Network hyperconnectivity and altered saccadic response suggests impairments in visuomotor skills following mild traumatic brain injury: A study of post-trauma vision syndrome 

Nicole S. Coverdale1, Allen A. Champagne1, Matti D. Allen2, Don C. Brien1, Juan Fernandez-Ruiz3, Jessica M. Trier2, Douglas J. Cook1,4

1.	Centre for Neuroscience Studies, Queen’s University, Kingston, ON, Canada 
2.	Department of Physical Medicine and Rehabilitation, Queen’s University, Kingston, ON, Canada
3.	Departamento de Fisiología, Facultad de Medicina, Universidad NacionalAutónoma de México, Ciudad de México, México
4.	Department of Surgery, Queen’s University, Kingston, ON, Canada

Background
A subset of mild traumatic brain injury (mTBI) patients experience prolonged symptoms that negatively affect quality of life. In particular, some patients report specific problems with vision and balance that can be termed post-trauma vision syndrome (PTVS), including binocular vision dysfunction, photophobia, balance impairment, and other visual symptoms such as objects appearing to move. PTVS is thought to be related to dysfunction relative to focal and ambient visual processing, but little is understood about its pathophysiology. In this study, we combined resting state analyses and eye tracking to characterize differences in network connectivity and eye movements between adults with mTBI and PTVS, and healthy age- and sex-matched controls.

Methods
Thirteen adults were recruited to participate in this study (n=7 mTBI, 5F, 48  13 years, 869  470 days since injury; n=6 controls, 4F, 45  14 years). Patients were included if they had a normal MRI or CT scan, and a physician had diagnosed them as having symptoms consistent with PTVS. A dual echo pseudocontinuous arterial spin labelling sequence was performed and blood oxygen level dependent (BOLD) data were extracted from the second echo for resting state analysis. Following pre-processing of the BOLD resting images, an independent component analysis was used to identify the spatial distribution of the network of interests, which were then clustered into nodes of interests (NOI). Mean regional BOLD timeseries were extracted for each node, and correlated across NOIs, and between networks. In addition to imaging data, eye tracking was performed during a pro- and anti-saccade protocol where the colour of the central fixation point indicated whether a pro- or anti-saccade should be performed. Complete eye tracking data was obtained on a subset of participants who completed the MRI (6 mTBI and 4 controls), in order to evaluate oculomotor skills, between the groups. 

Results
Compared to controls, the mTBI group had increased functional connectivity between nodes in the sensorimotor, salience, visuospatial, and high visual networks. Reaction time for voluntary saccades in the anti-saccade task was also significantly increased in the mTBI group, compared to controls (350  83 ms in mTBI versus 226  24 ms in control; p=0.02). 

Conclusions
Resting state network connectivity was altered in mTBI patients with a specific set of vision and balance problems, compared to healthy controls. Also, we identified behavioural changes, observable in anti-saccade reaction time, which suggests that bottom-up oculomotor processing is intact in this mTBI population, while top-down output is impaired. These results suggest that mTBI-related alterations in vision and balance affect top-down oculomotor responses, and resting state networks related to sensation, salience and high order visual processing. Further recruitment of mTBI patients will allow us to establish possible correlations between behavioral outcomes and resting state networks.

Network hyperconnectivity and altered saccadic response suggests impairments in visuomotor skills following mild traumatic brain injury: A study of post-trauma vision syndrome