Cerebral Dynamics of General Anesthesia in Childhood

After receiving the IARS Mentored Research Award in 2015 for her research on “Cerebral Dynamics of General Anesthesia in Childhood,” Laura Cornelissen, MSci, PhD, found her research career take off exponentially. A Post-Doctoral Research Fellow in Anaesthesia at Boston Children’s Hospital at the time, she found receiving the IMRA, her first independent funding, opened new pathways that had previously been unavailable. Dr. Cornelissen gained the opportunity to interact with thought leaders in the specialty who in turn opened new opportunities to her, introduced her to new contacts and helped her to excel in her career as a researcher. It helped that her initial research studying the brain activity in children undergoing anesthesia, which proved very successful, and funding for this area of research spun out from there. Many groups reached out to collaborate and the research has since been replicated. All of this, led to many unbiased, high-quality studies, and the opportunity for Dr. Cornelissen to work on clinical trials, including one looking at neurogenes, disease, and neurodegenerative disease in children. After 12 years of doing academic research, in April of 2023, she chose a change in path and joined the clinical development team at Eisai, a medium-sized pharmaceutical company with a strong neuroscience department. Dr. Cornelissen was intrigued by what innovative outcomes might be reachable in research in the industry sphere. Below, Dr. Cornelissen shares her journey as an investigator, her research interests, and her hopes for the future of anesthesia and neuroscience research.

1. What is your current position? How long have you been in this position? What was your role when you were first funded by IARS?

I applied for IMRA at the same time that I was applying for NIH K09 grants, which are the grants that help you to foster independence while still getting mentorship. I was probably at the end of my postdoc. As a reward for getting my IMRA, I got promoted to Assistant Professor. I had to prove that I was worthy of this new title which would ultimately lead to better things. I was a senior postdoctoral when I applied, so I was ready to do independent research. You have a mentor and series of mentors who can help you. I had a study with good research questions that were achievable, but also allowed to be a little risky in how that evolved. This is really good for someone when you’re starting out.

2. What drew you to anesthesiology and to your particular area of research? Has your research subject area evolved since the award?

I trained in pain as a pain neuroscientist working in the neonatal wards and was interested in brain activity. Then, I joined Boston Children’s for my postdoc. That was at a time where the FDA had released their guidelines about how we need to be mindful of giving anesthetics to young children, and it was a big discussion among colleagues. A discussion ensued – what can we do? The research was all based on animal work. I’ve got to give my patient an anesthetic but I don’t have any evidence to show either way what’s going on. So, there was a real push to think about how we could address this prospectively, and I think my research topic was just very timely.

I was doing pain studies and I was invited to come into the operating room and think about how I could apply my experience in EEG. There was a series of studies we did as a pilot to see if we could successfully collect EEG data in children without getting in the way of the anesthesiologists. My institution was on board with this line of research and provided internal funding. EEG is very rich in the data you can collect from one patient, so you can combine it with collecting heart rate data, and you can collect entire volumes – you can really capture exactly what’s going on.

So, I became very interested in anesthesia. The power to anesthetize someone and wake them up is interesting. Pain is part of what I was trained in. I really think brain development is fascinating. The brain is so plastic, thinking about what you’re doing when you’re caring for a child and the short-term and long-term effects it can have on their development.

3. What prompted you to leave academic medicine? In your current role, are you still involved in research? If so, in what ways? If not, how do you utilize the skills developed during your research path in this new role?

I just recently left in April of this year so I’m still very new to drug development. I really enjoyed the academic work and I really enjoyed the people I was working with. It was very rewarding.

It’s very tough to have a successful career in clinical medicine if you’re not an MD, from my perspective. It’s really hard, because I’m not mixing with colleagues on the floor and not building the same trust they build with each other from that interaction. As a clinical researcher, it’s really tough to rise through the ranks.

If you want to be an academic researcher, you have to promote yourself as often and wherever you can, either at conferences or you have to network with people. That’s really enjoyable and really fun. Before COVID, it was great. Then during COVID, we could do it virtually. But now we’re opening up again and I have a young family. I was balancing family commitments, travel and the amount of time I can dedicate to succeeding at that. I just had to put my family forward. But that’s not the case for everybody. It was just my decision.

I was also involved in some really exciting clinical trials. These were looking at neurogenes, disease and neurodegenerative disease in children, and I really enjoyed being a part of that. These were trials about compassionate use of giving a treatment to someone where you could improve their quality of life and it was just really exciting. After 12 years of doing academic research, I really wanted to see what clinical research was like in an industry environment. There are similarities and differences.

I am currently working in the clinical development team for Eisai, which is a medium-sized pharmaceutical company. They’ve got a really strong neuroscience department, which is what drew me to them. The clinical development team is involved in strategy. For example, when there is a new drug that’s of interest, many questions come up. How do we want to play it? Put it in a Phase One clinical trial? Put it in a Phase Two Clinical Trial? What kind of dose should we give? And how are the patients responding? Is a Phase Three Clinical Trial needed? And then you’re working with people from China, the US, and Europe on a big scale.

How is this drug working? Is it safe? Is it effective? And then there are strategies of designing those trials and then thinking about different ways you can administer the drugs. So, you’ll have one trial that might be sub queue and one trial that might be a fixed dose. The scalability of things is quite interesting. It’s huge.

4. How are the skills you developed as an IMRA recipient being utilized/helping you in this new role?

It’s project management, meeting deadlines and coordinating lots of pieces together. Again, it’s a lot of networking, a lot of liaising, and you have to be sensitive as each person works in a different style and everyone is busy. It is necessary to do a lot of reading about your disease area.

