Rethinking Generalised Epilepsy Networks and Deep Brain Stimulation - Dr. Frederic Schaper, Center for Brain Circuit Therapeutics of Mass General Brigham, Harvard Medical School, USA
Generalised epilepsy is often described as involving the whole brain at once. But does it start all at once? Dr. Frederic Schaper discusses research mapping subtle brain abnormalities to shared brain networks in generalised epilepsy, and how these networks overlap with targets used for deep brain stimulation. The conversation explores what this may reveal about seizure mechanisms and future neuromodulation research.
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Episode Highlights
Research suggests generalised epilepsy may involve shared brain networks rather than simultaneous whole-brain activity
Subtle brain abnormalities mapped to a common seizure network across generalised epilepsies
The central thalamus identified as a key node - aligning with targets used for deep brain stimulation (DBS)
New insights into how brain network mapping may guide future neuromodulation research
About Dr. Frederic Schaper
Frederic is an Instructor of Neurology and Director of Epilepsy Network Mapping at the Center for Brain Circuit Therapeutics of Mass General Brigham, Harvard Medical School. His research focuses on mapping epilepsy networks to better control seizures using brain stimulation and has been recognised through several grants and awards.
Full profile: Frederic Schaper
Topics mentioned
generalised epilepsy
neurodegeneration
supplementary Motor Area (SMA)
thalamus
brain network mapping
human connectome
cortical atrophy
neuromodulation
Related paper
“A generalized epilepsy network derived from brain abnormalities and deep brain stimulation” https://www.nature.com/articles/s41467-025-57392-7, Nature Communications, Gong-Jun Ji et al, 24 Mar 2025, DOI https://doi.org/10.1038/s41467-025-57392-7
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Trailer
00:00 Frederic Schaper
“We've mapped many neuropsychiatric symptoms and disorders to brain networks, including depression, amnesia (so disorders of memory), anxiety, and epilepsy, and seizures. But even more obscure and complex symptoms such as addiction or fundamentalism and these personality characteristics. So what one can do is when one measures before and after a certain perturbation in the brain, we can see the slight changes that happen in that behaviour or in that symptom.”
Intro
00:32 Torie Robinson
Generalised epilepsy is often described as when people haveabnormal electrical activity causing a seizure beginning in both halves (hemispheres) of the brain at the same time. But we have an interesting question here - does seizure activity really start everywhere at the same time? Or could specific brain networks be involved - playing the game separately?
Today we’re joined by Dr. Frederic Schaper from the Center for Brain Circuit Therapeutics and Harvard Medical School who’s going to share with us how he and other researchers are mapping the brain networks involved in generalised epilepsy - and his work points to a key hub deep in the brain that may help explain to us why neuromodulation treatments like deep brain stimulation (or DBS) can work.
If you’re new here, please subscribe so you don’t miss our chats with global leaders in the sphere of epilepsy - and let’s get into today’s episode - presented in partnership with EASEE®, by Precisis GmbH.
Generalised epilepsy: what does it mean?
01:29 Torie Robinson
So, tell us what is generalised epilepsy?
01:31 Frederic Schaper
Yeah, so epilepsy is classically subdivided into focal epilepsy and generalised epilepsy. Focal epilepsy is an epilepsy where we know exactly where the seizure is starting from, so it has a focus. With generalised epilepsy, we generally don't know. We don't know where exactly the seizure starts, and we think that it starts all across the brain; so a seizure of the entire brain.
01:53 Torie Robinson
When somebody says this, think, my god, are you having like sudden activity in different places all at once? Surely it must start in one place first, no?
02:01 Frederic Schaper
That's a great insight and many researchers are focusing on that, including us. So generalised seizures definitely have a pattern. Exactly what that pattern is, we don't know. We think that in epilepsy there's increasingly an involvement of brain networks, and what we do at the Center for Brain Circuit Therapeutics (where I work as faculty), is we try and map epilepsy onto brain networks, including generalised epilepsy, we use sources of information; that is either brain lesions or brain stimulation. These are both data sources that actually perturb the brain and therefore lead to a change in either behaviour or lead to a symptom. What we do is we use these data sources to combine them with a human connectome, also known as a wiring diagram of the human brain, to see what circuits are involved in a certain disease including epilepsy and seizures.
Mapping epilepsy and psychiatric symptoms to brain networks
02:57 Torie Robinson
And just to give us a bit of insight into a broader picture, I guess, what other diseases benefit from this?
03:10 Frederic Schaper
Yes, so we've mapped many neuropsychiatric symptoms and disorders to brain networks, including depression, amnesia (so disorders of memory), anxiety, and epilepsy, and seizures. But even more obscure and complex symptoms such as addiction or fundamentalism and these personality characteristics. So what one can do is when one measures before and after a certain perturbation in the brain, we can see the slight changes that happen in that behaviour or in that symptom. And therefore, you can use these data sources such as lesions and brain stimulation - in combination with a wiring diagram of the human brain - to map these symptoms to brain networks.
03:44 Torie Robinson
So, excuse my ignorance here, maybe I'm making a silly presumption, but it kind of appears that because you can look at all of these symptoms, is there a connection between the symptoms?
