Rehabilitating Visual Deficits Caused by Stroke

Rehabilitating Visual Deficits Caused by Stroke: Neurochemical and Neurophysiological Markers for Optimal Recovery

This research aims to understand the efficacy of a visual training task to improve visual loss after stroke, also known as hemianopia. The investigators aim to understand whether training can improve vision and which areas or pathways in the brain are responsible for this improvement.

Study Overview

• Status: Recruiting
• Conditions: Hemianopsia; Hemianopia; Quadrantanopia; Stroke Induced Vision Loss
• Intervention / Treatment: Behavioral: Training in the blind field

Detailed Description

Damage to the primary visual cortex (V1) due to stroke usually results in loss of visual function in half of the visual world, this is known as hemianopia. This visual loss can negatively affect quality of life, as most stroke survivors are no longer permitted to drive and have difficulties with navigation and socialising. There are currently limited treatment options, although recent evidence suggests that visual training can be effective in improving visual function (Huxlin et al, 2009; Cavanaugh & Huxlin, 2017). The aim of this research is to determine the capacity for visual rehabilitation after stroke using visual training and to understand the underlying brain mechanisms that might drive these improvements. This study will help the investigators to understand the brain mechanisms involved in visual rehabilitation and may allow the investigators to predict those most likely to benefit from visual rehabilitation in the future.

Twenty stroke survivors with hemi- or quadrantanopia will complete a 6-month visual motion discrimination training programme at home. Each participant will have three study visits; at baseline, 6-months and 9-months. At each visit the investigators will take measures of 1) visual fields 2) detailed tests of visual function 3) quality of life and 4) MRI scans of brain structure, function and neurochemistry. Between the baseline (0 month) and 6-month post-training session, participants will complete visual training at home. Between the 6-month post-training session and 9-month follow up, participants will not complete visual training at home. This study will therefore allow the investigators to determine whether rehabilitation improves conscious visual perception and quality of life as well as providing understanding of the neural mechanisms that underlie this improvement. The investigators will also determine whether improvements or neural changes persist after 3-months without training.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hannah Willis, MPsych; Phone Number: 01865 611458; Email: hannah.willis@ndcn.ox.ac.uk
• Study Contact Backup: Name: Holly Bridge, PhD; Phone Number: 01865 610482; Email: holly.bridge@ndcn.ox.ac.uk

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • Wellcome Centre For Integrative Neuroimaging, University of Oxford
      • Contact: Hannah Willis, MPsych; Phone Number: 01865 611458; Email: hannah.willis@ndcn.ox.ac.uk
      • Contact: Holly Bridge, DPhil; Phone Number: 01865 610482; Email: holly.bridge@ndcn.ox.ac.uk
      • Principal Investigator: Holly Bridge, DPhil
      • Sub-Investigator: Hannah Willis, MPsych
      • Sub-Investigator: Kate Watkins, PhD
      • Sub-Investigator: Krystel Huxlin, PhD
      • Sub-Investigator: Marco Tamietto, PhD
      • Sub-Investigator: Matthew Cavanaugh, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-80
• Participant is willing and able to give informed consent for participation in the study
• Fluent English-speaking healthy adults
• Has suffered damage to the visual cortex at least 6 months before the study

Exclusion Criteria:

• Previous eye disease or impairment other than hemianopia
• Neurological or psychiatric illness
• Contraindication to MRI
• Pregnant or breast feeding
• Second stroke during training

Data quality assurance (participant data will be removed from analysis for the following reasons):

• Concurrent participation in other "vision therapy"
• Unreliable visual fields, indicated by greater than 20% fixation losses, false positives, or false negatives
• Inability to demonstrate fixation stability on eye movement monitored testing
• Failure to complete at least 100 training sessions over 6-months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Training in blind field; All participants undergo this intervention. Internal control is comparing sighted and non-sighted parts of the field.

