Category Archives: Science

Attention Machines: The science of cinematic perception

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This post was contributed by Sofia Ciccarone (master student of Cognitive Neuroscience and Neuropsychology, Birkbeck University of London)

It was exciting to be a part of this event, which took place in Birkbeck cinema in Gordon Square during Science Week.

Birkbeck CinemaThe people who participated not only had the opportunity to experience the amazing and capturing cinematography of The Fountain by Darren Aronofsky; they could also be both the participants and the researchers of a live experimental study.

The experiment was interested in how viewers’ attention changes throughout a movie. To this aim, audience’s attention was measured by locating their eye position on the screen. This was done by making the image disappear sometimes during the film and briefly substituting it with a flashing grid, which filled the whole cinema screen and contained a series of letters and number combinations.

The audience was asked to pay attention to this grid and to report (using their smartphones) the letter and numbers pairs (e.g. S76) they could identify among the other pairs contained in the grid. This procedure, which is known as crowdsourcing gaze data collection, is a method proposed in 2012 by Rudoy and others for collecting gaze direction from any number of participants simultaneously.

The eye movements of one volunteer from the audience were instead recorded using a portable eye tracker. The eye tracker was calibrated right before the start of the film and the participant sat in the front row of the cinema and enjoyed the film while her eye movements were being recorded.

After a shot practice trial, the audience’s eye movements were collected for the first part of the film. During the second half, while participants were allowed to watch the film without distractions, Dr Tim Smith and his team used the available time (48 minutes!) to analyse the answers submitted through the smartphones and the data recorded by the eye tracker.

After the film finished, Dr Tim Smith presented the results of the experiment. It was really surprising to find out that the two eye movement collection methods showed similar results: people mainly focused their attention on the centre of the screen. This is where the more frequently detected letter-number pairs were located. The gaze of the volunteer who wore the portable eye tracker also seemed to be mainly focussing on that area of the screen.

Why does this happen?

The composition of the shots, the camera movements, the staging and the editing of the scenes are some of the ways in which filmmakers direct viewers’ attention. As opposed to films shot in the past, modern TV and Hollywood cinema use a compositional style which involves rapid editing, bipolar extremes of lens length, wide-ranging camera movements and close shots.

For example, the scene in “The shop around the corner” (Esnst Lubitsch, 1940) where the two protagonists meet in the café, lasts 9 minutes and contains 20 shots lasting 27 seconds each. The same scene from a recent remake of this film, “You’ve got mail” (Nora Ephron, 1998), lasts 9 minutes and contains 134 shots of 4 seconds each.

This style causes the audience to have a unified experience of the film being watched, as it induces spectators to focus their attention on the centre of the screen, a type of behaviour defined as central tendency by Le Meur and others in 2007.

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Curiosity: A study about babies and ways to learning

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This post was contributed by Aline Lorandi, a visiting postdoctoral researcher under the supervision of Prof Annette Karmiloff-Smith, investigating the precursors of phonological awareness in Down Syndrome.

Curiosity is unique to humans. There are many stories and quotes about curiosity in literature and in mythology. Sometimes you can get in trouble because of your curiosity, as Pandora did when she opened the box that she was given by Zeus and discovered what was inside.

Experiments at babylabWe are all curious, but there are some researchers who are curious about curiosity, as Katarina Begus, who talked about “The development of human curiosity: A few baby steps”, during Science Week.

Some researchers have shown that curiosity activates the same areas in the brain as when we consume chocolate, nicotine or when we win a race. If curiosity seems to be linked to pleasure, why is it so difficult to awaken curiosity in some people?

Driven by the curiosity about curiosity, Katarina is investigating curiosity on babies. She maintains that children seem curious about things, and that the universal gesture for showing curiosity about something is pointing. However, how can we know what babies mean by pointing?

Katarina presented a series of tests that aimed to verify in which situations babies point, including informative versus non-informative parents, different kinds of objects, and spontaneous pointing. She also reported that theta oscillation (during EEG/ERP) is found in the hippocampus during situations that involve reward.

The more motivate a child is, the more theta oscillation is found, and, consequently, the greater is his or her learning. Based on this assumption, Katarina invested on tests that can look at brain activation during play, in order to attest whether the babies would recognise some objects that they saw before as a sign of learning and motivation.

When testing learning of nonwords in informative versus non-informative contexts, she found greater theta oscillations in the brain when babies were expecting for information in informative contexts (contrasted to non-informative contexts, where no real information was available).

Although Katarina Begus has already found some very exciting results for how children demonstrate curiosity, her work is still going on, and her curiosity about curiosity never ends:

  • What is the role of technology in our curiosity?
  • How will children explore their curiosity using technology?
  • How the studies about curiosity and learning can help us prevent dementia?

Those were questions that Katarina would like to address in future researches. The audience was also curious, a fact that was shown by the questions made by the end of the talk:

  • How far children go with non-informative teachers?
  • What about their reaction to surprises?
  • What about the effects of surprise on learning?
  • How can we make people more curious?
  • What is the role of the environment on curiosity?

As Albert Einstein once said, “The important thing is not to stop questioning. Curiosity has its own reason for existing.” Let’s keep curious!

