The brain functions in networks and so does the science around the neurologist Irena Rektorová, which is driven by her network of colleagues in the lab and abroad. Along with her team at the Masaryk University CEITEC in Brno, she studies degenerative brain diseases such as Alzheimer’s and Parkinson’s. They ask unusual questions – and come up with striking answers.
Read the story in the Czech version here.
And so they found that brain function can noticeably improve with regular dancing and that a strong electromagnetic field can improve the speech of people with Parkinson’s. They also study the “cognitive reserve”, an extra brain capacity that is built over time and used in a time of need.
Although Professor Rektorová’s 15-member team began to take shape only six years ago, they already boast a series of grants, publications in major journals and partnerships with researchers from other countries.
“We are now managing eight projects and competing for three,” says Irena Rektorová with a smile as we speak in her office in the oval-shaped glass building of the Central European Institute of Technology (CEITEC) located in the Brno campus of Masaryk University. “Writing grant applications is a never-ending process and you have to justify those you’ve won by publishing papers with your research results.”
“Our PhD students are usually fully involved both in the grant applications and in the resulting projects: in this way, they learn and get some publications under their belt. And then we try to communicate the results to the rest of the world, because the Czech Republic is only a small part of it,” summarises Irena Rektorová. Her enthusiasm and dedication to neurosciences are underlined by her neuron-shaped earrings – a present from her daughter who also studies medicine.
Neurology was not my first choice...
When CEITEC at Masaryk University opened their brain research labs six years ago, Irena Rektorová took the bull by the horns – this was the opportunity she had been waiting for. Nevertheless, she retained part-time positions at St. Anne’s University Hospital Brno and the Faculty of Medicine: she teaches students, takes care of patients and heads a clinical team. She speaks of her research with passion, which is further boosted by her young and enthusiastic team.
Her eventual career choice was not her first love – as a student, she gravitated towards internal medicine. After graduating from the First Faculty of Medicine at Charles University, she nevertheless interviewed for a position at the faculty’s neurology clinic. “I didn’t really expect to get the job, I just wanted to experiment and try it out,” says the top Czech neurologist with a laugh. “I wasn’t really attracted to neurology back then, but I have absolutely no regrets.”
Once she got her feet wet, she quickly got excited about neurology then later on, about neurosciences. She speaks from experience when she says: “I tell my students that there is something fascinating about every field and that people matter more than specialisations. You should always remain open to new opportunities.”
Shortly before completing her residency, she met her future husband, the neurologist Ivan Rektor, at a conference. She later got a job at a clinic that he headed.
“I would never recommend anyone to work at a clinic managed by their partner. Eventually, I found my sphere of interest and started to develop independently,” she laughs as she remembers her early days in the field. She has since become so absorbed by the world of neurodegenerative diseases that she often spends her weekends at work.
“I enjoy working in research and making headway in our medical knowledge. And it is wonderful to see the real-life clinical improvement in our patients and how quickly you can help them.”
She knows from clinical experience how different the progress of the disease can be from patient to patient: “It’s not one disease, it’s different sub-types of one disease. Some patients with Parkinson’s suffer from tremors, others experience hallucinations, and you need to target your treatment accordingly.” As the treatment is often a lengthy process, it is only natural to build a relationship with your patient – perhaps a closer one that you would like. Therefore, Irena Rektorová often sincerely rejoices in any improvements together with the patients and their families.
“Parkinson’s causes a lack of dopamine, which causes a movement disorder but may also cause depression. Well-targeted pharmacotherapy can alleviate both symptoms. Some patients experience Tourette’s syndrome: they have tics, which are involuntary movements or sounds, sometimes even outbursts of obscene words. You can help them with botulinum toxin injections – the very same substance that some ladies use for wrinkle treatment. We inject it into the muscles where the tics occur, and it often helps us to avoid prescribing antipsychotics. It makes me happy to see that some patients can function normally in their daily activities.”
Brain degeneration in different languages
The journey of Irena Rektorová and her team is a prime example of how essential it is for researchers to travel, exchange ideas at conferences and work with colleagues abroad. In her case, the crucial connection was sparked a few years ago when she met Steven Rapcsak, a professor of psychiatry and neurology at the University of Arizona in Tucson and a language and speech researcher.
