Live chat with neuroscientist Esha Massand

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Good evening Nappy Science Gang! I’m pleased to present you with the write-up from our 15th live chat (15 already!) with Esha Massand, a postdoctoral research scientist at Birkbeck University London, in the Centre for Brain and Cognitive Development (CBCD). Esha investigates the links between Down’s syndrome (DS) and Alzheimer’s disease, because children with DS have a higher risk of developing Alzheimer’s in adulthood than do people in the general population. She works with teams of geneticists, psychiatrists and neuroscientists to answer questions about individual differences in the development of children with DS.

Her main questions are: why are children with DS more likely to develop Alzheimer’s and, more importantly, why do some DS children NOT develop it? What gives these kids resilience against the disease later in life? And also, can we find a correlation between neural activity/behaviour in children with DS and the later onset of Alzheimer’s?

To try and answer all these interesting questions, Esha and her colleagues use methods such as eye-tracking and electroencephalography to understand more about the cognitive development of very young children with DS.

Q: Can you explain a bit about how an EEG works for those who’ve never seen one being done?
Esha: Electroencephalography, or EEG for short, is a measurement of brain activity. To record this, we fit a hairnet with tiny sponges on the subject’s head, which measurea the natural electrophysiological activity of the brain, so it’s totally non-invasive and nothing gets into the brain! Whilst recording, we get the infant to do a variety of things designed to be engaging and stimulating for babies and toddlers. For example they watch fun objects or scenes on a TV screen while we monitor their eye movements to ascertain what they pay attention to, so that we can analyse the data afterwards. This is our babylab in picture, in case anyone is wondering what an EEG looks like!
 
Q: How do you relate your findings in children to adults? As you can’t study an individual to see Alzheimer’s
Esha : We have a team who are using a very similar protocol to the one we use with babies, but with adults with DS – in between the ages of 18 and 40 years. We also have a PhD student (Kate Hughes) who is again doing similar work with adolescents. The adult group will see individuals who will go on to get the symptoms of Alzheimer’s — other individuals, of course will not have symptomatology. But these individual differences are very interesting.

Q :
What is it about people’s brains that leads them to develop Down’s Syndrome and/or Alzheimer’s? How would it best be explained, to someone without medical knowledge?

Esha : There’s nothing ‘in’ the brain that causes it because for most cases, DS is caused by a random error in cell division that results in the presence of an extra copy of chromosome 21. In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46, but in Down’s syndrome, there are 3 copies of chromosome 21. The connection between this and the increased risk of developing Alzheimer’s is that on chromosome 21 lies a gene, called the APP gene, which contributes to the formation of the plaques and tangles typical of mature brains with Alzheimer’s. Thus individuals with DS over-express this gene due to the three copies of the chromosome that they possess and are more likely to go on developing the neurodegenerative disease. Nonetheless, many adults with DS don’t go on to develop the clinical symptoms of Alzheimer’s, such as loss of memory, so one doesn’t necessarily lead to the other.

Q : What is it you’re looking for in the brain when you do an EEG?
Esha : The goal is to be able to identify risk and resilience markers for Alzheimer’s. Some of our EEG tasks are designed to measure episodic memory (memories of personally experienced episodes like what you had for breakfast this morning), which are some of the first types of memories to decline in Alzheimer’s. We do this by measuring the activity in the neurons of the brain when an infant looks at toys that they’ve seen before or played with beforeThe EEG (or brain activity) is greater (higher amplitudes) when it’s a recognised item versus when it’s new and in this way we can have some indication as to whether the infant remembers the toy or not. We’re hoping that when we correlate these EEG data to some of our other measures (eye-tracking measures) we’re able to highlight subgroups of individuals – some of whom will get Alzheimer’s, and some who won’t. We want to combine our data with the adult teams too to get an overall picture.


Q: Is it easy to find baby volunteers?

Esha: We’ve had such a good response, but we need more! Our aim is to see 150 infants (6 to 60 months) with DS, and we’ve seen about 80 so far. Here is a link you can follow if anyone is interested in taking part in the study [smiley] We also need typically developing infants to take part in lots of research at the babylab, and volunteers are most welcome!


