A study led by Georgetown University neuroscientists reveals that the part of the brain that receives and processes visual information in sighted people develops a unique connectivity pattern in people born blind. They say this pattern in the primary visual cortex is unique to each person, akin to a fingerprint.
The findings, published in PNAS, have profound implications for understanding brain development and could help launch personalised rehabilitation and sight restoration strategies.
For decades, scientists have known that the visual cortex in people born blind responds to a myriad of stimuli, including touch, smell, sound localization, memory recall and response to language. However, the lack of a common thread linking the tasks that activate primary areas in the visual cortex has perplexed researchers. The new study, led by Lenia Amaral, PhD, a postdoctoral researcher; and Ella Striem-Amit, PhD, the Edwin H. Richard and Elisabeth Richard von Matsch Assistant Professor of Neuroscience at Georgetown University’s School of Medicine, offers a compelling explanation: differences in how each individual’s brain organizes itself.
“We don’t see this level of variation in the visual cortex connectivity among individuals who can see – the connectivity of the visual cortex is usually fairly consistent,” said Striem-Amit, who leads the Sensory and Motor Plasticity Lab at Georgetown. “The connectivity pattern in people born blind is more different across people, like an individual fingerprint, and is stable over time – so much so that the individual person can be identified from the connectivity pattern.”
The study included a small sample of people born blind who underwent repeated functional MRI scans over two years. The researchers used a neuroimaging technique to analyze neural connectivity across the brain.
“The visual cortex in people born blind showed remarkable stability in its connectivity patterns over time,” Amaral explained. “Our study found that these patterns did not change significantly based on the task at hand , whether participants were localising sounds, identifying shapes, or simply resting. Instead, the connectivity patterns were unique to each individual and remained stable over the two-year study period.”
Striem-Amit said these findings tell us how the brain develops. “Our findings suggest that experiences after birth shape the diverse ways our brains can develop, especially if growing up without sight. Brain plasticity in these cases frees the brain to develop, possibly even for different possible uses for the visual cortex among different people born blind,” Striem-Amit said.
The researchers posit that understanding each person’s individual connectivity may be important to better tailor solutions for rehabilitation and sight restoration to individuals with blindness, each based on their own individual brain connectivity pattern.
Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0
Contrary to the commonly-held view, the brain does not have the ability to rewire itself to compensate for conditions such as stroke, loss of sight or an amputation, say scientists in the journal eLife.
Professors Tamar Makin of Cambridge University and John Krakauer of Johns Hopkins University argue that the notion that the brain, in response to injury or deficit, can reorganise itself and repurpose particular regions for new functions, is fundamentally flawed – despite being commonly cited in scientific textbooks. Instead, they argue that what is occurring is merely the brain being trained to utilise already existing, but latent, abilities.
One of the most common examples given is where a person loses their sight – or is born blind – and the visual cortex, previously specialised in processing vision, is rewired to process sounds, allowing the individual to use a form of ‘echolocation’ to navigate a cluttered room. Another common example is of people who have had a stroke and are initially unable to move their limbs repurposing other areas of the brain to allow them to regain control.
Krakauer, Director of the Center for the Study of Motor Learning and Brain Repair at Johns Hopkins University, said: “The idea that our brain has an amazing ability to rewire and reorganise itself is an appealing one. It gives us hope and fascination, especially when we hear extraordinary stories of blind individuals developing almost superhuman echolocation abilities, for example, or stroke survivors miraculously regaining motor abilities they thought they’d lost.
“This idea goes beyond simple adaptation, or plasticity – it implies a wholesale repurposing of brain regions. But while these stories may well be true, the explanation of what is happening is, in fact, wrong.”
In their article, Makin and Krakauer look at a ten seminal studies that purport to show the brain’s ability to reorganise. They argue, however, that while the studies do indeed show the brain’s ability to adapt to change, it is not creating new functions in previously unrelated areas – instead it’s utilising latent capacities that have been present since birth.
For example, a 1980s study by Professor Michael Merzenich at University of California, San Francisco looked at what happens when a hand loses a finger. The hand has a particular representation in the brain, with each finger appearing to map onto a specific brain region. Remove the forefinger, and the area of the brain previously allocated to this finger is reallocated to processing signals from neighbouring fingers, argued Merzenich – in other words, the brain has rewired itself in response to changes in sensory input.
Not so, says Makin, whose own research provides an alternative explanation.
In a study published in 2022, Makin used a nerve blocker to temporarily mimic the effect of amputation of the forefinger in her subjects. She showed that even before amputation, signals from neighbouring fingers mapped onto the brain region ‘responsible’ for the forefinger — in other words, while this brain region may have been primarily responsible for process signals from the forefinger, it was not exclusively so. All that happens following amputation is that existing signals from the other fingers are ‘dialled up’ in this brain region.
Makin, from the Medical Research Council (MRC) Cognition and Brain Sciences Unit at the University of Cambridge, said: “The brain’s ability to adapt to injury isn’t about commandeering new brain regions for entirely different purposes. These regions don’t start processing entirely new types of information. Information about the other fingers was available in the examined brain area even before the amputation, it’s just that in the original studies, the researchers didn’t pay much notice to it because it was weaker than for the finger about to be amputated.”
Another compelling counterexample to the reorganisation argument is seen in a study of congenitally deaf cats, whose auditory cortex appears to be repurposed to process vision. But when they are fitted with a cochlear implant, this brain region immediately begins processing sound once again, suggesting that the brain had not, in fact, rewired.
Examining other studies, Makin and Krakauer found no compelling evidence that the visual cortex of individuals that were born blind or the uninjured cortex of stroke survivors ever developed a novel functional ability that did not otherwise exist.