Rektorová, on the other hand, studies imaging techniques, non-invasive brain stimulation and, in general, imaging, blood and other biomarkers that help to detect various diseases such as Parkinson’s or Alzheimer’s in time.
“One thing led to another, and we decided it would be useful to bring our interests together. We created a project that would run in three different countries and received a grant to implement it,” recounts Rektorová. The grant in question comes from the prestigious EU programme Horizon 2020, which provided about 306,000 euros (about 8 million Czech crowns) to the Brno research team.
Their project is the first-ever study that compares the effects of degenerative brain diseases in different language groups: the speakers of Czech, Hungarian and English.
As Rektorová explained in an interview early on in the research: “In both Czech and Hungarian, the pronunciation of words more or less corresponds to their spelling, but English words are spelt very differently from how they are pronounced, which means people use the neural pathways for understanding, word formation and writing in a slightly different way.” The hypothesis that their project is trying to verify suggests that since speakers of different languages use different parts of the neural speech pathway, the manifestations of the diseases – whose symptoms include speech disorders – will also be different.
With this Brno project, Irena Rektorová began laying the foundations of a research area that had so far been neglected in the Czech Republic: the study of speech disorders, language, the neural pathways that participate in speech production and understanding, and the changes that unfold in different patient groups. This year, she received the Rector’s Award for Long-term Excellence in Research from Masaryk University in recognition of her achievements.
The grant meant the teams could start collecting data and examining both patients and healthy volunteers. The Czech team alone collected diverse and detailed information on 150 subjects.
MRI tunnel ahead, focus please!
What can you expect when you participate in a large project like this? If you are a patient, you become part of the respective group of patients with Alzheimer’s or Parkinson’s although the project also needs healthy elderly people to make up the control groups.
One of the incentives on offer to healthy participants is a free and extensive examination of their cognitive and motor skills plus an MRI test. “MRI tests are expensive, and your doctor would normally order one for you only when they suspect a brain tumour, stroke or bleeding,” explains Irena Rektorová.
Occasionally, the examination will reveal a previously unsuspected complication or a developing health condition. When that happens, the researchers refer the participant to a neurologist or another specialist.
“When we study a larger group of people, we sometimes catch something that would otherwise go unnoticed,” confirms Rektorová. They might detect a mild cognitive disorder in an otherwise healthy volunteer, or exclude someone who, although right-handed, lacks left hemisphere dominance – this is because participants with right hemisphere dominance could distort the results of the study.
First, the participants undergo a speech exam: the researchers record them as they talk, interview them, have them do speech exercises including syllable scrambles, completion tests and repeating words and sentences and evaluate their speech comprehension and memory. “Some of the tests took place inside the MRI scanner – the patient would read words or sentences with varying intonation while we observed which parts of their brain would activate,” says Rektorová.
To give a specific example of these tests, the Arizona Semantic Test asks the subjects to choose which one of the four corner pictures best fits the one in the middle.
One of the tasks given to participants in the MRI is to “do nothing” – they are asked to lie with their eyes closed and try not to move and not to think of anything in particular. “When we test this on ourselves while preparing a new protocol, we fall asleep immediately,” says Irena Rektorová with a laugh. “But that doesn’t usually happen to our subjects, because they are a little tense and not used to the scanner noise.”
The researchers also examine the subjects’ handwriting and they collaborated with experts from the Brno University of Technology to study the acoustics of the subjects’ speech and language: “Acoustic analysis is objective and provides much more detail than can be detected by the human ear or even an experienced speech therapist. We looked for early changes and those that occur as the disease progresses, and we studied how therapy could improve the aspects of speech disrupted by something called hypokinetic dysarthria, which is typical for Parkinson’s.”
This is a disorder characterized by reduced pitch variation, change in volume and poor pronunciation. Irena Rektorová explains: “It is, in fact, a motor disorder of the muscles that control the vocal cords, the tongue and the rest of the speech organs. Since it reduces the patients’ ability to communicate, it also reduces their quality of life. It’s very hard on the patients and the regular treatment that works well for motor impairment in the limbs is ineffective.”
