Objective:

Evaluate associations between structural abnormalities in cerebellar peduncles (CP), executive functioning (EF) deficits, ADHD symptoms, and behavioral outcomes in youth with Neurofibromatosis Type I (NF1).

Background:

NF1 results from mutations in the NF1 gene, reducing neurofibromin, a negative regulator of the RAS pathway essential for nervous system (NS) development, including cerebellar formation. This mutation increases the risk of NS tumors and leads to cognitive challenges, such as deficits in attention and EF. Youth with NF1 (about 40%) are diagnosed with ADHD, but the underlying etiology of these impairments remains unclear. This study explores associations between impaired development of CP—white matter (WM) tracts connecting the cerebellum to the prefrontal cortex, critical for EF—and cognitive and EF in youth with NF1.

Design/Methods:

The study included 29 participants: NF1-only (n=15; mean age 10.8) and NF1+ADHD (n=14; mean age 9.94). Cognitive assessments included the WISC-V, TEA-Ch, NEPSY-II, BRIEF, and CBCL. MRI scans provided Diffusion Tensor Imaging (DTI) metrics of fractional anisotropy (FA) as an indicator of axonal integrity. T-tests compared scores and FA values between groups, and Pearson correlations explored relationships between FA and cognitive scores.

Results:

The NF1+ADHD group showed higher mean scores on the BRIEF and CBCL (p < 0.001), indicating greater EF, attention, and externalizing deficits. They also had lower mean scores on NEPSY inhibition and TEA-Ch tasks (p < 0.05), reflecting greater cognitive control difficulties. DTI analysis revealed reduced FA in the left inferior CP (p < 0.01) in the NF1+ADHD group, suggesting impaired axonal integrity. FA significantly correlated with NEPSY Inhibition (r = 0.308, p < 0.05) and the BRIEF Global Executive Composite (r = -0.404, p < 0.05) suggesting that reduced WM integrity may contribute to EF deficits.

Conclusions:

EF, inhibition, and attention deficits are heightened in youth with NF1+ADHD, with impaired WM integrity in the inferior cerebellar peduncle potentially contributing.