0.01, ***p < 0.001。
研究通过采用TAP变式, 运用高空间分辨率的功能磁共振成像技术, 探索性地对反应性攻击的神经机制进行了功能连接和效应连接分析, 为进一步理解反应性攻击的本质提供了实证支持。在功能连接分析中, 我们发现右侧角回、双侧尾状核与左OMPFC的功能连接以及右侧尾状核与右OMPFC的功能连接与反应性攻击相关显著。在进一步的格兰杰因果分析中, 我们发现右侧尾状核到右侧OMPFC的效应连接在反应性攻击中起着重要的作用, 这与以往采用任务态功能磁共振技术的研究中发现前额叶皮层以及尾状核在反应性攻击中起着重要作用的结果相一致(Krämer et al., 2007), 并且使用静息态功能磁共振的手段对已有研究进行有益补充。
OMPFC在情绪相关的决策, 尤其在社会互动背景下的情绪性决策中起着重要的作用(Rudebeck et al., 2008), 如在Gage个案以及一些类似案例中, 当OMPFC受损之后, 个体变得暴躁、攻击性强(Blair, 2012; Damasio et al., 1994)。具体而言, OMPFC与攻击冲动、敌意反应的抑制有关(Koenigs & Tranel, 2007; Pietrini et al., 2000)。在本研究中, 我们选取OMPFC作为种子点考察正常人群OMPFC与其他脑区的关系在反应性攻击中的作用, 结果发现OMPFC与尾状核的连接与反应性攻击相关显著, 这说明不仅OMPFC损伤的病人反应性攻击增多, 而且在正常人群中, OMPFC与尾状核的连接也与反应性攻击密切相关。因此, 在本研究中选取OMPFC作为种子点, 有效地反映了前额叶皮质与其他脑区的协同作用在反应性攻击中的作用。
尾状核是确保个体灵活应对环境的重要区域, 对奖赏的事件或者信号做出反应而对不带奖赏性质的信号则没有反应(Zink, Pagnoni, Martin-Skurski, Chappelow, & Berns, 2004)。然而, 有几种类型的非奖赏刺激也可以激活尾状核, 这表明尾状核能够编码所有显著刺激, 因为虽然这些刺激本身不具有奖赏的性质, 但是被个体认为是具有奖赏性质的(Zink, Pagnoni, Martin, Dhamala, & Berns, 2003)。研究者采用任务态功能磁共振技术探讨反应性攻击的神经机制时进一步发现了, 尾状核的激活可能与实施反应性攻击这一行为被个体认知为一种奖赏信号有关。例如, Krämer等人(2007)的研究采用TAP和任务态fMRI发现了尾状核的激活程度与被试为对手选择的惩罚强度成正相关关系, 也就是说当被试为虚拟对手选择了更大的惩罚等级时, 尾状核被显著激活。Beyer等人(2014)的研究也表明, 尾状核的激活程度与反应性攻击之间有着相关关系。另外一项研究发现早期反馈阶段尾状核的激活情况预测了后期决定阶段反应性攻击的强度(Krämer et al., 2011)。这些使用TAP的研究一致地发现了尾状核在反应性攻击产生过程中的作用, 当反应性攻击行为被认为是受到奖赏时则尾状核得到激活。
其他研究采用奖赏相关的任务发现, 患有与攻击性增强有关的精神疾病或者人格障碍的个体对奖赏的敏感性增强。例如, Völlm等(2007)对有反社会人格或者边缘人格障碍的个体以及正常个体进行研究, 在任务中对被试的某些反应给予奖赏而对另外一部分反应则不给奖赏, 研究结果显示, 对比奖赏与非奖赏条件(即奖赏-非奖赏), 有人格障碍的个体比正常控制组的个体的尾状核活动更低。随后的两项研究进一步证明, 这种有人格障碍的人之所以在奖赏和非奖赏条件下的尾状核活动差异减小, 是由于其在非奖赏条件下的活动高于正常群体所导致的(Gatzke-Kopp et al., 2009; Finger et al., 2008)。也就是说, 对于正常被试来讲, 在奖赏条件下尾状核激活, 而在非奖赏条件下, 尾状核激活强度下降或者不被激活; 而对于患有人格障碍的个体(例如, 边缘性人格障碍等)来说, 在奖赏和非奖赏条件下尾状核都被激活。综上, 尾状核的激活与反应性攻击密切相关, 那些攻击性较强的个体对奖赏的敏感性增强, 当刺激不具有奖赏性质时, 尾状核仍然激活, 甚至, 当实施反应性攻击被认为“受到了奖赏”时, 尾状核也会相应地被更大程度激活。
在发现与反应性攻击相关的关键脑区的基础上, 越来越多的研究者指出反应性攻击的产生是由于前额叶皮层与皮层下脑区功能连接失调引起的(Rosell & Siever, 2015; Siever, 2008; Nelson & Trainor, 2007)。一项研究同时使用了正电子断层扫描(Positron Emission Tomography, PET)和任务态功能磁共振技术的技术发现了尾状核和执行功能区域之间在结构和功能上都存在着很强的联系(Grahn, Parkinson, & Owen 2009)。da Cunha-Bang等人(2017)采用点减攻击范式(point subtraction aggression paradigm, PSAP)比较正常个体和暴力罪犯在受到敌意激发(输掉代金币)后大脑的活动情况, 结果显示比起正常个体, 暴力罪犯在受到敌意激发后, 反应性攻击更强, 尾状核的激活强度升高, 并且尾状核-前额叶的功能连接降低。我们的研究结果一致的发现了, 在正常群体中, 尾状核-前额叶(主要是OMPFC)的功能连接与反应性攻击负相关。
此外, 由于功能连接分析只能得到脑区之间的相关关系, 而无法确定影响方向的问题, 也就是说反应性攻击的增加到底是由于尾状核对OMPFC自下而上信息传递存在问题还是由于OMPFC对尾状核自上而下的调控功能不足导致的呢?因此, 在功能分析的基础上, 我们进一步使用格兰杰因果分析对效应连接与反应性攻击的关系进行探讨。结果表明, 右侧尾状核到右侧OMPFC的效应连接与反应性攻击呈显著的负相关关系, 右侧尾状核到右侧OMPFC的GCA值越大, 则反应性攻击越弱。因此, 我们推测反应性攻击的增强是由于个体大脑内部尾状核对OMPFC的自下而上的信息传递出现问题导致的。鉴于没有直接的相关研究可以对此作出解释, Sagvolden, Johansen, Aase和Russell (2005)关于注意缺损障碍(Attention Deficit Hyperactivity Disorder, ADHD)的理论为我们提供了新的思路, 他们认为ADHD的发生与多巴胺系统的信号传递失调有关。后来该理论也被用来解释其他行为问题的产生, 如外部行为障碍(Externalizing Behavior Disorders; Shannon, Sauder, Beauchaine, & Gatzke-Kopp, 2009)。已有关于多巴胺系统的研究显示, 在大脑内部存在4条多巴胺回路, 其中两条回路与攻击行为相关：第一条包括尾状核、杏仁核、海马等皮层下脑区; 另外一条包括背外侧前额叶、前部扣带回、颞叶和OMPFC等脑区(Gatzke-Kopp & Beauchaine, 2007)。有研究者进一步指出, 综合考虑多条多巴胺回路之间的关系可能对于揭示目标导向行为更为准确和合理(Björklund & Dunnett, 2007)。由于尾状核和OMPFC都是多巴胺回路的一部分, 因此, 我们推测比起正常的个体, 那些反应性攻击较强的个体也有可能是由于大脑内部多巴胺系统存在问题, 使得某些行为与可能结果之间的关系不能被正确认识, 从而导致在某些情境(如敌意情境)下, 皮层下那条回路被“误”激活, 致使尾状核对OMPFC的自下而上的信息传递出现了问题。但是反应性攻击与ADHD以及外部行为障碍还存在很大的差异, 因此至于这种尾状核到右侧OMPFC的效应连接中出现的信息传递问题究竟是否是多巴胺系统的失调导致尚需采用PET等技术进一步研究来揭示和证明。另外, 该分析结果还显示这种相关关系在激发条件下显著, 而在非激发条件下不显著, 这可能是由于激发条件下尾状核更容易被“误”激活引起的。
值得注意的是, 很多早期基于病人的研究提出杏仁核与反应性攻击相关, 例如, 在对癫痫病人的研究中, 一致地发现了电刺激杏仁核导致会攻击反应(Mark, Sweet, & Ervin, 1975), 切除杏仁核或者对杏仁核结构造成损伤则可以用来降低反应性攻击(Lee et al., 1998; Narabayashi, Nagao, Saito, Yoshida, & Nagahata, 1963)。近期一些研究也证明了杏仁核以及杏仁核-前额叶皮质的功能连接在反应性攻击中的作用, 例如上文提到的da Cunha-Bang等人(2017)的研究结果也显示比起正常人, 暴力罪犯在受到敌意激发后, 反应性攻击更强, 尾状核和杏仁核的激活强度升高, 并且尾状核-前额叶以及杏仁核-前额叶的功能连接降低。比起普通罪犯, 患有精神疾病的罪犯在静息状态下杏仁核-内侧前额叶的功能连接较低(Motzkin et al., 2011)。而在本研究中, 却未能发现杏仁核-OMPFC之间的功能连接与反应性攻击相关, 据推测, 可能是由以下原因导致的：首先, 越来越多的研究者提出, 杏仁核不是一个功能单一的区域, 也就是说不同的区域可能功能存在差异, 其中被广泛认同的一个观点是杏仁核主要由基底外侧、中央内侧以及表面组成(Sah, Faber, Lopez de Lopez, & Power, 2003), 其中表面的作用很少得到揭示, 而基底外侧主要负责感觉信息的输入, 中央内侧主要是负责输出到其他脑区。就反应性攻击来讲, 外侧杏仁核负责整合输入的信息并激发中央核唤起“战或逃”的反应(Davis & Whalen, 2001; Maren, 2001; LeDoux, 2000, 1998), 中央核则负责放大或抑制反应性攻击的倾向(Dębiec, 2005; Huber, Veinante, & Stoop, 2005)。以往关于脑形态学的研究也发现, 整个杏仁核的体积与特质攻击相关不显著, 而背侧杏仁核的体积则与特质攻击相关(Gopal et al., 2013), 因此, 在未来的研究中应该将杏仁核区分为不同的亚区来考察杏仁核-OMPFC的功能连接与反应性攻击的关系。其次, 在以往使用TAP范式的任务态研究中一致地没有发现杏仁核的激活(Krämer et al., 2007; Lotze et al., 2007), 因此, 是否TAP范式不能很好检测到杏仁核的激活甚至TAP范式的行为指标也不能反映出杏仁核-前额叶皮质的功能连接与反应性攻击的关系也有待进一步研究。
当然, 本研究也存在一些不足。例如, 种子点的选取差异可能会对结果产生影响, 因此, 在未来的研究中可以选择其他的种子点考察其与其他脑区的协同作用在反应性攻击产生过程中的作用。另外, 本研究以普通大学生为被试, 得到的结论是否适用于暴力罪犯或者患有精神分裂症等精神疾病的个体, 还有待进一步的考察。
