Human Brain Function And Drug Abuse

这个项目的总体目标是确定导致或导致药物依赖的大脑功能模式，并在开发新的治疗方法方面提出建议。我们的研究策略包括使用正电子发射断层扫描(PET)来评估各种药物滥用和认知激活对大脑活动的影响，使用[F-18]氟脱氧葡萄糖的大脑代谢率和使用[O-15]-水的局部脑血流和磁共振成像(MRI)来评估药物滥用的结构性后遗症。 前额叶皮质及其与边缘结构的联系调节着吸毒者可能受损的执行认知和情绪调节功能的特定方面，例如，冲动控制、决策、持续注意力、冒险和唤醒能力。戒毒者(N=21)和非使用者控制者(N=20)在情绪Stroop、冲动持续执行任务(CPT)和警戒CPT中的表现相似，但吸毒者在测量警觉性、冲动和情绪干扰的简单任务中表现出更强的皮肤传导反应。吸毒者在赌博和罗杰斯决策任务中的表现更差，这表明他们对后果的敏感度相对较低，冒险行为增加；吸毒者在这些任务中皮肤电导的增加也明显低于对照组。吸毒者在所有任务中表现出较低的心率。我们的结论是，涉及决策、对后果的敏感性和情绪调节的复杂任务区分了吸毒者和控制者。由于高风险决策是药物滥用的一种标志性行为表型，对其生物学基础的理解可能有助于开发成瘾障碍的治疗方法。因此，我们将测量这一功能的认知任务(罗杰斯决策任务)与区域脑灌注(PET-[O-15]-水)的测量配对，以识别可能导致禁欲吸毒者(3个月)和健康对照组受试者这类决策缺陷的大脑结构或回路。与对照受试者相比，吸毒者表现出更大的冒险精神和对奖励的高度敏感性。他们也表现出与任务相关的左侧前扣带回前皮质的失活，而对照组受试者表现出激活。在吸毒者组中，任务成绩与右侧杏仁核、左侧扣带回前回、左侧眶前皮质和左侧顶叶的激活呈负相关，而与右侧脑岛的激活呈正相关。药物滥用严重程度与右眶前额内侧活动度呈正相关。控制组被试的激活度与任务绩效之间没有显著的相关性。与任务相关的区域灌流和高风险决策之间的不同关联，对比这两组人，表明吸毒者在应对这类认知挑战时，大脑皮质边缘区域的分布网络出现了异常反应。 美沙酮维持是阿片成瘾的主要治疗方法，但在长期治疗中使用美沙酮的好处存在争议。15名非美沙酮(6-24个月)阿片类药物滥用者、12名阿片类药物滥用者接受美沙酮维持治疗(稳定剂量超过6个月)和13名对照受试者参加了这项研究。停用美沙酮的受试者双侧外周回和左侧扣带回的[F-18]氟代脱氧葡萄糖和正电子发射计算机断层扫描(PET)测量的相对代谢活性低于对照组。相比之下，服用美沙酮的受试者在左侧脑岛、丘脑和左侧顶下小叶表现出较低的相对活动(与对照组相比)；然而，他们在生殖器周围前扣带回和右侧顶下小叶的相对活动超过对照。在停用美沙酮的受试者中，抑郁程度与左侧生殖器周围回和扣带中回的相对活跃度呈正相关；在对照组受试者中，类似的联系呈负相关。服用美沙酮的受试者在抑郁状态指标和右侧顶下小叶和右侧扣带回周围前叶的相对活动之间，以及在左侧顶下小叶的抑郁特征指标和相对活动之间，显示出负相关。美沙酮的维持可以改善为负性情感状态服务的神经回路的功能异常，但会抑制某些高阿片受体密度区域的大脑功能。 我们证明，与不吸食大麻的人相比，吸食大量大麻的人在爱荷华州的决策任务上存在表现缺陷，但在Stroop冲突任务上没有表现出缺陷。使用基于体素的形态计量学方法，在结构磁共振图像上，与不吸食大麻的人相比，吸食大量大麻的样本发现海马区和中央前回的脑组织成分(灰质和白质)发生了变化。

The overall goal of this project is to identify patterns of brain function that contribute to or result from dependence on drugs, and to suggest leads in the development of new treatment methods. Our research strategies involve the use of positron emission tomography (PET) to evaluate the effect of various drugs of abuse and cognitive activation on brain activity using cerebral metabolic rates for glucose using [F-18]fluorodeoxyglucose and regional cerebral blood flow using [O-15]-water and and magnetic resonance imaging (MRI) to evaluate structural sequelae of drug abuse. The prefrontal cortex and its connections to limbic structures modulate particular aspects of executive cognitive and emotional regulatory functions that may be impaired in drug abusers, e.g., impulse control, decision-making, sustained attention, risk taking, and arousability. Performance of abstinent drug abusers (N=21) and nonuser control participants (N=20) in the Emotional Stroop, an impulsivity continuous performance task (CPT) and a vigilance CPT revealed similar performance during simple tasks that measured vigilance, impulsivity and emotional interference, but drug abusers showed stronger skin conductance responses. Drug abusers performed more poorly on the Gambling and Rogers Decision Making Tasks, suggesting relative deficits in sensitivity to consequences and increased risk taking; drug abusers also showed significantly less increase in skin conductance than controls during these tasks. Drug abusers exhibited lower heart rates throughout performance on all tasks. We concluded that complex tasks involving decision-making, sensitivity to consequences and emotional regulation discriminated between drug abusers and controls. As risky decision-making is a hallmark behavioral phenotype of drug