Unraveling the relations between post-traumatic stress symptoms, neurocognitive functioning, and limbic white matter in pediatric brain tumor patients

Abstract

Background: Pediatric brain tumor patients are at risk of developing neurocognitive impairments and associated white matter alterations. In other populations, post-traumatic stress symptoms (PTSS) impact cognition and white matter. This study aims to investigate the effect of PTSS on neurocognitive functioning and limbic white matter in pediatric brain tumor patients.

Methods: Sixty-six patients (6-16 years) completed neuropsychological assessment and brain MRI (1-year post-diagnosis) and parents completed PTSS proxy questionnaires (CRIES-13; 1-3 months and 1-year post-diagnosis). Mean Z-scores and percentage impaired (>1SD) for attention, processing speed, executive functioning, and memory were compared to normscores (t-tests, chi-square tests). Multi-shell diffusion MRI data were analyzed for white matter tractography (fractional anisotropy/axial diffusivity). Effects of PTSS on neurocognition and white matter were explored with linear regression models (FDR correction for multiple testing), including age at diagnosis, treatment intensity, and tumor location as covariates. Neurocognition and limbic white matter associations were explored with correlations.

Results: Attention (M = -0.49, 33% impaired; P < .05) and processing speed (M = -0.57, 34% impaired; P < .05) were significantly lower than healthy peers. PTSS was associated with poorer processing speed (β = -0.64, P < .01). Treatment intensity, age at diagnosis, and tumor location, but not PTSS, were associated with limbic white matter metrics. Neurocognition and white matter metrics were not associated.

Conclusions: Higher PTSS was associated with poorer processing speed, highlighting the need for monitoring, and timely referrals to optimize psychological well-being and neurocognitive functioning. Future research should focus on longitudinal follow-up and explore the impact of PTSS interventions on neurocognitive performance.

Keywords: PTSS; limbic system; neurocognition; pediatric brain tumor; white matter.

Figure 1.

Flowchart of participant enrollment and available data. ¹Patients who were initially treated at shared care centers, and continued treatment at the Princess Máxima Center, were invited for participation for the 1-year timepoint.

Figure 2.

White matter tracts that were constructed using TRACULA. Seven tracts are in/around the limbic system and the MCP is added as control tract. FA and AD scores were averaged across left and right.