"REM Sleep Behavior Disorder: A Window into Dreams" Isabelle Arnulf (11.04.2020)

November 06, 2020

ID5849

To CiteDCA Citation Guide

00:00We're recording great thank you.
00:26Alright, welcome everyone,
00:27I just got a message that my Internet
00:31connection is unstable. Are you guys able
00:33to hear me OK?
00:36Can you hear me Isabel OK?
00:39Alright, I think will
00:41begin so good afternoon.
00:42My name is Lauren Tobias.
00:44I'd like to welcome you to our
00:46Yale Sleep Seminar this afternoon.
00:49I have a few quick announcements
00:51before I introduce today's speaker.
00:54Um, first please take a moment to
00:56ensure that you're muted in order to
00:58receive CME credit for attendance,
01:00please see the chat room for
01:02instructions and you will need
01:03to text the unique ID for this
01:05conference anytime before 3:15 PM
01:07Eastern Time if you're not already
01:09registered with yellow, see me.
01:11You'll need to do that first.
01:12If you have any questions
01:14during the presentation,
01:15I encourage you to make use of
01:17the chat room throughout the hour.
01:19Recorded versions of these lectures
01:21will be available online within two
01:23weeks at the link provided in the chat.
01:25And finally,
01:26please feel free to share the
01:28announcements for our weekly
01:30lecture series to anyone that
01:31you think might be interested,
01:33or contact Debbie Lovejoy to
01:35be added to our email list.
01:37So now I'm delighted to introduce
01:39Doctor Isabella Al Nouf as our speaker.
01:42Today,
01:42Doctor Ave is a neurologist who
01:44graduated from the School of Medicine
01:46of Joseph Fourier University in Grenoble,
01:49France,
01:49and she received her PhD in
01:51neuroscience from the Pierre and
01:53Marie Curie University in Paris.
01:55She studied Pantin Cat models
01:57in the Sleep laboratory.
01:59Michelle Ruby in Lyon and then did
02:02clinical clinical studies on sleep
02:04in various neurologic diseases,
02:07including Parkinson's disease,
02:08a LS and Guyan Barre syndrome while
02:12visiting the Stanford Sleep Center in 2004.
02:15Five she coordinated the Stanford
02:18kleine Levin Syndrome research program
02:21under the direction of Immanuel Menu.
02:23Doctor Arnouk is currently head
02:26of the 20 sleep disorder.
02:28The 20 bed Sleep Disorder unit of
02:31PTA Salpetriere Hospital in Paris,
02:34which unfortunately she said just
02:36had to close this week due to
02:39Kovid and she's overseeing a large
02:42multidisciplinary team of neurologist.
02:44Neuro scientist,
02:45psychiatrists,
02:45pulmonologists and nurses there.
02:47Her current research focuses on central
02:50hypersomnia Zan parasomnias an I am
02:53delighted that she agreed to join us.
02:56Today to speak to us about REM
02:58sleep behavior disorder.
02:59A window into dreams.
03:01So with that I'll turn it over to you.
03:05Thank you Lauren and thank you Francesco.
03:09This invitation to speak about
03:11REM sleep behavior disorders.
03:13I would like you guys to stop to hear
03:16the news for 60 minutes and stop and
03:20forget this virus during 60 minutes
03:23and just think about dreams with this
03:26knew no scientific approach for those.
03:30Not go to the next one, can I know?
03:35Sorry I cannot.
03:37Change my video overnight.
03:40OK, so for those we need the
03:43cell phone and the code.
03:45It's it's shown here.
03:47This talk has nothing to do with
03:50the pharmaceutic industries and
03:51there is no conflict of interest.
03:55So REM sleep behavior disorder is Opossum.
03:58Yeah, you can see these guys
04:00sleeping here in her sleep and.
04:03Instead of being quiet,
04:06is moving and fighting.
04:15If you wake him up at that moment,
04:18he would tell you.
04:19That is fighting some people and
04:23then he wakes up and resume sleep.
04:26So I'm still behavior disorder
04:28is sorry is caused by a loss
04:32of the normal ram atonia that
04:34you can see here on the police.
04:37Sonography at some moment the what
04:40blocks our muscle tone during Hanslip
04:43disappears like here and then here.
04:46And when it disappears when we have possibly,
04:49this movements has here.
04:53YouTube awesome yeah so people join
04:55our refer to the Sleep Lab mostly
04:59because of the risk of injury.
05:01As you can see here because people
05:04have the eyes closed and have some
05:07violent movement they can injure
05:09themselves and ensure their schools.
05:12In addition,
05:13the person yeah has gained a lot of
05:16attention from the knowledge Ikle field
05:19becausw isolated patient patient with
05:21isolated REM sleep behavior disorders.
05:24No other symptoms,
05:25most of them have overtime conversion
05:28to parkinsonism and dementia.
05:30Here you can see more than 1000 of
05:33people with no other signs that
05:36ebbed and after 15 years most of them
05:40have developed Parkinson's disease.
05:42Although the dementia with Lewy bodies
05:45within a median time of seven years,
05:48so there's a lot of research on this program,
05:52all aspect of herbed.
05:54How could we,
05:55in the future,
05:57present ability to develop every
05:59patient to develop parkinsonism?
06:02I will not cover this part.
06:05But another third part of her
06:07body and I would like you guys to
06:10consider RBD as an important and
06:13new window on motor control during
06:16REM sleep and dreaming process.
06:18What could help her body tenses
06:21about motor control during REM sleep.
06:24What unblocks unblock the muscle tone?