Disproving assumptions is a part of science
Once the researchers collect all the data, they divide them among the teams who then process them further. Usually, they compare the results of each patient group with the results of the healthy volunteers of the same age.
“And then we pore over the results and try to figure out what they mean, how to interpret them and, most importantly, what the clinical implications are – such as, what is the effect of a specific therapy at a certain dose in relation to age, gender or duration of the disease on specific speech functions. That’s probably the most fun part,” says Rektorová.
As is often the case with research, some results are a surprise. So far, the original hypothesis – that speakers of English and Czech engage various parts of the speech networks to a different degree – has not been confirmed.
However, Rektorová remains optimistic: “We are still processing the study results. We might disprove one assumption but on the other hand, it could mean that when we apply non-invasive stimulation therapy, we could use the same targeting for both Czech and English speakers.”
At least one of the results of this major grant can directly help patients get better. In a novel approach, the researchers attempted to stimulate a specific area of the temporal lobe with a strong pulsed electromagnetic field – known as repetitive transcranial magnetic stimulation therapy – to see if it improves the speech of patients with Parkinson’s.
“It’s simply a coil shaped like a figure eight that is placed against the patient’s head. The patient feels clicking and mild twitching on their skin and in the underlying tissue. It’s not uncomfortable or painful in any way.”
It has long been known that the changing magnetic field, which causes electric stimulation of the brain, produces changes in neurons and neural pathways. It is already used to treat depression in people who do not respond well to drug therapy. Rektorová explains that “These patients must receive stimulation therapy for at least two weeks and the effects last over several months; then you need to repeat the therapy.”
A coil to the head improves speech in dysarthric patients
Rektorová and her team were the first to use this method to improve speech in Parkinson’s patients suffering from hypokinetic dysarthria. Compared to depression therapy, they targeted a different part of the brain at a lower frequency. They specifically focused on an area of the temporal lobe that serves as the assessment centre for our own voice, allowing us to speak and simultaneously listen to our own voice and vary the volume or pitch based on what we hear.
This section of the brain gives us auditory feedback and works together with other parts of the cerebral cortex and subcortex to fine-tune the nuances of our speech.
“What happens is that Parkinson’s patients get incorrect feedback. Although they actually speak quietly, they think they speak at a normal volume,” says Rektorová. They selected the targeted area of the brain based on the MRI scans. “We studied the connections of areas that are crucial for speech and discovered some misconnections in a certain section of the temporal lobe that are related to specific symptoms of the disease.”
Before they could start, they had to figure out how exactly to apply the magnetic stimulation, including the right frequency. To do this, they would do a quick MRI scan of a patient followed by thirty minutes of stimulation and another MRI scan. “We found that a low-frequency stimulation improves the connection between the auditory feedback area of our brain and the areas that control the movement of our speech organs. So, we proved that this treatment really could help Parkinson’s patients,” says Rektorová as she enthusiastically describes her team’s research results published in the prestigious journal Brain Stimulation.
“Regular stimulation over the course of two weeks improved our patient’s speech for at least eight weeks – that was the length of the study. On top of that, we were able to boost both functional and structural connections. Those are stronger and should last longer than just a few days or weeks,” says Irena Rektorová happily.
Plans for home brain stimulation
In the brain, everything is interconnected. “It doesn’t have centres specialising in a single activity; that would be inefficient. For example, there are networks that enable visual or auditory information processing, and, at the same time, there are general parent networks that control attention and also control and affect the speech, auditory, visual, motor, etc. networks,” says Rektorová.
Her team will now focus on studying how often and how exactly the stimulation needs to be repeated and how it impacts the “rewiring” inside the networks and the communication between them.
Interestingly, Rektorová mentions that the stimulation technique also comes with a placebo effect – and a particularly strong one: “It doesn’t matter what you do with the patients; when they receive a lot of care, they begin to feel like they are getting better. It turns out that their brain starts releasing dopamine and other neurotransmitters that can actually cause a slight improvement in some functions. The placebo effect is a very powerful phenomenon, but it stops as soon as you end the stimulation therapy, while the effect of repeated active stimulation keeps growing for a while when you stop the treatment.”