Makin and Krakauer do not dismiss stories such as blind people navigating using hearing, or individuals who have experienced a stroke regain their motor functions. They argue instead that rather than completely repurposing regions for new tasks, the brain is enhancing or modifying its pre-existing architecture — and it is doing this through repetition and learning.
Understanding the true nature and limits of brain plasticity is crucial, both for setting realistic expectations for patients and for guiding clinical practitioners in their rehabilitative approaches, they argue.
Makin added: “This learning process is a testament to the brain’s remarkable – but constrained – capacity for plasticity. There are no shortcuts or fast tracks in this journey. The idea of quickly unlocking hidden brain potentials or tapping into vast unused reserves is more wishful thinking than reality. It’s a slow, incremental journey, demanding persistent effort and practice. Recognising this helps us appreciate the hard work behind every story of recovery and adapt our strategies accordingly.
“So many times, the brain’s ability to rewire has been described as ‘miraculous’ – but we’re scientists, we don’t believe in magic. These amazing behaviours that we see are rooted in hard work, repetition and training, not the magical reassignment of the brain’s resources.”
A new study published in Brain shows that a genetic mutation which causes blindness in humans also increases intelligence, possibly through an increase in synaptic activity between the very same neurons damaged by the mutation.
The present study came about when Professors Tobias Langenhan and Manfred Heckmann, came across a paper on a mutation that damages a synaptic protein. The mutation caused patients to go blind, but then doctors noticed that the patients were also of above-average intelligence, something which piqued the two neurobiologists’ interest. “It’s very rare for a mutation to lead to improvement rather than loss of function,” said Prof Langenhan.
The two neurobiologists have been using fruit flies to analyse synaptic functions for many years. “Our research project was designed to insert the patients’ mutation into the corresponding gene in the fly and use techniques such as electrophysiology to test what then happens to the synapses. It was our assumption that the mutation makes patients so clever because it improves communication between the neurons which involve the injured protein,” explained Prof Langenhan. “Of course, you can’t conduct these measurements on the synapses in the brains of human patients. You have to use animal models for that.”
“75 per cent of genes that cause diseases in humans also exist in fruit flies”
Professor Tobias Langenhan
First, in collaboration with Oxford researchers, the scientists showed that the fly protein called RIM looks molecularly identical to that of humans. This was essential in order to be able to study the changes in the human brain in the fly. In the next step, the neurobiologists inserted the genetic mutation into flies. They then took electrophysiological measurements of synaptic activity. “We actually observed that the animals with the mutation showed a much increased transmission of information at the synapses. This amazing effect on the fly synapses is probably found in the same or a similar way in human patients, and could explain their increased cognitive performance, but also their blindness,” concludes Professor Langenhan.
The scientists also found out how the increased transmission at the synapses occurs: the molecular components in the transmitting nerve cell that trigger the synaptic impulses move closer together as a result of the mutation effect and lead to increased release of neurotransmitters. A novel method, super-resolution microscopy, was one of the techniques used in the study. “This gives us a tool to look at and even count individual molecules and confirms that the molecules in the firing cell are closer together than they normally are,” said Prof Langenhan.
“The project beautifully demonstrates how an extraordinary model animal like the fruit fly can be used to gain a very deep understanding of human brain disease. The animals are genetically highly similar to humans. It is estimated that 75% of the genes involving disease in humans are also found in the fruit fly,” explained Professor Langenhan, pointing to further research on the topic: “We have started several joint projects with human geneticists, pathologists and the team of the Integrated Research and Treatment Center (IFB) Adiposity Diseases; based at Leipzig University Hospital, they are studying developmental brain disorders, the development of malignant tumours and obesity. Here, too, we will insert disease-causing mutations into the fruit fly to replicate and better understand human disease.”
New research has shown that anti-HIV drugs may fight macular degeneration – overturning a preconception about DNA in the process.
Macular degeneration is the leading cause of blindness in developed countries. Even though HIV does not cause dry macular degeneration, the drugs prevented the loss of vision.
“We are extremely excited that the reduced risk was reproduced in all the databases, each with millions of patients,” said Jayakrishna Ambati, MD, a leading macular degeneration researcher at the University of Virginia School of Medicine. “This finding provides real hope in developing the first treatment for this blinding disease.”
A Big Data Archeology review of four health insurance databases showed that Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a commonly used HIV treatment, reduced the incidence of dry macular degeneration by 40%. The records spanned two decades and covered over 100 million patients. The drugs had also previously been shown to possibly prevent diabetes.
The finding also comes with the discovery that DNA can be produced inside the cytoplasm. Alu DNA (found exclusively in primates), which makes up 10% of the human genome, is transposable and can insert itself into other places on the genome. It was long considered “junk” DNA, but are now believed to have important functions, such as allowing for multiple expressions of proteins from a single Alu element. Since it cannot replicate itself, Alu DNA requires a transposon called L1 to accomplish this, which was now reported to allow the production of Alu DNA outside the chromosome. The buildup of Alu DNA in cells contributes to macular degeneration, by killing off cells that support the retina. The researchers are urging further investigation into NRTIs or safer derivatives known as Kamuvudines, both of which block a key inflammatory pathway, can be useful in preventing vision loss from dry macular degeneration.
“A clinical trial of these inflammasome-inhibiting drugs is now warranted,” said Ambati. “It’s also fascinating how uncovering the intricate biology of genetics and combining it with big data archeology can propel insights into new medicines.”
Journal Information: Shinichi Fukuda el al., “Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.202275111