06:29What we know from early as early
06:31as in 65 by Michelle Judy is that
06:34if you damaged very restricted
06:37area here in the palms of the cat.
06:39Took an only this area not
06:42know nothing around you can.
06:44Your cat will lose the normal atonia
06:47during atonia during REM sleep and
06:49will develop some complex behavior.
06:51I will not show you some cats but you
06:55probably all of you have already seen
06:58some dogs with their body like this
07:01one with sleeping in REM sleep with
07:04twitches of the legs and the names. And.
07:11Sitting too long during monthly and then.
07:17Localization. I think it's
07:21itself exactly like human.
07:24Because we know we knew from from
07:26my schedule is a place that was
07:29responsible for atonia during REM sleep.
07:32We wanted to look if the same place
07:35was altered or damaged in human brains.
07:38We started with no pathology,
07:40which means that patient has
07:43to be dead before and then.
07:47As early as in 2013,
07:49we found that this area here in in the palms,
07:54which contains both the subsidiaries,
07:56unserious lockers in human brands,
07:59could be recognized by using
08:01a new pigment in MRI.
08:03Three Tesla normal and in and you
08:06can see here the sub Solution
08:09series locus in the human brain
08:12is the 4th ventricle cerebellum.
08:15This area in human is the equivalent to
08:18the Perilo Quest series Alpha in cats,
08:22and it's equivalent to the sub Latino
08:25dorsalis in in rats in isolated air BD,
08:28you have a control here.
08:30With complete nucleus you can see a
08:33loss of the signal in the same area
08:37in patient having just be in addition.
08:40The hyest loss of the intensity
08:43in the signal on MRI.
08:45The higher the REM sleep without atonia,
08:48both in parking patient with
08:50Parkinson's disease a nobody and easy
08:53impatient with isolated air busy.
08:55So it seems that it's the same cause
08:58in human damage in this in this area
09:02in the brain stem that usually should
09:05blocked us during ahem sleep and
09:08which is partially partially damaged.
09:11Then one may ask what drives
09:15the movement in the behavior.
09:16We can see what unblock the muscle tone,
09:19but now we have to determine where do
09:22this movement come from in the brain.
09:26There is an old debate about what happens
09:30during REM sleep movement with two theories.
09:34One is that during her body we have
09:38some central pattern generators that
09:41activate some automatic archaic behaviors
09:44that are unmasked during abt like
09:47twitches or super twitches. The over.
09:52Theory is that we are activating our
09:55motor cortex or premotor cortex as we
09:58will do during wakefulness during.
10:00Air B and for the first theory there are
10:04evidence a lot of evidence that REM sleep
10:08twitches are generated by the brainstem,
10:11not by the motor cortex.
10:13For example, cats without neocortex
10:16till after which is during REM sleep.
10:20Plus, and this was shown by Michel
10:23Jouvet plus Twitchers in rats in young
10:26rats occurs before the motor cortex.
10:29Here is stimulated,
10:30suggesting that they are generated
10:33by some nucleus in the brainstem,
10:36possibly the red nucleus.
10:42In in the same ID came from the scenery.
10:46The idea that we have some central
10:48pattern generators for many behavior,
10:50like here the calling that you can see
10:53in animals that you can see here in
10:56new needs and that can happens exactly
10:59with the same sequence water sequence
11:02during an epileptic seizure here.
11:04So the scenery guy from Italy said
11:07we might activate during ebbed,
11:09some very archaic area providing some.
11:12Fighting behaviors during REM
11:14sleep in patient with RBT. Indeed,
11:18if you ask to patient with their body,
11:21what is the last dream you had in
11:24in the month in the previous month?
11:27Many of them remember 66% of them
11:30remember a dream of aggression in
11:33comparison with controls who less
11:35often remember a dream of aggression
11:37plus animals in their dreams are
11:40more frequent than in controls,
11:42and this these behaviors of fighting
11:44during sleep contrast with the very
11:47place it personality when awake.
11:49Suggesting it's not their usual brand
11:52which is at at at stake at budget time.
11:57Our weather and in you can see of course
12:00this patient is dreaming in MCPS,
12:03bringing the tag by Sarah's in here.
12:08The devil dreams.
12:11And you can see me using his see Pap with a.
12:16Very good ventilation at the same time.
12:21Parkinson's disease on a busy.
12:26It's a new thing and.
12:28Of course, this guy has never,
12:30never be interested by medieval
12:32times and is very surprised
12:34to have this sort of dreams.
12:36So where dreams changed without
12:39dreams really different in subject
12:41with and without their beady.
12:43To answer this question,
12:45there were two way.
12:46One was to wake up the the patient
12:49with and without RBD patient
12:51with Parkinson's disease and wake
12:54them during the behaviors and ask
12:57them about the dream content.
12:59And this was done by the Australian
13:02Group and surprisingly when collecting
13:04Dream report just from him sleep awakening,
13:07they found exactly the same rate of action,
13:11emotion and freight in patient
13:13with and without herbed.
13:15So possibly what was what?
13:18What is frequently reported by the patient
13:21has to do with the bias of recall.
13:25Possibly the violent behavior would be more.
13:29Remember more recalled than
13:31the normal behavior during Abt.
13:34To go in this direction,
13:37we decided to constitute video
13:38Bank of all the behaviors observed
13:41during our bid inpatient.
13:43We put camera in the lab into
13:4520 bed and each time they were
13:48behaviors we we kept it and we
13:51evaluated whether this behavior
13:53where always aggressive or primitive.
13:56That was the case indeed.
13:58In more than 80% of the cases,
14:01but in 18% of the patient we saw
14:04different things that were not reported
14:07or not often reported by the spooz.