本研究采用被广泛使用的TAP, 运用静息态功能成像技术对反应性攻击的脑机制进行了研究。功能连接的结果发现了双侧OMPFC与尾状核之间的功能连接与反应性攻击呈负相关。格兰杰因果分析的结果进一步表明右侧尾状核到右侧OMPFC的效应连接与反应性攻击负相关。与以往采用任务功能态的研究一致地发现了尾状核在反应性攻击中的作用, 为进一步揭示反应性攻击的神经机制提供了部分证据, 是首个利用静息态功能连接和效应连接对反应性攻击进行系统分析的研究。
Personality and aggressive behavior under provoking and neutral conditions: A meta-analytic review,
Abstract The authors conducted a comprehensive review to understand the relation between personality and aggressive behavior, under provoking and nonprovoking conditions. The qualitative review revealed that some personality variables influenced aggressive behavior under both neutral and provocation conditions, whereas others influenced aggressive behavior only under provocation. Studies that assessed personality variables and that directly measured aggressive behavior were included in the quantitative review. Analyses revealed that trait aggressiveness and trait irritability influenced aggressive behavior under both provoking and neutral conditions but that other personality variables (e.g., trait anger, Type A personality, dissipation-rumination) influenced aggressive behavior only under provoking conditions. The authors discuss possible relations between these patterns of aggressive behavior and the personality dimensions of Agreeableness and Neuroticism and consider implications for theories of aggression.
Emotional reactivity to threat modulates activity in mentalizing network during aggression,
Abstract Aggression is a common response to provocation, albeit with considerable interindividual differences. In this fMRI study, we investigated emotional reactivity to threat as possible link between provocation and aggression, as well as the neural correlates of this relationship. We hypothesized that emotional reactivity, measured as fear potentiation (FP) of the startle response, would be negatively associated with aggressive behavior and would modulate neural activity during an aggressive interaction. In 30 healthy female participants, FP was measured as the difference between blink amplitudes while watching threatening vs neutral pictures. Participants subsequently engaged in a variant of the Taylor Aggression Paradigm (TAP), while being scanned. During the TAP, participants selected a punishment level for either a highly provoking or a nonprovoking opponent. There was no difference in aggressive behavior between participants high and low in FP. However, we found a negative correlation between FP and the neural provocation effect in several regions of a network previously associated with mentalizing including the medial prefrontal cortex, precuneus and the temporo-parietal junction. Independently of the FP variability, aggressive behavior correlated with the provocation effect on activity in the caudate nucleus. Our results indicate that during a provocative confrontation, high emotional reactivity to threat suppresses recruitment of the mentalizing network. The Author (2013). Published by Oxford University Press. For Permissions, please email: firstname.lastname@example.org.
Orbitofrontal cortex reactivity to angry facial expression in a social interaction correlates with aggressive behavior,
Altered neural processing of social signals such as angry facial expressions has been associated with increased aggressive , but evidence for this relationship in healthy persons using ecologically valid experimental designs is lacking. We presented socially relevant videos of facial expressions in a functional magnetic resonance imaging (fMRI) version of the well-established Taylor Aggression Paradigm and investigated 41 healthy male participants, of whom 32 were included in the analysis. In each round of this competitive reaction time task, participants observed their opponent while he selected a punishment level for him, bearing either a neutral or angry facial expression. Afterward, participants in turn selected a punishment level for their opponent. Across participants, reactivity of the medial orbitofrontal cortex (OFC) to angry facial expressions was negatively related to aggressive . Within participants and across trials, activity in the anterior cingulate cortex () was positively related to aggressive specifically in response to angry expressions. Moreover, we found an effect of angry expressions on neural activity patterns during later stages of the task, demonstrating that the effect of angry expressions on neural reactivity is more than just a short-lived, stimulus-driven response. Our results underscore the importance of OFC and for the shaping of socially adaptive responses to provocation.
