Development Of Cognitive Activation Tasks For Functional Neuroimaging

去年，我们研究了工作记忆（WM）的两个组成部分：短时间内信息的维护和对高级认知功能（如语言、推理和解决问题）所必需的信息的操作。早期的WM研究表明，背外侧前额叶皮层（DLPFC）的活动随着维持和负荷需求的增加而增加。这表明DLPFC在信息的主动维持中起作用。很少有研究在行为和生理水平上仔细地消除了这两个WM过程的歧义。使用功能性磁共振成像（fMRI）和Sternberg任务的块设计，我们在前额皮质（PFC）区域内绘制了选择性负载敏感，延迟敏感或两者兼有的区域。在考虑Sternberg任务时，WM负载是通过改变内存集大小（3、5或8个字母）和字母串与探针之间的延迟时间来操纵的。在字母组和探针刺激之间使用两个时间延迟来检验记忆维持的效果。我们发现DLPFC在负荷操作中被强烈激活，而作为延迟功能的激活仅限于左侧运动前区和布洛卡区。右侧的PFC区域被发现完全受负荷影响。这些结果表明，在编码和/或决策过程中，注意力或认知控制的自上而下调节可能是由这些区域介导的。

Last year we examined two components of working memory (WM): maintenance of information for a short period of time and manipulation of information necessary for higher cognitive functions, such as language, reasoning and problem solving. Earlier WM studies demonstrated that dorsolateral prefrontal cortex (DLPFC) activity increases as maintenance and load demand increases. This suggested a role of DLPFC in the active maintenance of information. Few studies have carefully disambiguated these two WM processes at the behavioral and physiological levels. Using functional magnetic resonance imaging (fMRI) and a block design of the Sternberg task, we mapped within the prefrontal cortex (PFC) locales that are selectively load sensitive, delay sensitive, or both. In considering the Sternberg task, WM load was manipulated by varying the memory set size (3, 5, or 8 letters) and the delay period between the string of letters and probe. The effect of memory maintenance was examined by employing two time delays between the letter set and probe stimuli. We found the DLPFC was strongly activated in load manipulation, whereas activation as a function of delay was restricted to the left premotor regions and Broca areas. Regions of PFC on the right were found to be exclusively affected by load. These results suggest the possibility that top-down modulation of attention or cognitive control at encoding and/or decision making may be mediated by these areas. Little is known about the distributed neuronal networks impacted by dopamine modulation in the component process of WM, although working memory is critically mediated by dopaminergic tuning of signal-to-noise in cortical neural assemblies. Here we used the COMT val158met genotype as an index of relative cortical dopamine bioavailability and tuning efficiency. In this new study, we examined the spatial and subprocess specificity by which dopamine modulation occurs within the prefrontal-parietal-striatal network during WM, thus empirically showing that dopamine plays a key role in updating and stabilizing new information at the neural systems level. To do this we employed a cognitive paradigm which allowed separation of the encoding from the response phases in subsequent image analyses. By doing this, we allowed for the isolation of cognitive processes of interest using planned contrasts of activations at the response phases. This paradigm incorporated various aspects of WM and cognitive control, along with a set of control tasks. Each set of WM or control tasks had in common a response phase, which required a sensorimotor response, numerical size determination, or a more complex task that included numerical computation as well as numerical size judgment. We found that temporal updating operations, engaged relatively specific dopaminergic tuning at the DLPFC. Manipulating and rapidly updating representations were sensitive to dopaminergic modulation of neural signaling in a larger prefrontal-parietal-striatal network. These findings add to the integration of dopaminergic signaling in basic cortical assemblies with their roles in specific human brain networks during the orchestration of information processing in WM.