REWIRING OUR BRAIN TECHNIQUES

01.The visible touch: natural rewiring in the congenitally blind brain

Live 2019

Prof. Sylvain Baillet, Associate Dean, Research, Faculty of Medicine

New study sheds lights on pathways involved in rerouting the sense of touch to brain region originally used for vision in the congenitally blind.

The brain is plastic. Its billions of cells form trillions of interconnections whose strengths and purposes evolve as we grow, experience, learn and age. Brain regions do not map one-to-one with a specific function – most functions, such as recognizing a familiar face or voice, or trying to remember the name of an old school friend, are distributed in large brain networks.  Primary sensory brain areas are probably the most specialized, receiving direct input via the thalamus from sensing organs like our ears, taste buds, skin and eyes. But what happens to these primary sensory regions when they are deprived of their specific sensory inputs? Do they simply become useless or are they re-allocated to another sense? Think of a congenitally blind person (a person who is born blind) or a person who becomes blind later in life. Will their visual brain cells disappear, or will they adapt to take on another role, processing other types of sensory inputs?

Previous studies had shown that the visual cortex of congenitally blind individuals responds to various forms of non-visual stimuli such as touch, sounds, and even smell. However, a controversy exists as to which pathways are used to funnel non-visual information to the visual cortex in congenitally blind individuals. Most specialists have believed that the visual cortex activation represents a secondary, later downstream activation along brain networks, following the firing of early auditory or somatosensory brain regions. According to this line of thinking, tactile information, for example reading Braille, is first sent via the “tactile” or somatosensory thalamus to the primary somatosensory cortex, and from there moved along to the primary visual cortex. However, such an indirect pathway is intrinsically slow as it has to pass many synapses before reaching its final destination, casting doubts on its biological relevance.

 Challenging the perceived beliefs

Have neuroscientists been overlooking the possibility of an alternative and faster pathway that bypasses early auditory and somatosensory cortex? Prof. Ron Kupers, a neuroscientist who specializes in the study of congenital blindness at the University of Copenhagen, believed so and conceived a study to test this hypothesis in people suffering from the rare condition of congenital blindness.

Dr. Kupers holds a joint appointment at the École d’Optométrie, Université de Montréal, where he has been collaborating for many years on this question with Prof. Maurice Ptito. Together, they reached out to Prof. Sylvain Baillet, a specialist in time-resolved neuroimaging techniques at The Neuro, McGill University.

Their challenge to Dr. Baillet and his group was to detect proof of early activation in the “visual cortex” of congenitally blind participants following light tactile stimulation of the skin. If they were able to demonstrate that the visual cortex of blind subjects responds to tactile stimulation of the skin equally fast as the primary somatosensory cortex, this would prove that the rerouting of non-visual information to the visual cortex takes place at the level of the thalamus, even before it reaches the cortex. The thalamus is a deep brain structure which is the first recipient of sensory inputs and the gateway through which information from the outside world is further relayed to early sensory cortices. Hence, under normal conditions, visual stimulation is sent to the visual thalamus (the lateral geniculate nucleus, or LGN) and from there to the primary visual cortex (V1), whereas tactile information is received by the somatosensory thalamus (the ventroposterior complex) and further relayed to the primary somatosensory cortex (S1).

Sharing their findings

The outcome of their study was published November 11 in Nature Communications. Working in close collaboration, Franziska Müller (from the Copenhagen group) and Guiomar Niso (from the Montreal group), the co-lead authors of the article, together with Soheila Samiee (also from the Montreal group), used magnetoencephalography (MEG) imaging to track the millisecond changes in the brain of congenitally blind and sighted control subjects following tactile stimulation of the fingertips.

Using Brainstorm, a free, open-source app developed in Prof. Baillet’s lab with collaborators, the investigators were able to show that the primary visual cortex – which is normally devoted to vision – of blind participants responds nearly as fast to tactile stimulation of the fingertips as does the somatosensory cortex, the default processor of tactile information.

