February 2015 – The Brain Bank North West

Neurofeedback – or how the mind trains the brain

February 22, 2015 by The Brain Bank North West

There is no lack of advertisements for devices, games and tasks that are meant to train our thinking and memory, just as exercise trains muscle. And, wouldn’t it be great if we could increase our brain power like Lucy in Luc Besson’s movie? Whilst the claim that we ‘underuse’ our brains is controversial, scientists are developing techniques which allow us to regulate our own brain activity and improve our performance.

Image courtesy of ddpavumba at FreeDigitalPhotos.net

Neurofeedback has been around for a while and has developed in ways that fill us with enthusiasm and hope. It involves a brain-machine interface which measures brain activity and provides the participant with real-time feedback. The feedback might take the form of coloured shapes shown on the screen, with colours ranging from blue (low activity) to red (high activity). Depending on the task, participants are instructed to change the colour of the square using only their mind. For example, if the aim of the training is to increase activity in a part of the brain, participants need to try to change the colour of the square to red. If the aim is to decrease activity, they should aim try to turn it blue. Often it is up to the participants how they achieve the change in colour – as long as it works, it doesn’t matter!

This fun-sounding method of training our brain can improve our ability to think, often impaired in depression. Such difficulties include problems with working memory, i.e. holding and manipulating several pieces of information at the same time. In a study which used EEG to measure electrical activity of the brain, after eight training sessions patients with depression were better at the tasks that required working memory than patients who were not trained. They were also able to think faster.

Another target for neurofeedback training is the ability to regulate our feelings. A small part deep in the brain, called the amygdala, plays a major role in emotions. In people with depression and anxiety, the amygdala is hyperactive and its responses to sad objects or events can be exaggerated. This activity can normalize after therapy, however the treatment sometimes takes a long time. Is it possible to speed up the process with the use of neurofeedback training? Researchers scanned the brains of healthy participants (using fMRI) whilst presenting them faces with negative emotional expressions. Such images usually increase activity in the amygdala. Here too, participants saw the activity in the emotional center of their brain as colours. In this case, however, they used more specific strategies to reduce the activity in their right amygdala, which included thinking: ‘these are pictures, this is a study, these are actors’, or by distracting themselves. After 4 training sessions they were much better at down-regulating the activity in their brains than the participants who just looked at the faces without the instructions.

The task and the colour scheme of the feedback on the activity in the amygdala. Brühl, AB. et al. (2014) Real-time Neurofeedback Using Functional MRI Could Improve Down-Regulation of Amygdala Activity During Emotional Stimulation: A Proof-of-Concept Study. Brain Topography 27:138–148. — The task and the colour scheme of the feedback on the activity in the amygdala.
Brühl, AB. et al. (2014) Real-time Neurofeedback Using Functional MRI Could Improve
Down-Regulation of Amygdala Activity During Emotional Stimulation: A Proof-of-Concept Study. Brain Topography 27:138–148.

Perhaps one day the standard treatment for mental illness will include scanning peoples’ heads and providing them with online feedback. Would it not be great if we could regulate activity in our own brains? Only, who is regulating who exactly? Neurofeedback certainly gives a different meaning to the expression “mind over matter”…

Post by: Jadwiga Nazimek

Getting older, getting wiser?

February 15, 2015 by The Brain Bank North West

For some of us the New Year was the time to reflect on past experiences, and to consider what we have learned from them. Have we become wiser or more mature? Have these lessons helped us to live the rest of our lives as better and happier individuals? Many of us would like to think so, but what does it actually mean to be ‘more mature’, and does wisdom really come with age?

Maturity can offer greater contentment and satisfaction. Image courtesy of Dr Joseph Valks at FreeDigitalPhotos.net

Psychology offers various views on personal maturity. Some researchers understand it as personal growth, i.e. the development of our personality as we acquire deeper knowledge of ourselves, connect to others, and become more able to express ourselves.

How much can our personality change as we mature? McAdams (1996) proposes that there are different levels in personality: dispositional traits, personal concerns and self-concepts. The main traits of our personality consist of five broad dimensions: extraversion, neuroticism, conscientiousness, agreeableness and openness to experience. For example, some of us are extraverts, others – introverts, we also differ in our degree of conscientiousness. The second level of personality includes our goals, life tasks, motivations and plans. Finally, our identity, or how we see ourselves and our past, present and future form the third tier of personality. These basic traits do not tend to change. However, our personal concerns and goals do, depending on where we are in life.

Mature people are more able to express themselves in their goals and focus more on connections with others. Image courtesy of khunaspix at FreeDigitalPhotos.net

Research by Sheldon and Kasser (2001) showed that as we mature we set ourselves goals that better fulfill our psychological needs, i.e. the need for self-acceptance, to further develop connections with others that are close to us, and to contribute to the community. These new goals replace those with external motivations, such as popularity or financial status. Moreover, we learn to pursue these goals because we truly believe in their value, rather due to the pressures of our societies or cultures.

