How Does the Brain Work? – University of Copenhagen

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31 August 2017

How Does the Brain Work?

New Brain Theory

Brain researchers from The Faculty of Health and Medical Sciences take the first step towards a comprehensive theory about the functions of the brain. The ideas have been developed in cooperation with the world’s leading neuroscientific experts and were published in the scientific journal NEURON earlier this summer.

‘How does the brain work?’ The world’s leading brain researchers tried to answer this question at a symposium at the Carlsberg Academy in September 2016. The symposium was the first of its kind, and the objective was to share knowledge and cut the first sod of a universal brain theory. The event was organised by Professor Per Ebbe Roland and Assistant Professor Henrik Lindén from the Faculty of Health and Medical Sciences at the University of Copenhagen.

After the symposium the acclaimed scientific journal NEURON chose to compile 12 of the researchers’ conference contributions in a special issue, ’How Does the Brain Work?’, which was published on 7 June 2017 and which now frames the first official, theoretical attempt to describe how the brain works.

Neuroscience is still a young science, and its development is mainly based on technological advances and not on an overall theory that can be tested or further developed.

‘We lack knowledge of the basic principles of the brain, and when the science lacks a theory or coherent conceptual framework we are unable to fully test hypotheses, conduct experiments and gain a greater, overall understanding of the brain. Therefore, it is really exciting that we can now start to formulate the contours of the world’s first brain theory’, says Professor Per Ebbe Roland.

The Three Dynamic States of the Brain
The brain is a sophisticated organ, whose functions are controlled by complex processes of interaction between the neurons (brain cells), but the details of that interaction are still unknown. According to Per Ebbe Roland, neuroscience is experiencing rapid development and has generally adopted a worked-out understanding of how the individual brain cells work, but it is still difficult to determine how they interact and react in particular situations.  

For example, the researchers still have not managed to predict or calculate when nerve cells release action potential (signal mechanism that consists of a brief, strong electrical impulse in the nerve cell membrane). Therefore, they are also unable to uncover how the cells cooperate on creating perception and thoughts or planning complex behaviour.

The researchers were therefore asked to present their ideas of how the brain works. In areas where the science lacks answers, they were asked to speculate about a series of principles that may explain the basic mechanisms controlling the dynamics of the brain.  

To begin with the researchers focussed on basic brain mechanisms, that is, the fast, so-called synaptic transmissions – contact between the nerve cells – and the spread of action potentials in the brain. In brief: what the brain can do in a few seconds – for example, remember something, create a thought, perceive its surroundings and plan behaviour.

The researchers’ many accounts and discussions during the symposium were written down in 12 articles, which the researchers were able to comment on and further develop on an ongoing basis. Professor Per Ebbe Roland and Assistant Professor Henrik Lindén have subsequently analysed the content and are able to conclude that we, as a rule, can assume that the brain has three fundamental stages (basic states).

The Primary State – the Brain’s Primary Pulse
The primary state acts as the brain’s primary pulse, ensuring that the brain never comes to a complete standstill. At this state you can always measure the brain cells’ membrane potential in the cerebral cortex as slow oscillations. 

‘The live brain is usually in this state during deep sleep and when the person is difficult to wake up. We also know this state from, for example, fever coma patients or people experiencing an epileptic seizure. What is fascinating about this state is that the brain remains active by constantly releasing action potentials, even though it cannot react to changes registered by the senses (changes in external conditions are unable to communicate with the brain)’, says Per Ebbe Roland.

The nerve cells’ interaction in the brain generally takes place between excitatory and inhibitory neurons, respectively. At this stage, the excitatory neurons and the inhibitory neurons alternatively have the upper hand in a calm and autonomously changing state of balance. The result is that the membrane potential of the neurons autonomously oscillates between hyperpolarisation and depolarisation, and therefore external conditions have difficulties affecting the brain, which constantly maintains a basic primary pulse.

According to Per Ebbe Roland, this dynamic can be shown even in an isolated part of the brain’s network of neurons ­– that is, when you take a section of the brain and immerse in physiological brain fluid – revealing that the piece continues to produce the slow oscillations autonomously.

The Chaotic State
During light sleep and while awake, when the brain is not focussed on a particular activity, the activity and interaction of the neurons are more irregular. The excitatory and inhibitory neurons now release action potentials at relatively short, but unpredictable time intervals, and the membrane potentials therefore constantly experience minor, unpredictable oscillations.

Therefore, this state can be called ‘the chaotic state’. The excitatory and inhibitory neurons are well-balanced. The excitatory nerve cells are prevented from being active for long periods at a time, but are immediately subdued by the inhibitory nerve cells. The result is minor, but unpredictable changes in tension over the cell membranes. This entails that external conditions or action potentials from other parts of the brain can soon cause a change in state from the chaotic to the active. This makes the chaotic state a very efficient and important resting state. 

The Active State
When the brain becomes active, it is because many exhibitory nerve cells become active at the same time in a particular area of the cerebral cortex neuron network. This happens, for example, when the olfactory sense, hearing or the sense of touch is affected – or when the body has to carry out a particular task. If the impact of the exhibitory neurons is stronger than the inhibition of the local, active inhibitory neurons, the local network switches to the active state and the activity of the nerve cells becomes more predictable. When in the active state the nerve cells enable to brain network to create sense experiences, thoughts, dreams and wilful movements.

In the active state the exhibitory nerve cells spread their action potentials, after which the inhibitory nerve cells take over and redress the balance in the membranes. When the impact stops, the brain switches back to the chaotic state. When we are awake and active, the brain performs this interplay almost constantly.

Towards a Universal Brain Theory
According to the researchers, the advantage of having a theory about the three basic states of the brain is that it makes it possible for them to measure when and how the brain alternates between the different stages in particular situations. Their aim is to expand the conceptual framework with all aspects of the brain’s development focussing on, for example, plasticity and long-term memory.

The researchers hope that neuroscience within a number of years will be able to combine the new knowledge on brain mechanisms with the theory of the brain’s development and establish a universal brain theory and a standard model for neuroscience.

Read the ’How Does the Brain Work?’ special issue of NEURON 

Professor Per Ebbe Roland
Department of Neuroscience
Phone: 21 16 22 31

Andreas Westergaard
Senior Communications Adviser, Faculty of Health and Medical Sciences, University of Copenhagen
Phone: 53 59 32 80