“The brain signals in these occipital regions, about 35 milliseconds after skin stimulation, were clearly much earlier and stronger than in sighted controls. Such a short response time is compatible with the hypothesis of a rerouting at the thalamic level: tactile information is redirected from the somatosensory to the visual thalamus (LGN), from whence the information is sent via the optic radiations to the primary visual cortex. In normally sighted individuals, this pathway is exclusively used to convey visual information,” explains Prof. Baillet, who is a Professor of Neurology & Neurosurgery, Biomedical Engineering and Computer Science at McGill and Director of the MEG Core Unit of The Neuro. This arrangement provides support to the observation of faster reaction times to tactile inputs in congenitally blind individuals. In daily life, blind individuals may benefit from such a functional rearrangement, for instance in the fast processing of rich tactile information such as in Braille reading.

Prof. Kupers adds that, “Evidence in support of a thalamic rerouting and ensuing ‘hijacking’ of the preserved optic radiations by tactile stimuli in congenital blindness had been hypothesized from animal models but had never been demonstrated in humans. Our study brings strong evidence that blindness at birth is accompanied by a rewiring of the brain circuitry at early thalamic levels so that regions genetically programmed for vision are repurposed for fast processing of information from other senses.”

They further confirmed this hypothesis by measuring the direction of communication between these brain regions, using the millisecond precision enabled by MEG.

“We also found stronger communication directed from deep brain relays like the thalamus towards the occipital cortex in blind participants than in sighted controls,” notes Prof. Baillet. According to Prof. Kupers, “This brings additional evidence that entire visual circuits are used for other types of sensory neuronal processing in the absence of visual inputs.”

Using safe, noninvasive techniques, the study adds to the growing evidence that human brain networks form a fabric in constant lifetime evolution, adapting to adverse situations to maximize behavioural benefit. “The brain’s extraordinary capacity for plasticity needs to be better understood as it remains little exploited in re-adaptation programs for functional recovery after stroke and traumatic brain injury, for instance,” says co-investigator Prof. Ptito.

November 21, 2019

02

Deafness-causing protein deficiency makes brain rewire itself, research suggests

The brains of people with congenital deafness may be rewiring themselves in ways that affect how those people learn, suggesting a need to develop new teaching techniques tailored toward those who have never been able to hear.

Published today in Nature Scientific Reports, the findings by an Oregon State University research collaboration make the case that a protein mutation that causes profound hearing loss also alters the growth and wiring of certain neurons—cells that act as the building blocks of the nervous system.

While scientists continue looking for molecular therapies that may someday restore the hearing of those who carry the mutation, the research led by Colin Johnson of the OSU College of Science also has implications for improving the lives of people whose hearing can't come back.

"We hope this work is a step toward treatment, and also toward better schemes for those who are deaf, for interacting with them and teaching them," said Johnson, associate professor of biochemistry and biophysics. "People who are born deaf, their quality of life may be severely affected. They tend to drop out of high school at higher rates and generally not attain as high a level of education, and their incomes are not as great. We're working hard on the biology of deafness and also trying to work our research into the other areas to come up with new ways of improving things."

This research builds on earlier findings by Johnson that developed a new way of quantitatively studying the large protein, known as otoferlin, whose sole role is to encode sound in the sensory hair cells in the inner ear.

Mutations in the otoferlin gene are linked to severe congenital hearing loss, a common type of deafness in which patients can hear almost nothing. Research suggests otoferlin, which is in the cochlea of the inner ear, acts as a calcium-sensitive linker protein and that a mutation in it weakens the binding between the protein and a calcium synapse in the ear; deficiencies in that interaction are a likely cause of otoferlin-related hearing loss.

The size of the otoferlin molecule and its low solubility have made it difficult to study, including learning how otoferlin works differently than another neuronal calcium sensor in the brain, synaptotagmin.

In both the earlier study and the latest one, Johnson used zebrafish to probe otoferlin's mechanisms. Zebrafish are a small freshwater species that go from a cell to a swimming fish in about five days.

Zebrafish reproduce rapidly and are particularly useful for studying the development and genetics of vertebrates. They share a remarkable similarity to humans at the molecular, genetic and cellular levels, meaning many zebrafish findings are immediately relevant to humans.

Embryonic zebrafish are of special interest because they develop quickly, are transparent and can be easily maintained in small amounts of water.

