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Talk: Local sleep in the waking brain impairs attention: A pharmacological study

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Speaker: Elaine Rose Pinggal (she/her), Monash University (grid.1002.3)

Yep so thanks everyone for coming and for giving me the opportunity to talk as well i’ll be talking about local sleep in the waking brain and how this can impair attention so local sleep is a phenomenon that occurs in both sleep and wake in wake it refers to sleep slow waves occurring in some brain regions so this is time dependent so it depends on how long a

Person has been awake for so the longer a person has been awake for it the more local sleep tends to occur and it’s also task dependent so the more a person has been using a specific brain region the more likely that local sleep will occur in this region so it’s been theorized that an increase in local sleep can impair sustained attention however past studies

Have relied on sleep-depriving individuals so the direct effects of local sleep on sustained attention is difficult to determine to improve this you regulated the levels of local sleep using pharmacological means so you’re regulated three neuromodulators the first one being noradrenaline using adamoxetine so noradrenaline is responsible for modulating attention

Vigilance and arousal and it also inhibits sleep promoting systems in the brain an increase in our adrenaline tends to increase wakefulness and improve toss performance so adam oxtein works by blocking the reuptake of noradrenaline and it’s a non-stimulant medication used for adhd we then use methylphenidate to increase both noradrenaline and dopamine levels

So dopamine works very closely with no adrenaline and impacts reward processing and motivation so methylphenodate is a stimulant medication used for adhd as well and it works by blocking the reuptake it tends to improve reaction time and tasks and it also has an impact on sleep so the ingestion of methylphenidate is suggested to be early on in the day as it

Can cause insomnia finally we use the top prime to increase the levels of serotonin so serotonin has been theorized to be involved in building up sleep pressure and it also has inhibitory effects and activation systems a subdivision of cetalopram acetalpram was found to reduce activity in regions of the brain responsible for attention and arousal so the tile

Problem works by blocking the reuptake of serotonin so the first aim of our study was to establish the effects of neuromodulators on behavior and local sleep so implement the delidium mixed effect model to look at the effects of treatment on behavior from a sustained attention task so we looked at reaction time and missed targets which in this study was defined

As 1 minus targets detected and we also wanted to see the effects of treatment on local sleep so for methylphenidate and atomoxetine because the increased neuromodulators involved in attention we hypothesized that there would be an improvement in behavior so that there would be a faster reaction time and a lower amount of misses for citalopram we hypothesized

That there would be an impairment in behavior because serotonin is involved in inhibiting activation systems so we hypothesized that there would be an increase in reaction time and an increase in missed targets similarly for local sleep because methylphenidate and atomoxetine um the increased neuromodulator is involved in arousal we hypothesize that there will

Be less local sleep detected and that versatile pram because serotonin is involved in increasing sleep pressure that there would be more local sleep detected so the second aim was to determine whether local sleep mediated the effects of neuromodulators on behavior so we hypothesized that instead of treatment just having a direct effect on behavior the local

Sleeps was the middle ground or the mediator between these two variables so the data that we analyzed was conducted a few years ago and it was by professor mark bellgrove and it has two papers published on it it comprises of 32 ml participants age 18 to 45 and the design of the study was placebo-controlled so each participant came to the lab at four different

Time points and they randomly administered one of these drugs so both the participant and the researcher didn’t know which drug they’re administered they completed a questionnaire at three time points just before drug administration before the sustained attention task and after the sustained attention task and the sustained attention toss they completed was

A c-t-e-t or the continuous temporal expectancy task and that’s shown here participants were required to monitor this visual stimulus and the duration of the stimuli presentation so the target stimulus was presented for a longer duration to indicate that they detected the stimulus said to quickly press a button so each participant completed 10 blocks of this

Task with each block lasting approximately three minutes so before i go into results i just wanted to reiterate what i looked at so i looked at reaction time in seconds and also percentage of mean missed targets i used the linear mixed effect model and used bonferroni to correct for multiple comparisons and i also wanted to look at the mean slow wave density

Per minute for a local sleep for each treatment so these were detected through eg and we looked at the delta band for each electrode and looked for the waves to the highest amplitude we then compared this to the slow waves to placebo hence the amplitude for the treatments had to exceed the top 10 percent of slow waves detected for placebo to be classified as

Local sleep in the study we corrected for multiple comparisons by adjusting the p-value using false discovery rate so the results that we found for the first hypothesis is shown here the bar graphs show the effects of treatment on the behavior variable which in this case is reaction time in seconds in comparison to placebo and the error bars represent the center

Of the means so in line with the hypothesis we found that methylphenidate had a lower reaction time compared to placebo and this was evident across time adamoxetine in cetalopram had a higher reaction time compared to placebo similarly we found that methylphenidate had a lower amount of mean missed targets whilst cetapham had a higher amount so this figure just