14:10For example,
14:11this patient is in REM sleep and is.
14:15Could you just imagine what
14:17he is dreaming about?
14:24So just from his gesture.
14:27He seems to under a fork
14:29in his right hand and then
14:31the bread in the left hand.
14:33I think it will come yes, OK?
14:35So this might be archaic,
14:38but using a fork and an bread
14:41doesn't seem to be very hot cake.
14:43Then this patient is in him
14:45sleep and you can hear him.
14:56Is very happy.
14:59Singing. Speaking.
15:06OK, that's quite
15:07long. We found a lot of speeches,
15:10even some people giving lectures during VD,
15:14people singing some long behavior
15:16like selling things King,
15:18playing football, smoking,
15:19so smoking baby arcade, by the way,
15:22but not the over behavior.
15:24So Abby would not display some difference,
15:27arcane behavior.
15:28So all the behavior we have seen before,
15:32like eating or singing should
15:34be driven by the cortex.
15:36Exactly as awake behavior.
15:38Otherwise, I don't know which part
15:42of the brain would drive them.
15:45Then all the patient that I I show you
15:49before we are at Parkinson's disease,
15:52but you cannot see it.
15:54We discovered that Parkinsonism
15:56disappears during a body movement.
15:58The first cases was this patient
16:01dreaming that he was attacked
16:03by Caymans and defending itself
16:05with paddle at the same time in
16:09the bed he was handling the heavy
16:11bed table over over his head
16:14shouting there caimans came and.
16:16Like in his dreams,
16:18which which is typical of RBD.
16:20It's dream enacted behavior.
16:22But what was surprising in this
16:25case was that the guy had during
16:28wakefulness very strong parkinsonism.
16:30He was Braddock kinetic.
16:31He could not speak very loud,
16:34yet he was hyper phonic.
16:36In sharp contrast with the behavior
16:39during REM sleep where he was very
16:43rapid and had a strong voice.
16:45We were surprised by that,
16:48so we decided to launch a study on 100
16:51patient with Parkinson's disease and verse.
16:55Close Alpha of them add Air B
16:58and we ask to dispose during RBD.
17:01Is your husband having a normal
17:04speech compared to wakefulness?
17:06Even without and with levodopa?
17:10And what is in red here is when it's
17:13better than during wakefulness,
17:16and you can see that the speech
17:19they speak with more intelligible,
17:22more articulated.
17:22I or volume voices and their movement
17:25are more frequently smoothed,
17:28more rapid and with higher strength
17:31than during wakefulness,
17:32and the facial expression,
17:33which is very a mimic in Parkinson's
17:36disease during wakefulness,
17:39is restored during.
17:40I'm sleep so all patient had an
17:44improvement in gesture in speech
17:47and in facial expression during
17:50air BD as if parkinsonism was
17:53disappearing during ABT.
17:55You can see an example here.
17:58This patient is awake and you can see
18:01our slow movement is when they move awake.
18:05This is typical of Parkinson's disease,
18:08slow movements.
18:11This is wakefulness and during REM
18:13sleep is just slapping like that.
18:16But you can see just how fast the
18:18hand movements are compared to
18:20what they are during wakefulness.
18:26So what is the source of
18:29this rapid movements?
18:30We just know from before that there
18:33are not some primitive behavior
18:35by central pattern generators,
18:37so we ask whether during REM
18:39sleep there could be a transient
18:42restoration of dopamine transmission,
18:44as it can sometimes occur during wakefulness.
18:48To determine this point,
18:50we turned toward another
18:52model of parkinsonism.
18:55Rare cuisines causing of Parkinson's disease.
18:59Disorder called multiple system atrophy.
19:01Invis disorders patient have lots of
19:04dopamine neurons and in addition which
19:06is the same as in Parkinson's disease.
19:10But in addition they have loss of
19:13postsynaptic dopamine receptors.
19:14Consequently,
19:15this patient are unresponsive to leva DOPA.
19:19We interviewed them and there's booze
19:21and some of them went to the sleep lab.
19:25Almost 88% of them had air BDL
19:28be this extremely frequent in
19:30in multiple system atrophy,
19:32and we found exactly the same aspect
19:35during RBD as in Parkinson's disease.
19:38You've got an example here.
19:40This patient is awake and you can
19:43see how I mimic. She is an hour slow.
19:47She is to move.
19:52Mrs. Parkinson is typical and
19:54the same during REM sleep.
20:04She showed that we can see our faces with.
20:08A clear expression of pain which
20:10is typical of something normal
20:12not because of parkinsonism.
20:14So if a leveled up a insensitive
20:18parkinsonism improves during REM sleep,
20:20it means that the motor improvement
20:22that we see cannot be due to
20:26parking to dopamine release.
20:30Then we we found that these movements
20:32during LB had not remove nobody kinesia,
20:36but at the same time,
20:38if you look very well at that,
20:41they are not totally normal.
20:43So we decided to make some some
20:46strong analysis of movements awake
20:48during our results, for example.
20:51And during REM sleep in total,
20:53in a totally blind,
20:55without knowing if they were asleep or awake.
20:59And we compare them.
21:01So Trimmer was present during a
21:03hooser in Parkinson's disease,
21:05but not during our body movement
21:08during hours are mostly self oriented.
21:11I'm sure you look at your patient
21:14often when they have someone who's
21:16always scratch their nose or the
21:19turn in the bed or the position.
21:22The pillow.
21:23It's mostly self oriented compared to
21:26LPD and the in contrast the movements.