The previous research uncovered a smaller version of otoferlin, a size that could be used in gene therapy.

"We worked with the mini otoferlin and found that yes, it looks like the smaller pieces of otoferlin can restore hearing," Johnson said. "After that, we took a step back, and the new question became: When you lose this gene, when you have mutations, is expression of other genes affected? Is it a ripple effect, like a stone in a pond? No one had looked at that."

The answer is yes, expression of some other genes is affected.

"We took fish that had the otoferlin gene knocked out and looked at all of the genes, the entire genome, and compared them to the genes of a normal fish," Johnson said. "We came up with a list of abnormally expressed genes—some in the hair cells, and there were also neuronal genes altered, genes involved in the growth and wiring of neurons."

Adding otoferlin back in restored expression of those genes, but only partially.

"This is a bit of a cautionary tale," Johnson said. "If you grow up without that protein, it's not just a matter of throwing the gene back in. If you're born deaf and grow up deaf, it seems the physical wiring of your brain is a little different. That kind of complicates the goal of doing gene therapy. We need to go beyond looking at those hair cells and look at the brain itself. Does the brain process information differently? That's one area we need to think about."

It's possible, Johnson added, that future gene therapies may be best targeted toward very young patients, whose brains have not undergone as complete a rewiring as those of adult patients.

More information: Aayushi Manchanda et al. Otoferlin Depletion Results in Abnormal Synaptic Ribbons and Altered Intracellular Calcium Levels in Zebrafish, Scientific Reports (2019). DOI: 10.1038/s41598-019-50710-2

Citation: Deafness-causing protein deficiency makes brain rewire itself, research suggests (2019, October 7) retrieved 28 January 2020 from https://medicalxpress.com/news/2019-10-deafness-causing-protein-deficiency-brain-rewire.html

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03- ReWiring Your Anxiety

Sometimes it’s a matter of seeing past the illusion. For example, fears of planes. You can break down your fears of flying and do the research to examine the data.

If you avoid planes altogether, your anxiety will always build and your brain will rewire itself for the danger of flying. If in the face of your fears, you book a flight and arrive at your destination, your brain thinks oh well maybe this is safe after all and rewires itself.

Over time, your fight-or-flight response regarding flying will decrease to the point you stop avoiding planes. Maybe you still get nervous, but that’s okay. I am not afraid to fly, yet when I fly I get nervous. Once I’m boarded on the plane, I relax eat snacks and read. I’m fine and excited about my destination.

It sucks if there is turbulence when your flying or a bad storm arises. That’s no fun for anyone. I ignore it and don’t give in to the worst-case scenario thinking. I focus on my reading and it always resolves itself and as my dad would say, if it doesn’t you will never know.

Establish New Rules for yourself: It’s okay for fear arising and suck when you’re facing your anxieties. It’s okay to get nervous in situations. It’s okay to sweat when staying present with the fear. It’s okay. The key is, you are not running. It’s okay to begin with small exposures and work your way up to the long exposures. Over time you will find, exposure to that fear grows longer and longer and your emotional response decreases.

You can book a flight and fly somewhere without sweating and going nowhere. You can be around dogs without running away. If you are like me, you can meet someone and date and it will either go well or not. Life goes on. We can experience life without being overtaken by our developed fears. We can rewire our brains to live fearlessly.

Let’s also remember some stress and fear is a healthy response. For example, you see a baby bear while hiking in the mountains and you are terrified. That’s a normal healthy response to a dangerous situation. There is a resolution for that situation. Don’t avoid hiking. Chances of you running into a bear are so minuscule.

Start today tackling your fears and rewiring your neuroplasticity.

Update on the co-worker: I have had no more encounters with him. Yay! I have not had to work with him at all. In fact, I believe he left for the season. I used my coping techniques to control my reaction to this situation. He is who he is and instead of resisting his behavior I accept him as he is. Acceptance of any situation is magical. I didn’t think about him or give his behavior my energy. I didn’t obsessively rehash the events. I could stay away from him and go in the opposite direction if I needed to. I would exchange no energy either way. I let it go, and it resolved itself. I wasn’t home stressed and anxious reliving and recreating the encounters. It worked itself out.