Upload
vuongduong
View
215
Download
1
Embed Size (px)
Citation preview
Harvard Medical School Beth Israel Deaconess Medical Center
Boston, MA
Robert Stickgold
Some of the work presented here was sponsored by Sepracor, Inc.
Sleep, Memory and Dreams:
Putting It All Together
OHSU Brain Institute, Portland OR April 2017
Today’s Outline
1) The physiology of sleep
2) The diversity of memory evolution
a) Stabilization and enhancement
b) Selection, gist, rules and insight
3) Sleep, memory and dreams
4) Sleep and psychiatric disorders
Neuromodulation Varies Across
the Wake-Sleep Cycle
Active Wake
ACh
NE 5-HT
Quiet Wake
REM SWS
Ach: Atropine (belladonna) and scopolamine
NE: MAO inhibitors, cocaine
5-HT: SSRI’s, LSD
M
em
ory
Recognitio
n
neutral negative positive
Deprived
Sleep
Emotional Memory After Sleep Deprivation
• Matthew Walker
• Tiffany Brakefield
• Alexandra Morgan
1 2 3 4
Sequence
4-1-3-2-4
Sleep Enhances
Procedural Learning
• Matthew Walker
• Tiffany Brakefield
• Alexandra Morgan
1 2 3 4
Sequence
4-1-3-2-4
Sleep Enhances
Procedural Learning
Learning Rate Saturates Rapidly
10 PM
10 AM
1
Post-training Baseline Training Trials
(lasting 12 mins)
2 3 4 5 6 7 8 9 10 11 12
12
# S
eq
uen
ces /
30 s
ec
16
20
24
Walker et al. Neuron 35, 205 (2002)
10PM
p<0.0001
SLEEP
10AM 10PM 20
22
24
26
28
# S
eq
uen
ces /
30 s
ec
10AM 20
22
24
26
28
n.s.
Walker et al. Neuron 35, 205 (2002)
Motor Sequence Learning
30 min
100
90
80
70
60
50
Neutral Emotional
Item
s R
ecogniz
ed (
%)
30 min
Emotional Trade-off
Objects
Backgrounds
0
-4
-8
-12 Change fro
m 3
0 m
in (
%)
Neutral Scenes
Changes Over 12 Hr Wake or Sleep
Objects
Backgrounds
12 hr wake
Emotional Scenes
12 hr sleep
12 hr wake
12 hr sleep
n.s. n.s.
Sleep Consolidates Episodic
Declarative Memory
• Jessica Payne
• Ruth Propper
Word Lists Door House Ledge
Glass Open Breeze
Pane Frame Curtain
Shade View
Verbal Memory Task
nurse sick lawyer medicine health hospital dentist physician ill patient office stethoscope table doctor cotton
nurse
sick
lawyer
medicine
health
hospital
dentist
physician
ill
patient
office
stethoscope
+
D-R-M: 12-Hour Deterioration
15
0
-15
-30
-45
-60 Studied words
Gist words
*
% C
hange (
rela
tive t
o 2
0 m
in
Wake
Sleep
*
Payne et al., Neurobiol Learn Mem 92, 327 (2009)
?!?
Probabilistic Learning
Card 1 Card 2 Card 3 Card 4
80% 60% 40% 20%
Djonlagic et al., Learn Mem 16, 751 (2009)
Sleep Enhances Performance
0
2
4
6
8
10
12
14
p = 0.01
Observation
Impro
vem
ent
(% o
f tr
ials
)
Wake
Sleep
Djonlagic et al., Learn Mem 16, 751 (2009)
Sleep Enhances Insight
Number Reduction Task
1 1 4 4 9 4 9 4
1 4 4 1 9 9 1
• Ulrich Wagner
• Jan Born
Wagner et al. (2004) Nature 427: 352
Development of Insight
Wake/ Night
Wake/ Day
Sleep/ Night
0%
20%
40%
60% S
ub
jec
ts g
ain
ing
in
sig
ht
1 1 4 4 9 4 9 4
1 9 1 4 4 1 9 9
New Experiences are Replayed
at Sleep Onset Hypnagogic dreams
• April Malia
• Denise Maguire
• David Roddenberry
• Karen Emerge
• Laura Babkes
Hypnagogic Images of Tetris
Group (n) Nights % Ss % Rpts
Novices 2 75% 10.4%
Experts 2 or 3 50% 4.7%
Reports of Tetris Imagery
“Just seeing Tetris shapes floating around in my head like
they could in the game, falling down, sort of putting them
together in my mind” (JEG - Day 2)
NOVICE
“…seeing in my mind how the game pieces kind of float
down and fit into the other pieces and am also rotating
them” (TRP - Day 2)
EXPERT
Amnesiacs 3 60% 7.4%
Hypnagogic Images of Tetris
Group (n) Nights % Ss % Rpts
Novices 2 75% 10.4%
Experts 2 or 3 50% 4.7%
Reports of Tetris Imagery
“Just seeing Tetris shapes floating around in my head like
they could in the game, falling down, sort of putting them
together in my mind” (JEG - Day 2)
NOVICE
“…seeing in my mind how the game pieces kind of float
down and fit into the other pieces and am also rotating
them” (TRP - Day 2)
EXPERT
“I see images that are turned on their side. I don’t know
what they are from, I wish I could remember, but they’re
like blocks” (JEG - Day 2)
AMNESIAC
Dream Content Predicts
Sleep-Dependent Consolidation
NREM Napping
• Erin Wamsley
• Matt Tucker
NYTime.com April 22, 2010
± NREM
Nap
12 pm 2 4 6 pm
Train Test
WAKE (n=16)
SLEEP (n=16)
-100
Impro
vem
ent
(sec)
150
100
50
0
-50
p=.01
Wamsley et al. Curr Biol 20, 850 (2010)
± NREM
Nap
12 pm 2 4 6 pm
Train Test
WAKE SLEEP
REPORTS
p=0.0003
WAKE (n=16)
SLEEP (n=16)
-100
Impro
vem
ent
(sec)
150
100
50
0
-50
p=.01
n.s.