Dopamine neuron systems in the brain: An update,
Abstract The basic organization of the catecholamine-containing neuronal systems and their axonal projections in the brain was initially worked out using classical histofluorescence techniques during the 1960s and 1970s. The introduction of more versatile immunohistochemical methods, along with a range of highly sensitive tract-tracing techniques, has provided a progressively more detailed picture, making the dopamine system one of the best known, and most completely mapped, neurotransmitter systems in the brain. The purpose of the present review is to summarize our current knowledge of the diversity and neurochemical features of the nine dopamine-containing neuronal cell groups in the mammalian brain, their distinctive cellular properties, and their ability to regulate their dopaminergic transmitter machinery in response to altered functional demands and aging.
Considering anger from a cognitive neuroscience perspective,
Abstract The goal of this paper is to consider anger from a cognitive neuroscience perspective. Five main claims are made: First, reactive aggression is the ultimate behavioral expression of anger and thus we can begin to understand anger by understanding reactive aggression. Second, neural systems implicated in reactive aggression (amygdala, hypothalamus and periaqueductal gray; the basic threat system) are critically implicated in anger. Factors such as exposure to extreme threat that increase the responsiveness of these systems, should be (and are in the context of Post Traumatic Stress Disorder), associated with increased anger. Third, regions of frontal cortex implicated in regulating the basic threat system, when dysfunctional (e.g., in the context of lesions) should be associated with increased anger. Fourth, frustration occurs when an individual continues to do an action in the expectation of a reward but does not actually receive that reward, and is associated with anger. Individuals who show impairment in the ability to alter behavioral responding when actions no longer receive their expected rewards should be (and are in the context of psychopathy) associated with increased anger. Fifth, someone not doing what another person wants them to do (particularly if this thwarts the person's goal) is frustrating and consequently anger inducing. The response to such a frustrating social event relies on the neural architecture implicated in changing behavioral responses in non-social frustrating situations.
Region of interest analysis using the MarsBar toolbox for SPM 99,
react-text: 361 To encourage more journals to require the deposition of code and data underlying a publication. /react-text react-text: 362 /react-text
Granger causality via vector auto-regression tuned for fMRI data analysis
Conclusions: We developed a platform-independent modeling tool that provides valid and consistent multivariate Granger causality analysis particularly suited for FMRI data. The program identifies patterns of association among brain ROIs that have been identified with
Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression,
Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression.Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior.Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces.These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.
Corticolimbic function in impulsive aggressive behavior,
Building on animal and human lesion evidence, neuroimaging studies are increasingly identifying abnormalities in corticolimbic circuits mediating aggressive behavior. This review focuses on three neural systems involved in impulsive/reactive aggression: 1) subcortical neural systems that support the production of aggressive impulses; 2) decision-making circuits and social-emotional information processing circuits that evaluate the consequences of aggressing or not aggressing; and 3) frontoparietal regions that are involved in regulating emotions and impulsive motivational urges. We review psychiatric disorders, including borderline personality disorder and antisocial personality disorder, characterized by elevated reactive aggression, focusing on abnormalities in these three neural systems.
Violent offenders respond to provocations with high amygdala and striatal reactivity,
The ability to successfully suppress impulses and angry affect is fundamental to control aggressive reactions following provocations. The aim of this study was to examine neural responses to provocations and aggression using a laboratory model of reactive aggression. We used a novel functional magnetic resonance imaging point-subtraction aggression paradigm in 44 men, of whom 18 were incarcerated violent offenders and 26 were control non-offenders. We measured brain activation following provocations (monetary subtractions), while the subjects had the possibility to behave aggressively or pursue monetary rewards. The violent offenders behaved more aggressively than controls (aggression frequency 150vs84,P=鈥0.03) and showed significantly higher brain reactivity to provocations within the amygdala and striatum, as well as reduced amygdala-prefrontal and striato-prefrontal connectivity. Amygdala reactivity to provocations was positively correlated with task-related behavior in the violent offenders. Across groups, striatal and prefrontal reactivity to provocations was positively associated with trait anger and trait aggression. These results suggest that violent individuals display abnormally high neural sensitivity to social provocations, a sensitivity related to aggressive behavior. These findings provide novel insight into the neural pathways that are sensitive to provocations, which is critical to more effectively shaped interventions that aim to reduce pathological aggressive behavior.
The return of Phineas Gage: Clues about the brain from the skull of a famous patient,
When the landmark patient Phineas Gage died in 1861, no autopsy was performed, but his skull was later recovered. The brain lesion that caused the profound personality changes for which his case became famous has been presumed to have involved the left frontal region, but questions have been raised about the involvement of other regions and about the exact placement of the lesion within the vast frontal territory. Measurements from Gage's skull and modern neuroimaging techniques were used to reconstitute the accident and determine the probable location of the lesion. The damage involved both left and right prefrontal cortices in a pattern that, as confirmed by Gage's modern counterparts, causes a defect in rational decision making and the processing of emotion.
The amygdala: Vigilance and emotion,
Abstract Here we provide a review of the animal and human literature concerning the role of the amygdala in fear conditioning, considering its potential influence over autonomic and hormonal changes, motor behavior and attentional processes. A stimulus that predicts an aversive outcome will change neural transmission in the amygdala to produce the somatic, autonomic and endocrine signs of fear, as well as increased attention to that stimulus. It is now clear that the amygdala is also involved in learning about positively valenced stimuli as well as spatial and motor learning and this review strives to integrate this additional information. A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies. Where appropriate, we attempt to integrate basic information on normal amygdala function with our current understanding of psychiatric disorders, including pathological anxiety.
Peptides of love and fear: Vasopressin and oxytocin modulate the integration of information in the amygdala,
Abstract Neuropeptides vasopressin and oxytocin regulate a variety of behaviors ranging from maternal and pair bonding to aggression and fear. Their role in modulating fear responses has been widely recognized, but not yet well understood. Animal and human studies indicate the major role of the amygdala in controlling fear and anxiety. The amygdala is involved in detecting threat stimuli and linking them to defensive behaviors. This is accomplished by projections connecting the central nucleus of the amygdala (CeA) to the brain stem and to hypothalamic structures, which organize fear responses. A recent study by Huber et al demonstrates that vasopressin and oxytocin modulate the excitatory inputs into the CeA in opposite manners. Therefore this finding elucidates the mechanisms through which these neuropeptides may control the expression of fear.