There are differences in clinical research; You start with planning and medical writing. But in the industry, they have resources for that. But you still have to be able to talk to the clinician, or the medical monitor, or talk to the biostatistician in a language that they can relate to. So, coming from an academic background allows you to do that.

5. What was the goal of your initial research project? Was it met?

It is something I’m very, very proud of, not just because we had good preliminary data to put into the project, but because of the funding, it just spun out a lot of studies that were very unbiased, high-quality studies that we had a real joy to write up and submit to journals. They were all very successful.

In academia, you hear stories of writing a project together and they can’t get it published anywhere. We didn’t have that with this series of projects.

It was a clinical research project. I’m a PhD person so I don’t have an MD. But I do clinical research and the goal was to study the brain activity in children while they were having general anesthesia. We wanted to find a way that would help us to learn a lot about anesthetic depth and the right anesthetics to give children. Anesthetics have such a wide effect on the body and the brain and kids are so vulnerable, we really wanted to understand more about what was going on in the brain.

Commercially, there are a lot of monitors that are available when you’re putting an adult under anesthesia; you are able to monitor if they are going too deep. You can titrate your anesthetics and predict when they’re about to wake up. But in very young brains, because there’s not much brain activity going on, it was difficult to really use something commercial. So, we used EEG as a tool to do that. Various outcome measures and various features of the patient and various parts of the anesthetic management program would be looked at with these tools.

It was net 99 brain activity. It’s just like an EKG, but one of the innovative parts of the program that was funded was to combine EEG with their infrared spectroscopy, which is a tool where you use light to look at blood flow. This tool allowed us to determine if enough blood was being supplied to various brain regions.

Our pilot study was funded by IARS. Operating rooms are very light environments and our tool relies on lights, skin that’s very transparent like baby skin, made the situation quite challenging. With EEG I can write things in the code to get rid of movement, flip off things, while staying clear of the surgeon. We had success with that aspect, but we didn’t go further with it.

The research has been replicated. A lot of people contacted us to say, “can we join your group? We’ll get experience with you.” We’ve had a lot of collaborations as a result that I wouldn’t have even thought about. There was a group in Germany that’s an animal lab that looks at brain development in the animal totally unrelated to anesthesia. But they’ve done some anesthesia studies and asked if we could combine our results together to translate things from animal to human. It is machine learning. It was a cool and unexpected outcome.

More people wanted to join us and more collaborations became available. We’ve got another collaboration in the UK and one in Australia and then within the US, of course.

6. How did your findings impact patient care and the field of anesthesiology?

I don’t know how they impacted patient care, but I would say we advanced the field in other ways.

Previously, what a lot of people had done was look at EEG in children, but grouped them from age one to 18 years and said generally speaking, this is what brain activity looks like. But this funded study allowed us to break that down on a month-by-month basis. For the first 3 years of life, a one-year-old, a one-month-old look very different to a 6-month-old and a 3-year-old. The brain is different and it’s not the same as an adult. We were able to really zoom in on that. There were features that we saw which the young brain was more likely to have, like some discontinuity or flat brain activity compared to an older brain, particularly at the beginning of an anesthetic procedure, when a high-dose drug is used. So that was new and important to share with our community.

I don’t know that people changed their practice because of this but it was certainly quite a hot topic when we published it. I think we brought up a lot of dynamic discussion.

7. How did the award affect your research/professional trajectory?

It’s huge. I showed I could have independent funding. It gave me a promotion. I felt more valid applying for other grants because someone had endorsed me. It provided additional networking opportunities which helped a lot; it was an exponential circle of positivity.

8. How do you feel about having received the IARS Mentored Research Award?

I’m very, very proud. Having the award was really good. I felt validated that I’m a good scientist, that we are doing good and this science is important for the field.

As a result of getting the award, there were people I got to interact with regularly. Dr. Emery Brown wrote a letter of recommendation. He actually was our collaborator. I would meet with him, and then he would put my name forward to speak at conferences. Then, at that conference, I would talk to people who I wouldn’t normally talk to, and they would put my name forward to speak at another conference, or to write a review with them. It had this trickle-down effect. There’d be people who would visit my institution. I could say, “I’m an IMRA recipient. I’m sponsored. I’ve got this grant.” Then you can pitch to them what you’re doing, so that when the paper comes down the line to the editor who you’re talking to, they’re already aware of it and they’ve actually talked to you about confounds.

I was able to be more productive as a researcher through networking and the IARS brand endorsements, which was great. Also, I spoke at a few IARS conferences and that was also incredible.

I really want to make sure IARS keeps funding PhDs who are doing clinical research. A PhD is smart, and they can learn medical knowledge even if they don’t have the experience of treating a patient. They are still very useful to have on a team when they’re doing clinical research. They can read very dry papers and find details that can be applied. I see a lot of requests for people doing basic science. But if you have more PhD people doing clinical research, it can only improve the quality of the work and making that available to them will really help.

9. What is something that someone would be surprised to learn about you?

I like to run. I run marathons. My favorite marathon to run is Big Sur. It’s the most beautiful scenery. It’s gorgeous. You are looking at the sea the whole run. So when you finish, you got like a bit of a crick. I love running.

10. What is your vision for the future of anesthesia research?

We need to keep doing research. We need to bring people together from all different backgrounds.

The future of AI is quite interesting.