abuse, an understanding of its biological bases might inform efforts to develop therapies for addictive disorders. We therefore paired a cognitive task that measures this function (Rogers Decision-making Task) with measures of regional cerebral perfusion (PET-[O-15]-water) to identify brain structures or circuits that may underlie deficits in this type of decision-making in abstinent drug abusers (> 3 months) and healthy control subjects. The drug abusers showed greater risk-taking and heightened sensitivity to rewards than the control subjects. They also exhibited task-related deactivation of the left pregenual anterior cingulate cortex, whereas the control subjects showed activation. In the drug abuser group, performance on the task negatively correlated with activation in the right amygdala, left anterior cingulate gyrus, left lateral orbitofrontal cortex, and left parietal lobule, but positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. No significant correlations were found between activation and task performance of control subjects. The different associations between task-related regional perfusion and risky decision-making, comparing the two groups, suggest an abnormal response in a distributed network of corticolimbic regions in drug abusers responding to this type of cognitive challenge. Methadone maintenance is the primary treatment for opiate addiction, but controversy surrounds the merits of its use in long-term treatment. Fifteen methadone-free (6-24 months) opiate abusers, twelve opiate abusers receiving methadone maintenance (stable dose over 6 months), and thirteen control subjects participated in this study. Methadone-withdrawn subjects had lower relative metabolic activity measured by [F-18]fluorodeoxyglucose and PET than control subjects in bilateral perigenual and the left middle cingulate gyrus. In contrast, methadone-maintained subjects exhibited lower relative activity (vs. control) in the left insula, the thalamus, and the left inferior parietal lobule; however, they exceeedded control aactivity in the perigenual anterior cingulate gyrus and the right inferior parrietal lobule. Measures of depression covaried positively with relative activity in the left perigenual and mid-cingulate gyrus in methadone-withdrawn subjects; analogous associations in control subjects covaried negatively. Methadone-maintained subjects exhibited negative covariance between state measures of depression and relative activity in the right inferior parietal lobule and the right perigenual anterior cingulate, and between trait measures of depression and relative activity in the left inferior parietal lobule. Methadone maintenance ameliorates functional abnormalities in the neural circuitry sub-serving negative affective states, but depresses brain function in some regions of high opiate receptor density. We demonstrated that heavy marijuana users have performance deficits on the Iowa decision-making task, but not on the Stroop conflict task when compared to non-users. A sample of heavy marijuana users was found to have altered brain tissue composition (gray matter and white matter) in the hippocampa region and precentral gyrus on structural MR images compared to non-users using voxel-based morphometry.