Behavioral: Training in the blind field; Participants will complete visual training at two locations in the blind field. These two locations of training will be determined at the baseline study visit (0 months) and will be located within the perimetry-defined blind field. The training programme involves discriminating the direction of motion in a small circle of moving dots. The computer software and a chin-rest will be loaned to each participant to complete training at home. Participants will perform 300 trials at each location in their blind field, 5 days a week for at least 24 weeks (40-60 minutes in total). The computer programme will automatically generate a record of participant performance after each home training session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motion discrimination thresholds after 6 months of training	Change in normalised discrimination thresholds on psychophysical motion discrimination task at two trained locations between baseline (0-month) and 6-month follow up. These assessments will be based on what motion can be reliably detected at a 75% correct level of performance.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of improvement in motion discrimination thresholds at 9-month follow up.	No change in normalised discrimination thresholds on psychophysical motion discrimination task at two trained locations between 6-month and 9-month follow up. These assessments will be based on what motion can be reliably detected at a 75% correct level of performance.	9 months
Change in area improved on the Humphrey perimetry (24-2 and 10-2)	Change in area improved on a composite measure of deficit size calculated from 24-2 and 10-2 across both eyes. Area of improvement will be calculated as the area where the sensitivity improved by more than 6 decibels (dB) relative to pre-training.	6 months
Maintenance area improved on the Humphrey perimetry (24-2 and 10-2)	No change in area improved on a composite measure of deficit size calculated from 24-2 and 10-2 across both eyes. Area of improvement will be calculated as the area where the sensitivity improved by more than 6dB relative to pre-training.	9 months
Change in contrast detection at trained locations	Change in detection of stimulus at 1%, 5%, 10%, 50% and 100% contrast baseline (0-month) and 6-month follow up.	6 months
Maintenance contrast detection at trained locations	No change in detection of stimulus at 1%, 5%, 10%, 50% and 100% contrast between the 6-month and 9-month follow up.	9 months
Change in visual quality of life	Change on the Visual Function Questionnaire 25 between baseline (0-month) and 6-month follow up.	6 months
Maintenance of visual quality of life	No change in visual quality of life as measured by the Visual Function Questionnaire 25 between 6-month and 9-month follow up.	9 months
Change in white matter integrity	Change in white matter integrity in lateral geniculate nucleus (LGN) to extrastriate motion area (hMT+) and LGN to primary visual cortex (V1) tracts between baseline (0-month) and 6-month follow up, assessed by diffusion-weighted imaging	6 months
Maintenance of white matter integrity	No change of integrity in LGN-hMT+ and LGN-V1 tracts between 6-month and 9-month follow up, assessed by diffusion-weighted imaging.	9 months
Change in neurochemistry	Change in neurochemistry in visual motion area, hMT+ between baseline (0-month) and 6-month follow up, assessed by Magnetic Resonance Spectroscopy (MRS).	6 months
Maintenance of neurochemistry	No change in neurochemistry in visual motion area, hMT+ between 6-month and 9-month follow up, assessed by Magnetic Resonance Spectroscopy (MRS).	9 months
Change in brain activity during visual stimulation (Blood-oxygen-level-dependent imaging, or BOLD, signal change)	Change in brain activity during moving visual stimulation, assessed by functional magnetic resonance imaging (BOLD signal) in visual motion area, hMT+ between baseline (0 month) and 6-month follow up.	6 months
Maintenance of brain activity during visual stimulation (BOLD signal change)	Maintenance of brain activity during moving visual stimulation, assessed by functional magnetic resonance imaging (BOLD signal) in visual motion area, hMT+ between the 6-month and 9-month follow up.	9 months
Change in resting state connectivity	Change in resting state connectivity in the visual cortex between baseline (0-months) and 6-months, assessed by resting state functional magnetic resonance imaging (BOLD signal)	6 months
Maintenance of resting state connectivity	Maintenance of resting state connectivity in the visual cortex between 6-month and 9-month follow up, assessed by resting state functional magnetic resonance imaging (BOLD signal)	9 months

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: University of Rochester; University of Turin, Italy; University of Texas at Austin
• Investigators: Principal Investigator: Holly Bridge, PhD, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2020
• Primary Completion (Anticipated): October 16, 2024
• Study Completion (Anticipated): October 16, 2024

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Stroke; Vision; Visual training; Blindsight; Visual pathway
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Vision Disorders; Blindness; Stroke; Hemianopsia
• Other Study ID Numbers: R60132/RE001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We plan to share subsets of the data as appropriate.
• IPD Sharing Time Frame: After conclusion of study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes