[00:00:07]
>> I mean I'm sure he said this you know I think. Ok. Also. You know. There's. Ok thank you very much for a lot of pressure Thanks for inviting me thanks for being here I really appreciate it it's a great opportunity to be here at Georgia Tech which I have the enormous respect for the Bible to ensuring department's been a wonderful thing as well I've met some faculty like that like Garrett for example and a ball and also I've had the luxury of having an undergrad student who's been a rock star I'll talk about her work in a little while as well so today I want to talk about epilepsy and sleep actually a little bit and the importance is that in neuroscience we talk we often study local circuits but I think that we really need to study large scale circuits and that's the whole point of this talk really is to look at different ways of studying those innovating to do that and also justifying why that's necessary so start out by talking about the clinical problem just as an example from epilepsy and then talk about sleep wake networks as a modulatory target for epilepsy I'll talk about a more specific example of a particular circuit that I've been studying and then I'll talk about the development of novel technologies for studying large scale circuits in epilepsy and elsewhere.

[00:02:03]
So the clinical problem is that one in 26 of us will develop epilepsy over the course of our life it's actually very prevalent disorder the population prevalence is about one percent at any time and until recently people with epilepsy would end up institutionalized I don't know with anyone knows where this is in Georgia but this is the Milledgeville psychiatric center and people there were in you know even a 100 years ago when really degraded this is less than a 100 years ago by the way this in the ninety's sixty's and this actually from a similar institution in Massachusetts but nonetheless people were in really degrading circumstances in these institutions and a lot of them had epilepsy because it wasn't treatment for epilepsy until about a 100 years ago.

[00:02:41]
Just out of interest local history 30000 people died in Milledgeville it's the biggest psychiatric institution United States pretty crazy someone supposedly accidentally knock down these terms don't see you can't find out how many people died anymore but anyway that's the history nonetheless people because of these institutions people really started to study epilepsy and so ours is the 1st person that wrote in detail about epilepsy and he was able to do this and he was able to compile 2000 cases of patients with epilepsy in a book which is still worth reading and really precise because he was running one of these institutions and you could just see tons of patients they had uncontrolled seizures they had no medications and so he could actually observe them have seizures all the time he could examine them all they were and he learned a lot about epilepsy.

[00:03:28]
Now that all sounds terrible and we glad that we're not living in the past but in fact despite the. Number of anti convulsive drugs that we have increasing it remains true that a 3rd of people are medically refractory to medications so 30 people are really continue to have daily seizures or frequencies is despite the fact that there are medicines and those 2 thirds that are treated with medicines often have side effects and so yes we've made a lot of progress the last 100 years but it's not great.

[00:03:58]
So what happens to the 3rd of patients that untreated it all with medicines as they go through a surgical pathway eventually but this is the general lay of the land with regards to what happens you know you start one Dragan 47 percent percent of people respond often people with generalized epilepsy s. which are where they have an unexpected seizure without a warning and they have a convulsion and then when you get to the 3rd or 4th agents or others you still have a lot of people having uncontrolled seizures a 3rd and a most of those are people with focal epilepsy and so that means the future is at least putatively start in one part of the brain and then spread and that also makes them a candidate for surgery.

[00:04:37]
Just thinking about the social impact of epilepsy today. Which is sudden unexpected death in epilepsy which is where people have a seizure and die unexpectedly because they face down on the contrary they are sometimes just because they're probably a brain stem be polarizes in order to make functions impaired it's actually the 2nd leading cause of productive life years lost after a stroke or neurologic disease.

[00:04:58]
Because a lot of these other diseases happen later in life stroke of course cause it's just very prevalent cause a lot of disability This often happens to people in their twenty's and thirty's and they die so there's a Obviously huge loss of productive life years. Now I just I want to preach sort of forecast to preempt the discussion about sleep wake by saying that most of the people that die from sudden unexpected death in epilepsy in hospitals because it happens there it's very hard to resuscitate some of these people it happens during the night or during sleep Ok so there's a really thought to be a strong association with maybe rem sleep or maybe non room sleep and it really doesn't happen much during the day when people are awake.

