Amblyopia, or “lazy eye,” has a well-understood cause — early disruption of balanced input from the two eyes — yet treatment success remains frustratingly inconsistent, even when normal visual input is restored. In a study published this week in PNAS, the Martinos Center’s Shahin Nasr, PhD, and colleagues offer a possible reason why: the brain doesn’t simply leave the affected circuits idle — it repurposes them for other visual tasks, and seems reluctant to give them back even after the eyes are corrected. We spoke with Dr. Nasr about the study, and about what it suggests for improving how we treat amblyopia. Here’s what we learned.
What motivated the study?
Our motivation was to better understand the remarkable ability of the brain to adapt to changes in its sensory inputs—a property known as neuroplasticity. Despite decades of research, our understanding of how the human brain reorganizes itself at the level of individual neural circuits remains surprisingly limited. Most previous studies have examined the brain at a relatively large scale, where little or no structural or functional change is often observed.
To address this gap, we investigated neuroplasticity at a much finer spatial scale in the human visual cortex. We focused on amblyopia (“lazy eye”), a common developmental condition in which balanced visual input from the two eyes is disrupted early in life. By examining how this altered visual experience reshapes the fine-scale functional organization of the visual system, we hoped to uncover the mechanisms by which the human brain adapts to developmental changes in sensory input.
What is most novel about the study?
We found that, rather than allowing neural resources to remain idle when they no longer receive normal visual input, the brain reallocates those resources to visual functions that are relatively spared by the impairment. In other words, the brain compensates by strengthening the processing of information it can still use.
The surprising finding was that this reorganization appears to persist even after the original visual input is restored. Instead of simply returning to its “normal” state, the brain seems to hold onto its compensatory strategy. This suggests that recovery may require not only correcting the sensory problem itself but also helping the brain “unlearn” the adaptations it developed over time.
This discovery was only possible because we could visualize the brain’s fine-scale functional architecture in living humans. Using ultra-high-resolution imaging, we were able to distinguish neighboring neural circuits that support different visual functions—details that were previously hidden because conventional brain imaging lacked the necessary spatial resolution.
What was the most important finding?
One of the biggest puzzles in amblyopia is that, although its underlying cause is relatively simple—a disruption of balanced visual input early in life—treatment is often far less successful than we would expect. It has long been assumed that restoring vision and practicing visual tasks should allow the brain to recover. When this does not happen, one explanation has been that the affected neural circuits have been lost or permanently damaged.
Our findings suggest a different possibility. Rather than becoming inactive or disappearing, these neural circuits appear to have been repurposed to support other visual functions that remain mostly spared. As a result, they may no longer be readily available to resume their original role, even after normal visual input is restored.
This changes how we think about amblyopia treatment. Improving vision may require more than simply training the brain to perform the desired task. It may also require helping the brain let go of the compensatory strategies it has developed over many years. In other words, successful rehabilitation may depend not only on learning new skills but also on promoting the “unlearning” of adaptations that have become deeply ingrained.
What’s next in your research?
This study is just the beginning. We are now pursuing several new questions that build directly on these findings.
One of the most exciting is understanding what happens to the visual functions that acquire these “repurposed” neural resources. Do they actually become better because they have more neural circuitry available? Or does recruiting additional circuits make the system less efficient by disrupting its normal organization? We do not yet know the answer, but understanding these tradeoffs will tell us much more about how the brain adapts to developmental disorders.
We also want to better understand what we call “spared” visual functions. Because the visual system is highly interconnected, these functions may not be completely unaffected by amblyopia. Instead, the brain may be redistributing its resources as a way of minimizing the overall impact of the disorder. Exploring this possibility will help us understand whether neuroplasticity is primarily beneficial, maladaptive, or a combination of both.
At the same time, we are collaborating with colleagues at Boston Children’s Hospital on a clinical trial to investigate whether pharmacological approaches can help trigger the “unlearning” process that may be needed for the brain to reassign these neural circuits back to their original function. If successful, this could open the door to new therapies that complement traditional vision training and improve treatment outcomes for people with amblyopia.
