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Is there an association between reduced cortico-spinal tract (CST) integrity and severe visual impairment in childhood neural development?



Background: Severe congenital visual impairment (VI) possibly impacts on motor development because of lack of visuo-motor activity from birth, though very limited systematic research has investigated associated neural pathways. The present study investigated if differences are found in diffusion parameters within the cortico-spinal tract between children with severeVI and typically developing (TD).Methods: Six VI children with congenital disorders of the peripheral visual system (9.19–12.34y, three girls) and 10 TDcontrols (8.56–12.13y, six girls).Diffusion-weighted MRI with 60 directions was acquired with an isotropic image resolution of 2.5 mm. The CST in each hemisphere was reconstructed with probabilistic fibre tracking using a 3 mm spherical seed in the pons and a20 mm spherical inclusion ROI covering the precentral sulcus.Diffusion parameters (fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD)) within theCST were compared between groups.Results: FA within the CST was reduced in the VI compared to the control group (right: VI: 0.510.011; control:0.540.008; left: VI: 0.50.008 control: 0.520.001) while whole brain FA was not significantly different (VI:0.0380.0013; control: 0.0390.0029). RD was higher in theVI group (right: VI: 7.9291043.29105control:6.7291041.629105; left: VI: 7.1291042.3405, control: 7.63910339105) and ADC was not significantly different (right: VI: 8.6591041.39106control:8.59910416.069106, left: VI: 7.129104 1.39105; control: 8.1991041.319105).Discussion: This is the first study to identify reduced micro-structural integrity (FA) of the CST in VI, with differences inRD suggesting reduced axonal density or myelination. The causation of these structural differences in the motor systemin children with VI is unknown, but questions are raised of the impact of differences in early visuo-spatial motor experiences
Joe Bathelt1, Jamie M Kawadler1 , Michelle de Haan1, Naomi J Dale1,2, Chris A Clark1
Is there an association between reduced cortico-spinal tract
integrity and severe visual impairment in childhood neural
1 University College London Institute of Child Health!
2 Great Ormond Street Hospital for Children NHS Foundation Trust
Congenital disorders of the peripheral visual system (CDPVS) are disorders leading to
reduced vision due to defects of the globe of the eye, retina or anterior optic nerve. Primary
defects are isolated in many cases, but secondary effects of visual impairment are likely. For
instance, severe congenital visual impairment (VI) possibly impacts on motor development
because of lack of visuo-motor activity from birth.!
The present study investigated differences in diffusion parameters within the cortico-spinal
tract (CST) in school-age children with VI. The CST is the main motor pathway that relays
information from the primary motor cortex to peripheral effectors via the spinal cord. !
The preliminary results indicate reduced fractional anisotropy in the right CST and trend-level
reductions in FA within the right CST. These results suggest micro-structural changes in the
CST in children with congenital visual impairment.!
Children with visual impairment are particularly vulnerable to adverse developmental
outcome (Dale & Sonksen 2002). Based on previous behavioural studies that found changes
in motor skills and behaviour in children with visual impairment (Houwen et al., 2009), the
current study aimed to investigate potential neural correlates within the cortico-spinal tract as
the main motor tract between the motor cortex and peripheral effectors.
The current investigation identified reduced fractional anisotropy within the CST in school-
age children with congenital disorders of the peripheral visual system. A reduction in FA
indicates reduced overall microstructural integrity. Differences in other diffusion measures
were less clear. Further, the data shows considerable variability in diffusion parameters in the
VI group: some cases show similar diffusion measures to the controls, while others are
markedly different. This variability does not seem to be explained by variation in age, gender
or verbal IQ. However, correlation analyses are tentative given the limitations of the current
sample. Future studies will evaluate the relationship of these findings to vision level and
performance on motor tasks.
Dale, N., & Sonksen, P. (2002). Developmental outcome, including setback, in young children with
severe visual impairment. Developmental Medicine & Child Neurology, 44(9), 613–622.
Houwen, S., Hartman, E., & Visscher, C. (2009). Physical activity and motor skills in children with and
without visual impairments. Medicine and Science in Sports and Exercise, 41(1), 103–109.
Imfeld, A., Oechslin, M. S., Meyer, M., Loenneker, T., & Jancke, L. (2009). White matter plasticity in the
corticospinal tract of musicians: a diffusion tensor imaging study. NeuroImage, 46(3), 600–607. doi:
Potentially simple disorders of the peripheral visual system (‘simple’ CDPVS) are rare
disorders affecting the globe of the eye, retina or optic nerve up to the optic chasm; no
other brain involvement is diagnostically indicated in potentially simple disorders
Visual impairment may have secondary effects leading to alterations in neural and
cognitive development compared to typically sighted peers (Dale & Sonksen, 2002)
Early studies had identified the constraints that visual impairment poses on motor
development in infants and preschool children through diminished drive, poor body image
and deficits in sensori-motor integration (Houwen et al., 2009).
This study investigated differences in diffusion parameters within the cortico-spinal tract, as
the main motor tract, between typically-sighted children and with children with ‘simple’
We want to thank all families that participated in this
research and the charities that supported this work
Materials & Methods
Children with visual impairment were recruited through Great Ormond Street Hospital for Children
and Moorfields Eye Hospital. Control participants were scanned as part of a different study using an
identical MRI protocol. Participants were 6 VI children with CDPVS (9.19-12.34y, 3 girls) and 10
typically developing controls (8.56-12.13y, 6 girls). Vision levels in the VI group according to WHO
definitions: profound VI (light perception at best, n=1), severe VI (basic ‘form’ vision to max. 6/36;
n=3), mild/moderate VI (6/36-6/24; n=2)
MRI data acquisition
Magnetic resonance imaging data was acquired on a 1.5 T clinical system with a 32 channel
quadrature head coil. Diffusion MRI was acquired using an isotropic set of 60 directions with an
image resolution of 2.5 x 2.5 x 2.5 mm.
Diffusion model: The
Spherical deconvolution
(CSD) model and colour-
coded eigenvector
directions are shown for
a section of a coronal
slice with parts of the
cortico-spinal tract and
corpus callosum
Processing of diffusion-weighted volumes for probabilistic
Preprocessing included correction for eddy currents, motion artefact
correction and brain extraction using FSL tools.A spherical
deconvolution (CSD) model was fitted to the diffusion data, which
accounts for multiple diffusion directions in each voxel.
Probabilistic tractography of the cortico-spinal tract
Tractography of the CST was based on a spherical seed ROI in the
pons of the brainstem with 3mm radius and a spherical inclusion ROI
with a radius of 20mm including the pre-central sulcus. Both ROIs
were identified on the b0 images for each participant. Probabilistic
tracking in MRTrix was performed separately for each hemisphere with
a target of 1,000 streamlines. For statistical comparison, a visitation
map of voxels that contained at least 100 streamlines was created.
Statistical description
Median scores were used to describe group level effects. Confidence
intervals for median scores were based on bootstrap resampling with
2000 repetitions. Confidence intervals were calculated with bias
correction. The original data points are included for reference.
Significance values were based on independent sample t-tests.
Illustration of the 3D structure of the corticospinal tract obtained through
probabilistic tractography The CST was reconstructed using a seed ROI in the
cerebral peduncle and an inclusion ROI over the motor cortex close to the
precentral sulcus. The figure shows representative tractography results for one
participant overlaid on a b0 image.
* based on Wechsler Intelligence Scale for Children 4th edition
Diffusion parameters indicate microstructural alterations within
the cortico-spinal tract in children with visual impairment
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