Neuroscience often compares adolescence to springtime. An apple tree, if skilfully pruned in this season of the year, will blossom and bear abundant fruit. If neglected, it will have many leaves but hardly any apples. And, if pruned improperly, it may not even come into buds. Something similar happens to human brain – research leader Ilona Kovács says. – There is an optimal state of “wiredness” which is influenced by developmental processes, as well as hormonal and environmental impacts. In the case of adolescents, we have set out to examine how the adult brain develops and how distant cortical areas are wired. Recent research results have shown that sleep has an extremely important role both in brain maturation and in adult brain plasticity.
The current project is partly based on the results of an earlier funded project in which sleep-related maturation and learning processes were studied in typical and atypical brain development. The researchers were inspired by young patients with Williams syndrome (and thus suffering from chronic sleep problems) to continue the analysis of the cortical structure in relation to sleep and learning during adolescence. (Their study on the relationship revealed between sleep problems and motor learning of patients with Williams syndrome will be published soon in Scientific Reports)
What methods do you use to monitor brain development and communication in the brain?
It is not easy to examine the internal system of relations of the adult cerebral cortex. One option is to monitor whole-night sleep with electroencephalography (EEG). This makes it possible to map cortical connectivity (a method developed together with Ferenc Gombos and Róbert Bódizs in another project dealing with patients with Williams syndrome: Scientific Reports, 21 July 2017) and also enables a fine-tuned analysis of the process of sleep. The ongoing project employs a well-established methodology. In the lab we monitor the sleep of young subjects aged 12, 16 and 20.
So they are required to sleep in the laboratory?
Yes, we have a test room comprised of a small electrically shielded bedroom and a bathroom. Each patient is required to spend three nights in the lab, and if a parent wishes to stay nearby we can accommodate them as well. They are not required to stay in during the day but they are requested not to engage in any special activities as that would influence sleep patterns. This is why the test is carried out on weekends (outside school days). The “test sleep” is followed by “reference sleep” on Saturday and then, after waking up on Sunday morning, they start practicing the tasks. They practice a simple motor and a perceptual task three times. This methodology was taken over from our earlier Williams syndrome projects. They repeat the tasks once more Monday morning.
 |
| Illustration of the behavioural tests. |
In the centre, there is a lateral view of the human brain where the primary visual cortex (V1) is marked with blue, the primary motor cortex (M1) is marked with red. The cerebral cortex is usually divided into six layers with different functions, and the primary sources of long-term within-layer connections are in the second and third layers. The contour integration task is addressing the long-term connectivity of the primary visual cortex, while the finger tapping task is aimed at those of the primary motor cortex. In the contour integration task certain tiny elements show a horizontal oval shape among the randomly organised elements. The three rectangles show increasingly difficult tasks.
Apparently, the finger tapping exercise does not strain the brain too much.
In most learning processes the task to be performed is obviously not so simple as the ones defined in this project. But if the tasks were made too complex (such as learning to ice skate or to shoot basketball, or memorising a bunch of foreign words) that would put the whole brain into action making it impossible to precisely match the processes with the changes triggered in the cortex. So we rather restrict tasks to small specific exercises about which we already know what cortical areas they activate, enabling us to monitor the changes in such areas.
To this end, we first install 128 electrodes on the subject’s head in a special EEG cap resembling a swim cap. For our EEG assistant, Zoltán György, who is really professional in this, it takes one and a half hours to fit the cap, injecting gel under each electrode, positioning them and checking whether they are in the right place. The cap is not too uncomfortable to wear and, if fit properly, it stays in place the whole night. We only seldom lose a few electrodes which is quite an achievement in making the measurement successful.
 |
| Fitting the cap |
What can you deduce from these measurements?
We used to think that the whole brain is asleep throughout the night but we now know that this is not the case. Different parts of the brain sleep with different intensity and measurements suggest that different things happen in our brain during sleep depending on what we did during the day. In our project we expect that it is not only sleep that has an impact on the exercises but also vice versa: if someone is practicing finger tapping a lot it will increase activity in the motor cortex. Thus, in the post-exercise phase we expect to find much more special oscillations or “spindles” in the sleep pattern compared to the previous night (“spindles” are generated by nerve cells activated at the same time at a given moment which is thought to refer to the molecular process of storing information in long-term memory). Hopefully, this assumption will be confirmed soon – currently we are busy with analyses but new findings are about to come.
What is the novelty of this experiment?
