Neurobiological Basis of Reinforcement-Based Decision-Making in Adults With ADHD Treated With Lisdexamfetamine Dimesylate
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".