21:29During everywhere much more violent,
21:32much more rapid than during awake,
21:35and in addition there were jerky,
21:38like if there were repeated twice
21:41like that and looking like Charlie
21:45Chaplin movement more than than like.
21:48Wakefulness movements so we imagine
21:51that the motor system that drives
21:54the movements that we see in RBD in
21:58movements in RAM sleep may bypass the
22:01basil ganglia because if they use the
22:04bus fare had used the basil ganglia,
22:07there should be slow.
22:09There should not be rapid.
22:12So we might unmask during RBD
22:15the rough unfilter expression of
22:18motor cortex during REM sleep.
22:23To support this hypothesis that we based
22:26only on an analysis of videos during IBD,
22:30there were two recent studies by the
22:33German group here and the Swiss group.
22:36In this study, the gappmayer
22:38injected tracer using SPECT
22:40imaging during our body movements.
22:42You cannot sleep in America.
22:45You have to inject marker during the
22:48movement that you do in seizure and then
22:51bring the patient to gamma camera and
22:54what we found was that during a body
22:58movement there were strong activation
23:00here of the motor cortex of the.
23:03At the same time of the pons like in.
23:07This is expected in home sleep,
23:09but no activation of the basil
23:12ganglia here at the same time.
23:15Exactly as we had suggested
23:17in the same direction,
23:19the Swiss group used the electrodes
23:22that are placed inside the basil
23:24ganglia in Parkinson's disease.
23:26Usually this electrode as you as you
23:29are used to stimulate this area,
23:32but they can also be used to monitor
23:35in the other direction what happens in
23:39the basil ganglia during REM sleep and
23:43when we are moving during wakefulness.
23:46There is a dialogue between the sub
23:49dynamic nucleus from the basil ganglia.
23:51It's an output nuclear nucleus
23:53of the basil ganglia.
23:55There is during wakefulness a
23:57dialogue between the cortex motor
23:59cortex and the basil ganglia,
24:01and during Hensley movements this
24:04dialogue is lossed exactly as predicted
24:06by the analysis of the movement.
24:09So the extra pyramidal pathway,
24:11which is driven by the basil ganglia is
24:14not at work during our body movement.
24:17So they are probably the pure expression
24:20of the promoter of the motor cortex,
24:22and they're probably not at work
24:25during Britain. Friend movement too.
24:29This is what will be taught us about
24:31the motor control during REM sleep,
24:34but everybody can teach us a lot of
24:37things about the dreaming process.
24:39Just think a minute on what.
24:42What are usually just study on dreams.
24:46Dreams occur during sleep.
24:47Then we wake up and in some cases
24:51rare cases we would recall the dreams
24:55during Awakenings and then if we
24:57choose to tell them or to write them,
25:01we will report them during wakefulness,
25:04at each step of this process there is here
25:08encoding and irreversible verbalizing.
25:10You can lose the information.
25:12Amnesia is extremely frequent.
25:14They can be a bias of recall,
25:17whereas when you think about their body,
25:20their body is what is enacted.
25:22Dream. So you you can see directly
25:25from an external POV.
25:26So live, dream the dream.
25:28At the moment it is produced by the brain.
25:33And if you think about this
25:36guy who was fighting Sarazin.
25:39In some manner you can see some
25:42of his mental images that are
25:45make like solid during her pity.
25:48So this could help us to provide insight
25:51in a lot of questions about dreams.
25:55The first one is about non dreamers,
25:59we know for a long time that 20% of the
26:03general population rarely remember a
26:06dream and less than 1% of the population.
26:10Add never,
26:11ever remember any dreams we don't know
26:14if the non dreamers do dream but do not
26:17recall them or if they do not produce dream.
26:21This is an inner experience.
26:23So how to access to it?
26:25They have the same amount
26:27of REM sleep as we do.
26:30They have the same amount of memory.
26:33So we can answer this question
26:36using the Airbnb model.
26:38Because when we looked at our
26:40first theory of patient with
26:42their bid in the sleep lab,
26:44there were more than 289 patient monitored.
26:47We found eight of them being non
26:50dreamers forward and no more dreams
26:52for more than 20 years and four of
26:55them and we never ever had any dreams.
26:58They don't know what we.
27:00Speak about when we speak about
27:03dreams despite there's assembly.
27:05Pathetic memory as Abd dreamers
27:07and this non dreamers and act of
27:11dreaming acted behavior during sleep.
27:13Just an example here these patients
27:17they told me I never dreamed you
27:20can see him in REM sleep there.
27:24Quite a very longer behavior
27:26and this is really no big deal.
27:29He opened the eyes and even
27:31managed to stand up,
27:33which is exceptional during every day,
27:35but no cure.
27:40I will not translate what you saying
27:42because it's a lot of slang word.
27:48But it seems to fight with the neighbor
27:51so far as I understand. What she says.
28:02Yeah.
28:05Some of his movements are quite clumsy.
28:25OK, this is finished.
28:28And then the nurses enter the
28:30room and told him what happens,
28:32and he said no, there is a mess in this
28:36room and I wonder who did the Mace.
28:38He did not realize that he made this
28:42dream and he made the mess is a mess.
28:45So non dreamer do dream or At's here
28:48at least I've dreaming acting behavior
28:51but do not recall their dreams.
28:54Then we tried to use the air body
28:57model to solve an old question
29:00about eye scanning during REM sleep.
29:04You know, I movements in I'm sleep as
29:06soon as they were discovered in the 54
29:09where suppose or I put it eyes to be
29:12a link with the scanning of dream images.
29:15As you can see in this little baby.
