Neural correlates of sleep recovery following melatonin treatment for pediatric concussion: a randomized control trial
Bibliographic record
Abstract
ABSTRACT Evidence-based treatments for children with persistent post-concussion symptoms (PPCS) are few and limited. Common PPCS complaints such as sleep disturbance and fatigue could be ameliorated via the supplementation of melatonin, which has significant neuroprotective and anti-inflammatory properties. This study aims to identify neural correlates of melatonin treatment with changes in sleep disturbances and clinical recovery in a pediatric cohort with PPCS. We examined structural and functional neuroimaging (MRI) in 62 children with PPCS in a randomized, double-blind, placebo-controlled trial of 3mg or 10mg of melatonin ( NCT01874847 ). The primary outcome was the total youth self-report Post-Concussion Symptom Inventory (PCSI) score after 28 days of treatment. Secondary outcomes included the change in the sleep domain PCSI score and sleep-wake behavior (assessed using wrist-worn actigraphy). Whole-brain analyses of (i) functional connectivity (FC) of resting-state fMRI, and (ii) structural grey matter (GM) volumes via voxel-based morphometry were assessed immediately before and after melatonin treatment and compared to placebo in order to identify neural effects of melatonin treatment. Increased FC of posterior default mode network (DMN) regions with visual, somatosensory and dorsal networks was detected in the melatonin groups over time. FC increases also corresponded with reduced wake periods ( r= −0.27, p= 0.01). Children who did not recover ( n =39) demonstrated significant FC increases within anterior DMN and limbic regions compared to those that did recover (i.e. PCSI scores returned to pre-injury level n =23) over time, ( p= 0.026). Increases in GM volume within the posterior cingulate cortex were found to correlate with reduced wakefulness after sleep onset ( r= −0.32, p= 0.001) and sleep symptom improvement ( r= 0.29, p= 0.02). Although the melatonin treatment trial was negative and did not result in PPCS recovery (with or without sleep problems), the relationship between melatonin and improvement in sleep parameters were linked to changes in function-structure within and between brain regions interacting with the DMN.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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 source (direct Gemma or distilled Codex), 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".