This is the first time such tests are carried out on humans. Experiments where electrodes were implanted in rats showed that the maze visited by the animals was “reimaged” in their hippocampus (the area of the brain responsible for storing information, located in the medial temporal lobe) during the night. Thus, the activity of the cells of the hippocampus responsible for assessing situations shows what the rat dealt with during the day. We are more and more confident – although it is still only a hypothesis – that the brain areas used in the exercises during the day show rhythmic activity during the night. It is also important that the task should be meaningful so that we want to be better at doing it.
So “knowledge” is stored when the brain activity is triggered?
For me, the most exciting thing is how knowledge is stored but this is utterly difficult to find out. For instance, we learn to ride a bike with many imperfect movements. It is a huge mystery what is stored in a beginner’s brain. If everything is imprinted in the beginning there should be a way at a later stage to somehow filter out and “forget” errors.
You have suggested earlier that a similar process takes place in the brain of adolescents...
This is “pruning”: the removal of erroneous or redundant connections. This is still only theory without much evidence. But how does the brain tell what is erroneous and select between cortical connections? We do not know the answers yet, but these are important questions! Nevertheless, the experiment will provide unprecedented data on how the fine pattern of sleep develops during adolescence, how the typical development of cortical wires in adolescents look like on the basis of sleep patterns, and how sleep determines learning.
The four years of the project taught us another great lesson which I owe to my colleagues, particularly to Orsolya Filep who meticulously analysed the behavioural data of adolescents together with Patrícia Gerván, another long-serving member of our research group. They found that in addition to patients with Williams Syndrome there is also a high standard deviation in the performance of healthy adolescents. Though the experiment dealt with only a narrow age group, performance varied so widely that it was difficult to tell who is typical and atypical. Thanks to Orsolya, we reconsidered this question time and time again. Evidently, the adult-like nature of adolescent’s cerebral cortex is not only influenced by their age but there is a factor, we might call maturity, which is primarily determined by hormones – or at least so we believe because so far nobody has examined separately the effects of maturity and age on adolescent cortical change.
Our argument is that bone age defines biological age, and it is assumed that bone age is strongly connected with hormonal and cortical maturation. It might be that adolescent cortical changes, such as pruning, are also triggered by hormones. This is interesting because the biological age of two children with “typical performance” may show a difference of up to five years. We have found an expert partner for such tests: the Sports Sciences and Diagnostics Centre where the determination of bone age is a routine task. Together with the Diagnostics Centre, we have made a great step by trying ultrasound for bone age estimation which does not burden the body in contrast with traditional x-ray imaging. (Although this type of measurement has not yet been involved in research but it already has a data base and the measured values very well match the values determined through x-ray, so it is safe to use it.) We have created a paradigm to show how maturation and experience affects cognitive function. This, however, will be examined in the framework of another project (2017–2022: Adolescent Development Research Group of the Hungarian Academy of Sciences and the Pázmány Péter Catholic University).
Is there any finding of your research that can already be useful for people in general?
Both the obtained and the anticipated results of the project about to be concluded show a clear correlation between sleep and learning skills and underline the importance of sleep in learning. This empowers parents to positively influence the quality of sleep of their children. Obviously, there are no strict rules but today it takes just a few clicks to learn that children will sleep better if they have eaten almonds or banana and drunk milk than if they had eaten some fatty food before going to bed.
Both parents and professionals have to be aware that adolescent maturation of children follows a special course. Although influenced by genetically inherited features, environmental factors and dietary habits, this course is by all means very unique and characteristic of each individual child. Some children mature earlier and others later. This can also affect motivation and the ability to learn things at a given age. Parents do best if they take into consideration their children’s personal abilities when deciding on whether to send them to a preparatory course or a demanding Math course. I am very cautious when talking about parent’s awareness as it is still not clear to us how cognitive performance is affected by maturity and by experience. These two effects have never been tested separately in this period of human development and this is exactly the direction we are moving toward with our research.
I am confident that the causalities identified during the research will not only contribute to science. If such research findings are published on the appropriate forums it can reach the wider publicity: a lesson that is considered worthy to write about by an authoritative educational magazine or on the BBC website may have an impact on the behaviour of individuals. In general, besides contributing to scientific theory, I also find it important to share our latest findings with the larger public as soon as possible. This is why we are now organising a master’s programme in translational behavioural science together with two partners in London and in Leuven, Belgium. The term “translational” refers to the fact that students not only study theory and methodology but they also learn how to apply this knowledge even to everyday problems.
The researcher’s previous relevant funded project:
2006-2011: Procedural learning in typical and atypical brain development – NF 60806 (HUF 30.34 million)
Funded project: NK 104481
Sculpting the teenage brain: Adolescence as a critical period in brain development
Duration: January 2013 – December 2017
Project leader: Ilona Kovács, head of the Institute of Psychology, Pázmány Péter Catholic University,
Amount of funding: HUF 64.6 million