29:19Building meant was the first one to try
29:22to show some correlation between the
29:25direction of the rapid eye movements
29:28collected before awakening and the dream
29:31content that is remember just after
29:34you may remember he studied some dreams
29:37of tennis player looking right and left,
29:40and that was in the good direction.
29:44So there was a lot of enthusiasm
29:47in the early 60s about.
29:50This scanning epatha SIS,
29:51but happily some other groups,
29:54showed that there was some weak correlation
29:57between the eye movements you had.
30:00Before awakening and the Dream report and
30:04the correlation was less than 30 percent,
30:0730%, which is quite low.
30:09Later, another group in Prime,
30:12it shows that.
30:15Did I movements are not always conjugated,
30:18which may suppose that we are not
30:22focusing on a dream images unless
30:25we have one dream pair eyes.
30:28And uh,
30:29over groups say that features and blind
30:33people have rapid eye movements despite
30:36their no image to see during REM sleep.
30:41So there was a debate and
30:44how fog in in the 80s said,
30:47OK,
30:47we cannot solve this debate because
30:50I movement we see in him sleep are
30:53not exactly translating the gaze
30:56of the dreamer because the guest is
30:59determined by the combination of the
31:01neck movements and rapid eyes movements
31:04and the neck movements are paralyzed,
31:07paralyzed, atonic during REM sleep.
31:11But but but we saw this cases
31:14and I showed him a lot.
31:17It's the next smoker,
31:19with narcolepsy was Air BG and you can see
31:24him smoking the saturation sensor here.
31:27What surprises during his behavior was
31:29that he seems to look at these cigarettes.
31:33Fictive cigarettes,
31:34when he scratched it in the ashtray.
31:38As if it had an ice where in
31:42the direction of the cigarette.
31:45Detroit away. As you can see.
31:48So we decided to monitor the eye movement,
31:52the eye direction with the way
31:54that is more complex than during
31:56normal police sonography.
31:58We use some yuge to monitor the
32:01vertical and the horizontal movement
32:03that you can you know separate here on
32:07the policy of nogra FI and we monitor
32:10all subsequent patient with herbed
32:12lookin 76 where necessary looking
32:14to find some goal directed behavior
32:17which has which are behavior that.
32:20If you are done, then during
32:22wakefulness you would need to use your
32:25eyes to follow what you were doing.
32:28For example, when you are sending a
32:30kiss like I'm doing here to somebody,
32:33usually you look at the face of the
32:36people you are sending the kiss too.
32:39So we found some goal directed
32:42behavior like for example in this
32:44narcolepsy patient with LVAD,
32:46the patient is taking a pictures with is.
32:50IPad and we looked whether the eye
32:55movement were within the frame for
32:58frame of the of the fictive iPad
33:02because it's a dream of course.
33:05And what we found is that first.
33:10During a goal, directed behavior,
33:13only 1756% of behavior are
33:15associated with rapid eye movements.
33:18The over goal directed behavior
33:20have no rapid eye movement,
33:22so it's not normal to re.
33:25But when there are some eye movements,
33:29they are in the same direction
33:32as the limb action.
33:34An example here is this guy
33:37who clients level ladder in.
33:39This is dreaming in this behavior.
33:42And he first started by looking up
33:45here to the ladder run before he
33:48put his and erase this end on it.
33:51And then he looked down here
33:54with the eyes closed.
33:56Of course,
33:57that's why we need a TV
34:00electrocardiography before he put his
34:02his feet on the lower ladder rank.
34:05So from all this study,
34:08we and what we know in animals too,
34:12we can imagine that we are like a puppet
34:16puppet model during REM sleep apart.
34:20Nucleus in our poster generators is both
34:24activating our motor cortex to move.
34:28These movements are translated
34:29to the spinal motor neuron,
34:31but at this place they are blocked
34:34by the otoniel system and at the
34:36same times are as opposed generator
34:39is generating the motor cortex.
34:41So the movements it's generating
34:43also the rents and the rapid eye
34:46movements and possibly stimulated
34:48the visual cortex at the same times.
34:52This seems to be a colorie similton.
34:54He was discharged in parallel,
34:56not in series like during wakefulness.
35:01Then this is what we learn from the
35:05high scanning during her body we
35:08we thought about using the herbed
35:11as a model to see if we're if we
35:14were replaying the task during the
35:18night for equalling them better.
35:21And we used it to test the replay
35:23I put this is we all know that
35:27memory is consolidated during sleep.
35:29It's about 20% more.
35:31That is remember after having slept on it.
35:35But we don't know unless using animal models,
35:39whether we are producing what we
35:41have learned the task during sleep.
35:44Or is it something totally different
35:47that we are doing during sleep?
35:50So we try to teach something and
35:53choreography or a text in the
35:55evening to Airbnb patient 20 each
35:58types and we look whether it was
36:01consolidated during sleep,
36:03which was the case in the consolidated.
36:06Very well,
36:07the memory and we looked at the
36:10video whether the other he played
36:13the uncover graffiti or the other.
36:16If they're learning text by heart,
36:18would they speak it?
36:21And would they tell it during RBD or not?
36:25So it took us a few years to do with
36:29studies and to make the Long story
36:32short for procedural memory page,
36:35our patient at two learned and
36:37choreography before sleeping.
36:39No patient with video replayed recently
36:41learn motor sequence the control group
36:44were sleepwalkers 20 sleepwalkers
36:45and one of the three polka reproduce
36:48what she had learned before sleeping.
36:51As for available episodic memory,
36:53patient had to learn by heart.
36:56A quite long and emotional text.