Abnormal ventromedial prefrontal cortex function in children with psychopathic traits during reversal learning,
Reactive/proactive aggression and the development of internalizing problems in males: The moderating effect of parent and peer relationships,
The current study examined whether reactive and/or proactive aggression in adolescent males prospectively predicted increased levels of internalizing symptoms (depression and anxiety) in late adolescence. It was postulated that reactive aggression would be robustly related to later internalizing problems, but only among adolescent males who had problematic family or peer social relationships. Participants were a racially diverse group of 289 adolescent males (Mean age65=6516). Measures of reactive and proactive aggression, peer rejection, and poor parent–adolescent communication were examined as predictors of both depression and anxiety symptoms assessed approximately 3 years later. The interactive effects between the two facets of aggression and measures of peer rejection and poor parent–adolescent communication in predicting internalizing problems was also examined. Adolescents with high levels of reactive aggression were more likely to exhibit elevated internalizing problems during late adolescence, even when controlling for pre-existing levels of anxiety/depression. However, this association only emerged for adolescents who had high levels of peer rejection and/or poor communication with their parent. Consistent with expectations, proactive aggression was unrelated to internalizing symptoms regardless of social relationship quality. Adolescent reactive, but not proactive, aggression is a risk factor for the development of internalizing problems. However, the findings suggest that interventions designed to foster positive social relationships among reactively aggressive youth may help protect them from developing significant internalizing problems over time. Aggr. Behav. 40:69–78, 2014. 08 2013 Wiley Periodicals, Inc.
Amygdala- orbitofrontal resting state functional connectivity is associated with trait anger,
Abstract An important distinction in research on the neural mechanisms of emotion regulation involves the relatively limited duration of emotional states versus emotional traits that are defined as the stable tendency to experience particular emotions in daily life. Neuroimaging investigations of the regulation of anger states point to the involvement of reciprocal changes in the prefrontal cortex and amygdala activity, but the neural substrate of trait anger has received less attention. We used resting-state functional MRI to determine whether the variation in the strength of functional connectivity between the amygdala and the orbitofrontal cortex is associated with trait anger. Sixteen healthy men completed the Spielberger State-Trait Anger Expression Inventory. Correlational analysis for resting-state functional connectivity (RSFC) was carried out with the left and the right amygdala as separate seed regions. Anger measures were correlated to RSFC involving the right and the left amygdala on a voxel-by-voxel basis across all individuals. We found that Trait Anger was inversely associated with the strength of RSFC between the amygdala and the contralateral middle orbitofrontal cortex. The association was stronger for the right amygdala-left orbitofrontal connection. Anger Control, the tendency to try to control expressions of anger, showed the opposite pattern of being positively correlated with amygdala-orbitofrontal connectivity. The present study provides evidence that RSFC in a corticolimbic circuit might subserve stable differences in anger regulation. Our findings also suggest that RSFC may prove valuable as a trait marker for disorders characterized by emotional dysregulation such as depression, anxiety, and personality disorders.
Central nervous system substrates of impulsivity: Implications for the development of attention-deficit/hyperactivity disorder and conduct disorder
Abstract Lisa M. Gatzke-Kopp and Theodore P. Beauchaine review the evidence for a frontostriatal, dopaminergic deficit in developmental disorders of impulsivity. In particular, they review findings indicating nigrostriatal, mesocortical (cognitive), and mesolimbic (motivational) system deficits in attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). Although the precise mechanism--in terms of hyperactivity or hypoactivity of the dopaminergic system--remains unknown, it appears that each of these functionally integrated systems may contribute to different symptoms observed in the ADHD syndrome. The authors suggest that this complex etiology may result in different patterns of symptoms across individuals diagnosable with ADHD and may necessitate a combined behavioral and neurobiological approach to diagnosis. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Neurological correlates of reward responding in adolescents with and without externalizing behavior disorders,
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Further evidence for the validity of the Taylor aggression paradigm,
Abstract The purpose of this study was to evaluate the validity of a modified version of the Taylor Aggression Paradigm (TAP) as a measure of direct physical aggression. Hypotheses were generated from recent theory pertinent to the categorization and measurement of aggressive behavior as well as widely supported effects of alcohol intoxication and gender on aggression. Participants were 328 (163 men and 165 women) healthy social drinkers between 21 and 35 years of age who completed self-report personality inventories designed to assess one's propensity toward direct physical aggression, verbal aggression, trait anger, and hostility. Following the consumption of either an alcohol or a placebo beverage, participants were tested on the TAP, in which mild electric shocks were received from, and administered to, a fictitious opponent during a competitive task. Direct physical aggression was operationalized as the shock intensities (i.e., first trial shock intensity, mean shock intensity, proportion of highest shock) administered to the fictitious opponent. Although all self-report measures were significantly associated with the three TAP indices, the associations involving physical aggression were strongest. In addition, self-report measures of physical aggression consistently predicted higher levels of aggression on the TAP indices in men, compared with women, and in intoxicated, relative to sober, participants. Taken as a whole, this pattern of findings provides further evidence for the validity of the TAP as a measure of direct physical aggression for men and women. Aggr. Behav. 34:214 229, 2008. 2007 Wiley-Liss, Inc.
The potential role of the striatum in antisocial behavior and psychopathy,
In this review, we examine the functions of the striatum and the evidence that this brain region may be compromised in antisocial individuals. The striatum is involved in the processing of reward-related information and is thus important in reward-based learning. We review evidence from a growing number of brain imaging studies that have identified differences in the structure or functioning of the striatum either in antisocial groups or in relation to personality traits that are associated with antisocial behavior such as impulsivity and novelty seeking. Evidence from structural imaging studies suggests that the volume of the striatum is increased in antisocial populations, although evidence of localization to specific subregions is inconsistent. Functional imaging studies, which similarly tend to find increased functioning in the striatum, suggest that the striatum is not necessarily hypersensitive to the receipt of reward in antisocial individuals but instead may not be appropriately processing the absence of a reward, resulting in continuous responding to a stimulus that is no longer rewarding. This may impair the ability of individuals to flexibly respond to the environment, thus contributing to impulsivity and antisocial behavior. We conclude by discussing genetic and environmental factors that may affect the development of the striatum.
Dorsal/ventral parcellation of the amygdala: Relevance to impulsivity and aggression,
Investigations into the specific association of amygdala volume, a critical aspect of the fronto-limbic emotional circuitry, and aggression have produced results broadly consistent with the 'larger is more powerful' doctrine. However, recent reports suggest that the ventral and dorsal aspects of the amygdala play functionally specific roles, respectively, in the activation and control of behavior. Therefore, parceling amygdala volume into dorsal and ventral components might prove productive in testing hypotheses regarding volumetric association to aggression, and impulsivity, a related aspect of self-control. We sought to test this hypothesis in a group of 41 psychiatric patients who received standard magnetic resonance imaging and a psychometric protocol including aggression and impulsivity measures. Whole amygdala volumes were not associated with aggression or impulsivity, but significant correlations were found when dorsal/ventral amygdalae were analyzed separately. Specifically, left and right ventral amygdala volume was positively associated with motor impulsivity, and left dorsal amygdala was negatively associated with aggression. Results are discussed in terms of an activation and control model of brain-behavior relations. Potential relevance to the continuum of amygdala hyper- to hypo-activation and aggression is discussed.
The role of the basal ganglia in learning and memory: Neuropsychological studies,
In recent years, a common approach to understanding how the basal ganglia contribute to learning and memory in humans has been to study the deficits that occur in patients with basal ganglia pathology, such as Parkinson's disease and Huntington's disease. Pharmacological manipulations in patients and in healthy volunteers have also been conducted to investigate the role of dopamine, a neurotransmitter that is crucial for normal striatal functioning. When combined with powerful functional neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging, such studies can provide important new insights into striatal function and dysfunction in humans. In this review, we consider this broad literature in an attempt to define a specific role for the caudate nucleus in learning and memory, and in particular, how this role may differ from that of the putamen. We conclude that the caudate nucleus contributes to learning and memory through the excitation of correct action schemas and the selection of appropriate sub-goals based on an evaluation of action-outcomes; both processes that are fundamental to all tasks involve goal-directed action.
Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus,
Abstract BACKGROUND: Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network--the default-mode network--that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls. METHODS: Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRI scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity. RESULTS: Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate. CONCLUSIONS: This is the first study to explore default-mode functional connectivity in major depression. The findings provide cross-modality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.
Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder,
Investigating neural primacy in major depressive disorder: Multivariate Granger causality analysis of resting-state fMRI time-series data,
Major Depressive Disorder (MDD) has been conceptualized as a neural network-level disease. Few studies of the neural bases of depression, however, have used analytic techniques that are capable of testing network-level hypotheses of neural dysfunction in this disorder. Moreover, of those that have, fewer still have attempted to determine directionality of influence within functionally abnormal networks of structures. We used multivariate Granger causality analysis a technique that estimates the extent to which preceding neural activity in one or more seed regions predicts subsequent activity in target brain regions to analyze blood-oxygen-level dependent (BOLD) data collected during eyes-closed rest in depressed and never-depressed persons. We found that activation in the hippocampus predicted subsequent increases in ventral anterior cingulate cortex (vACC) activity in depression, and that activity in medial prefrontal cortex and vACC were mutually reinforcing in MDD. Hippocampal and vACC activation in depressed participants predicted subsequent decreases in dorsal cortical activity. This study shows that, on a moment-by-moment basis, there is increased excitatory activity among limbic and paralimbic structures, as well as increased inhibition in activity of dorsal cortical structures, by limbic structures in depression; these aberrant patterns of effective connectivity implicate disturbances in the mesostriatal dopamine system in depression. These findings advance neural theory of depression by detailing specific patterns of limbic excitation in MDD, by making explicit the primary role of limbic inhibition of dorsal cortex in the cortico-limbic relation posited to underlie depression, and by presenting an integrated neurofunctional account of altered dopamine function in this disorder.
Brain mechanisms underlying reactive aggression in borderline personality disorder—Sex matters,
AbstractBackgroundAggression in borderline personality disorder (BPD) is thought to be mediated through emotion dysregulation via high trait anger. Until now, data comparing anger and aggression in female and male patients with BPD have been widely missing on the behavioral and particularly the brain levels.MethodsThirty-three female and 23 male patients with BPD and 30 healthy women and 26 healthy men participated in this functional magnetic resonance imaging study. We used a script-driven imagery task consisting of narratives of both interpersonal rejection and directing physical aggression toward others.ResultsWhile imagining both interpersonal rejection and acting out aggressively, a sex × group interaction was found in which male BPD patients revealed higher activity in the left amygdala than female patients. In the aggression phase, men with BPD exhibited higher activity in the lateral orbitofrontal and dorsolateral prefrontal cortices compared with healthy men and female patients. Positive connectivity between amygdala and posterior middle cingulate cortex was found in female patients but negative connectivity was found in male patients with BPD. Negative modulatory effects of trait anger on amygdala–dorsolateral prefrontal cortex and amygdala–lateral orbitofrontal cortex coupling were shown in male BPD patients, while in female patients trait anger positively modulated dorsolateral prefrontal cortex–amygdala coupling. Trait aggression was found to positively modulate connectivity of the left amygdala to the posterior thalamus in male but not female patients.ConclusionsData suggest poor top-down adjustment of behavior in male patients with BPD despite their efforts at control. Female patients appear to be less aroused through rejection and to successfully dampen aggressive tension during the imagination of aggressive behavior.
Amygdalofrontal functional disconnectivity and aggression in schizophrenia,
A significant proportion of patients with schizophrenia demonstrate abnormalities in dorsal prefrontal regions including the dorsolateral prefrontal and dorsal anterior cingulate cortices. However, it is less clear to what extent abnormalities are exhibited in ventral prefrontal and limbic regions, despite their involvement in social cognitive dysfunction and aggression, which represent problem domains for patients with schizophrenia. Previously, we found that reduced white matter integrity in right inferior frontal regions was associated with higher levels of aggression. Here, we used resting-state functional magnetic resonance imaging to examine amygdala/ventral prefrontal cortex (vPFC) functional connectivity (FC) and its relation to aggression in schizophrenia. Twenty-one healthy controls and 25 patients with schizophrenia or schizoaffective disorder participated. Aggression was measured using the Buss Perry Aggression Questionnaire. Regions of interest were placed in the amygdala based on previously published work. A voxelwise FC analysis was performed in which the mean time series across voxels for this bilateral amygdala seed was entered as a predictor in a multiple regression model with motion parameters and global, cerebrospinal fluid, and white matter signals as covariates. Patients showed significant reductions in FC between amygdala and vPFC regions. Moreover, in patients, the strength of this connection showed a significant inverse relationship with aggression, such that lower FC was associated with higher levels of self-rated aggression. Similar results were obtained for 2 other measures--Life History of Aggression and total arrests. These results suggest that amygdala/vPFC FC is compromised in schizophrenia and that this compromise is associated with aggression.
Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala,
Abstract Vasopressin and oxytocin strongly modulate autonomic fear responses, through mechanisms that are still unclear. We describe how these neuropeptides excite distinct neuronal populations in the central amygdala, which provides the major output of the amygdaloid complex to the autonomic nervous system. We identified these two neuronal populations as part of an inhibitory network, through which vasopressin and oxytocin modulate the integration of excitatory information from the basolateral amygdala and cerebral cortex in opposite manners. Through this network, the expression and endogenous activation of vasopressin and oxytocin receptors may regulate the autonomic expression of fear.
Irrational economic decision-making after ventromedial prefrontal damage: Evidence from the ultimatum game,
Tit-for-tat: The neural basis of reactive aggression,
Aggressive behavior is a basic form of human social interaction, yet little is known about its neural substrates. We used a laboratory task to investigate the neural correlates of reactive aggression using functional magnetic resonance imaging. The task is disguised as a reaction-time competition between the subject and two opponents and entitles the winner to punish the loser. It seeks to elicit aggression by provocation of the subject. As each single trial in this task is separated into a decision phase, during which the severity of the prospective punishment of the opponent is set, and an outcome phase, during which the actual punishment is applied or received, the paradigm enables us to analyze the neural events during each of these phases. Specific neural responses in areas related to negative affect, cognitive control and reward processing provide additional information about the cognitive, emotional and motivational processes underlying reactive aggressive behavior and afford us with the possibility to test and expand theories on aggression such as the General Aggression Model.
An fMRI study on the role of serotonin in reactive aggression,
Fear and the brain: Where have we been, and where are we going?,
Abstract In recent years, there has been an explosion of interest in the neural basis of emotion. Much of this enthusiasm has been triggered by studies of the amygdala and its contribution to fear. This work has shown that the amygdala detects and organizes responses to natural dangers (like predators) and learns about novel threats and the stimuli that predict their occurrence. The latter process has been studied extensively using a procedure called classical fear conditioning. This article surveys the progress that has been made in understanding the neural basis of fear and its implications for anxiety disorders, as well as the gaps in our knowledge.
Emotion circuits in the brain,
Clinical and physiological effects of stereotaxic bilateral amygdalotomy for intractable aggression,
The amygdala is thought to be an important neural structure underlying the "fight-or-flight" response, but information on its role in is scarce. The clinical and psychophysiological effects of amygdalar destruction were studied in 2 patients who underwent bilateral amygdalotomy for intractable . After surgery, both patients showed a reduction in autonomic arousal levels to stressful stimuli and in the number of , although both patients continued to have difficulty controlling . The "taming effect" reported after bilateral amygdalar destruction may be due to the amygdala's inadequate processing of perceived threat stimuli that would normally produce a fight-or-flight response.