03:58 Frederic Schaper
We've definitely investigated that. What we do is we map a symptom and then we see is there any similarity between this symptom and other symptoms. And we've definitely seen similarities of symptoms that are actually comorbid with each other too. One included is depression and epilepsy. We've mapped certain focal epilepsies to brain networks and we've also mapped using lesions depression onto brain networks. And we see, definitely, some commonalities there in their network location, which is in line with the high depression rate and anxiety rate in patients with epilepsy.
Neurodegeneration and generalised epilepsy
04:33 Torie Robinson
So, what about neurodegeneration in epilepsy? Because this is something that many patients are scared to talk about or ask and also something that many clinicians are scared to talk about.
04:41 Frederic Schaper
Yeah, neurodegeneration and epilepsy are far more common than we think. And what we know is not necessarily that we know that it acts as a neurodegenerative disease, but there's definitely studies that propose that. We've known most of it in temporal epilepsy and focal epilepsy. And what we are looking at is more delving into generalised epilepsy. What are the locations that are atrophied or hyperactive in patients with generalised epilepsy versus people that don't have generalised epilepsy? And there is what is what we see is that the pattern of slight neurodegenerative changes, so atrophy in generalised epilepsy, is a consistent pattern that is published time and time again. And in our study what we did is we tried and mapped those locations of atrophy to a brain network.
05:30 Torie Robinson
Tell us more about the study, how it took place, what were the outcomes, what did you learn, and any surprises?
Deep Brain Stimulation (DBS) identifying abnormal activity
05:37 Frederic Schaper
So generalised epilepsy is usually considered a seizure of the whole brain. But there's increasingly studies that show that actually focal perturbations, such as deep brain stimulation deep within the brain and the thalamus (kind of the control centre of the brain), are able to stop generalised seizures. So those things contradict each other! The fact that it's a seizure of the whole brain, but that focal small perturbations can disrupt the seizure. So, what we did is we thought to see, if generalised seizures are indeed amenable to focal perturbations such as with deep brain stimulation, is there then a kind of key point or is there a node that has a wider role in the network that is involved? And let's try and map that network. And to do that, we use these subtle brain abnormalities that happen in patients with generalised epilepsy to try and use them as data sources to find what is the network involved in generalised seizures. And could that be related to where we place deep brain stimulation electrodes.
There are small neuroimaging changes, small brain abnormalities that happen. See, these areas of atrophy where the cortex is slightly smaller compared to a person with the same age and sex. So, these small clues, these small hints, is what we use as potential traces of where the seizure either starts or travels to in the brain.
Subtle brain changes that reveal seizure patterns
07:00 Torie Robinson
Interesting. So it's almost like it could look a little bit squished almost, or like a slight abnormality in shape, maybe? And it can be tiny but sometimes it's not anything bad, it just looks “funny”.
07:12 Frederic Schaper
So, a patient with generalised epilepsy, by a clinician, they would say, brain is normal, right? We did an MRI; there's no brain lesion that could explain the seizures. Brain looks generally normal. But there's been a huge neuroimaging studies worldwide. One of them is the ENIGMA study, where they have thousands of patients and compared them to a set of people with an MRI too, but with normal, a similar age and a similar sex. And there they see that there are consistent small, imaging abnormalities that happen. And the step that we took is we tried to map these small abnormalities to brain networks and see if there was a common network involved.
07:52 Torie Robinson
And?!
07:53 Frederic Schaper
There was! So, what we found was a consistent pattern. We saw a consistent pattern that kept popping up time and time again. And this was a small atrophy pattern in the sensorimotor cortex, SMA, the thalamus, which is that control centre of the brain, going into the cerebellum and also on other cortical lobes, so the outside of the brain. And that consistent pattern mapped to a common brain network. And what that means is that these patterns, where these atrophy abnormalities fall, they fall in a common network, in a brain network. And that brain network is the network that is involved in motor control and loss of consciousness. So, these two networks are kind of the yin and yang of the seizure network that kind of determine and explain where these brain abnormalities happen.
A shared network across seizure types
08:44 Torie Robinson
Was that a surprise? Was that what you expected?
08:48 Frederic Schaper
It was a surprise that there was a common network involved because one thinks that every epilepsy patient is different, every subtype and seizure such as myoclonic seizures, absence seizures, generalised tonic clonic seizures are different and they definitely are different and different patients are different too. So, there's definitely things that distinguish patients and epilepsy subtypes from another. But that doesn't preclude the possibility that there's also networks that are common between them. I think both are true. There are both networks that are between patients and networks that are specific to patients and subtypes. What we mapped in this paper here is the network that is common across different patients and subtypes with generalised epilepsy. And when doing that, there is of course the promise that this network may be a target, a potential brain stimulation or neuromodulation target to try and treat multiple epilepsies. And that is kind of what we did here. And what we found that really shocked us was when we really looked deeper into the specific nodes of this generalised epilepsy network is that the number one peak in the whole brain was the thalamus, the central thalamus, which is exactly the location where neurosurgeons place their deep brain stimulation electrodes to treat generalised seizures.
Sponsor mention
Before we move on - with thanks to EASEE®, by Precisis GmbH.
