Neuroimaging Of Frontal Lobe Functioning During Cognitio

通过功能性神经成像来确定局部神经元活动，我们发现正常受试者在执行涉及工作记忆的任务时使用的皮质网络包括背外侧前额叶皮层、下顶叶小叶和下颞枕皮层。在其他与前额叶皮层相关的任务中，我们已经表明，在迷宫任务中，空间数据的获取而不是检索涉及前额叶皮层（Van Horn等人，Brain Research 1998），特别是在右侧；在单词生成任务中，语义和语音线索激活了类似的大脑区域，包括前扣带、左额叶皮层、丘脑和小脑，但它们之间存在微妙的差异，这与病变文献一致（Gourovitch et al .，提交）。我们还进行了几个实验，旨在调查正常情况下与精神分裂症认知症状相关的工作记忆系统。首先，在可能模拟患者有限工作记忆容量的双任务范式中，前额叶皮层的一个基本特征是，至少在双任务条件下，面对刺激处理和反应选择的超极大需求时，激活被减弱（Goldberg et al, 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，在精神分裂症中观察到能力限制和大脑激活减少。第二，在工作记忆容量内增加工作记忆负荷的影响实验中，增加工作记忆中的“工作”（即对记忆材料的操作次数）和“记忆”（即材料的数量）在额叶内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，主要是在运动域准备反应的区域，包括语言反应。增加记忆材料被操纵的程度，会在与工作记忆系统更相关的区域产生分级的生理反应，包括背外侧前额皮质。在一项关于正常衰老过程中认知激活的研究中，我们发现神经生理变化依赖于环境（Esposito et al, Brain 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，这取决于特定任务中特定神经系统的作用。在年轻受试者执行任务时生理活动通常被抑制的区域，年长受试者激活的更多，而且，他们激活的越多（或未能抑制），他们在任务中的表现就越差。在其他领域，年轻人在执行任务时通常会增加生理活动，而老年人的活动较少；这些区域越不活跃，他们的表现就越差。我们开发了一种估算认知激活研究中与统计参数图相关的体素级统计能力的技术，并说明了图像平滑对显著激活的预期再现性的影响（Van Horn等人，NeuroImage, 1998）。在WCS范式中对40名受试者进行扫描。使用SPM对注册数据进行分析，并使用非中心f分布方法对t-map结果图像生成体素统计功率估计。在临界α值为0.01，功率阈值为80%和95%时，在N值为5和10的情况下，拒绝与任务相关的大脑区域的零假设的能力可能不足以确保重大发现的可重复性。当样本量超过20名受试者时，在右侧DLPFC、双侧下顶叶和双侧下颞叶中发现功率超过90%，包括在WCS中典型观察到的皮质网络。最大化统计能力所需的过滤器大小变化很大，但系统地跨区域，倾向于遵循已知的解剖标志和功能反应性脑结构的并置于一起。

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.