The role of GABAergic inhibition in the function and dysfunction of the human binocular visual system
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
When you catch a ball in mid-air, or point your finger to press a button, you are using your sensation of depth. The most precise sensation of depth, called 'binocular' depth, comes from using our two eyes together. The two eyes at the front of the face allow two views of the world, with one view slightly shifted to the side with respect to the other. During early childhood, the brain learns to combine these two images to form a single image seen in depth. To do this successfully, the eyes have to point in the same direction and give equally clear images. If the eyes point in different directions, or one eye gives a very blurry image, children can develop a 'lazy eye' where one eye works better than the other. This leads to the weaker eye being ignored by the brain. Lazy eye is one of the most common visual problem in children.
Scientists think that one of the reasons why the weak eye is ignored by the brain is because of a neurochemical in the brain called GABA. GABA is an inhibitory neurochemical, which means that it can weaken the signal from other brain cells. We think that GABA weakens the signal from the 'lazy eye' because it is less useful than the other eye. More generally, GABA may actively control what we see and do not see. It is important, therefore, to understand the role of GABA in vision. We will do this by measuring how changing GABA levels in the brain change the way we see in binocular depth.
We will use a brain scanner and a method to measure GABA in the living human brain, known as MR Spectroscopy. We aim to determine the importance of GABA in binocular vision using three studies. In Study 1, the goal is to test whether increasing GABA with a prescription drug, known as clobazam, improves binocular depth perception. This may also make brain cells more selective to visual input in general. To ensure that any differences are exclusively due to the drug, we will also ask the same participants to take a placebo pill while repeating the experiments on another day. Comparing drug to placebo data will reveal the contribution of the increase in GABA. In study 2, we will train adults with lazy eye to learn to use their eyes together, by performing a visual task for an hour each day for 2 weeks. This has been shown to improve the ability of the eyes to work together. We will measure the level of GABA before and after training, which will show whether GABA level is related to improvements due to training, and the places in the brain where any activity changes occurred.
In the final study, we will recruit children aged 6-13 who are at risk of developing lazy eye. Such children usually wear a patch for 6 months over their stronger eye for several hours a day to try to prevent the development of lazy eye. This 'occlusion therapy' helps the weaker eye work better as it is the only eye that is seeing, and the brain is forced to use its signal. We will scan 30 of these children, along with age-matched children with healthy vision, to test whether patching therapy changes the GABA concentration in the visual brain. We will also test whether improvement in vision is related to changes in GABA levels. Understanding the way in which patching therapy shapes the child brain can improve future treatment regimes.
This series of studies focusing on the role of GABA in the brain will allow us to design treatments to help improve binocular vision for children and adults.
Scientists think that one of the reasons why the weak eye is ignored by the brain is because of a neurochemical in the brain called GABA. GABA is an inhibitory neurochemical, which means that it can weaken the signal from other brain cells. We think that GABA weakens the signal from the 'lazy eye' because it is less useful than the other eye. More generally, GABA may actively control what we see and do not see. It is important, therefore, to understand the role of GABA in vision. We will do this by measuring how changing GABA levels in the brain change the way we see in binocular depth.
We will use a brain scanner and a method to measure GABA in the living human brain, known as MR Spectroscopy. We aim to determine the importance of GABA in binocular vision using three studies. In Study 1, the goal is to test whether increasing GABA with a prescription drug, known as clobazam, improves binocular depth perception. This may also make brain cells more selective to visual input in general. To ensure that any differences are exclusively due to the drug, we will also ask the same participants to take a placebo pill while repeating the experiments on another day. Comparing drug to placebo data will reveal the contribution of the increase in GABA. In study 2, we will train adults with lazy eye to learn to use their eyes together, by performing a visual task for an hour each day for 2 weeks. This has been shown to improve the ability of the eyes to work together. We will measure the level of GABA before and after training, which will show whether GABA level is related to improvements due to training, and the places in the brain where any activity changes occurred.
