Sex-specific differences in resting-state functional brain activity in pediatric concussion
Bibliographic record
Abstract
ABSTRACT Importance Pediatric concussion has a rising incidence and can lead to long-term symptoms in nearly 30% of children. Resting state functional magnetic resonance imaging (rs-fMRI) disturbances are a common pathological feature of concussion, though no studies have examined sex-differences with respect to this outcome. Despite known sex-differences in how pediatric concussion presents, females have remained understudied in rs-fMRI studies, precluding a sex-specific understanding of the functional neuropathology of pediatric concussion. Objective To provide the first insights into sex-specific rs-fMRI differences in pediatric concussion. Design, setting, and participants Secondary data analysis of rs-fMRI data collected on children with concussion recruited from in a pediatric hospital setting, with control data accessed from the open-source ABIDE-II database. In total, 27 children with concussion (14 females) approximately one-month post-injury and 1:1 age- and sex-matched healthy controls comprised our sample. Exposure Patients received a physician diagnosis of concussion. ABIDE-II healthy controls were typically developing. Main outcomes & measures Seed-based (which permitted an examination of whole-brain connectivity, fitting with the exploratory nature of the present study) and region of interest (ROI) analyses were used to examine sex-based rs-fMRI differences. Threshold-free cluster enhancement (TFCE) and a family-wise error (FWE) corrected p-values were used to identify significantly different clusters. Results In comparing females with concussion to healthy females, seed-based analyses (in order of largest effect) showed hypo-connectivity between the anterior cingulate cortex of the salience network and the precuneus (TFCE=1173.6, p=FWE=0.002) and cingulate gyrus (TFCE=1039.7, p-FWE=0.008), and the posterior cingulate cortex (PCC) of the default mode network and the paracingulate gyrus (TFCE=870.1, p-FWE=0.015) and sub-callosal cortex (TFCE=795.4, p-FWE=0.037); hyper-connectivity was observed between the lateral pre-frontal cortex and inferior frontal gyrus (TFCE=1215.4, p-FWE=0.002) and lateral occipital cortex (TFCE=854.9, p-FWE=0.020) and between the PCC and cerebellum (TFCE=791.0, p-FWE=0.038). ROI analyses showed primarily patterns of hyper-connectivity in females. No differences were observed between males with concussion and healthy males on seed-based or ROI analyses. Conclusions and relevance There are alterations in rs-fMRI in females with concussion at one-month post-injury that are not present in males, which provides further evidence that recovery timelines in pediatric concussion may differ by sex. KEY FINDINGS Question Are there sex-differences in resting state functional brain activity in pediatric concussion? Findings Females with concussion show both hyper- and hypo-connectivity between multiple brain regions when compared to healthy age- and sex-matched controls. The same analyses revealed no differences in resting state brain activity when comparing males with concussion to their age- and sex-matched healthy peers. Meaning There are sex-differences in resting state brain activity in pediatric concussion. This suggests that the functional neuropathology of the injury differs between males and females, which may account for sex-differences in the clinical presentation of pediatric concussion.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.003 | 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".