Neuroanatomical correlates of working memory performance in Neurofibromatosis 1

Abstract

Introduction Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits in working memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspects of cognition. Methods 29 adolescents aged 11-17 years were compared to age and sex-matched controls. NF1 subjects were assessed using detailed multimodal measurements of working memory at baseline followed by a 3T MR scan. A voxel-based morphometry approach was used to estimate the total and regional gray matter(GM) volumetric differences between the NF1 and control groups. The working memory metrics were subjected to a principal component analysis (PCA) approach. Results The NF1 groups showed increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain and cerebellum bilaterally in the NF1 group as compared to controls. Principal component analysis on the working memory metrics in the NF1 group yielded three independent factors reflecting high memory load, low memory load and auditory working memory. Correlation analyses revealed that increased volume of posterior cingulate cortex, a key component of the default mode network (DMN) was significantly associated with poorer performance on low working memory load tasks. Conclusion These results are consistent with prior work showing larger subcortical brain volumes in the NF1 cohort. The strong association between posterior cingulate cortex volume and performance on low memory load conditions supports hypotheses of deficient DMN structural development, which in turn may contribute to the cognitive impairments in NF1.

Pediatric Patient With Neurofibromatosis I Presenting With Perceptual Disturbances and a Suicide Attempt

“…NFI has been found to present with more psychiatric and mood disorders than the general population, likely due to social and physical disabilities as well as alterations in cognition [1]. Brain imaging in patients with NF1 compared to controls without NF1 has shown increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain, and cerebellum bilaterally [2]. Researchers have hypothesized these brain findings correlated with low memory load, learning disabilities, and ADHD in nearly 45% of patients and autism spectrum disorder in nearly 25% of the population [3].…”