Neuroanatomical correlates of working memory performance in Neurofibromatosis 1

Author:

Sawyer Cameron1ORCID,Green Jonathan12,Lim Ben2,Pobric Gorana1,Jung JeYoung3,Vassallo Grace4,Evans D Gareth45,Stagg Charlotte J6,Parkes Laura M17,Stivaros Stavros78,Muhlert Nils1,Garg Shruti12

Affiliation:

1. Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Oxford Road, Manchester M13 9PL , United Kingdom

2. Child & Adolescent Mental Health Department, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre , Manchester, Oxford Road, M13 9WL , United Kingdom

3. School of Psychology, Precision Imaging Beacon, University of Nottingham, University Park , Nottingham NG7 2RD , United Kingdom

4. Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust , Oxford Road, Manchester M13 9WL , United Kingdom

5. Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Oxford Road, M13 9PL , United Kingdom

6. Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences & MRC Brain Network Dynamics Unit, University of Oxford , OX3 9DU , United Kingdom

7. Geoffrey Jefferson Brain Research Centre, Northern care Alliance NHS Foundation Trust , Stott Lane, Manchester M6 8HD , United Kingdom

8. Academic Unit of Paediatric Radiology, Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust , Oxford Road, M13 9PL , United Kingdom

Abstract

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.

Funder

Neurofibromatosis Therapeutic Acceleration Program

National Institute for Health Research

Beacon Anne McLaren Research Fellowship

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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