Lynne Malcolm: It’s the All in the Mind on RN, Lynne Malcolm with you. Today we investigate the structure that links the right and left sides of our brain, and what happens when it lets us down.

Abbie Kinniburgh: I often get told, well, you look fine, you act fine and you fit into the norms, so you mustn’t have any challenges. That’s often frustrating because I have a lot of challenges that people don’t see. So just casual social situations are very, very awkward, and recognising social cues, very high anxiety. A lot of the characteristics with corpus callosal conditions are similar to autism. I think a lot of it is often from society’s reactions and expectations.

Lynne Malcolm: Abbie Kinniburgh is 25 years old and she has a rare brain disorder, a partial agenesis of the corpus callosum, which means that the middle part of this brain structure is missing.

Today we hear how disorders of the corpus callosum affect people’s lives and what this structure is teaching us about brain plasticity.

Professor Linda Richards, deputy director of the Queensland Brain Institute, specialises in corpus callosal research.

Linda Richards: The corpus callosum is the largest fibre tract in the brain, so it’s the connections between nerve cells in the two hemispheres of the brain. So it is really the conduit between the two sides of the brain, and it allows that information transfer from one hemisphere to another.

So the corpus callosum is required for any functions that the brain has that need to be integrated between the two sides of the body, if you like, and so the information that comes into the brain needs to be integrated, and the corpus callosum is the fibre tract that enables that to happen.

It’s also very important for other functions which are lateralised more to one side of the brain. For example, reading and language. Those functions require one side of the brain to dominate and the other side of the brain to be somewhat inhibited to allow that to occur.

Lynne Malcolm: So what are some of the disorders associated with this part of the brain?

Linda Richards: This is a disorder that usually occurs during development prior to birth. And the corpus callosum starts to develop around 12 weeks of human gestation, and then continues on after that even after birth. So by around 20 weeks of gestation at the ultrasound at that stage the doctor will be able to tell whether or not the child has a normally developing corpus callosum.

Because it is a developmental disorder, some of the genes that regulate formation of the corpus callosum are also important for regulating formation of other organs. It could be the kidneys, heart, lungs, other organs of the body. So sometimes children have a deficit in the corpus callosum, but they also have other life-threatening deficits. They are the deficits that the doctors really have to concentrate on because they are really quite life-threatening.

There are people that have isolated corpus callosum disorder. So that means that they only have a corpus callosum disorder as far as we can tell. And they don’t have major other organ system deficits. So the dilemma actually at the 20-week gestational period is to be able to provide some degree of certainty to the doctor and to the family as to the possible prognosis for that child, and we are not in a position to be able to do that at the moment because we can’t do a genetic test really for it at the moment.

And the outcome can be everything from a very poor quality of life for the child, they may be blind, deaf, never learn to walk or talk and not interact with their parents, to a very high-functioning individual, everything in between. So you can imagine that it’s an incredibly difficult time for parents who have this diagnosis. What kind of decisions might they make? They may even be considering terminating the pregnancy at that stage. They are desperate to understand whether or not if they have another pregnancy, what’s the risk of having the same thing happen. And so it’s a really important issue that as scientists and doctors we are really trying to address this issue right now, and it’s just the hardest thing for parents at that time.

Lynne Malcolm: It’s thought that about 1 in 3,000 people have a significant corpus callosal disorder, but some say that’s an underestimate. Linda Richards explains what’s known so far about the causes of the disorder.

Linda Richards: We have some understanding now of some of the cells that are required for forming a bridge between the hemispheres to allow the corpus callosum axons to cross over, and that developmental process is controlled by a large range of different genes. So if a person happens to have a mutation in one of those genes, then often this occurs what we call de novo, so just in that child there was an accident of genetic engineering, if you like, as the baby was made, and there’s a mutation in that gene, then these processes don’t proceed in the correct way.

Most of this work has been done in animal models, particularly in a mouse model, so what we are trying to do now is working with our clinical colleagues to take this research into the clinic so we can have a genetic test that would at least allow some understanding of the clinical syndrome that might be being presented in utero with that ultrasound at 20 weeks. Because at that point if there was information given to the parents it would help in terms of management of the pregnancy and also the child after birth, so they can be given the best possible chance.

Lynne Malcolm: So we’ve talked about genetic influences on corpus callosum disorders. Are there environmental factors as well?

Linda Richards: There are environmental factors that can cause corpus callosum malformations. So one of the best known ones is foetal alcohol syndrome disorder or FASD. What happens in those children is the mother is usually an alcoholic and drinking a lot during the pregnancy, and this can have a significant and severe impact on brain development. And the corpus callosum is one of the structures that is vulnerable in foetal alcohol syndrome disorder.