Q: 
Do the EEG changes show up before the onset of symptoms?
Esha: It would be fantastic if we could establish that, but research to date has been done after diagnosis of AD, so we don’t have an answer yet.
Q : You said a baby has more brain activity when looking at a toy they’ve seen before. Why is that? You might expect the opposite.
Esha: We would expect when a child sees something they’ve seen before, to be bored by it and look at something new, but measuring EEG is a bit different to measuring looking patterns- which is what we do with the eye-tracker! The increased amplitudes in the brain that we record when an individual recollects an item is thought to reflect all the effort of contextual retrieval that is involved. It’s called an Old-New effect and it’s a very slow and long lasting brain response. This is characteristic of recollection – trying to recall where you had your last holiday, or what the last film was that you saw at the cinema.
 
Q : So it’s harder work to remember all the details about something that you’ve seen before, than it is to take in the details of something new?
Esha: Not necessarily. There’s research to suggest that encoding (when you see a new stimulus) is just as important as retrieval (recalling back). They both require some effort, but if we contrast a memory for say, recollecting your last holiday, with a memory for what your mother’s maiden name is (for example) we can see that the former one requires more effort and probably takes more time, than the latter type of memory.

Q: Is there an effect if an infant sees a toy that’s similar to something they’ve already played with?Esha: We would observe this familiarity effect in adults (you even see the effects in adults when they see a word that’s similar to previous ones), but the age at which we can measure the effect is still unclear – and even more so in individuals with DS.

Q: What age do you see this from? How early can infants remember that they’ve seen a thing before?We have a large age range in our study, so this is a question we should be able to answer once we have finished the study!

We’re currently doing a study where we play with a set of toys with our babies, and then present them during the EEG for them to ‘study’. We also present pictures of new toys and we can compare the brain’s activity for each set of toys.

Q: Are there any interesting unexpected challenges you’ve faced when doing this research?
Esha: There are many unexpected challenges with infant research! One of our tasks requires an infant to sit still (while we record spontaneous EEG/ brain activity). This is somewhat easy with adults, but not with children! We’ve had to make many modifications to studies to make them ‘work’ with babies. We have to be very creative, and very good bubble-blowers!

Q: Do you have babies who come in for repeated experiments? Or do you usually just see them once?
Esha: We are following 40 of our infants at multiple time points and we’re hoping to track them over time. The study runs for 5 years and we’re already in the 3rd. We have a PhD student who is doing a similar project with 4-16 year olds and she has indeed seen some of our participants again, when they’ve aged a couple of years.


Q: 
How long do you expect this study to run? Will the infants graduate to being adolescent participants?
Esha: At the moment, we’re hoping to tie the ‘streams’ of the project together (infant, adolescent & adult) to present a large set of data at the end.


Q: You said at the start that there are typical features of mature brains that develop Alzheimer’s – so are those features not present in infants?

Esha: The features of a brain with Alzheimer’s are the plaques (protein fragment clusters) and tangles (twisted strands of protein). The APP (protein coding) gene lies on chromosome 21, so individuals with Down’s syndrome over-express this gene due to the three copies of the chromosome that they possess instead of two. But, although the brains of infants with DS are developing differently (even before birth), I must stress that many children with DS do not go on to develop Alzheimer’s. It’s these resilience and protective markers that we’re also trying to identify in our research!


Q: 
By researching this, is there a chance that one day it’ll be possible to work out the chance of developing Alzheimer’s (in everyone) a bit like the tests for Down’s in pregnancy, and then maybe it’ll be possible to do something to lessen the effects of it before/when it starts to develop in older age?
Esha: That is one of the aims of the study, to create intervention strategies at some or all of these levels in order to enhance the protective factors and positively impact the development of individuals with Down’s syndrome. But also we can apply these findings to typically developing individuals who are developing AD too.

Q: But what about non-DS children? Lots of non-DS adults develop Alzheimer’s too. Are there differences in their brains before Alzheimer’s develops?
Esha: Alzheimer’s disease is a progressive condition, which means the symptoms develop gradually and become more severe over the course of several years. But, we never really investigate if the plaques and tangles of AD are present in typically developing older adults! It may be that an older adult has the plaques and tangles but no AD.

Thank you Esha for the fascinating chat and once again, if anyone would like to volunteer to help Esha with her research, do check out her research page. Also, if anyone has a child, whether with DS or a typically developing child, up to 5 years old, and would like to get involved in the study, please email: downsyndrome@bbk.ac.uk
Thank you!
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