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），a 作为局部神经元活动的标志，我们发现， 受试者执行涉及工作记忆的任务时， 包括背外侧前额叶皮层、顶叶下部 小叶和下颞枕叶皮质。在其他相关任务中 前额叶皮层，我们已经证明，通过迷宫任务， 空间数据的获取而非检索涉及额叶皮层 (Van Horn等，Brain Research 1998），尤其是右侧; 在单词生成任务中，语义和语音线索激活 类似的大脑区域包括前扣带回，左额叶皮层， 丘脑和小脑，但它们之间存在细微的差异 这与损伤文献（Gourovitch等人， 提交）。我们还进行了几项实验， 研究正常人的工作记忆系统， 与认知症状相关的疾病 精神分裂症首先，在一个双任务范式中， 病人有限的工作记忆能力， 前额叶皮层的特征是激活减弱， 面对刺激处理的超大需求， 反应选择，至少在双重任务中检查时 条件（Goldberg等，NeuroImage，1998）;这些结果可能 提供了一个类似的理解认知失败， 精神分裂症，其中容量限制和大脑功能减退 已经观察到激活。第二，在实验探索中， 增加工作记忆负荷对工作记忆的影响 内存容量，增加“工作”（即数量 操纵记忆材料）和“记忆”（即 工作记忆中的材料量） 额叶的不同激活模式增加 产生的记忆材料的数量分级生理 主要是在编写对策方面发挥作用的领域的对策 包括语言反应在内的运动领域。增加 记忆材料被操纵的程度 产生了分级的生理反应， 与工作记忆系统相关，包括背外侧 前额皮质在一项关于正常衰老的认知激活的研究中， 我们发现神经生理学变化是依赖于环境的， （Esposito等人，提交）。也就是说，在生命中的明显变化 跨度在不同的任务中不同，这取决于 特定的神经系统来完成特定的任务。的地区 当年轻的受试者 执行任务的年龄较大的受试者激活更多，而且，此外， 他们越是活跃（或无法抑制），他们的表现就越差。 任务。在其他区域，生理活动通常 增加了年轻人执行的任务，老年受试者 激活越少;这些区域激活越少， 削弱了他们的表现。我们开发了一种技术， 估计与统计相关的体素级统计功率 认知激活研究中的参数图，并说明了 图像平滑对预期再现性的影响 显著激活（范霍恩等人，NeuroImage，1998）。四十 在WCS范例期间扫描受试者。注册 数据采用SPM和体素统计功效进行分析 使用以下方法为t图结果图像生成估计值： 测量功率的非中心F分布方法。在 临界α为0.01，功效阈值为80%和95%， 在大脑区域中拒绝零假设的能力 N为5和10任务可能不足以确保可复制性 重大发现。当样本量超过20名受试者时， 右侧DLPFC的功率大于90%，双侧下PFC的功率大于90%， 顶叶小叶和双侧下颞叶，包括 皮质网络通常在WCS期间观察到。过滤器大小 需要最大限度地提高统计能力差异很大，但 系统地，跨区域，倾向于遵循已知的解剖结构， 标志和功能反应脑的并列 结构

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