There are a number of other environmental influences that we are interested in as scientists to try and see whether there could be a link. Of course one of the topical ones are just recently is zika virus, which does cause significant brain abnormalities, and the most severe brain abnormality is microcephaly. So this is a severe brain disorder where not enough cells are made in the brain, so the brain is smaller in the children. And the most significantly affected areas are the cerebral hemispheres that are connected by the corpus callosum. So generally people with microcephaly can sometimes have callosal abnormalities as well. So that’s just an example of a viral infection that could potentially cause this.

There are possibly other viral infections that might have an impact on corpus callosum development that we don’t know about as well. But certainly foetal alcohol syndrome disorder is one where the link is very clear.

Lynne Malcolm: Professor Linda Richards.

Maree Maxfield didn’t find out that her daughter Abbie had a corpus callosal disorder until she was two years old.

Maree Maxfield: Abbie has a couple of brain conditions. She was also born without a pituitary gland, and when she was 16 hours old she stopped breathing and went blue, and that was the first thing that alerted us to something being wrong. And for a couple of years the focus was on those adrenal issues. And then before her second birthday she had an MRI and we were told that she also had partial agenesis of the corpus callosum, but not to worry about that because she didn’t need it.

Lynne Malcolm: And so how was she as a young child?

Maree Maxfield: She got sick a lot, she had to be hospitalised a lot because she had no adrenal glands, so she doesn’t make cortisone, so that’s a medical issue that means she had to be rushed off to hospital quite often. So she was regarded as someone who had to go to hospital a lot I suppose. But the corpus callosum part of it, there were lots of things that I have looked at in retrospect that were actually corpus callosal issues but everyone just used to shrug their shoulders and say, oh, it must be something to do with the pituitary gland. But it wasn’t.

Lynne Malcolm: How did you find out that it was a corpus callosum issue?

Maree Maxfield: Well, there was no internet back in those days, there were no mobile phones, we were living in the country, and when we were living in Melbourne I was looking on the internet to try and get a bit more information and came across a group in America which was the National Organisation for Disorders of the Corpus Callosum, called NODCC. And I wrote to someone there and just said, look, I have someone here, I’ve been told there is nobody else, can you tell me little bit more about it. And I got a letter back with some of the information about it and I wrote back sort of in disbelief immediately and just said, oh, someone’s been looking in my window for the last 20 years, that describes my daughter perfectly.

Lynne Malcolm: Maree Maxfield’s daughter Abbie is now 25. She noticed she was different to others her age as she approached adolescence.

Abbie Kinniburgh: I started to get very anxious about everything, just social situations and being a bit behind my peers in what I was doing. I went from a happy little kid that didn’t have much worry to worrying about just about everything and not being very happy.

Lynne Malcolm: Do you think that that had something to do with the way you felt you were comparing yourself to the other kids or the way they were treating you?

Abbie Kinniburgh: Yes, I started to notice because they would exclude me from things because they thought I would tell on them because I was worried about things and they weren’t.

Lynne Malcolm: And what were you interested in that was different to what they were interested in?

Abbie Kinniburgh: I was interested in being very organised with things, so I would unpack my clothes in my cupboard and fold them up and put them back in, just for a hobby sort of thing. And I would still play with cartoon toys and stuff at the age of 12, 13.

Lynne Malcolm: And what about your schoolwork and reading and writing, were you a bit behind other kids in that?

Abbie Kinniburgh: I was, I was a very slow hand-writer all through primary school and secondary school, and I’m in the first percentile of handwriting speed, so that’s quite slow. And it takes me a long time to process information, so I read things over and over again and that takes me a while. So I was behind but I didn’t actually notice it as much until I got to secondary school.

Lynne Malcolm: Were you able to make friends at all?

Abbie Kinniburgh: I had some friends in primary school and they were actually often a lot younger than me, so my best friend was five years younger than me, and most of my primary school friends were a year or two younger. I think it was just because I could relate better to younger kids than kids my own age. So we were still playing make-believe games in grade six. I never fitted in to the popular groups and I didn’t get invited to things, and it didn’t go any further than being at school.

The most challenging thing is because I’ve been so encouraged to do things and I’ve come such a long way from what people expect, I often get told, well, you look fine, you act fine and you fit into the norms, so you mustn’t have any challenges. So that’s often frustrating because I have a lot of challenges that people don’t see. And the reason that I am so capable is because I’ve had 25 years to learn to fit in and cover it up, I guess, and I have been encouraged to do things, so I’m a lot better off than I could be.

But I know that the doctors said to my parents that I would probably never learn to read and write and wouldn’t be able to do lots of things and I might turn out to be mentally retarded. They didn’t have much information about it at all. But my parents just kept letting me do things as I was growing up, and they were both primary school teachers, so they thought, well, we are going to just keep aiming at the highest and just keep pushing a little bit further each time, and it doesn’t matter if it takes a bit longer. So they never had the attitude of, oh well, she won’t be able to do that so we’re not going to try.

