fMRI Measures of Serotonin and Cognitive Measures

其目标是研究调节认知、情感和奖励的大脑系统 并确定这些系统如何受到晚年抑郁症的影响，通过 与抑郁和5-羟色胺实验操作相关的遗传风险因素 级别。在功能磁共振成像(FMRI)期间将使用行为挑战任务来 调查四个具体目标：(1)我们将完成在当前资助期内启动的研究 探讨血管病变对情绪腹侧系统相互作用的影响 老年抑郁症患者执行控制的调节和背部系统。这些 正在进行的研究还包括对当前临床状态的评估，以及治疗是否 导致抑郁症得到缓解。(2)我们将描述遗传对神经的影响 使用在当前时期开发的任务来处理情绪和奖励刺激 测量杏仁核、腹内侧额叶皮质和眼眶额叶皮质以及腹侧额叶皮质的活动，并 第二项任务，测量纹状体、中脑和背部系统的活动，与 关于奖励的决定。(3)我们将评估神经递质水平对神经的影响 情绪和奖赏刺激的处理。神经影像和神经生理学研究 揭示神经元活动的量度和行为状态的量度之间的相关性(例如， 情绪、决策偏好、响应时间)。这种关联表明了功能关系，但 通常都是未经测试的。从功能上探讨情绪/奖励系统对 执行处理系统，我们将从药理上操纵神经递质的水平 使用ATD的5-羟色胺。观察情绪、行为偏好或敏感度的系统性变化 奖励结果将对理解表型变异具有深远的意义 与抑郁、上瘾和焦虑症等症状相关的行为。(4)我们 将评估情绪变化对情绪和奖励的神经处理的影响 刺激物。抑郁的一个常见后果是快感缺失，或无法获得快乐(或 其他情绪反应)来自通常有益的刺激。我们将使用在 当前时期在短时间间隔内操纵情绪状态，我们将研究如何 短暂的负面情绪影响处理情绪和奖励的大脑系统的激活 刺激物。

The goal is to investigate brain systems that mediate cognitive, affective, and reward processing in humans and to determine how these systems are influenced by late life depression, by genetic risk factors associated with depression, and by experimental manipulations of serotonin levels. Behavioral challenge tasks will be use during functional magnetic resonance imaging (fMRI) to investigate four specific aims: (1) We will complete studies initiated in the current funding period that investigate the influence of vascular lesions upon the interaction of ventral systems for emotional regulation and dorsal systems for executive control in patients with late life depression. These on-going studies also include an assessment of current clinical status, and whether treatment has led to a remission from depression. (2) We will characterize genetic influences upon the neural processing of emotional and rewarding stimuli using a task developed in current period that measures activity in amygdala, ventromedial and orbital frontal cortex, and ventral frontal cortex, and a second task that measures activity in striatal, midbrain, and dorsal systems associated with decisions about rewards. (3) We will evaluate the effects of neurotransmitter levels upon the neural processing of emotional and rewarding stimuli. Neuroimaging and neurophysiological studies reveal correlations between measures of neuronal activity and measures of behavioral states (e.g., mood, decision preference, response time). Such correlations suggest functional relationships, but typically remain untested. To functionally probe the effects of emotional/reward systems upon executive processing systems, we will pharmacologically manipulate levels of the neurotransmitter serotonin using ATD. Observation of systematic shifts in mood, behavioral preferences, or sensitivity to reward outcomes would have profound implications for understanding phenotypic variation in behavior associated with conditions such as depression, addiction, and anxiety syndromes. (4) We will evaluate the effects of mood changes upon the neural processing of emotional and rewarding stimuli. A common consequence of depression is anhedonia, or the inability to derive pleasure (or other emotional reaction) from normally rewarding stimuli. We will use procedures developed in the current period to manipulate mood state over short time intervals, and we will investigate how transient negative mood influences activation in brain systems that process emotional and rewarding stimuli.