Not maze related
Maze related
0
100
200
300
400
Impro
vem
ent
(sec)
Wamsley et al. Curr Biol 20, 850 (2010)
n.s.
SLEEP WAKE
Not maze related
Maze related
0
100
200
300
400
Impro
vem
ent
(sec)
Quiet wakefulness
“I was thinking about the game that I used to play in high school, “Counter-Strike”, because of the same layout . . . and also I was just planning, and trying to remember the maze and trying to figure out the route”
“ . . . thinking [about] what we have to do in the second maze test . . . wondered if it was going to be, like, the same . . .”
Dream reports
“I was thinking about the maze and kinda having people as check points, I guess, and then that led me to think about when I went on this trip few years ago and we went to see these bat caves, and they're kind of like, maze-like”
“Looking for something” in a maze
“Just hearing the music” from the task
Quiet wakefulness (useful?)
Dream reports (useless?) p=0.0003
Wamsley et al. Curr Biol 20, 850 (2010)
• Stabilization and enhancement
• Salience selection
• Rule and gist extraction
• Network integration
Imagined scenarios
Narrative development
Future projection
Sleep-Dependent Memory Processing:
A Whole-Brain Process
DREAMING
Hippocampus
Neocortex
Sleep-Dependent Learning
is Impaired in Schizophrenia
(Study funded by Sepracor & Co.)
• Dara Manoach
• Erin Wamsley
• Ann Shinn
• Donald Goff
Motor Skill Learning in Chronic Schizophrenia
Manoach et al. Biol Psychiatry 56, 951 (2004)
9
11
13
15
17
19
21
2 4 6 8 10 12 2 4 6 8 10 12
Trials
# S
equences / 3
0 s
ec (
contr
ols
)
4
6
8
10
12
14
16
# S
equences / 3
0 s
ec (S
Z)
Stage 2 NREM Spindles in
SZ and Controls
Controls SZ
2.0
1.5
1.0
0.5 Sp
ind
le d
en
sit
y (
min
-1)
p < .0001)
Manoach et al. Biol Psychiatry 56, 951 (2004)
Impact of Eszopiclone
Over
nig
ht
Impro
vem
ent
(%)
5
0
10
15
20
25
30
*
baseline baseline placebo
*
eszopiclone
Controls Schizophrenia patients
Wamsley et al. Sleep 36, 1369 (2013)
Improvement and Stage 2 NREM
0%
60%
40%
20%
-20%
20 40 60 80 100
% Stage 2 NREM sleep – 4th Quarter
% Initia
l im
pro
vem
ent
SZ pts w/ eszopiclone
Young controls
PTSD – What is it?
Stickgold (2002) J Clin Psychol 58, 61–75
Traumatic
Event Trauma
Memory
PTSD
Stasis
Sleep!
Trauma
Resolution Processing
? (the therapist’s job!)
Trauma Resolution and
Sleep-Dependent Memory Evolution
The normal resolution of trauma requires:
• Normalizing emotional memories
• Separating emotions from their contexts
• Extracting gist representations and rules
• Integrating the trauma memory with older
memories
• Gaining insight
Stickgold (2002) J Clin Psychol 58, 61–75
This memory processing occurs preferentially in
REM sleep, which guide the evolution of
memories over time
PTSD – A Failure of Sleep-Dependent
Memory Evolution
When processes involved in the normal sleep-
dependent evolution of trauma memories fail,
PTSD may inevitably follow.
Stickgold (2002) J Clin Psychol 58, 61–75
• Sleep plays a critical role in the evolution of memories, stabilizing and strengthening them.
• But it also identifies, analyzes, and maintains our most important memories, finding patterns in them, extracting gist and facilitating insight.
• Disruption of these processes may contribute to psychiatric disorders, including SZ and PTSD.
Summary
But perhaps more importantly, these
systems carry out what may well be the
most sophisticated function that the
human brain performs – the building of
models of ourselves and our world,
providing clues to the course of our future
and creating the very meaning of our
lives.