Shows that the local seed that we detected was very much centralized and that it also increased across time so again in line with the hypotheses we found that the mean slower density that we detected from methylphenidate was lower across time and atomoxy and citalopram were higher compared to placebo and these topographical maps just show which electrodes had a

Higher or lower amount of local sleep in comparison to placebo again consistent with the hypotheses we found that methylphenidate had a lower amount of local sleep detected in the frontal regions and this extended to the central regions and the parietal occipital regions for adamoxetine we found a lower amount of local sleep as well in the frontal region but we

Found an increase in local sleep as well in the left temporal region and the right priority occipital region versatile prime we also found an increase in local sleep in the left temporal region extending to the central region the right temporal region and the right pariet exhibitor region so before i go into the mediation results i just wanted to reiterate what

A mediation tests it tests whether the effects of treatment on behavior is mediated through a third variable which in this case is local sleep so we’re trying to see if local sleep explains the causal relationship between these two variables so we found that the effects of the teleprime on local sleep of increasing it significantly media mediated the effects

Of reaction time and also missed targets so for our hypothesis about methylphenidate our results were consistent with past studies such as from bedard and colleagues who tested the difference between atomoxetine and methylphenidate consistent with the results they also found that methylphenidate had a lower reaction time compared to atomoxetine and had a lower

Amount of mean missed targets these perhaps could be due to a decrease in local sleep in regions that regulate this behavior vitamoxetine our hypothesis was partly disproved this could be due to the dosage of atomoxetine that they were given they might have needed more or less for behavioral improvements to have occurred moreover a past study by bontoya and

Colleagues found that improvements usually occurred at six to eight weeks after continuous use of atomoxetine perhaps due to this study single dose cross sectional design improvements were not observed in behavior the increase in reaction time may also be due to local sleep occurring in regions that regulate this behavior however despite this it should be noted

That we found a decrease in local sleep as well in the frontal regions versatile problem the results obtained are also consistent with findings from a past study by ringing and colleagues they found an impairment and vigilance after a single dose of acetal prime moreover another study by vyasovsky also found that with an increase in sleep pressure a decrease in

Toss performance was evident these results also relate to the mediation that we found so the results that we found for the mediation gets us closer to learning about the underlying mechanisms of these treatments past studies such as bedard and colleagues have only looked at the drug and its direct effects on behavior but these results could provide us with a

Better understanding of the mechanisms that could lead to a better prescription of treatments to patients the effects found by vyazovsky are consistent with the results found here that an increase in slow wave mediates reaction time and also misses however it should be noted that the satellite direct path for misses was still significant this perhaps could be

Due to the threshold we had set for local sleep we have only taken into account specific clusters and thus we may not we may not have captured all local sleep present this could also indicate that there are other mechanisms at play that citaprim affects that mediates the effects of misses so to conclude this study provides evidence on how these treatments and

Their effects on neuromodulators have an effect on local sleep it also showed that an increase in neuromodulators involved in attention and arousal results in a decrease in local sleep moreover increasing serotonin a neuromodulator involved in increasing sleep pressure resulted in impairments in behavior but also an increase in levels of local sleep detected

Thank you for taking the time to listen and i’m happy to take any questions thank you elaine for a very clear and compelling presentation uh i have again a broad question because uh you know this idea of local sleep is new to me and i’m caught up on just sort of um getting my head around it so do you do you consider local sleep a sort of continuum where you a

Sort of irreversible continuum to where you have these local regions that are in a task-dependent way fatigued and then you slowly go to global sleep essentially or are they really local events that remain localized um so i’m not too sure if i’ll be answering your question so do you speculate okay um so i do know that local sleep um it occurs when there’s

Fatigue in certain in certain regions so it’s um that when that brain region is trying to um why do i say this um so when there’s okay i’ve lost my chain of thought i’m so sorry um oh um does it have to do with local sleep that’s just that’s just a pun uh okay well here’s another question um okay so we do have a pretty clear understanding that local sleep

Increases with fatigue in a unidirectional way that’s probably a better way of asking my question yes so it’s um an objective marker of fatigue yes okay great and then do we know as far as you know neuronal mechanisms do do we have any understanding of how we can have local sleep because everything you know in um neuroscience 101 that i’ve been taught is that

Sleep is really a brain wide phenomena in part because you have these sort of brainstem nuclei that send neurotransmitters worldwide so do can you speculate on how local sleep can remain local i mean this is a huge question but um that’s a good question and i’m gonna need to ponder on that that seems fair that seems fair and we’re also actually a few minutes

Over time so thank you so much elaine and thank you penchant and thank you thomas and

Transcribed from video
Talk: Local sleep in the waking brain impairs attention: A pharmacological study By Neuromatch Conference