Future research on generalised epilepsy and DBS
10:08 Torie Robinson
what are the next steps then for you regarding this? Because this is exciting. I've got all these ideas going through my own head but tell us what your imminent plans are.
10:19 Frederic Schaper
Well I'm of course happy to hear that you're excited, I am too! So, our plans are, what we don't know yet of course, is whether this network that we identified that unifies different generalised epilepsies, if this network is a safe target for neuromodulation, an effective target, and if it's an effective target for every subtype of generalised epilepsy. So, on the future realm, on the research level, we are very interested to work together with other collaborators and we are doing so currently and would invite anyone that is interested in this topic too to r each out to map using patient specific data and replicate this network again, and then also look into the specific patient-specific atrophy patterns and subtype-specific atrophy patterns so we at least know what are the networks that are common between patients and what are the networks that are different between patients, and that will inform our next step onto therapy. And onto therapy what we need to do is design new clinical trials to try and modulate this network either invasively with deep brain stimulation or responsive neurostimulation or modulate this network with non-invasive brain stimulation such as transcranial magnetic stimulation or electric stimulation.
Where neuromodulation fits in treatment
11:34 Frederic Schaper
So, this brings us to an important question of “where does neuromodulation belong in the treatment sequence, in the paradigm of how we treat a patient with drug-resistant epilepsy?”. And currently where it's at, it's at the point where it's after surgery. So, if a patient has been deemed to not be suitable for epilepsy surgery for their focal-onset epilepsy, or if the patient opts out of surgery, then neuromodulation will be offered. And that can be in the form of deep brain stimulation or of neurostimulation. What we always tell patients is that neuromodulation can reduce seizures, but we don't have hard evidence yet that it can lead to seizure freedom. So, it can reduce the frequency and the severity of seizures. One thing is why we still always offer surgery to and not place neuromodulation before the surgery treatment paradigm is that epilepsy surgery in around 60-70% (depending on what patient specifically it is being performed in), can lead to seizure freedom. So, it can lead to seizure freedom in up to 70% of patients in the first one to two years. So that is why we don't place neuromodulation yet before surgery, but it's increasingly being considered at an earlier stage and by patients it's also increasingly considered as a viable option because we also know that surgery doesn't always lead to seizure
Neuropsychiatric symptoms of epilepsy
13:09 Torie Robinson
Was there anything in your paper regarding the psychiatric morbidities or symptoms of epilepsy and how they can be minimised potentially in the future?
13:19 Frederic Schaper
So this paper focused on seizure control, the brain stimulation and on atrophy in generalised epilepsy in general, but we know that of course epilepsy is not just seizures. So, in this paper we were not able to focus on other symptoms of epilepsy such as depressive symptoms or anxiety or at a larger message on quality of life. And I think where definitely an opportunity lies is to really try and improve quality of life and measure those in future and current trials of epilepsy to see what are their networks or what are the main determinants of an improvement of quality of life after deep brain stimulation or in epilepsy and generalised epilepsy in general.
14:05 Torie Robinson
I think it's important to say and reassure people that even though, for instance, this paper doesn't specifically look at that, the research that you've done and are doing and the same for others as well is long-term looking at improving quality of life. And we need to have this data in order to achieve that long term.
14:22 Frederic Schaper
Yeah, 100%. So, what we do at the Center for Brain Circuit Therapeutics here is we try and map neuropsychiatric symptoms to brain networks. And that spans across epilepsy. That includes depression, anxiety, amnesia, disorders of memory, etc. So, our goal at the centre is to improve the burden to people with neuropsychiatric disease and improve their life by mapping and targeting and modulating brain networks. So, we do that for patients with depression, anxiety, and epilepsy. And our dream is that at some points these networks will inform our treatment in either disease so that a patient with epilepsy and depressive symptoms can benefit from neuromodulation to targets either identified in patients with depression or patients with epilepsy. And that is our, I think, ultimate overarching goal.
15:17 Torie Robinson
Or those with both, two in one!
15:19 Frederic Schaper
Definitely. So also, the patients that have depression and might have seizures, which usually is an exclusion criterion for TMS treatment. So, getting to know more about those patients will also help us treat those people that have both depression and epilepsy.
Thank you to patients contributing to research
15:34 Frederic Schaper
I just want to thank you and I want to thank all of the patients that openly share their information and their data with clinicians to perform scientific research. This is very, very important and allows us to make these serendipitous findings, such as with this generalised epilepsy paper where we saw that a network includes the locations that are being targeted with brain stimulation. If patients would not have given their data to be available for this type of research, we were not able to do it. So, I want to thank patients and thank researchers that share their data.
Closing thoughts & thanks
16:10 Torie Robinson
Thank you so much to Fred for sharing his cool, exciting research highlighting how combining large neuroimaging datasets with brain stimulation research might help identify the networks involved in generalised epilepsy.
Understanding these networks could help guide future therapies - including neuromodulation approaches designed to target the individual circuits involved in seizures, and potentially improve outcomes for people living with an epilepsy.
Again, huge thanks to EASEE®, by Precisis GmbH, for partnering with us at Epilepsy Sparks.