Immediately after the therapy was completed, there was essentially no difference between the patients in the placebo control group and those who received the stimulation. “However, the effect lasted for the whole eight weeks of observation only in the patients who were stimulated,” adds Rektorová.
In the times of Covid, she and her team came up with another innovative idea: since the pandemic stranded people in their homes, the researchers are now working on a method that would allow patients to perform the stimulation at home – after they have received the initial training in a laboratory – and avoid the journey to a hospital or lab.
They will need to attach the electrodes (anode and cathode) they receive from the lab to specific places on their head. Then they will work on a speech exercise to activate the same networks in their brain that will be stimulated by the electrodes with a low-intensity direct current.
“The therapy is less effective than pulsed magnetic field stimulation but can be done at home over an extended period of time. We can teach people how to attach the electrodes and then help direct them at home through Skype or Zoom if needed,” explains Rektorová. The only thing the patients will really need is discipline: the electrodes must be attached for 30 minutes every day for six weeks. Even that can be regularly checked online.
“We are already purchasing the equipment. The project has got the green light from the ethics committee – and it would be wonderful if we could also get a grant to pay for it,” she concludes. That would allow them to provide a complete therapy package to the patients, including online speech therapy sessions. The electrode sets for home use are one of the medical innovations brought about by the pandemic and this would be the first time they are used in Czechia.
How to fortify your brain against the risks
Before applying any treatment, the researchers check to what degree it can help the person and what kind of shape their brain is in. One of the indicators of this is called cognitive reserve, which is another major research topic studied by Irena Rektorová and her team. Throughout our lives, we build up untapped reserves in the brain that can be measured and can come in handy when necessary.
Every one of us has up to a hundred billion neurons that transmit nerve impulses. However, a brain affected by Alzheimer’s disease loses about ten billion neurons before the first symptoms even start showing. The first area to deteriorate is the hippocampus, which is embedded in the temporal lobe and is crucial for storing and recalling memories. In 18 months, the brain can lose about half a sugar cube worth of matter.
“Cognitive reserve is a very interesting research field because it helps the brain cope with brain pathology as well as regular ageing. The brain is better equipped to deal with injury, stroke, dementia, etc.,” says Rektorová. She and her colleagues look at how the size of this reserve impacts the rate of ageing or when the first symptoms of Alzheimer’s or Parkinson’s start showing and how the diseases progress. “When you have a sizeable reserve, the symptoms start showing later even if the pathology is already present in the brain. What hasn’t really been studied yet is how they progress and react to treatment.”
So how do you build up this reserve? Some of it is genetic but you can also make a dramatic difference by building up your reserve over your lifetime: “One of the things you can do is to keep learning new things or have a job that requires you to think and exercise your cognitive skills. Another factor is prompt treatment of high blood pressure, blood fat levels or cholesterol. Do not skip your preventive check-ups – even in thirty-somethings, they are really key, because this is when problems can start popping up and it’s important to start the treatment early.”
Frequent brain injuries are also detrimental. “Boxers risk complete dementia. I don’t understand how boxing can even be a sport – those who fall unconscious when they are knocked out are purposefully damaging their brain,” says Irena Rektorová.
Besides putting your helmet on when the sport requires it, or when you are riding your bike, Rektorová confirms that your diet can also help grow the reserve: “The Mediterranean diet, which is high in fish, fruit and veggies, seems to be the best. And large amounts of alcohol are definitely detrimental to your brain, especially liquor.”
Exercise is another contributing factor: regular and reasonable exercise and social engagement over your lifetime are beneficial to the brain. It’s never too late to start, as the Brno researchers confirmed in a study where healthy elderly people and people with a mild cognitive disorder attended dancing sessions in the gyms of the Faculty of Sports Studies at the Masaryk University campus. The sessions were scheduled three times a week for six months.
Dance your way to improved focus and memory
“About one-third of the people had a mild cognitive disorder while the others were healthy. We had a grant for four years, so we had several groups, the final total was about 120 people,” says Rektorová. As expected, there were more female participants, so they were taught circle and line dances, such as Greek or African ones, rather than partner dances. “There was something new every time. The sessions also included aerobic sequences and the people learned dance routines to music that would develop over time.”