Short-term effects of prosocial video games on aggression: An event-related potential study,
Previous research has shown that exposure to violent video games increases aggression, whereas exposure to prosocial video games can reduce aggressive behavior. However, little is known about the neural correlates of these behavioral effects. This work is the first to investigate the electrophysiological features of the relationship between playing a prosocial video game and inhibition of aggressive behavior. Forty-nine subjects played either a prosocial or a neutral video game for 20 min, then participated in an event-related potential (ERP) experiment based on an oddball paradigm and designed to test electrophysiological responses to prosocial and violent words. Finally, subjects completed a competitive reaction time task (CRTT) which based on Taylor's Aggression Paradigm and contains reaction time and noise intensity chosen as a measure of aggressive behavior. The results show that the prosocial video game group (compared to the neutral video game group) displayed smaller P300 amplitudes, were more accurate in distinguishing violent words, and were less aggressive as evaluated by the CRTT of noise intensity chosen. A mediation analysis shows that the P300 amplitude evoked by violent words partially mediates the relationship between type of video game and subsequent aggressive behavior. The results support theories based on the General Learning Model. We provide converging behavioral and neural evidence that exposure to prosocial media may reduce aggression.
Evidence for a different role of the ventral and dorsal medial prefrontal cortex for social reactive aggression: An interactive fMRI study,
Interactive paradigms inducing reactive aggression are absent in the brain mapping literature. We used a competitive reaction time task to investigate brain regions involved in social interaction and reactive aggression in sixteen healthy male subjects with fMRI. Subjects were provoked by increasingly aversive stimuli and were given the opportunity to respond aggressively against their opponent by administering a stimulus as retaliation. fMRI revealed an increase of medial prefrontal cortex (mPFC) activity during retaliation. The dorsal mPFC was active when subjects had to select the intensity of the retaliation stimulus, and its activity correlated with the selected stimulus strength. In contrast, ventral mPFC was active during observing the opponent suffering but also during retaliation independent of the stimulus strength. Ventral mPFC activation, stronger in low callous subjects, correlated positively with skin conductance response during observation of the suffering opponent. In conclusion, dorsal mPFC activation seems to represent cognitive operations related to more intense social interaction processes whereas the ventral mPFC might be involved in affective processes associated with compassion to the suffering opponent.
Neurobiology of Pavlovian fear conditioning,
Learning the relationships between aversive events and the environmental stimuli that predict such events is essential to the survival of organisms throughout the animal kingdom. Pavlovian fear conditioning is an exemplar of this form of learning that is exhibited by both rats and humans. Recent years have seen an incredible surge in interest in the neurobiology of fear conditioning. Neural circuits underlying fear conditioning have been mapped, synaptic plasticity in these circuits has been identified, and biochemical and genetic manipulations are beginning to unravel the molecular machinery responsible for the storage of fear memories. These advances represent an important step in understanding the neural substrates of a rapidly acquired and adaptive form of associative learning and memory in mammals.
Deep temporal lobe stimulation and destructive lesions in episodically violent temporal lobe epileptics
Amygdala hyperactivation to angry faces in intermittent explosive disorder,
Abstract BACKGROUND: Individuals with intermittent explosive disorder (IED) were previously found to exhibit amygdala hyperactivation and relatively reduced orbital medial prefrontal cortex (OMPFC) activation to angry faces while performing an implicit emotion information processing task during functional magnetic resonance imaging (fMRI). This study examines the neural substrates associated with explicit encoding of facial emotions among individuals with IED. METHOD: Twenty unmedicated IED subjects and twenty healthy, matched comparison subjects (HC) underwent fMRI while viewing blocks of angry, happy, and neutral faces and identifying the emotional valence of each face (positive, negative or neutral). We compared amygdala and OMPFC reactivity to faces between IED and HC subjects. We also examined the relationship between amygdala/OMPFC activation and aggression severity. RESULTS: Compared to controls, the IED group exhibited greater amygdala response to angry (vs. neutral) facial expressions. In contrast, IED and control groups did not differ in OMPFC activation to angry faces. Across subjects amygdala activation to angry faces was correlated with number of prior aggressive acts. CONCLUSIONS: These findings extend previous evidence of amygdala dysfunction in response to the identification of an ecologically-valid social threat signal (processing angry faces) among individuals with IED, further substantiating a link between amygdala hyperactivity to social signals of direct threat and aggression. Copyright 漏 2016. Published by Elsevier Ltd.
Social structure, adversity, toxic stress, and intergenerational poverty: An early childhood model,
Why are children of poor parents more likely to be poor as adults than other children? Early-childhood adversities resulting from social structures and relation
Reduced prefrontal connectivity in psychopathy,
Abstract Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.
Stereotaxic amygdalotomy for behavior disorders,
Abstract The purpose of this communication is to present the results of stereotaxic oil-wax destruction of the amygdaloid nucleus, either unilaterally or bilaterally, on behavior disturbances. It was originally our intention to investigate the value of amygdalotomy upon patients with temporal lobe epilepsy characterized by psychomotor seizures and focal spike discharges on the electroencephalogram as well as marked behavior disturbances such as hyperexcitability, assaultive behavior, or violent aggressiveness. The indications for amygdalotomy were then extended to include patients without clinical manifestations of temporal lobe epilepsy but with EEG abnormalities and marked behavior disturbances. Finally, cases of behavior disorders without epileptic manifestations, clinically and electrically, but associated with various degrees of feeblemindedness or with subnormal intelligence were also included in the series. It has been known for a long time that patients with temporal lobe seizures often exhibit disturbances of emotional behavior and conversely, that patients manifesting abnormalities of general behavior frequently
Neural mechanisms of aggression,
Amygdala-prefrontal disconnection in borderline personality disorder,
Neural correlates of imaginal aggressive behavior assessed by positron emission tomography in healthy subjects,
Aggression, and some related psychological constructs (anger, hostility, and impulsivity) Some comments from a research project,
The purpose of the present study was: first, to offer a few theoretical considerations on the concept of human aggression and its main types; and second, to analyse the relationship between those types of aggression and other related psychological constructs, such as anger, hostility, and impulsivity, summarizing the main empirical results of our research in progress. In order to assess their eventual correlations, several self-report techniques were compared: (a) AQ, used to measure several kinds of aggression, anger, and hostility; (b) CAMA, a questionnaire already used in a variety of cultures, for measuring attitudes toward interpersonal aggression in different instrumental and hostile situations; (c) ASQ, an instrument for measuring experienced anger and its expression in assertive or aggressive ways; and (d) BIS, used to prove three impulsiveness sub-traits: motor, attentional, and non-planning impulsiveness. The different definitions of aggression may be grouped according to whether the primary goal is distress or harm, focusing primarily on the objective infliction of harm, or on the subjective intention of harming. Most classifications in the literature show two kinds of aggression, even if different names are used: Hostile Aggression (among other names it is also known as ‘reactive, impulsive, or affective’) is an act primarily oriented to hurt another individual; and Instrumental Aggression (also known as ‘proactive, premeditated, or predative’) is a means or tool for solving problems or for obtaining a variety of objectives. As predicted, there was a positive correlation between experience and expression of anger. Anger involved physiological arousal and prepared for aggression. Anger and impulsiveness were also positively correlated with hostile aggression, but not with instrumental aggression. In the case of impulsiveness, non-planning impulsiveness was positively correlated with some situations related to hostile aggression, such as emotional agitation or lack of communication, but not with instrumental one. Finally, hostility positively correlated with anger and different kinds of aggression, but not its degree of justification. In sum, aggression can be reflected in the different personality constructs, measured by self-reports.
