Background: The objective of this study was to examine changes in the activation of the brain reward system following treatment with lisdexamfetamine (LDX) vs. placebo (PL) as a function of clinical improvement in attention deficit/hyperactivity disorder (ADHD) symptoms. Methods: Twenty adults with ADHD were included in a randomized cross-over study. Participants underwent two functional magnetic resonance imaging (fMRI) scans, after receiving 3 to 5 weeks of treatment with both LDX and PL. During scanning, participants performed the passive-avoidance learning task to assess reward-related learning using computational variables (e.g., estimated value and prediction error). Pre-treatment to post-treatment symptom change was assessed via the ADHD Rating Scale (ADHD-RS). The imaging contrasts were Object Choose or Object Refuse during the object choice component of the task, modulated by expected value (reward vs. nonreward cue), and Reward vs. Punishment during feedback, modulated by prediction error (expected vs. actual outcome). To address the primary objective, we performed group-level mass univariate analyses between pre-treatment to post-treatment percent change of the ADHD-RS total scores and the four contrast images under the choice and feedback conditions, with significance set at a whole-brain voxel-wise threshold of p < .05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. Results: Improvement in ADHD symptoms was accompanied by significant increases of brain activation during the Object Refuse, Reward and Punishment contrasts in a widespread network including left caudate and putamen, and right orbitofrontal cortex (i.e., reward-related signaling) and left middle frontal, superior frontal, and precentral gyri (i.e., executive control). Conclusions: These findings are the first to show that the increase in responsiveness of systems engaged in reward processing with LDX treatment is positively related to symptom improvement. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD.

背景：本研究的目的是检查用 lisdexamfetamine (LDX) 与安慰剂 (PL) 治疗后大脑奖励系统激活的变化作为注意力缺陷/多动障碍 (ADHD) 症状临床改善的函数。方法：一项随机交叉研究包括 20 名患有 ADHD 的成年人。在接受 LDX 和 PL 治疗 3 至 5 周后，参与者接受了两次功能性磁共振成像 (fMRI) 扫描。在扫描期间，参与者执行被动回避学习任务以使用计算变量（例如估计值和预测误差）评估与奖励相关的学习。通过 ADHD 评定量表 (ADHD-RS) 评估治疗前到治疗后症状变化。在任务的对象选择部分，成像对比是对象选择或对象拒绝，由预期值（奖励与非奖励提示）调制，反馈期间的奖励与惩罚，由预测误差（预期与实际结果）调制。为了实现首要目标，p < .05，采用家庭错误 (FWE) 校正和 50 个连续体素的范围（集群）阈值。结果：ADHD 症状的改善伴随着对象拒绝、奖励和惩罚对比期间大脑激活的显着增加，包括左尾状核和壳核、右眶额叶皮层（即奖励相关信号）和左中额叶，额上回和中央前回（即执行控制）。结论：这些发现首次表明，通过 LDX 治疗参与奖励处理的系统的反应性增加与症状改善呈正相关. 结果支持这样的假设，即 LDX 治疗可以恢复 ADHD 成人大脑奖赏回路内功能障碍（例如，低激活）的平衡。