Alpert Nathaniel M, Badgaiyan Rajendra D, Livni Elijahu, Fischman Alan J
Division of Nuclear Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Neuroimage. 2003 Jul;19(3):1049-60. doi: 10.1016/s1053-8119(03)00186-1.
Over the last decade, it has become possible to study theories of cognition using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These methods yield statistical parametric maps of changes in cerebral blood flow (CBF) elicited by cognitive tasks. A limitation of these studies is that they provide no information about the underlying neurochemistry. However, it is possible to extend the concept of activation studies to include measurements targeting neurotransmitters and specific receptor populations. Cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level. The increased neurotransmitter level can be used to alter the kinetics of specifically bound radioligands. We describe a new approach to the design and analysis of neuromodulation experiments. This approach uses PET, a single-scan session design, and a linear extension of the simplified reference region model (LSSRM) that accounts for changes in ligand binding induced by cognitive tasks or drug challenge. In the LSSRM, an "activation" parameter is included that represents the presence or absence of change in apparent dissociation rate. Activation of the neurotransmitter is detected statistically when the activation parameter is shown to violate the null hypothesis. Simulation was used to explore the properties of the LSSRM with regard to model identifiability, effect of statistical noise, and confounding effects of CBF-related changes. Simulation predicted that it is possible to detect and map neuromodulatory changes in single-subject designs. A human study was conducted to confirm the predictions of simulation using (11)C-raclopride and a motor planning task. Parametric images of transport, binding potential, areas of significant dopamine release, and statistical parameters were computed. Examination of the kinetics of activation demonstrated that maximum dopamine release occurred immediately following task initiation and then decreased with a half-time of about 3 min. This method can be extended to explore neurotransmitter involvement in other behavioral and cognitive domains.
在过去十年中，利用正电子发射断层扫描（PET）和功能磁共振成像（fMRI）来研究认知理论已成为可能。这些方法能生成由认知任务引发的脑血流量（CBF）变化的统计参数图。这些研究的一个局限性在于它们没有提供关于潜在神经化学的任何信息。然而，有可能扩展激活研究的概念，将针对神经递质和特定受体群体的测量包括在内。认知激活会提高神经元的 firing 速率，增加内源性神经递质水平。增加的神经递质水平可用于改变特异性结合放射性配体的动力学。我们描述了一种用于神经调节实验设计和分析的新方法。这种方法使用PET、单次扫描会话设计以及简化参考区域模型（LSSRM）的线性扩展，该扩展考虑了由认知任务或药物激发引起的配体结合变化。在LSSRM中，包含一个“激活”参数，该参数表示表观解离速率是否发生变化。当激活参数被证明违反原假设时，通过统计学方法检测神经递质的激活。使用模拟来探索LSSRM在模型可识别性、统计噪声影响以及CBF相关变化的混杂效应方面的特性。模拟预测在单受试者设计中有可能检测和绘制神经调节变化。进行了一项人体研究，以使用（11）C - 雷氯必利和一项运动规划任务来证实模拟的预测。计算了转运、结合潜力、多巴胺显著释放区域的参数图像以及统计参数。对激活动力学的检查表明，最大多巴胺释放在任务开始后立即发生，然后以约3分钟的半衰期下降。这种方法可扩展用于探索神经递质在其他行为和认知领域中的作用。