Maturity can also be defined as becoming more adept at regulating our emotions and to experience more positive feelings, which in turn is related to finding meaning in life. All of us regulate our emotions by influencing the way we feel about other people or events, e.g. cheering ourselves up by giving ourselves a treat when we feel low, or calming ourselves down when we get anxious. Better regulation of our emotions also helps us to achieve goals, by protecting us from becoming easily discouraged. Whilst maturity does not have to correlate with chronological age, it seems that older people focus more on interactions with people who are emotionally close to them, and prefer not to spend their energy on wider social networks of acquaintances (Carstensen, Fung and Charles, 2003). They also experience fewer negative emotions than younger people, with such changes thought to result from different coping strategies. Younger people put more effort into solving their problems, which can benefit them in the long term. Their elders, in turn, might instead try to change the way they feel about the situations, for example by focusing more on positive experiences, and selectively remembering more positive memories.

As we age, we try to deepen our connections with our loved ones. Image courtesy of photostock at FreeDigitalPhotos.net

The evidence would therefore suggest that we do indeed become happier as we mature: we stick to our own values, get better at fulfilling our psychological needs, get more control over our emotions, and learn that worrying about the opinions or approval of others does not give us the satisfaction that we crave. Something that we can all look forward to as we continue to age.

Post by: Jadwiga Nazimek

References:

McAdams, D.P. (1996) Personality, modernity and the storied self: A contemporary framework for studying persons. Psychological Inquiry 7:295-321

Carstensen, L.L., Fung, H. H. and Charles, S.T. (2003) Socioemotional Selectivity Theory and the Regulation of Emotion in the Second Half of Life. Motivation and Emotion 27 (2):103-123 http://link.springer.com/article/10.1023%2FA%3A1024569803230#page-2

Sheldon, K.M. and Kasser, T. (2001) Getting Older, Getting Better? Personal Strivings and Psychological Maturity Across the Life Span. Developmental Psychology 37(4): 491-501 http://psycnet.apa.org/journals/dev/37/4/491/

Sensation: “it’s the rat’s whiskers!”

February 8, 2015 by The Brain Bank North West

When I tell people I study rodent whiskers I’m often met with a slightly puzzled look. More often than not, I get asked ‘why?’ which is probably fair enough since to the general population it might seem like a slightly odd thing to do. Unlike my colleagues studying Alzheimer’s disease or chronic pain, there’s no obvious reason why we should be interested in the whisker system- after all humans don’t have whiskers (hipster beards aside) and at first glance there’s no obvious medical benefit. However, there are in fact many amazing features of the rodent whisker system which could provide fundamental insights in neuroscience, alongside many opportunities for technological and medical advances.

One key problem in neuroscience is understanding how the sense organs (eyes, ears, nose, tongue and skin) take information from the outside world and translate it into something we can perceive. Take olfaction for example: a smell begins life as a small number of air borne chemicals hitting receptors in our nose. But, from these humble beginnings it can – with the help of a bit of brain power – become so much more; the appetising aroma of freshly baked bread or the memories of summers long-past engrained in the smell of petrol and freshly cut grass.

Another sense we sometimes take for granted is our sense of touch, how do we manage to distinguish between smooth and rough surfaces? Rodents are experts at navigating the world in the dark using only their sense of touch and they use their whiskers in much the same way that we would use our fingertips – to get information about something in front of them. Rodents rhythmically brush and tap about 60 large vibrissae (whiskers) against objects to determine their size, shape, orientation, and texture. This behaviour is called ‘whisking’. When a whisker bends against an object, forces and torques are generated at the whisker base. By quantifying these mechanical signals we are able to understand what information the rat’s brain is receiving.

The fact that the whisker system uses mechanical information is a great advantage for scientists as it means that we can measure the exact inputs coming into the receptors at the base of the whisker (forces and bending moments are easier to measure than the equivalent input for every other sensory system). For example, the equivalent in the visual system would be attempting to measure every single photon of light hitting the retina- something that is currently impossible. Furthermore, the whisker system has a well-defined neural pathway, meaning we know the route that information takes from the base of the whisker, through the brainstem and thalamus all the way up into the cortex. In this pathway, each whisker is faithfully represented so that at any stage along the neural pathway, you will find neurons that fire to the movement of a single whisker and no other. These features provide an unparalleled opportunity to study how the neurons ‘code’ information from the external world and how the brain ‘decodes’ it.

If we can understand the way information from the outside world is transduced within the nervous system, we can use this knowledge for a surprisingly wide-range of applications. One of the most promising applications is the construction of robotic whiskers which can be used in situations where visual information is difficult to obtain. For example, fog, darkness and glare can all interfere with optical sensors. A tactile based sensor, however, could provide crucial information where optical sensors fail. For example, fault detection in piping, machinery or ducts.

Another potential application is in the field of intravascular surgery. This application would require our robotic whiskers to be miniaturized in a biocompatible manner. An increasing number of surgeries are being conducted non-invasively. Although there are several optical sensing methods available to the surgeon, none of these methods can replicate the sense of touch that is lost when performing non-invasive surgery.