36:59Nobody repeat repeated during the night.
37:01The text affair learn before sleeping,
37:04but one one of the patient during
37:07RBD authored some sentences
37:08that are semantically linked,
37:11not a copy and past,
37:13but the semantic link with the
37:16text learn before sleeping as if
37:18he had incorporated in his dreams.
37:21Part of what we are learn before,
37:24but would not produce it.
37:26Osoo by chance.
37:29Last year we had this patient
37:32were doing during wakefulness.
37:36It's a test we do for testing for
37:40bradykinesia in isolated everybody
37:42score and during the next night.
37:46During Abd his patient.
37:49Seems to have reproduced his gesture,
37:51which is not something complex to learn.
37:54As you know, it's simple,
37:56maybe because he laughed at the same time.
37:59Maybe he found it funny.
38:02What we have done to him, we can't.
38:05It's it's called finger tapping.
38:11You got it here. Single
38:15setting. Then he laughs.
38:26It's not a usual gesture on it,
38:28so just you're just for the United
38:32Parkinson's disease Rating Scale.
38:34So every day, not every yes,
38:36every day is very narrow window.
38:39It's fascinating. Window on dreams,
38:41but only 9% of REM sleep contains movement.
38:44And the thing scanning behaviors as
38:47we have seen before are quite rare.
38:50But a few that direct evidence suggests
38:53that we incorporate in our dreams
38:56what in our behaviors during dreams,
38:58what we have done, or long before sleeping.
39:02As it is known from the study
39:06of dream themselves.
39:08Last but not least,
39:09we use the air BD model to work on emotion.
39:14I'm sure you are familiar with
39:18the role of sleep and REM sleep,
39:22especially in regulating emotion too.
39:26I guess you guys have already received a
39:31very disagreeable email in the evening and.
39:35Wanted to answer it quite emotionally.
39:40As you know, you should not.
39:43You should sleep on it and the next
39:46morning answer to the Mail on a more
39:49rational and less emotional way.
39:51This is one of the major role of
39:54sleep to desensitize our negative
39:56emotion to the model.
39:58To sleep to remember and.
40:00Need to forget that has been
40:03developed by mature worker.
40:05Remember better and not being
40:07exposed again to the emotion.
40:09So now we know that sleep is
40:12important in regulating emotion,
40:14but how to access to the
40:16emotion during REM sleep?
40:18Using MRI focused on the amygdala,
40:20is aware that it will tell us whether
40:24the emotion are positive or negative.
40:26Waking up people is quite complex.
40:29It will interrupt.
40:30The dreaming process.
40:32But now if you think about it,
40:35emotion is something very visible on the
40:39face of somebody and you can see here.
40:42So values emotion developed by by Trump.
40:46We are wired since birth to recognize
40:50the emotion on on human faces,
40:54disgust, happiness, sadness,
40:56angriness, afraid and surprise.
40:58No think.
40:59That you can recognize them very well
41:02in an awake person like Trump ear,
41:05but maybe it could be interesting
41:08to look at people sleeping at
41:10their emotion on their face,
41:12and it's what we did here in the first
41:16theory of patient we focus 1 camera
41:18on the face and one on the full body.
41:22We put electrodes on the chin of course,
41:25but also on the measure of the faces
41:28of the expression like the Giga Matic.
41:31For smiling and on the corrugator
41:33here for you know being happy and it
41:36allowed to look at the place where
41:39you have the EMG signal and signal
41:42and look at at the video at the
41:45same time she's smiling here asleep.
41:48And every patient I've lost of
41:51Atonia that concern also their face.
41:54So we we found a lot of emotion
41:58during REM sleep on the face of
42:02our patients and to avoid.
42:05To to leave them anonymous because
42:07the face is easy to recognize.
42:10We asked to an artist to change slightly
42:13the general face without changing
42:15the expression or in our slippers so
42:18you can see what they do during REM sleep.
42:22'cause they have the eye closed during
42:25REM sleep, but we found some expression of
42:28happiness and less angriness discussed fear
42:31and surprise quite easily in RBD patient but
42:35also to a lesser degree in normal people.
42:38We started by working on
42:40smiling during sleep.
42:42You need to put a cinematic and you
42:45can see the smiling faces here.
42:49And we started to work on 180 person
42:52and an 100 of them were normal adults.
42:55We found smile on adult faces
42:58in 8% of normal adults.
43:00We know it's extremely frequent in babies,
43:02but so far nobody news whether
43:05it exists in adults.
43:06It does.
43:07It's rare, it's more frequent in Ram,
43:10sleep that in non REM sleep
43:13it can occasionally be seen in
43:15non REM sleep in normal adults.
43:18In contrast to this rare smile, smile.
43:21See normal subject Alf of our Air B
43:25patient smiled or laughed during ability.
43:28An Alpha of the smiles worsen
43:31konus with rapid eye movements.
43:33We later looked weather of his work,
43:36true or untrue, smiles.
43:37You know that we can determine if
43:40a smile is true if people have at
43:42the same times, not only the lip,
43:45the corner of the lip that goes like that,
43:48but also the eyes, that closer little.
43:51Which means that you are more happy.
43:53Whereas when you just do like that small,
43:56polite smile.
43:57So there were a lot of true smiles
44:00with his condition.
44:01Smiles during ahem slipper ability
44:03and laughs.
44:04Big laughs were quite frequent
44:06in Air B patients.
44:08In a few cases,
44:10very few case because we try
44:13not to wake up our patient.
44:15We collected some happy
44:17dreaming scenario after them.