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Infants, Down syndrome and the Alzheimer disease: A multidisciplinary approach

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This post was contributed by Aline Lorandi, a visiting postdoctoral researcher under the supervision of Prof Annette Karmiloff-Smith, investigating the precursors of phonological awareness in Down Syndrome. She also is a collaborator in the infant stream of the London Down Syndrome Consortium (LonDownS), which investigates the links between Down syndrome and the Alzheimer disease

One of the premises of developmental neuroscience is based on the fact that, in order to understand certain phenotypes, it is crucial that we investigate their origins, that is, that we track the developmental trajectory that leads us to different sorts of behaviour, cognitive profiles, disorders, and diseases.

DNA StrandsWe must also acknowledge that the advances made by the field of developmental neuroscience allow us to take the debate between the contribution of genes and environment to another level: It is a fact that it is only possible to understand such contribution in a bilateral way, in which one modifies the other all the time.

With all that in mind, we can understand the curious title that Dr Esha Massand gave to her talk: ‘What can infants possibly tell us about Dementia?’ It seems a bit odd to think how studying babies can provide us any kind of relevant information about a condition typically related to ageing. Nevertheless, from the study of Down Syndrome arose the inspiration to establish the link between child development and Alzheimer’s disease.

The research described by Dr Massand is part of the LonDowS Research Consortium, involving different universities, which works in five sites: Genetics, mouse models, cells, adults, and infants.

The aim of the infant stream, according to Dr Massand, is to understand individual differences in infancy that may point to early signs of Alzheimer’s Disease. It is known that individuals with Down Syndrome have an extra copy of chromosome 21, and there is a gene in this chromosome, called APP gene, that produces a protein that, because of this extra chromosome, will be overexpressed in all individuals from the womb throughout development.

This APP gene produces plaques that are found in the brains of individuals with Alzheimer’s Disease. As the APP gene is overexpressed in Down Syndrome, it is very important to investigate its relationship with Alzheimer disease. One of the interesting facts is that, although all individuals with Down Syndrome will present, by the age of 30 onwards, the plaques in their brains, not all of them will develop signs of Alzheimer’s Disease.

Using a varied range of methodologies (eye tracking, sleep pattern measuring, EEG/ERP, behavioural tasks), Dr Massand and colleagues aim to understand how behaviour and neural responses may shed some light on whether it is possible to track some early biomarkers that can point to the onset of the disease in a developmental way. Among the cognitive and neural underpinnings, they are looking at several abilities, such as memory, attention, language, sleep fragmentation, mother/father/infant interactions, and many others. All those methodologies are very child-friendly.

Although preliminary, many interesting results already point to important individual differences, like the relationship between language and the gap-overlap/disengaging effect (the ability to disengage from one stimulus to look at another one, concomitantly or not).

Dr Massand’s team found that the fewer words a child understands and produces, the longer he or she takes to disengage from the stimulus presented in the task. Additionally, the disengaging effect was positively correlated to aggressive behaviour. That means that the higher the score that the child reached in the behaviour questionnaire (related, among other measures, to aggressive behaviour), the longer he or she took to disengage from the stimuli.

They also found a positive correlation between the ability to pay attention to novelties and detect them, to more sleep. Analysing several trials during a test to find the location of the objects, they also discovered that children with Down Syndrome may take longer to habituate to the objects and may take longer in the tasks: While typically developing children can detect a change of location of the objects in a first trial, observable by the duration of them looking at the screen in the eye tracking, children with Down syndrome do better – or more ‘typically’ – in a second trial, presenting more variability in the first trial than typically developing children. All these findings are related to individual differences that may be correlated to those who will be at risk of developing Alzheimer disease.

Exciting trends and lots more to do for Dr Esha Massand’s team! There are more data to collect, especially from controls, findings from EEG/ERP to analyse, which may point to underlying neural differences related to Alzheimer’s Disease, and the exciting combination with the data from the other streams (cells, mouse models, genetics, and adults) to explore.

As the questions from the audience show, this is the kind of research that makes us excited and curious about! Should the participants be followed longitudinally? How long do children take to get familiarised to the cap in the EEG tests? These and other questions about the relationships between the different cognitive abilities were answered by Dr. Massand, who also highlighted that the hope is to find those individual differences in adults as well, in order to seek a better understanding of the factors that might indicate early clinical signs of the Alzheimer’s Disease.

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Protein machines in the molecular arms race

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This post was contributed by Clare Sansom, Senior Associate Lecturer at the Department of Biological Sciences

Birkbeck’s Science Week 2015 was held from Monday 23 to Thursday 26 March and included three evenings of public talks by senior researchers. The first two lectures, on the Tuesday, were given by two of the college’s most distinguished women scientists: Helen Saibil from the Department of Biological Sciences and Karen Hudson-Edwards from Earth and Planetary Sciences; they were billed together as a ‘Women in Science Evening’.

Pathways of pore formation – illustration by Adrian HodelThe lectures were all introduced by the Dean of the Faculty of Science, Nicholas Keep who described Saibil, a close colleague, as “our most eminent female scientist”. She came to Birkbeck from Canada via a PhD at King’s College London under the supervision of Nobel laureate Maurice Wilkins and post-doctoral work at Oxford.