In the final study, we will recruit children aged 6-13 who are at risk of developing lazy eye. Such children usually wear a patch for 6 months over their stronger eye for several hours a day to try to prevent the development of lazy eye. This 'occlusion therapy' helps the weaker eye work better as it is the only eye that is seeing, and the brain is forced to use its signal. We will scan 30 of these children, along with age-matched children with healthy vision, to test whether patching therapy changes the GABA concentration in the visual brain. We will also test whether improvement in vision is related to changes in GABA levels. Understanding the way in which patching therapy shapes the child brain can improve future treatment regimes.
This series of studies focusing on the role of GABA in the brain will allow us to design treatments to help improve binocular vision for children and adults.
Technical Summary
The ability to see in-depth using two eyes is acquired early in development, and critically requires normal binocular visual experience. Abnormal binocular experience, through a squint or unequal refraction, causes long-lasting and severe deficits in visual perception. This condition called Amblyopia, affects around 3% of the population. As binocular vision is achieved by the brain, amblyopia is a disorder not of the eyes but of the brain. One of the key elements in determining experience-dependent plasticity in the binocular visual system is the inhibitory neurotransmitter GABA. This programme of research is designed to determine the role of GABA in binocular function and dysfunction in the human visual cortex.
The proposed research aims to use multi-modal magnetic resonance imaging (MRI) to determine (i) whether pharmacologically modulating GABA levels in the brain interferes with binocular functions; (ii) whether a binocular visual training leads to a reduction in GABA in amblyopes that is correlated with improvement in binocular vision and; (iii) how the visual system of children at risk of amblyopia differs from those without binocular deficits and how patching therapy changes cortical structure and function underlying binocular vision.
In combination, we will non-invasively quantify the concentration of GABA in the visual cortex, obtain population receptive field measures of depth and assess binocular vision acuity to determine the relationship between neurochemistry, neural organisation and perception. By performing experiments in healthy adults, adults with amblyopia and children at risk of amblyopia, we aim to build a unifying framework that can account for changes during early development and in adulthood. Not only will these studies provide important data for improving therapy for amblyopia, but the binocular vision system can act as a model for neurodevelopmental disorders of higher cognitive function, such as autism or schizophrenia.
The proposed research aims to use multi-modal magnetic resonance imaging (MRI) to determine (i) whether pharmacologically modulating GABA levels in the brain interferes with binocular functions; (ii) whether a binocular visual training leads to a reduction in GABA in amblyopes that is correlated with improvement in binocular vision and; (iii) how the visual system of children at risk of amblyopia differs from those without binocular deficits and how patching therapy changes cortical structure and function underlying binocular vision.
In combination, we will non-invasively quantify the concentration of GABA in the visual cortex, obtain population receptive field measures of depth and assess binocular vision acuity to determine the relationship between neurochemistry, neural organisation and perception. By performing experiments in healthy adults, adults with amblyopia and children at risk of amblyopia, we aim to build a unifying framework that can account for changes during early development and in adulthood. Not only will these studies provide important data for improving therapy for amblyopia, but the binocular vision system can act as a model for neurodevelopmental disorders of higher cognitive function, such as autism or schizophrenia.
People |
ORCID iD |
Holly Bridge (Principal Investigator) | |
Ifan Ip (Co-Investigator) |
Publications
Ip B
(2021)
Mapping the visual world to the human brain.
in eLife
Tang-Wright K
(2022)
Intra-Areal Visual Topography in Primate Brains Mapped with Probabilistic Tractography of Diffusion-Weighted Imaging.
in Cerebral cortex (New York, N.Y. : 1991)
Koolschijn RS
(2023)
Event-related functional magnetic resonance spectroscopy.
in NeuroImage
Bridge H
(2023)
Investigating the human binocular visual system using multi-modal magnetic resonance imaging.
