The effects of ROBO1 on Interhemispheric Connections in Neurotypical Adolescents and Young Adults

Poster No:

1036 

Submission Type:

Abstract Submission 

Authors:

Nea Rinne1, Patrik Wikman1, Elisa Sahari2, Juha Salmi3, Elisabet Einarsdottir4, Juha Kere5, Kimmo Alho1

Institutions:

1University of Helsinki, Helsinki, Uusimaa, 2University of Turku, Turku, Varsinais-Suomi, 3Aalto University, Espoo, Uusimaa, 4KTH-Royal Institute of Technology, Solna, Södermanland, 5Karolinska Institutet, Huddinge, Södermanland

First Author:

Nea Rinne  
University of Helsinki
Helsinki, Uusimaa

Co-Author(s):

Patrik Wikman  
University of Helsinki
Helsinki, Uusimaa
Elisa Sahari  
University of Turku
Turku, Varsinais-Suomi
Juha Salmi  
Aalto University
Espoo, Uusimaa
Elisabet Einarsdottir  
KTH-Royal Institute of Technology
Solna, Södermanland
Juha Kere  
Karolinska Institutet
Huddinge, Södermanland
Kimmo Alho  
University of Helsinki
Helsinki, Uusimaa

Introduction:

Corpus callosum (CC) is a white matter (WM) structure in the human brain connecting the two hemispheres. It enables interhemispheric communication facilitating many cognitive functions. Maturation of the posterior CC, which connects areas critical in linguistic processing, may be related to the development of reading skills. Notably, the dyslexia susceptibility gene ROBO1 plays a role in axonal crossing between the hemispheres, suggesting that reduced hemispheric lateralisation in dyslexia might be due to genetic variation. The preregistered aim of this study was to determine, whether genetic variation in ROBO1 explains variation in the interhemispheric WM tracts. We conducted tractography for the CC and studied whether five single nucleotide variations (SNVs) in ROBO1 explain differences in the number of CC streamlines.

Methods:

The participants (n = 177) were healthy 13-to-25-year-olds with normal reading skills. Diffusion weighed images consisting of 70 slices were acquired using 64 diffusion gradients, with 3T MAGNETOM Skyra whole-body scanner in the Advanced Magnetic Imaging centre at the Aalto University. Diffusion tensor images (DTI) were analysed with the Explore DTI software (Leemans et al. 2019). Tractography through anterior, middle anterior, central, middle posterior, posterior and the whole CC was conducted based on FreeSurfer (http://surfer.nmr.mgh.harvard.edu/) parcellation. The number of WM tracts delineated from the five CC segments were normalised against the number of tracts derived from the whole CC tractography. The genotyping of five SNVs from ROBO1 (rs6770755, rs7651370, rs7631357, rs7637338, rs9853895) was performed at a certified core facility at Karolinska University Hospital, using the Agenda iPLEX platform. Mixed ANOVAs were employed to assess the relationship between the SNVs and the number of WM tracts.

Results:

Two ROBO1 SNVs were significantly associated with the number of CC tracts: Variation rs7637338 was associated with the number of tracts in the whole CC (F(1,172) = 6.49, p = 0.012, η2 = 0.036), whereas variation in rs7631357 was associated with the number of tracts in the central CC (F(2,170) = 3.79, p = 0.025, η2 = 0.043).

Conclusions:

The present results provide further evidence that the dyslexia susceptibility gene ROBO1 is important for the development of interhemispheric WM tracts. Our results suggest that the reduced hemispheric lateralization in developmental dyslexia may be attributed to genetic factors.

Disorders of the Nervous System:

Neurodevelopmental/ Early Life (eg. ADHD, autism)

Genetics:

Genetic Association Studies

Language:

Reading and Writing 1

Novel Imaging Acquisition Methods:

Diffusion MRI 2

Keywords:

Language
MRI
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - imaging genetics

1|2Indicates the priority used for review

Provide references using author date format

Leemans, A.J. (2019) 'ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data.', Proceedings of the International Society for Magnetic Resonance in Medicine, vol. 17, no. 1, pp. 3537