Lynne Malcolm: That must have been really helpful for you.

Abbie Kinniburgh: It’s definitely was. And, as I said, I didn’t notice…all through primary school I really didn’t know much about it.

Lynne Malcolm: Abbie Kinniburgh has what’s known as partial agenesis of the corpus callosum.

Professor Linda Richards explains how people with this disorder usually present.

Linda Richards: So the agenesis of the corpus callosum generally means that there are none of the fibres crossing over the midline. But there are a large number of people that have some fibres crossing the midline. But the people with agenesis of the corpus callosum generally have difficulties with social interaction, that’s one of the major difficulties that they face. They may have difficulties in learning. So as children that means that in the classroom they are the kids that are different, might potentially be disruptive. But as adults they may be people that have trouble holding down a job, trouble forming meaningful relationships with other people. And obviously this really affects their quality of life.

Lynne Malcolm: So if the corpus callosum is there to pull the two sides of the brain together, it’s surprising that people can cope with a problem there.

Linda Richards: Yes. So what’s really interesting is that people may have heard about the split brain subjects that Roger Sperry studied in the ’80s. Those subjects had intractable epilepsy, many, many seizures a day, up to maybe 100 seizures a day. And a neurosurgical procedure is performed to cut the corpus callosum, and that prevents the seizures from travelling from one side of the brain to the other.

Now, one of the interesting things after those surgeries are performed was that the patients are really unable to integrate information from two sides of the brain properly. That has actually formed the basis…in fact Roger Sperry won a Nobel Prize for this work…that really forms the basis of our understanding of the function of the corpus callosum. But people who are born without a corpus callosum have a completely different presentation to people who have had this surgical section of the corpus callosum.

So in recent years it has become evident through scientific research that in fact there are plastic processes in the brain that try to compensate for the lack of the corpus callosum forming. So there have been recent reports of some magnetic resonance imaging studies, MRI studies showing that people can have what we call ectopic tracts. So the fibres that would normally cross the corpus callosum find a different route to cross and actually connect the two hemispheres together. So that’s perhaps an explanation for why people are able to function without a corpus callosum.

Lynne Malcolm: That’s a fairly spectacular example of brain plasticity, isn’t it.

Linda Richards: It’s an example of a different kind of brain plasticity than what we normally think about. When we think of brain plasticity we usually think of plasticity at the level of connections between individual neurons. So we call them synapses. This is where one neuron talks to the next neuron. And the small synapses are the structures in the brain that we know are altered as we learn a new thing or throughout life these small synapses can change. And so that’s what we normally think of when we think of plasticity. This kind of plasticity is axonal plasticity. This is completely new growth or a new direction of the growth of these fibres across a completely different tract during brain development.

Lynne Malcolm: So how useful is this in further study of the brain per se?

Linda Richards: Well, it’s extremely important, because if we could understand how those plastic processes occur during brain development, to enable the brain to wire itself such that it can function in an optimal way, we may be able to repair the brain, even in perhaps during childhood or perhaps in the adult brain. For example, one of the processes might be the kind of stimulation that a young child receives as it is developing. And so some work from my laboratory actually has shown that stimulation, sensory input from both sides of the body is very important for wiring the corpus callosum, and that that input is balanced, in a way. And so if we can understand those processes it might be possible to help make sure that that kind of stimulation is there as a child is developing so that we can maximise their potential later in life.

Lynne Malcolm: Linda Richards.

You’re with All in the Mind on RN, Radio Australia and online. I’m Lynne Malcolm. Today we’re looking at the brain structure called the corpus callosum, and what happens when it is missing or doesn’t develop properly.

Maree Maxfield was a primary school teacher and did not give up on her daughter. She worked really hard with Abbie to help her to learn to read and write, and manage her social challenges. Maree Maxfield was then instrumental in setting up the only Australian support group for people with corpus callosal disorders, it’s called AusDoCC.

Maree Maxfield: We are all volunteers. And one thing that we are really, really focused on is that so many things that I found with Abbie, there are age gaps. Like, you get to 12 and doors shut, you get to 16 and doors shut, she is at 25, big doors have slammed at 25. And I think we are going to try to focus on the whole lifespan, from birth to death virtually, and all the bits in between, because that’s something that has made our life particularly difficult, that lots of things just have this age barrier. And being rare, it needs support all the way through. It’s no good slamming the door at 18 and then there’s nowhere to go and you spend the next two years picking up the pieces, it’s very disruptive for a life.