Some of the participants that met through the study still keep in touch – they meet for a chat or a walk and some even attend other dance classes in Brno.
“It turns out that even when you start around 60, you can improve your cognitive skills and forge connections between some areas of your brain,” highlights Rektorová.
The results were almost too good to be true: after just six months, the participants’ cognitive skills improved, particularly their ability to pay attention and focus. These skills also help boost your memory. Rektorová says that “While some specific functions improved, so did the overall fitness of their brains. I wouldn’t believe it if I didn’t see it: their cerebral cortex actually grew thicker in some of the areas involved in learning new motions, which is crucial in dancing.”
Alzheimer’s and Parkinson’s disease cause deterioration in specific parts of the brain that are responsible for memory and movement. “The disease usually develops in people over 60 but if you have a large cognitive reserve, the onset of symptoms could be delayed by ten or more years,” explains Rektorová.
Those of us who have won the genetic lottery are called “superagers” – people whose brains function at age eighty as though they were twenty years younger. While Rektorová’s team does not focus on superagers, they were recently the subject of a study by her husband, the leading neurologist Ivan Rektor.
He decided to focus on holocaust survivors who, having gone through an unbelievable ordeal, have lived to a ripe old age of over ninety with good cognitive skills. Although focusing on this group and trying to decipher their “recipe” for long life and dignified ageing seems like the obvious choice, the researchers must be realistic and careful when their subjects are very old. “They only undergo basic tests, even the MRI scans are short,” says Rektorová.
However, being a superager does not mean that your brain is free from the pathology of Alzheimer’s disease. Whether or not you are likely to develop a neurodegenerative disease can be predicted quite early when you are around fifty.
Assuming, of course, that you would actually like to know. Irena Rektorová says she will give the test a pass. “I don’t find it very tempting,” she says and adds half-jokingly, “It’s probably useless to try and find out what’s going to happen in twenty years when I could die in a car accident tomorrow.” At the moment, there is no treatment for the early stages of the disease anyway: “The only preventive measure you can take is to build up your cognitive reserve.”
Breakthroughs thanks to mice and an Indian expert
Despite the lack of treatment, researchers keep trying to come up with new methods for early diagnosis. Amit Khairnar, a postdoc and one of Rektorová’s team members, recently discovered an entirely new method. Using mice models and strong MRI designed for small animal research, he was able to pin down a specific change that can be observed in the brain before the onset of brain tissue loss in Parkinson’s patients. His research was made possible by a Marie Curie Fellowship grant of over 3.5 million Czech crowns (about 140,000 euros) and by Rektorová’s invitation to her team.
Together with associate professor Jana Rudá from the Faculty of Medicine whose specialisation is animal research, Rektorová was looking for postdocs from abroad. “Although I’m a doctor and have always done clinical research on patients, we wanted to put the two together,” says Rektorová, who had received positive feedback on the talented Indian researcher from her friend, Khainar’s PhD supervisor.
“We focused on experiments with animal models of Parkinson’s disease. Amit had a control group of healthy mice and a group of genetically modified mice whose brains were producing a pathology similar to the pathology in the brains of human Parkinson’s patients. Other mice were fed a toxin, such as the pesticide Rotenone, which can cause the onset of the pathology.
Yet another group of mice models had a different sign of the disease: a decrease in the number of cells producing dopamine. “These mice don’t have tremors, but they are stiff. They undergo a series of motor function tests, such as crossing a narrow bridge where they tend to slide down,” says Rektorová about the experiments. Khairnar worked on his research with Professor Rudá as behavioural studies are one of her specialisations.
The researchers looked for imaging markers – indicators that allow early diagnosis – in four mice model groups.
One of the tools they used was an unusual MRI scanner from the Institute of Scientific Instruments of the Czech Academy of Sciences in Brno. “The animals undergo MRI and behavioural testing while alive. They are then killed, and their brains undergo more tests. In this way, we can see what the brain looks like when the animal is alive and dead. This allows us to look for a new indicator of the early stages of this disease that would help us detect people at risk,” says Rektorová.