Whilst there is a still a way to go before whisker based technologies can be fully used in the situations outlined above, we are certainly making significant headway – for example take a look at the following video showing ‘Whiskerbot’- a robotic active touch system created by scientists at the University of West England and the University of Sheffield.

[youtube http://www.youtube.com/watch?v=TBxjChQ6SjA]

Hopefully, projects like this will not only inspire others to study this fascinating sensory system, but also pave the way for innovative technological advances.

Post by: Michaela Loft

What we can learn from sharks: Ancient antibodies

February 1, 2015 by The Brain Bank North West

Now I’m sure that many will agree with the statement that, at least in the literary sense of inspiring awe, sharks are awesome creatures. They are one of the apex predators in their environment, the structure of their skin at a molecular level makes them swim faster and they can constantly replenish their teeth in conveyor belt like fashion!

As creatures go the shark model is pretty old, about 420 million years old, and yet they also still have amazing complexity. Of particular interest to this article is their highly evolved – if ancient – immune system.

shark2 — Strand model of an antibody, the structural heavy chains are shown in green whilst the light chains that help to form the antigen binding sites are seen in red.

Just like us a shark’s immune system is reliant on a class of proteins known as antibodies to function correctly. Antibodies are a class of protein that play a variety of different roles in the body, most notably in their recognition and immobilisation of invading pathogens. This occurs through the binding of small macromolecules, called antigens, to a special recognition site of the antibody. These are typically exposed at the surface of pathogens or else secreted by them.

This is however not the only reason many researchers are interested in antibodies. Their ability to recognise very small quantities of antigens with a high specificity makes them useful in bio sensing or as treatments to disease by binding to specific proteins thus blocking their function.

For these applications it is useful to have a large amount of such antibodies, and in fact for a lot of fields of biological research (not just immunology), antibodies are a critical reagent in many experiments.

shark3 — Outline of antibody production via hybridoma cells

The typical method for producing these antibodies is to first induce their production in a model organism, such as a mouse, then extract cells from the mouse’s spleen, fuse them with a myeloma (a benign cancer cell that divides rapidly) and then use this hybrid cell (known as a hybridoma) to produce many copies of the antibody. Following this the antibodies must be carefully purified before they can be used.

This is a complicated process and fraught with difficulties, getting mice to make the right antibodies and producing the hybridoma is difficult enough for a start. A better approach is to produce recombinant antibodies by inserting DNA encoding them into model cells such as E-coli or yeast, which are much easier to handle. A big advantage here is that it is also possible to make human antibodies, critical for any clinical work. However this synthetic approach is still tough as many recombinant antibodies are not stable enough to survive purification.

This is where the sharks come in. Sharks live in a highly saline environment, the sea, and so to avoid their bodies just shrivelling up through osmosis their bodily fluids contain high concentrations of osmolytes that prevent water moving out of their tissues. One of the major osmolytes in sharks is urea, typically at a concentration of several hundred millimolar.

Urea is a powerful denaturant and is a go to reagent for biochemists who want to study how stable a particular biomolecule is. Since shark blood contains high concentrations of urea scientists suspected that their circulating proteins, including antibodies, would be more stable than their human counterparts.

This hypothesis proved to be true however it was not just enough to know that they were more stable, they also needed to know how and why. The best way to understand the inner workings of a protein is to have an atomic resolution structure and to get that you require two things; protein crystals and x-rays.

Unfortunately making protein crystals is not so straightforward (see my earlier post on the topic), and in this case it proved impossible. Instead fragments of the complete shark antibody were crystallised and analysed by x-ray crystallography. The atomic images were then put together by researchers like a jigsaw puzzle to gain an insight into the inner workings of the antibody,

What they found is that whilst the sequence of amino acids that make up shark antibodies is very different to human antibodies, the overall shape and fold is remarkably similar. This is an example of convergent evolution, were two different species evolve the same solution to a problem independently.

shark4 — Over lay of human antibody heavy-chain fragments (Red, Blue and Green) with the same region from a shark antibody (Grey)

There were however still some important differences. In particular the shark antibodies contained several extra intermolecular interactions at key points within their structure that helped to make the molecule more robust to chemical stress.

Armed with this new knowledge the researchers went one step further and modified recombinant human enzymes to now include these extra interactions to test the impact they would have on stability. Happily the stabilisation was transferrable and the modified enzymes could survive in temperatures up to 10 degrees higher than unmodified, as well as being almost twice as resistant to urea.

What was most pleasing is that the rate of secretion for the modified antibodies was vastly improved. The researchers suggested that this would likely be a boon to the antibody industry and could potentially have significant diagnostic and therapeutic application. This all goes to show that sources of scientific innovation can come from the most unlikely of places…oh and of course reinforces my point that sharks are super awesome.

This post, by author Marcus Gallagher-Jones, was kindly donated by the Scouse Science Alliance and the original text can be found here.

References

Feige, M.J. et al., 2014. The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins. Proceedings of the National Academy of Sciences. Available at: http://www.pnas.org/content/early/2014/05/14/1321502111.abstract.