And the other thing that’s difficult for us is we are scattered all over Australia and we need funds. We need funds to run the organisation, we need funds to produce resources for teachers and resources for doctors. One of the main things that has really held us together and spearheaded AusDoCC has been our association with the Queensland Brain Institute with Professor Linda Richards, and she is so good to us, and she is so accessible. And we’ve been invited there and we have toured the lab, and she has just really, really helped us. And at one stage when things were crumbling a bit she brought us all back together and said, no, you can do it, you need AusDoCC. But she has been our guiding light, I suppose you’d say, so we are very indebted to Linda, and we hope that we can continue to work with her for a long time into the future.

Lynne Malcolm: Maree Maxfield was inspired by her experience with her daughter’s corpus callosal disorder to study a Masters in Public Health at Melbourne University.

Professor Linda Richards and her team at the Queensland Brain Institute have recently launched an international research collaboration on disorders of the corpus callosum. Having access to a larger population gives them a much better chance of identifying the genes involved at a much faster rate. It also may lead to potential treatment and prevention.

Linda Richards: So at the moment it would not be possible to regrow a corpus callosum. And in fact that may not be what we want to do anyway. Given that the brain is plastic and may have made these other connections, what we need to understand is some of these ectopic connections are good, but it appears that there are some that are not beneficial to the subject. So there’s an ectopic projection that has been identified by our collaborators in Brazil and in San Francisco in some children that have a partial corpus callosum. So these children don’t have a full corpus callosum but they have some fibres crossing. And in some of those patients they have a connection from the right frontal cortex to the left occipital, let’s say the back of the head, and that projection doesn’t normally form. And those children tend to be more intellectually disabled. So potentially this ectopic projection may be contributing to that. So we really want to understand these mechanisms to see whether we can prevent them from happening if possible, or to modify them during early development so that we can maximise the chance for the child to have a full and productive life.

Lynne Malcolm: So to what extent do you think there are children and even adults that have a disorder with the corpus callosum but don’t know it?

Linda Richards: It’s very common. So there have been a number of adults that have contacted me recently because we’ve launched our website and the international consortium, and they have found our research through the AusDoCC Association, and they have realised that they don’t have a corpus callosum for some other reason. So they’ve had an accident and they’ve gone into the hospital and had an MRI because they hit their head or something like that, and then they discover they have a corpus callosum malformation. And this can be a very scary and confusing time because even within the medical community there’s not a lot of awareness about the corpus callosum and that it’s an important brain structure and it can affect your life. And so it can be quite a scary and confusing times are people who could be even in their 60s and find out that they’ve had this brain malformation all their lives. But I think with time and certainly in our discussions with them and explaining to them what’s happened, it helps to put things in place a little bit for them, and it helps them explain to their families this is what I’ve been struggling with all my life, and it isn’t just because I had this particular personality disorder, if you like, this has been affecting me.

Lynne Malcolm: So if people are listening to this and feel that there might be something possibly with them or with their children, what do you suggest?

Linda Richards: The only way to diagnose this is with an MRI. And so I would suggest if people are concerned that they should discuss this with their doctor and decide if for them it’s something that they want to do. Having an MRI is not going to be able to lead to a cure for this, but it could help them understand what’s going on.

Lynne Malcolm: Professor Linda Richards and her team are asking for people with corpus callosum malfunctions to register with their new Australian database to help with further research. We’ll put a link to that on our website.

Abbie Kinniburgh is now 25, and after steadily persevering through high school and TAFE courses she is now at university studying social work. She’s written an article on the AusDoCC website about her personal experience of her condition. She writes that people with corpus callosal disorders and their families are in many ways ahead of the rest of society. What does she mean by that?

Abbie Kinniburgh: I think I mean that they have had a lot of experience and had to deal with a lot of adversity that a lot of people don’t have to deal with, and they’ve had to change how they deal with things to fit in with society. So I think in a lot of ways we are very resilient and able to cope with adversity because we deal with it every day almost.

Lynne Malcolm: What advice would you give to people who have similar difficulties?

Abbie Kinniburgh: Make sure that you are recognised for things that you can do, so don’t let people say that you won’t be able to do certain things because nobody knows with this condition, it is very varied in the degrees that you can get. And basically don’t let people tell you that you can’t do something too early on, and also be recognised for challenges that you do face. So if we are not acknowledged for things that we do have to push through and hurdles that we have to jump over, that’s also a bit insulting. So make sure that people know what you are actually facing, even if you look fine to them.

Lynne Malcolm: So what are your hopes and goals for the future?

Abbie Kinniburgh: Definitely to build more awareness for the AusDoCC organisation and corpus callosal conditions to get more support for myself and other adults around Australia. And also to hopefully do something with my social work course. If I’m able to stick to it, I would like to tie in the volunteer stuff that I’m already doing with the social work course. That’s sorted my aims at the moment.

Lynne Malcolm: Abbie Kinniburgh.