44:19So it seems that sleep smiling
44:21seem to reflect through inner
44:23smeared in in our patients.
44:25So if this is true,
44:27it means that using the
44:30fashion emotion during Airbnb,
44:31open the windows on what emotion are
44:34treated are expressed during REM sleep
44:37directly without needing the memory of our.
44:40Patience we continue on negative
44:45and positive emotion and.
44:48We looked whether they were always or
44:52not associated with over channels,
44:54especially with the eye movements.
44:57The PhD in charge at to look at video
45:01by very small screens of three seconds,
45:05Mini Airport and saying OK,
45:08no smile, no smile.
45:10Positive negative neutral emotion
45:12here and then to look at the
45:16concomitant eye movement recording.
45:18Whether they were slow,
45:20I movements which ocurred so during
45:22him sleep isolated I movements.
45:24Happy Day movement or burst
45:26as it occur during him sleep.
45:29So it looks in a lot of time because
45:33he had to score more than 24,000
45:36mini book of triskel seconds or
45:39from sleep and what we found is
45:42extremely interesting.
45:43The positive emotion are mostly
45:45associated with slow and isolate.
45:48I movements were.
45:49In contrast the negative emotion
45:51are strongly associated with burst
45:53of eye movement, as if.
45:56To desensitize our negative emotion,
45:59we may need to concomitantly
46:01have this burst of movement
46:04for any reasons.
46:05During REM sleep we don't
46:07know the reason for that,
46:10but it remembers us.
46:12It makes us remember about the
46:14technique that is used to decrease
46:17the emotion in patients with trauma.
46:20The high movement desensitisation reaction
46:23where you ask the patient with psychotrauma.
46:26To remember and to remember the trauma
46:31by looking at the same times at the
46:35I'm at the movements which help her
46:40to desensitize herself to the emotion.
46:44So as a conclusion, I speak too much.
46:47Of course, Airb drivel reveals specific
46:49motor control during REM sleep.
46:51There is an activation of the
46:53motor cortex of the brain stem,
46:56but not of the basil ganglia.
46:58And there should be a reason for that.
47:02Plus the improvement of movement in
47:05Parkinson's disease during Airbnb
47:07without any treatment suggests that
47:09there there is an alternative,
47:11not impaired motor system in this
47:14patient that could be maybe in our best
47:18dreams reactivated during wakefulness.
47:20Plus the scanning input report.
47:22This show is partly verified here,
47:25at least when they are moved by movement.
47:29We can see a coordinated coactivation of
47:32rapid eye movements and limb movements.
47:35At the same times.
47:38And gesture vocalization and facial
47:40expression during her body and mask.
47:43Some cognitive and emotional
47:45processes at play during dreaming.
47:48Before ending,
47:49I'd like to think the PhD neurologist
47:52of my team and our sponsor.
47:55You can see very questionable
47:57Delphine with yet Lauren look layer,
48:00Miquel J and Roberts Muncie,
48:02working on facial expression.
48:04Thank you for your attention.
48:08Thank you very much doctor enough.
48:11That was a phenomenal talk and
48:13doctor Tobias had to step away but
48:16we have a number of questions.
48:19If you have a few minutes that came
48:22up on on the chat and hopefully have
48:26an opportunity for other questions.
48:28One question was a more clinical question,
48:31which is how do you counsel patients
48:34and families about REM behavior
48:36disorder as a predictor of.
48:38Dementia or are Parkinsonian ISM.
48:44We always cancel them because we don't
48:47want them to discover them on Internet.
48:51We want to have quite.
48:56Asked if relationship,
48:58but what I usually used to say
49:03is to say there is a risk of.
49:07Developing without telling them it's 8085%.
49:09If they want to know I I try to be
49:12more Vegas because you don't know
49:14for a given person and as you can
49:17see there is still 10% of patients
49:20who have not converted and they
49:22can die off of their things before.
49:24But we discuss that with our colleagues
49:27from the Mayo Clinic and they say that
49:31in other cases you should ask first
49:34if the patient wants to know or not.
49:37I always try to to say, you know,
49:40we know that it can evolve too,
49:43and then we can start to say what
49:46you can do to avoid this fate.
49:48Change your way of life.
49:50Have more sport, change your way of eating.
49:53Make your brain working or what
49:56we know about.
49:57No prevention can be applied to.
50:00Very good, very helpful.
50:03Another question somewhat related question,
50:06is a patient who may start up as
50:09having idiopathic REM behavior
50:11disorder then ultimately progress
50:14is to Parkinson's disease.
50:16Does the does?
50:17Are you aware of whether the
50:20dream enactment behavior changes
50:22and are there differences in
50:25dream enactment behavior between
50:27Parkinson's multi system atrophy?
50:30Lewy body dementia?
50:31Are we not that granular?
50:36For the dream content, so far as I know,
50:41it has not been compared, at least not
50:44in a longitudinal in a follow up way.
50:48Too many patients say that their
50:51dream are changing at a time.
50:53The develop PD.
50:54What we have looked it about the the
50:57motor motor aspect and motor signature
51:00that we have described in Parkinson's
51:03disease with jerky repeated twice movement.
51:06Is exactly the same in narcolepsy,
51:08which is not a movement disorders and in MSA
51:11and in the liberties and in isolated habite,
51:15which suggests it's the same
51:16way of doing the movements.
51:18But it does not answer to the
51:21question about dreams, of course.
51:25Very good.
51:26There are a couple of questions.
51:29Follow up questions related
51:31to medications and arbeed.
51:33Are there classes of medications
51:36that may increase the risk
51:38of run behavior disorder?