[00:05:39]
And so we'll come back to that. But I just want to talk about the surgical treatment again now so uncontrolled epilepsy can be treated surgically there's a lot of different surgical options. They I want to go through these in great detail but basically it amounts to either removing tissue or destroying tissue there are more invasive invasive ways of doing that Emery which we'll talk about a 2nd and if a minimally invasive investigations a neurosurgeon epilepsy is something that we're proud of and Neuromodulation is a possibility as well so stimulating to prevent seizures or to abort seizures is also probably a possibility the treatment of generalized epilepsy which is about a quarter of those patients that don't have well treated seizures is still a problem and it's essentially experimental.

[00:06:26]
So we have something to be proud of here and including some of the a couple of the labs here are a part of Georgia Tech as well so Stanley's labs mentioned here as well but we have a very large number of basic science labs in Atlanta studying epilepsy is probably the largest concentration of fop basic science labs at least that I know of I think some places like Uva comes close maybe Stanford has a few labs but actually we have numerically have a lot more than 12 labs studying epilepsy in some way or another.

[00:06:53]
And we have a highly active Epilepsy Program as well clinically which for people like me presents a problem because there's so much clinical work that sometimes it's a bit of a descriptor structure from doing being academic in doing research actually that we do about $45.00 implantations per year intracranial which is the kind of base basically enables you to do electrophysiology and people will talk about some of that work later and we have about a 1000 new visits a year and cetera et cetera so it's a pretty big center.

[00:07:20]
Now despite all the technologies that are available for Neuromodulation and surgery the outcomes are still terrible and this isn't just as Anna it's actually universal that if you start to look at patients who have extra temporal lobe meaning seizures starting outside the temporal lobe and they don't have a lesion then the outcomes are horrible it's like about a 3rd of them have effective treatment of seizures with surgery so imagine going through all the process of trying all these medicines you still having seizures you go through the process of intracranial monitoring and then brain resection and you still have seizures right there's a 2 thirds chance that you'll still have seizures in this circumstance so that really encourages us to ask why that is what it what are we missing what's the problem in epilepsy that we don't understand that's causing these patients to continue to have seizures so probably some of the common ones.

[00:08:12]
Taking a side possible genetic contributions which there can talk about that if you're interested afterwards but. Really these are the kinds of things that we don't take enough tissue you know there's evidence that if you take more brain tissue that the patient does better but then of course they may have worse outcomes from a cognitive standpoint or an emotional standpoint.

[00:08:31]
The epileptic network might be why didn't we appreciate it and that's something I'm going to show you is definitely the case and that's something we need to really work on. A large scale network hyper excitability can be trans Lobos or some of use you have a patient who has a Frontotemporal epilepsy and you just really don't want to take the temporal lobe and part of the frontal lobe at the same time some centers do but it's pretty aggressive.

[00:08:51]
And then finally and this is been I think a big problem in North America is is not really actually employing the brain in a way that we can study the season at work so if you put the electrodes in the wrong place you going to think the seizure starts in the place where 1st invades the electrode network not where it actually starts in the brain right that's a huge problem.

[00:09:10]
So I'm going to just talk talk about history briefly and why that might be the case and I think probably most of you would know about or maybe I'll skip here the homunculus right so everybody in neuroscience want to one hears about the hymn Oculus and it comes it was described by Penfield and justice pacifically I guess more Penfield.

[00:09:28]
And actually if you look in the German literature it was described by his mentor for a 1st us so I don't think just was then painful because as original as we think there are in the English literature but nonetheless this is the kind of thing you can see now this was meant as a as a cartoon to show you that there is a topographic or some out of topic representation of the body on the brain surface but it doesn't turn out to be quite like this it turns out to be multiple.