Neuroimaging Of Frontal Lobe Functioning During Cognitio

使用功能神经成像来确定局部神经元的活动，我们发现正常受试者在执行涉及工作记忆的任务时使用皮质网络，包括背外侧前额叶、顶下小叶和颞枕叶下部。在与前额叶皮质相关的其他任务中，我们已经表明，通过迷宫任务，空间数据的获取而不是提取涉及额叶皮质，尤其是在右侧；通过词汇生成任务，语义和语音线索激活了类似的大脑区域，包括前扣带回、左额叶皮质、丘脑和小脑，但它们之间存在细微的差异，与病变文献中的损伤文献一致(Gourovitch等人，提交)。我们还进行了几项实验，旨在研究正常人在与精神分裂症认知症状相关的条件下的工作记忆系统。首先，在一个可以模拟患者有限的工作记忆容量的双任务范式中，前额叶皮质的一个基本特征是，面对对刺激处理和反应选择的超最大需求，至少当在双重任务条件下被检查时，激活被减弱(Goldberg等人，NeuroImage 1998)；这些结果可能为理解精神分裂症的认知失败提供了一个类比，在精神分裂症中既观察到了容量限制，又观察到了大脑激活的减少。第二，在探索工作记忆容量中工作记忆负荷增加的影响的实验中，增加工作记忆中的“工作”(即对记忆材料的操作次数)和工作记忆中的“记忆”(即材料的量)会在额叶中产生明显不同的激活模式。增加记忆材料的数量会产生分级的生理反应，主要发生在那些在准备运动领域的反应方面发挥作用的区域，包括言语反应。增加记忆材料被操纵的程度，会在与工作记忆系统更典型地联系在一起的区域产生分级的生理反应，包括背外侧前额叶皮质。在一项关于正常衰老过程中认知激活的研究中，我们发现神经生理学的变化是与背景相关的(Esposito等人，脑1999)。也就是说，在不同的任务中，生命周期的明显变化是不同的，这取决于特定神经系统在特定任务中的作用。在年轻受试者执行任务时生理活动通常受到抑制的区域，年长受试者激活得更多，而且，他们激活(或抑制失败)得越多，他们在任务中的表现就越差。在执行任务的年轻人通常会增加生理活动的其他区域，年龄较大的受试者活动较少；这些区域激活得越少，他们的表现就越受损。我们开发了一种在认知激活研究中估计与统计参数图相关的体素水平统计能量的技术，并说明了图像平滑对显著激活的预期重现性的影响(Van Horn等，NeuroImage，1998)。40名受试者在WCS检查期间接受了扫描。用SPM分析配准数据，并使用用于测量功率的非中心F分布方法生成t-map结果图像的体素统计功率估计。在临界阿尔法为0.01，功率阈值为80%和95%的情况下，在N为5和10的任务中涉及的大脑区域拒绝无效假设的能力可能不足以确保重大发现的可重复性。当样本大小超过20名受试者时，在右侧DLPFC、双侧顶下小叶和双侧颞叶下叶，能量超过90%，构成了WCS中典型的皮质网络。最大化统计能力所需的过滤器大小差异很大，但系统地，跨地区，倾向于遵循已知的解剖地标和功能反应性大脑结构的并列。

Using functional neuroimaging to determine local neuronal activity, we have found that normal subjects performing tasks involving working memory use a cortical network including dorsolateral prefrontal cortex, inferior parietal lobule, and inferior temporo-occipital cortex. In other tasks related to prefrontal cortex, we have shown, with a maze task, that acquisition but not retrieval of spatial data involves frontal cortex (Van Horn et al, Brain Research 1998), particularly on the right; with word generation tasks semantic and phonologic cues activate similar brain regions including anterior cingulate, left frontal cortex, thalamus and cerebellum, but subtle differences exist between them that are consistent with the lesion literature (Gourovitch et al, submitted). We have also carried out several experiments aimed at investigating the working memory system in normals under conditions that have relevance for cognitive symptoms of schizophrenia. First, in a dual-task paradigm that may model patients' limited working memory capacity, a fundamental characteristic of prefrontal cortex was activation was attenuated in the face of supramaximal demands for stimulus processing and response selection, at least when examined in the dual task condition (Goldberg et al, NeuroImage 1998); these results may provide an analog for understanding cognitive failures in schizophrenia where both capacity limitations and reduced cerebral activation have been observed. Second, in experiments exploring the effects of increasing working memory load within working memory capacity, increasing the "working" (i.e. number of manipulations on remembered material) and the "memory" (i.e. the amount of material) within working memory produced markedly different patterns of activation within the frontal lobes. Increasing the amount of remembered material produced graded physiological responses primarily in areas that play a role in preparing a response within the motor domain, including verbal responses. Increasing the degree to which the remembered material was manipulated produced graded physiological responses in regions more classically associated with the working memory system, including dorsolateral prefrontal cortex. In a study of cognitive activation in normal aging we found that neurophysiological changes were context dependent (Esposito et al, Brain 1999). That is, apparent changes over the life span differed in different tasks, depending on the role of the particular neural system for the particular task. In regions where physiological activity is normally suppressed when young subjects perform the tasks older subjects activate more, and, moreover, the more they activate (or fail to suppress), the worse they perform on the tasks. In other areas, where physiological activity is normally increased in young people performing the tasks, older subjects activate less; and the less they activate these regions, the more impaired their performance. We have developed a technique for estimating voxel-level statistical power associated with statistical parametric maps in cognitive activation studies and illustrated the effects of image smoothing on the expected reproducibility of significant activation (Van Horn et al, NeuroImage, 1998). Forty subjects were scanned during the WCS paradigm. The registered data were analyzed with SPM and voxel-wise statistical power estimates were generated for t-map result images employing the Non-Central F-Distribution method for measuring power. At a critical alpha of 0.01 and power thresholds of 80% and 95%, the power to reject the null hypothesis in brain regions implicated in the task at N's of 5 and 10 may not be sufficient to assure replicability of significant findings. When sample sizes exceed 20 subjects, power above 90% was found in the right DLPFC, bilateral inferior parietal lobule, and bilateral inferior temporal lobe, comprising the cortical network typically observed during the WCS. The filter size needed to maximize statistical power varied widely, but systematically, across regions, tending to follow known anatomical landmarks and and the juxtaposition of functionally reactive brain structures.