51:41Yes, mostly the antidepressant and
51:44to some degree is a beta blocker.
51:48But the antidepressant, our father,
51:50the Hyest way to increase their
51:53body and to decrease their busy,
51:56we commonly use some clonazepam
51:58and even melatonin can do a lot
52:02of coding in this direction.
52:04And there have been a few
52:06evidence for Rivastigmine,
52:08which is a nautical, not work.
52:10Increasing acetylcholine to improve beady,
52:13especially in patients with cognitive defect.
52:17And are there newer therapies besides
52:21melatonin or clonazepam that are in
52:25the pipeline for REM behavior disorder
52:28or alternative therapies right at
52:31least the idea of preventing Parkinson's
52:35disease is quite high in the field.
52:39So far the preventive therapy has been
52:43tested in Dinovo PD patient because.
52:47We are sure that they're Parkinson's
52:50disease and the drugs were aimed at at
52:53decreasing the progression of the disorder,
52:56but the same drugs that are
52:59in the pipelines should be,
53:01we hope at least it's hard to convince
53:04the pharmaceutical company because
53:06seven years of conversion is quite high.
53:10Quite long for company,
53:11but most of the ideas are around using some
53:15monoclonal antibodies against the Alpha.
53:18Any clean which accumulate within the brain
53:21stem and then within the system semi graph.
53:26There also some patient you know develop
53:29Parkinson's disease in link with GBA
53:33mutation which is an automatic mutation.
53:36There are now some enzymatics implementation
53:39that can be used in GP mutation and
53:43it should be tested in RPD to prevent
53:47conversion toward Parkinson's disease.
53:50Very good, very good.
53:53We have a couple more minutes and there
53:56are more questions that are coming up.
54:00One of the many of many of the
54:04clinicians on the call care for
54:07patients in our VA system as well as
54:11veterans which tend to be an older
54:14population of patients with a high
54:17prevalence of post traumatic stress
54:19disorder and oftentimes clinically
54:22it's very challenging to distinguish.
54:24Some of the nocturnal behaviors that occur
54:27in the context of post traumatic stress
54:30disorder from REM behavior disorder.
54:32Some of the nightmare content and so
54:35wondering if there are ways that clinical
54:38ways that you're aware of that might
54:41help besides doing Poly sonography and
54:43looking for sleep onset REM periods.
54:48That's classic, all.
54:49I mean PTSD in the acute phase of the
54:53best ETS D There are frequent nightmares
54:56which are replaying the trauma,
54:59and they might be enacted in some
55:02patient like going out of the bed and
55:06fighting as they did during the war.
55:11It's in the acute phase in the chronic phase,
55:15the patient with the trauma
55:18usually at best sit on the bed,
55:21but they might not do a lot of behavior
55:24compared to a body where they have really
55:28repetitive and more values behaviors,
55:30even if it's African they can laugh so
55:34you can ask your patient, or the spokes.
55:38Is he laughing during 3
55:40pieces speaking with normal?
55:42Nontraumatic aspect that could help,
55:44of course with the police and nogra
55:47fi you will answer the question
55:50easy easily because post traumatic
55:53stress disorders occur during all
55:56sleep stages in two and three,
55:59an air B&B are is quite
56:03quite repetitive whereas.
56:05During time sleep.
56:06So maybe user laughing and speaking
56:09and singing as a way to differentiate.
56:15Another question Doctor Krieger.
56:18Just please. Do patients with
56:21narcolepsy and arbeed also progressed
56:24to neurodegenerative disorders?
56:27So good question so far.
56:30What we know is that do not,
56:33they do not evolve towards that.
56:36Abd in narcolepsy is less severe
56:39than isolated on PD associated.
56:43Some patients.
56:44Sometimes some some strong
56:46behaviors very own behavior,
56:48but most of them are not very severe.
56:51If you compare, for example,
56:54the rate of friends sleep without
56:56atonia or the number of behaviors,
56:59but no, they do not progress and
57:02even there I saw hypothesis whether
57:04narcolepsy or at least hypocretin
57:07deficiency would expose less
57:09patient to not dementia with little
57:12bodies but alsheimer dimension.
57:14Because there is an interaction
57:16between hypocretin and amyloid
57:18which accumulate in the brain of
57:21patient with unsigned notices.
57:23So narcolepsy might be protective.
57:26As I know disorder this
57:29is and finally Doctor Rue is asking
57:33how do you follow patients who have
57:37sub clinical arved so assume may have
57:42evidence of REM sleep without a tonia but?
57:47Not manifesting a whole lot of
57:49dreaming at something you picked up
57:51incidentally on us on a sleep study.
57:54I would follow them every year and the
57:58first time I would apply exactly the same.
58:01Same test as we do in isolated orbite
58:06looking whether they have a loss of smell.
58:10If they have auto static hypotension
58:13is examining them about having some.
58:16Some code will movements and doing
58:20Montreal cognitive assessment as
58:22we do every year with any isolated
58:25LPD patients we know from two
58:28teams so they know Pat teams from.
58:31Germany and also the Austrian
58:34teams that patient with.
58:36I just isolated there WA progress
58:40to our towards their billing
58:43and so follow them and. Very
58:47good, very excellent. Thank you very
58:49much for a wonderful presentation and
58:51thoughtful answers to these questions.
58:53This was very well received and just as a
58:57reminder for folks on the call next week.
59:00There will not be asleep seminar but
59:02will resume resume the following week.
59:05Thank you again Doctor.
59:07An offer for wonderful talk.
59:08Thank you. Goodbye.
59:10Bye bye bye bye.