RCT Methylphenidate & Memory/Attention Training in Traumatic Brain Injury

描述（由申请人提供）：创伤性脑损伤（TBI）是一个重大的公共卫生问题，每年有150万至200万美国人受伤。认知缺陷，尤其是记忆和注意力领域的认知缺陷，往往是脑外伤后挥之不去的残疾的根源，也是受伤个体及其家人/照顾者巨大痛苦的来源。迄今为止，改善慢性认知缺陷的干预措施要么针对药物干预，要么针对认知康复。我们建议(1)比较三种干预措施的效果：记忆和注意力训练（MAAT）、哌醋甲酯和记忆/注意力训练联合哌醋甲酯；(2)使用功能磁共振成像（fMRI）来表征MAAT单独、哌醋甲酯单独和MAAT联合哌醋甲酯对记忆和注意力神经回路激活的影响。这是一个二对二的设计，药物（哌醋甲酯/安慰剂）和认知疗法（记忆和注意力训练（MAAT）或注意力控制干预）作为可能的干预措施。采用随机、安慰剂对照、双盲设计，200名MTBI后6-12个月的持续性认知缺陷患者将被随机分为(1)MAAT和安慰剂、(2)MAAT和哌甲酯（0.3 mg/kg BID）、(3)注意控制干预和哌甲酯（0.3 mg/kg BID）或(4)注意控制干预和安慰剂。在基线和四种治疗条件下，进行fMRI时的症状困扰、注意和记忆表现以及注意和记忆神经回路的激活模式。这项研究将提供关于三种干预措施的重要信息，以解决一个巨大的公共卫生问题的最严重的致残后遗症。此外，它将有助于阐明潜在的神经机制，并提出额外的治疗可能性。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a significant public health problem, with 1.5-2.0 million Americans injured each year. Cognitive deficits, particularly in the domains of memory and attention are frequently the source of lingering disability after TBI and a source of enormous distress to the injured individuals and their family/caregivers. To date, interventions to ameliorate chronic cognitive deficits have been directed at either pharmacological interventions or cognitive rehabilitation. We propose to (1) To compare the efficacy of three interventions: memory and attention training (MAAT), methylphenidate, and memory/attention training in combination with methylphenidate and (2) use functional MRI (fMRI) to characterize changes in activation of the neural circuitry of memory and attention due to MAAT alone, methylphenidate alone, and MAAT in combination with methylphenidate. This is a two by two design with medication (methylphenidate/placebo) and cognitive therapy (Memory and Attention Training (MAAT) or an Attention control intervention) as possible interventions. Using a randomized, placebo-controlled, double-blind design, 200 individuals with persistent cognitive deficits 6-12 months after MTBI will be randomized to receive a six week trial of either (1) MAAT and placebo, (2) MAAT and methylphenidate (0.3 mg/kg BID) (3) attention control intervention and methylphenidate (0.3 mg/kg BID) or (4) attention control intervention and placebo. Symptom distress attention and memory performance, and activation patterns of the neural circuitry of attention and memory while undergoing fMRI will be characterized at baseline, and after the four treatment conditions. This study will provide important information on three interventions for the most disabling sequelae of an enormous public health problem. Further, it will help to clarify underlying neural mechanisms and suggest additional treatment possibilities.