And she is very happy with the results: “Thanks to Amit, we were able to adopt a new marker and start using it in studies of people with Parkinson’s disease.”
Further grants allowed the researcher to remain on the team for almost six years before he returned to India, where he now runs his own lab and supervises a team of twelve people. However, he is considering a move back to Czechia, which offers a better research environment as well as other perks. He enjoyed working at the Brno campus in Bohunice and the trips around Brno as well as the reliable public transport and the ice cream in the city centre. “I will never forget Brno, not least because that’s where my daughter was born,” recalls Amit Khairnar in an online interview.
He appreciates the teamwork and support he received from Irena Rektorová and notes: “She never said no to me, no matter what I needed for my research – she simply trusted me.”
The researchers published their findings in two papers in the renowned journal Brain, Behavior and Immunity and the Journal of Neurochemistry. An editor of the latter even commented that this type of research should continue.
“There is a protein called alpha-synuclein that is closely related to Parkinson’s disease. It plays a key role in neural connections and accumulates in the brain. We showed a way to observe this accumulation using a method called diffusion kurtosis imaging,” explains Khairnar. This protein is studied by many researchers and the Brno team was able to offer them an imaging method that could show it early on in the disease using live animal models.
“Amit has a good publication record and he’s someone who can take care of himself and his students, so I’m sure he would be a fantastic addition,” says Rektorová.
Ongoing battle and rampant capitalism
Opening up Czech science, or at least her own laboratory and department, to the world is one of the main goals of Irena Rektorová. “My clinical experience is an advantage; I used to be the head of a centre for cognitive disorders and now I manage the Movement Disorders Center at the First Department of Neurology of the Faculty of Medicine and St. Anne’s University Hospital in Brno. I’m on various committees of international organisations and have a very strong professional network, which helps me obtain international grants and remain in the know. The more you know, the more new ideas you get,” says Rektorová about the success of her research group.
Although she is the one who is polishing the ideas and determining the direction of their research, she is not the only driver of her team: “My students come up with their own ideas, attend congresses with their presentations and bring back awards, which is very important. And as they gain more experience, they want to do their own thing, which is great.”
She built her 15-member team from scratch six years ago and has been trying hard to obtain enough grant funding to be able not only to pay them well but to keep them together in the long term. “It’s rampant capitalism out there, the competition is always fierce, and you are always trying to get somewhere. It’s an ongoing battle, we often stay up late to finish yet another grant application.” It bothers her that the current system of research funding means people have no stability.
Far from being made up of only physicians, her team includes engineers and social scientists; physicians are actually in the minority. “Psychologists from the Faculty of Social Studies are very well-versed in statistics and can work independently.”
Variety is the recipe against burnout
Irena Rektorová’s schedule is divided between her surgery, lab, auditorium and offices. She says the variety helps her avoid burnout. Among her many projects is a programme for talented med students that helps prepare them for PhD studies. Working with young people is a rich source of energy for the researcher.
“You have to be enthusiastic and very hard-working, but you do need that little bit of luck, whether in winning grants or in getting your research results,” says Rektorová. Having many innovative ideas and luck with bringing them to life is her long-standing wish. “I have a lot of faith in the members of my team at CEITEC MU. They are great and that makes me very happy.”
On top of everything else, Irena Rektorová recently won the selection procedure for the post of the Scientific Director of the International Clinical Research Center at St. Anne’s University Hospital. She mentions that the centre has been bogged down by old grudges and that she would like to see it reasonably well-connected with international research institutions. Her term starts at the beginning of next year.
“There is a limited number of scientists who are capable and interested. We have the potential to attract top researchers from abroad but only if we have a good reputation and good results,” she adds openly.
“Many people try to get published no matter what – publishing for the sake of getting published, where the papers are never used by anyone else. We want our papers to be cited and noticed by other researchers so that they can build on what we’ve been able to discover, and to be published in major journals and fit into the mosaic of our overall research goals.”
The author is an editor of Deník N.
Tento projekt je financován z prostředků programu EU pro výzkum a inovace Horizont 2020 na základě grantové dohody č. 101036051.
Tento projekt je financován z prostředků programu EU pro výzkum a inovace Horizont 2020 na základě grantové dohody č. 101036051.