Neuromodulation can reduce aggressive behavior elicited by violent video games. Cognitive, Affective,,
The neurobiology of aggression and violence,
Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.
The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making. Cognitive, Affective,,
Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses.
A dynamic developmental theory of attention- deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes,
Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Inattentiveness, overactivity, and impulsiveness are presently regarded as the main clinical symptoms. The dynamic developmental behavioral theory is based on the hypothesis that altered dopaminergic function plays a pivotal role by failing to modulate nondopaminergic (primarily glutamate and GABA) signal transmission appropriately. A hypofunctioning mesolimbic dopamine branch produces altered reinforcement of behavior and deficient extinction of previously reinforced behavior. This gives rise to delay aversion, development of hyperactivity in novel situations, impulsiveness, deficient sustained attention, increased behavioral variability, and failure to "inhibit" responses ("disinhibition"). A hypofunctioning mesocortical dopamine branch will cause attention response deficiencies (deficient orienting responses, impaired saccadic eye movements, and poorer attention responses toward a target) and poor behavioral planning (poor executive functions). A hypofunctioning nigrostriatal dopamine branch will cause impaired modulation of motor functions and deficient nondeclarative habit learning and memory. These impairments will give rise to apparent developmental delay, clumsiness, neurological "soft signs," and a "failure to inhibit" responses when quick reactions are required. Hypofunctioning dopamine branches represent the main individual predispositions in the present theory. The theory predicts that behavior and symptoms in ADHD result from the interplay between individual predispositions and the surroundings. The exact ADHD symptoms at a particular time in life will vary and be influenced by factors having positive or negative effects on symptom development. Altered or deficient learning and motor functions will produce special needs for optimal parenting and societal styles. Medication will to some degree normalize the underlying dopamine dysfunction and reduce the special needs of these children. The theory describes how individual predispositions interact with these conditions to produce behavioral, emotional, and cognitive effects that can turn into relatively stable behavioral patterns.
The amygdaloid complex: Anatomy and physiology,
Abstract A converging body of literature over the last 50 years has implicated the amygdala in assigning emotional significance or value to sensory information. In particular, the amygdala has been shown to be an essential component of the circuitry underlying fear-related responses. Disorders in the processing of fear-related information are likely to be the underlying cause of some anxiety disorders in humans such as posttraumatic stress. The amygdaloid complex is a group of more than 10 nuclei that are located in the midtemporal lobe. These nuclei can be distinguished both on cytoarchitectonic and connectional grounds. Anatomical tract tracing studies have shown that these nuclei have extensive intranuclear and internuclear connections. The afferent and efferent connections of the amygdala have also been mapped in detail, showing that the amygdaloid complex has extensive connections with cortical and subcortical regions. Analysis of fear conditioning in rats has suggested that long-term synaptic plasticity of inputs to the amygdala underlies the acquisition and perhaps storage of the fear memory. In agreement with this proposal, synaptic plasticity has been demonstrated at synapses in the amygdala in both in vitro and in vivo studies. In this review, we examine the anatomical and physiological substrates proposed to underlie amygdala function.
Disrupted effective connectivity between the medial frontal cortex and the caudate in adolescent boys with externalizing behavior disorders,
Studies addressing the neural correlates of criminal behavior have focused primarily on the prefrontal cortex and the amygdala. However, few studies have examined dopaminergic inputs to these or other brain regions, despite the fact that central dopamine (DA) dysfunction is associated with both trait impulsivity and novelty seeking. Given long-standing associations between both of these personality traits and externalizing psychopathology, the authors examined effective connectivity between the caudate nucleus and the anterior cingulate cortex, two areas that rely on DA input to facilitate associative learning and goal directed behavior. Dysfunction in top-down and bottom-up processing within this dopaminergically mediated frontostriatal circuit may be an important biological vulnerability that increases one likelihood of engaging in delinquent and criminal behavior. When compared with controls, reduced effective connectivity between these regions among adolescents with externalizing psychopathology was found, suggesting deficiencies in frontostriatal circuitry.
Neurobiology of aggression and violence,
Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala芒聙聯frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.
REST: A toolkit for resting-state functional magnetic resonance imaging data processing,
Resting-state fMRI (RS-fMRI) has been drawing more and more attention in recent years. However, a publicly available, systematically integrated and easy-to-use tool for RS-fMRI data processing is still lacking. We developed a toolkit for the analysis of RS-fMRI data, namely the RESting-state fMRI data analysis Toolkit (REST). REST was developed in MATLAB with graphical user interface (GUI). After data preprocessing with SPM or AFNI, a few analytic methods can be performed in REST, including functional connectivity analysis based on linear correlation, regional homogeneity, amplitude of low frequency fluctuation (ALFF), and fractional ALFF. A few additional functions were implemented in REST, including a DICOM sorter, linear trend removal, bandpass filtering, time course extraction, regression of covariates, image calculator, statistical analysis, and slice viewer (for result visualization, multiple comparison correction, etc.). REST is an open-source package and is freely available at http://www.restfmri.net.
The association between resting functional connectivity and creativity,
The analysis of functional connectivity at rest (rFC) enables us to know how brain regions within and between networks interact. In this study, we used resting-state functional magnetic resonance imaging and a creativity test of divergent thinking (DT) to investigate the relationship between creativity measured by DT and rFC. We took the medial prefrontal cortex (mPFC) to be the seed region and investigated correlations across subjects between the score of the DT test and the strength of rFC between the mPFC and other brain regions. Our results showed that the strength of rFC with the mPFC significantly and positively correlated with creativity as measured by the DT test in the posterior cingulate cortex (PCC). These results showed that higher creativity measured by DT is associated with rFC between the mPFC and the PCC, the key nodes of the default mode network (DMN). Increased rFC between these regions is completely opposite from that is generally expected from the association between higher creativity and reduced deactivation in DMN during an externally directed attention-demanding task shown in our previous study but is similar to the pattern seen in relatives of schizophrenia. These findings are comparable to the previously reported psychological associations between schizotypy and creativity.
Aggressive behavior and physiological arousal as a function of provocation and the tendency to inhibit aggression,
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain,
An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463鈥468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254鈥266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.
Neuronal correlates of reward and loss in cluster B personality disorders: A functional magnetic resonance imaging study,
Abstract Decision making is guided by the likely consequences of behavioural choices. Neuronal correlates of financial reward have been described in a number of functional imaging studies in humans. Areas implicated in reward include ventral striatum, dopaminergic midbrain, amygdala and orbitofrontal cortex. Response to loss has not been as extensively studied but may involve prefrontal and medial temporal cortices. It has been proposed that increased sensitivity to reward and reduced sensitivity to punishment underlie some of the psychopathology in impulsive personality disordered individuals. However, few imaging studies using reinforcement tasks have been conducted in this group. In this fMRI study, we investigate the effects of positive (monetary reward) and negative (monetary loss) outcomes on BOLD responses in two target selection tasks. The experimental group comprised eight people with Cluster B (antisocial and borderline) personality disorder, whilst the control group contained fourteen healthy participants. A key finding was the absence of prefrontal responses and reduced BOLD signal in the subcortical reward system in the PD group during positive reinforcement. Impulsivity scores correlated negatively with prefrontal responses in the PD but not the control group during both, reward and loss. Our results suggest dysfunctional responses to rewarding and aversive stimuli in Cluster B personality disordered individuals but do not support the notion of hypersensitivity to reward and hyposensitivity to loss.
Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI,
Treatment-refractory depression (TRD) represents a large proportion of the depressive population, yet has seldom been investigated using advanced imaging techniques. To characterize brain dysfunction in TRD, we performed resting-state functional MRI (rs-fMRI) on 22 TRD patients, along with 26 matched healthy subjects and 22 patients who were depressed but not treatment-refractory (NDD) as comparison groups. Results were analyzed using a data-driven approach known as Regional Homogeneity (ReHo) analysis which measures the synchronization of spontaneous fMRI signal oscillations within spatially neighboring voxels. Relative to healthy controls, both depressed groups showed high ReHo primarily within temporo-limbic structures, and more widespread low ReHo in frontal, parietal, posterior fusiform cortices, and caudate. TRD patients showed more cerebral regions with altered ReHo than did NDD. Moderate but significant correlations between the altered regional ReHo and measures of clinical severity were observed in some identified clusters. These findings shed light on the pathophysiological mechanisms underlying TRD and demonstrate the feasibility of using ReHo as a research and clinical tool to monitor persistent cerebral dysfunction in depression, although further work is necessary to compare different measures of brain function to elucidate the neural substrates of these ReHo abnormalities. Hum Brain Mapp, 2011. 2010 Wiley-Liss, Inc.
DPARSF: A MATLAB toolbox for “pipeline” data analysis of resting-state fMRI,
Resting-state functional magnetic resonance imaging (fMRI) has attracted more and more attention because of its effectiveness, simplicity and non-invasiveness in exploration of the intrinsic functional architecture of the human brain. However, user-friendly toolbox for “pipeline” data analysis of resting-state fMRI is still lacking. Based on some functions in Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST), we have developed a MATLAB toolbox called Data Processing Assistant for Resting-State fMRI (DPARSF) for “pipeline” data analysis of resting-state fMRI. After the user arranges the Digital Imaging and Communications in Medicine (DICOM) files and click a few buttons to set parameters, DPARSF will then give all the preprocessed (slice timing, realign, normalize, smooth) data and results for functional connectivity, regional homogeneity, amplitude of low-frequency fluctuation (ALFF), and fractional ALFF. DPARSF can also create a report for excluding subjects with excessive head motion and generate a set of pictures for easily checking the effect of normalization. In addition, users can also use DPARSF to extract time courses from regions of interest.
Identifying major depression using whole-brain functional connectivity: A multivariate pattern analysis,
Recent resting-state functional connectivity magnetic resonance imaging studies have shown significant group differences in several regions and networks between patients with major depressive disorder and healthy controls. The objective of the present study was to investigate the whole-brain resting-state functional connectivity patterns of depressed patients, which can be used to test the feasibility of identifying major depressive individuals from healthy controls. Multivariate pattern analysis was employed to classify 24 depressed patients from 29 demographically matched healthy volunteers. Permutation tests were used to assess classifier performance. The experimental results demonstrate that 94.3% (P鈥<鈥0.0001) of subjects were correctly classified by leave-one-out cross-validation, including 100% identification of all patients. The majority of the most discriminating functional connections were located within or across the default mode network, affective network, visual cortical areas and cerebellum, thereby indicating that the disease-related resting-state network alterations may give rise to a portion of the complex of emotional and cognitive disturbances in major depression. Moreover, the amygdala, anterior cingulate cortex, parahippocampal gyrus and hippocampus, which exhibit high discriminative power in classification, may play important roles in the pathophysiology of this disorder. The current study may shed new light on the pathological mechanism of major depression and suggests that whole-brain resting-state functional connectivity magnetic resonance imaging may provide potential effective biomarkers for its clinical diagnosis.
Human striatal response to salient nonrewarding stimuli,
Although one proposed function of both the striatum and its major dopamine inputs is related to coding rewards and reward-related stimuli, an alternative view suggests a more general role of the striatum in processing salient events, regardless of their reward value. Here we define saliency as an event that both is unexpected and elicits an attentional-behavioral switch (i.e., arousing). In the present study, human striatal responses to nonrewarding salient stimuli were investigated. Using functional magnetic resonance imaging (fMRI), the blood oxygenation level-dependent signal was measured in response to flickering visual distractors presented in the background of an ongoing task. Distractor salience was manipulated by altering the frequency of distractor occurrence. Infrequently presented distractors were considered more salient than frequently presented distractors. We also investigated whether behavioral relevance of the distractors was a necessary component of saliency for eliciting striatal responses. In the first experiment (19 subjects), the distractors were made behaviorally relevant by defining a subset of them as targets requiring a button press. In the second experiment (17 subjects), the distractors were not behaviorally relevant (i.e., they did not require any response). The fMRI results revealed increased activation in the nucleus accumbens after infrequent (high salience) relative to frequent (low salience) presentation of distractors in both experiments. Caudate activity increased only when the distractors were behaviorally relevant. These results demonstrate a role of the striatum in coding nonrewarding salient events. In addition, a functional subdivision of the striatum according to the behavioral relevance of the stimuli is suggested.
Human striatal responses to monetary reward depend on saliency,
Abstract While the striatum has been implicated in reward processing, an alternative view contends that the striatum processes salient events in general. Using fMRI, we investigated human striatal responses to monetary reward while modulating the saliency surrounding its receipt. Money was maximally salient when its receipt depended on a correct response (active) and minimally salient when its receipt was completely independent of the task (passive). The saliency manipulation was confirmed by skin conductance responses and subjective ratings of the stimuli. Significant caudate and nucleus accumbens activations occurred following the active compared to passive money. Such activations were attributed to saliency rather than the motor requirement associated with the active money because striatal activations were not observed when the money was replaced by inconsequential, nonrewarding stimuli. The present study provides evidence that the striatum's role in reward processing is dependent on the saliency associated with reward, rather than value or hedonic feelings.
The oscillating brain: Complex and reliable,
The human brain is a complex dynamic system capable of generating a multitude of oscillatory waves in support of brain function. Using fMRI, we examined the amplitude of spontaneous low-frequency oscillations (LFO) observed in the human resting brain and the test–retest reliability of relevant amplitude measures. We confirmed prior reports that gray matter exhibits higher LFO amplitude than white matter. Within gray matter, the largest amplitudes appeared along mid-brain structures associated with the “default-mode” network. Additionally, we found that high-amplitude LFO activity in specific brain regions was reliable across time. Furthermore, parcellation-based results revealed significant and highly reliable ranking orders of LFO amplitudes among anatomical parcellation units. Detailed examination of individual low frequency bands showed distinct spatial profiles. Intriguingly, LFO amplitudes in the slow-4 (0.027–0.07302Hz) band, as defined by Buzsáki et al., were most robust in the basal ganglia, as has been found in spontaneous electrophysiological recordings in the awake rat. These results suggest that amplitude measures of LFO can contribute to further between-group characterization of existing and future “resting-state” fMRI datasets.
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