Effects of Cognitive Training in Methadone Maintenance Patients

描述(申请人提供)：阿片类药物依赖是一个严重的公共卫生问题。阿片依赖患者表现出额脑功能障碍和认知障碍。认知障碍除了可能影响在工作场所执行日常活动(如开车或执行复杂任务)的能力外，还可能影响参与药物滥用治疗的认知/心理社会方面并从中受益的能力。然而，很少有研究试图补救物质滥用者的认知功能，也没有研究专门针对阿片类药物依赖。工作记忆(WM)是一种重要的认知功能，其核心成分是中央执行功能(一组执行功能)，是执行其他认知功能的必要构件。WM在阿片类药物依赖方面受到损害，已被证明调节药物滥用者的抑制性控制和决策，并预测药物滥用治疗结果。所提出的理论驱动的认知训练程序(WM训练)以工作记忆为目标，并已被证明在各种临床人群(包括与额叶功能障碍相关的疾病)中增加工作记忆容量并转移到其他认知领域，这在训练研究中很少观察到。这项创新性的研究将以对照设计测试25次西医训练的效果，包括3组：进行西医训练的美沙酮维持患者(美沙酮维持组)、不进行西医训练的美沙酮维持组(对照组)和进行西医训练的健康志愿者(高压训练组)。在培训前后将实施一系列最先进的认知测量，药物滥用治疗结果将被列为次要结果。具体目的1是检验一种假设，即在工作记忆训练结束时，工作记忆训练结束时比训练开始时表现出更好的工作记忆成绩。具体目标2是检验这样一种假设，即与基质金属氧化物对照相比，基质金属氧化物训练将在工作记忆和其他认知任务中显示出显著更大的改善。具体目标3是检验这样一种假设，即HV训练后比WM训练前表现出更好的工作记忆和认知表现(作为先前WM训练研究的重复)。第二个目的是比较与没有药物滥用史的健康志愿者相比，西医训练后基质金属蛋白酶的表现改善的幅度，并测试西医训练后基质金属蛋白酶是否显示出改善的物质滥用治疗结果。研究结果将提供关于认知训练改善阿片依赖患者认知功能的潜力的临床相关信息，并将加强对学习能力和基于额叶的认知过程对阿片依赖训练程序的延展性的科学理解。除了对日常功能的广泛影响外，明确确定认知训练对认知功能的影响是系统研究训练对药物滥用治疗结果的影响的必要的第一步。 公共卫生相关性：阿片类药物依赖患者表现出认知障碍，这可能会影响日常功能和药物滥用治疗结果。这项研究将测试一种创新的、基于理论的认知训练程序的能力，以改善美沙酮维持患者的认知功能。

DESCRIPTION (provided by applicant): Opioid dependence is a significant public health problem. Individuals with opioid dependence exhibit frontal brain dysfunction and cognitive impairment. In addition to potentially affecting the ability to perform daily activities such as driving a car or performing complex tasks in the workplace, cognitive impairment may affect the ability to participate in and benefit from cognitive/psychosocial aspects of substance abuse treatment. Yet, few studies have attempted to remediate cognitive functions in substance abusers, and no study has specifically targeted opioid dependence. Working memory (WM) is a critical cognitive function whose core component is the 'central executive' (set of executive functions), and is a necessary building block for the performance of other cognitive functions. WM is impaired in opioid dependence and has been shown to modulate inhibitory control and decision making in substance abusers and to predict substance abuse treatment outcomes. The proposed theoretically driven cognitive training procedure (WM Training) targets working memory, and has been shown to increase working memory capacity in a variety of clinical populations (including conditions associated with frontal dysfunction) and to transfer to other cognitive domains, which is rarely observed in training studies. This innovative study will test the effects of 25 sessions of WM Training in a controlled design with 3 groups: methadone maintenance patients (MMP) who perform WM Training (MMP TRAIN), MMP who do not perform WM Training (MMP CONTROL), and healthy volunteers who perform WM Training (HV TRAIN). A battery of state-of-the art cognitive measures will be administered before and after training, and substance abuse treatment outcomes will be included as secondary outcomes. Specific Aim 1 is to test the hypothesis that MMP TRAIN will show improved performance on the trained working memory tasks at the end versus the beginning of WM Training. Specific Aim 2 is to test the hypothesis that MMP TRAIN will show significantly greater improvement in working memory and other cognitive tasks, relative to MMP CONTROL. Specific Aim 3 is to test the hypothesis that HV TRAIN will show improved working memory and cognitive performance after relative to before WM Training (as a replication within the study of previous WM Training studies). Secondary aims are to compare the magnitude of improved performance following WM Training in MMP relative to healthy volunteers without drug abuse histories, and to test whether MMP show improved substance abuse treatment outcomes following WM Training. Study findings will provide clinically relevant information about the potential of cognitive training to improve cognitive functioning in opioid dependent patients, and will enhance scientific understanding of learning capacity and the malleability of frontally based cognitive processes to training procedures in opioid dependence. In addition to the broad implications for daily functioning, definitively establishing the effects of cognitive training on cognitive functions is a necessary first step in the systematic study of training effects on substance abuse treatment outcomes. PUBLIC HEALTH RELEVANCE: Individuals with opioid dependence exhibit cognitive impairment, which may affect daily functioning and substance abuse treatment outcomes. This study will test the ability of an innovative and theoretically based cognitive training procedure to improve cognitive functioning in methadone maintenance patients.