Since arriving here in the 1980s she has built up an internationally renowned structural biology lab, focusing in particular on the technique of electron microscopy. She has been a Fellow of the Royal Society since 2006 and of the Academy of Medical Sciences since 2009.

Saibil began her lecture by explaining that proteins can act as little machines, performing mechanical tasks that are essential for the maintenance of life. Her group has been interested for some time in proteins that can punch holes in the walls of cells. This allows the cell contents to leak out in a damaging process known as lysis, and it also allows toxins to enter the cells. These proteins can therefore be thought of as powerful weapons, and they are deployed on both sides of a ‘molecular arms race’: by pathogens and by the immune systems of humans and other animals.

Most soluble proteins fold into a single stable structure that tries, as far as possible, to keep their hydrophobic (“water-hating”) parts – the side chains of certain amino acids – in the interior of the protein, with the hydrophilic (“water-loving”) side chains on the outside, in contact with the watery environment inside or outside cells.

Pore-forming proteins, however, have a ‘Jekyll and Hyde’ like identity: they can form two distinctly different shapes, one as individual, soluble molecules and the other when they associate with each other into membrane-bound rings to form cylindrical pores. These structures, and the conformational change between them, are remarkably similar in proteins from bacteria and from the immune system.

Pore-forming toxins have been found in types of bacteria that are responsible for some deadly human diseases, including meningitis and pneumonia. The structure of a monomeric form of these proteins in solution was first solved in 1998, using X-ray crystallography. However, large complexes of many protein molecules are more readily solved by electron microscopy, particularly when those complexes are embedded in membranes.

In 2005 Saibil and her group described structures of the pore-forming toxin pneumolysin, from Streptococcus pneumoniae, in complex with a model cell membrane. They found that the proteins formed two distinctly different ring-shaped structures. Initially, they formed into a ring sitting on top of the membrane, which was termed the pre-pore; then they changed shape to burrow part of each protein deep into the membrane and form the pore itself. Each monomer in the pre-pore had a structure that was similar to that of the molecule in solution, but they underwent large structural changes to form the pore.

Most structures solved by electron microscopy are at lower resolution than those solved by X-ray crystallography, and it is not possible to trace the positions of individual atoms at lower resolutions (eg worse than 3 A). Saibil and her colleagues were able to interpret the structure of the proteins making up the pore by fitting pieces of the X-ray structure of the isolated molecule into their electron density.

They found a dramatic change in structure, with the tall, thin protein structure collapsing into an arch and a helical region stretching out to form a long, extended beta hairpin. It is these hairpins that join together to form the walls of the pore. The process of pore forming therefore has three stages: firstly the toxin molecules bind to the surface of their target cells, then they associate into the circular pre-pores and finally they change shape in a concerted manner, punching holes in the cell membranes by ejecting a disc of membrane, letting other toxins in and cell contents out.

Saibil then turned the focus of her talk from attack by bacteria to the human immune system’s defence. Natural killer (NK) cells are specialised lymphocytes (white blood cells) that kill virally-infected and cancerous cells in the bloodstream. They kill on contact with their target cells by releasing a toxic protein into those cells that stimulates those target cells to commit suicide in a process known as programmed cell death or apoptosis. We have only recently learned that the mechanism through which the NK cells work is very similar to the mechanism of the bacterial pore-forming toxins.

Natural killer cells express a protein called perforin that has a similar structure in solution to the bacterial pneumolysin. Although there is very little sequence similarity between these proteins – there is only one amino acid conserved throughout all the known bacterial and vertebrate proteins of this family, a glycine at a critical position for the conformational change – the structures are similar enough to suggest that the proteins all once had a common ancestor.

Saibil and her colleagues used electron microscopy to discover that this protein forms a pore through a similar mechanism to pneumolysin: the helical region that unfolds into the beta hairpin to form the pore forms the core of the molecular machine and is largely unchanged between the structures. There are some differences between the structures, however; in particular, there is no need for the perforin structure to ‘collapse’ as the molecule has ‘arms’ that are long enough to form the hairpin and punch the hole without bending into an arch.

The mechanism through which the NK cells kill their target cells is now quite well understood. When the two cells come into contact they form a temporary structure called an immune synapse that allows the pore to form and proteases called granzymes, which induce apoptosis, to enter the target cells. This YouTube video illustrates the natural killer cells’ mechanism of action, and this one shows a detailed view of the immune synapse. Other, similar proteins have been identified in oyster mushrooms; these form more rigid structures that are easier to work with. Saibil’s group and their collaborators have been able to solve the structure of this protein in intermediate stages of pore formation and are beginning to gain an understanding of exactly how it unfolds.

Mutations in perforin that prevent it from functioning cause a rare disease called haemophagocytic lymphohistiocytosis, which is almost invariably fatal in childhood. Understanding the mechanism of action of this important family of protein ‘weapons’ in both attack and defence may help find a cure for this devastating condition, as well as for some commoner disorders of the immune system and important infectious diseases.

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Image Caption: Pathways of pore formation – illustration by Adrian Hodel