in Perception
Clarke W
(2024)
Universal dynamic fitting of magnetic resonance spectroscopy
in Magnetic Resonance in Medicine
Title | Your Amazing Brain at Aylesbury |
Description | This is a museum exhibition at Discover Bucks museum in Aylesbury that includes artwork and 3D printed brains along with a number of visual illusions. |
Type Of Art | Artistic/Creative Exhibition |
Year Produced | 2022 |
Impact | None yet |
Description | Football on the Brain |
Amount | £218,545 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 04/2022 |
End | 04/2026 |
Description | Amblyopia with Dennis Levi |
Organisation | University of California, Berkeley |
Country | United States |
Sector | Academic/University |
PI Contribution | We have designed and had programmed a virtual reality training program based on the recommendation of Professor Levi. We are also setting up testing protocols to use before and after training based on Professor Levi's experience. |
Collaborator Contribution | Professor Dennis Levi is an expert in amblyopia and is advising us on the optimal testing and training protocols for our study investigating the change in neurochemistry with training of binocular vision. |
Impact | None yet |
Start Year | 2022 |
Description | Amblyopia with Jun-Yun Zhang |
Organisation | University of Beijing |
Country | China |
Sector | Academic/University |
PI Contribution | Our team is applying a visual perceptual training paradigm using a virtual reality headset. We will test and validate the paradigm on this new platform and our collaboration extends the capacities of the visual training paradigm to allow at-home training. |
Collaborator Contribution | JunYun Zhang is providing expertise on a binocualr vision training paradigm that she has developed and tested in amblyopes. The paradigm is very valuable, as it has shown to improve vision in the amblyopic eye in adults and children. |
Impact | We have developed a visual training app that runs on the MetaQuest headset. |
Start Year | 2022 |
Description | Paris binocular plasticity |
Organisation | École Normale Supérieure, Paris |
Country | France |
Sector | Academic/University |
PI Contribution | This is a collaboration between Dr Claudia Lunghi, Dr Betina Ip and Prof Holly Bridge. We will lead 7T scanning during visual training |
Collaborator Contribution | Dr Lunghi will be providing behavioural testing expertise and testing paradigms. The work is funded through her ERC grant HOPLA. |
Impact | 10.1038/s41598-021-95685-1 |
Start Year | 2021 |
Title | Amblyopia Training App |
Description | The app consists of a visual training regime to help re-balance vision in amblyopic participants on a Meta Quest 2 headset. The app is coded in Unity. |
Type Of Technology | Webtool/Application |
Year Produced | 2023 |
Impact | TBC |
Description | Brain presentation to Football Beyond Borders |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | I gave an interactive workshop on the brain and how it changes during development to practitioners from the charity Football Beyond Borders who work with children at risk of exclusion in key stage 3. This was part of our Football on the Brain project. It was the first presentation in a number that we will deliver over the course of the project. |
Year(s) Of Engagement Activity | 2022 |
Description | Football blog (Men's World Cup) |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | I wrote a blog about how hot temperatures might affect performance playing football to coincide with the 2022 mens World Cup in Qatar. |
Year(s) Of Engagement Activity | 2022 |
Description | SheKicks pullout |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | We produced a 'pullout' about the regions of the brain involved in playing football and how the brain is important for many aspects of football. This was distributed in the centre of the Women's European Championship edition of SheKicks magazine which is the main magazine for women's football in the UK. |
Year(s) Of Engagement Activity | 2022 |
Description | Touch Tour at museum |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | I ran a touch tour of the 'Your Amazing Brain' exhibition at Discover Bucks museum for visually-impaired adults and their carers. Around 8 people participated. |
Year(s) Of Engagement Activity | 2023 |
Description | Touch tour for visually-impaired children at Banbury Museum |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | I gave a touch tour of the Your Amazing Brain exhibition at Banbury museum followed by a workshop investigating how the brains of animals differ depending on what senses are most important to them. I also helped to design the exhibition. |
Year(s) Of Engagement Activity | 2022 |