NEUROIMAGING OF FRONTAL LOBE FUNCTIONING DURING COGNITION IN HEALTHY SUBJECTS

利用氧-15水正电子发射 断层扫描测量局部脑血流量(RCBF) 局部神经元活动的标志，我们发现正常 执行涉及工作记忆的任务的受试者使用大脑皮层 网络包括背外侧前额叶皮质、顶下皮质 小叶和下颞枕皮质。在其他相关任务中 对于前额叶皮质，我们已经通过迷宫任务证明了 获取而不是提取空间数据涉及额叶皮质 (van Horn等人，脑研究，1998)，特别是在右边； 在词汇生成任务中，语义和语音线索被激活 类似的脑区包括前扣带回，左额叶皮质， 丘脑和小脑，但它们之间存在细微的差异 这与损伤文献一致(Gourovitch等人， 已呈交)。我们还进行了几项实验，目的是 正常人群工作记忆系统的研究 与认知症状相关的情况 精神分裂症。首先，在双重任务范式中，可能会建立 患者有限的工作记忆容量是一个基本的 前额叶皮质的特征是激活减弱 面对刺激处理的超大需求和 回答选择，至少在双重任务中检查时是这样 条件(Goldberg等人，NeuroImage，1998)；这些结果可能 为理解认知失败提供了一个类比 精神分裂症，既有能力限制，又有脑功能减退 已经观察到了激活。二是在实验探索中 工作中工作记忆负荷增加的影响 内存容量，增加“工作”(即 对记忆材料的处理)和“记忆”(即 材料的数量)在工作记忆中显著地产生 额叶内不同的激活模式。渐增 记忆材料的量产生了分级的生理 答复主要是在准备答复方面发挥作用的领域 在运动领域内，包括口头反应。增加了 记忆材料被操纵的程度 在更经典的区域产生分级的生理反应 与工作记忆系统相关，包括背外侧 前额叶皮质。在一项关于正常衰老中认知激活的研究中 我们发现，神经生理学的变化与环境有关。 (Esposito等人，提交)。也就是说，生活中的明显变化 SPAN在不同的任务中有所不同，具体取决于 特定任务所需的特定神经系统。在以下地区 年轻受试者的生理活动通常会受到抑制 执行任务时，年龄较大的受试者会更活跃，而且 他们越活跃(或未能抑制)，他们的表现就越差 任务。在其他地区，生理活动通常是 执行任务的年轻人、年长的受试者增加 激活的越少，这些区域的激活就越多 影响了他们的表现。我们已经开发出一种技术来 估计与统计相关的体素级别统计功率 认知激活研究中的参数图，并举例说明 图像平滑对预期重复性的影响 显著激活(Van Horn等人，NeuroImage，1998)。四十 受试者在WCS检查过程中接受扫描。已登记的 数据用SPM和体素统计功率法进行分析 对t-map结果图像使用 测量功率的非中心F分布法。在一次 临界阿尔法为0.01，功率阈值为80%和95%， 在大脑区域拒绝无效假设的权力 5和10中的N个任务可能不足以确保可复制性 重大发现的证据。当样本量超过20个受试者时， 右侧DLPFC功率90%以上，双侧下 顶小叶和双侧下颞叶，组成 大脑皮层网络通常在WCS期间观察到。过滤器大小 最大化统计权力所需的因素千差万别，但 系统性的，跨地区的，倾向于遵循已知的解剖学 标志性事件和功能反应性脑的并列 构筑物

Using oxygen-15 water positron emission tomography to measure regional cerebral blood flow (rCBF), a marker of 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, submitted). 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