S L E E PS L E E P

國立政治大學 心理學系

S L E E PS L E E P

國立政治大學 心理學系

由基礎研究到臨床應用 ─談失眠的病理機制

政治大學心理學系楊建銘

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Outline

Neurophysiological Mechanisms of

Sleep/Wake Regulation

Neurobehavioral Model of Insomnia

Clinical Implications

睡SLEEP NEUROPHYSIOLOGICAL MECHNISMS

OF SLEEP/WAKE REGULATION

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Brain Systems for Sleep/Wake Regulation

“Sleep is of the brain, by the brain and for the brain.”

~ Allan Hobson, 2005, Nature

睡SLEEPNeurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

Two-

process

model

of sleep

regulation

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Neurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

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Homeostatic Regulation

of Sleep The homeostatic sleep drive is determined by the

amount of prior sleep and waking/activities.

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Neurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

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Free Running Study

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Forced

Desynchrony

Protocol

20 hours/”day”

Core body

temperature &

Melatonin rhythms

= 24 hrs 15 mins

(Czeisler, 2000)

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Intrinsic Circadian Period

(Forced desynchrony protocol)

0

1

2

3

4

5

6

7

8

23.8 23.9 24 24.1 24.2 24.3 24.4 24.5 24.6

Intrinsic circadian period (hours)

Num

ber

of

subje

cts

Young (n = 11)

Older (n = 13)

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Circadian Regulation of Sleep

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Light & Circadian Rhythms

Neural pathway

- Melanopsin in ganglion cells of retina

- Retinohypothalamic tract

- SCN

PRC of light on phase shifting

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PRC Curve of Light

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Circadian Regulation of Sleep

Genetic control of circadian process

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Neurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

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Arousal System

The arousal system does not regulate sleep directly, but may inhibit sleep by promoting waking and arousal.

Factors that may trigger arousal:

- Sensory stimulus

- Emotion and motivation

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睡SLEEP NEUROBEHAVIORAL MODEL

OF INSOMNIA

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Neurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

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Homeostatic Regulation in Insomnia Neurophysiological findings

- Reduced EEG slow wave activity (Merica & Gaillard, 1992)

- Reduced brain GABA measured by Proton Magnetic Resonance Spectroscopy (Winkelman et al., 2008)

- The increase of slow wave activity after sleep deprivation seen in normal sleepers was less obvious in insomnia patients (Gaillard, 1978; Reynolds et al., 1984; Schneider-Helmert, Whitehouse, Kumar, & Lijzenga, 2001)

Psychological/Behavioral factors- Sleeping outside of the nocturnal sleep period

- Reduced daytime activities

- Increased resting in bed

- Coffee drinking

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Neurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

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Circadian Regulation in Insomnia Neurophysiological findings

- Shifting in circadian phase: Circadian

Rhythm Sleep Disorders

- Extreme circadian type or less flexible

circadian system as a predisposing factor

- Decreased melatonin level in insomniacs?

Psychological/Behavioral Factors

- Irregular or changes of sleep-wake schedule

- Sleep-in during weekend to catch up lost sleep

- Lack of environmental time cues (e.g. light

exposure)

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A Case of Young Adults Complaining of Insomnia

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SSS SSS

週末晚睡晚起的影響研究

延後實驗情境

週一至

週四

週五

週六

週日 SSS SSS

pm am

*8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00

* The timing indicated is for subjects whose habitual

bedtime is 11:00 pm and wake-up time is 7:00 am.

VAMS VAMS

Sleep Log

Cognitive Tests

pm am

*8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00

基準實驗情境

VAMS VAMS

Sleep Log

Cognitive Tests

Wake Sleep

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SSS ratings on Sunday night

BT = bedtime; * p< .05

0

1

2

3

4

5

6

BT-3h BT-2h BT-1h BT-1/2h* BT*

SS

S R

ati

ng

Time

Baseline Week

Delayed Week

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Sunday Night Sleep Logs

Baseline Delayed

Item Mean SD Mean SD t p

SOL 12.98 15.86 19.69 27.98 1.81 0.083

WASO 1.13 2.03 0.67 1.33 -1.33 0.196

TBT 476.74 37.51 474.41 38.13 -0.66 0.516

TST 465.65 39.39 454.00 44.06 -1.78 0.087

Sleep Quality 5.62 1.17 5.62 1.13 0.00 1.000

Diff. Waking 3.31 1.38 3.35 1.47 0.14 0.890

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Cognitive Tests on Monday Morning

0

5

10

15

20

25

30

Baseline Week

Delayed Week

0

2

4

6

8

10

12

Controlled Oral Word-list

Word Association Memory Test

t = -3.49, p = .002 t = -2.71, p = .011

Number

of

Words

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Monday MorningMood Scales

Baseline Delayed

Item Mean SD Mean SD t p

Monday morning

Alert 48.96 24.74 34.96 18.26 -2.49* 0.019

Sad 14.98 19.42 19.64 18.83 1.01 0.321

Tense 29.07 24.42 34.20 21.99 0.83 0.414

Effort 57.77 24.92 44.61 26.75 1.97 0.059

Happy 44.57 25.50 37.38 18.89 -1.22 0.232

Hungry 38.07 30.60 34.61 26.27 -0.48 0.634

Weary 41.02 31.81 49.36 25.52 1.38 0.180

Irritable 30.70 30.52 45.95 28.95 2.75* 0.010

Sleepy 47.34 29.15 68.00 21.17 3.25** 0.003

Angry 18.61 20.95 30.25 25.97 2.21* 0.036

Sexual 17.80 19.11 16.96 18.80 -0.29 0.775

Overall 59.71 23.60 44.48 18.40 -2.78* 0.010

*p < .05 **p < .005

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Salivary DLMO: After delayed

weekend schedule

19.00

20.00

21.00

22.00

23.00

24.00

Friday Monday

Tim

e

#1

#2

#4

#5

#7

#11

#12

#16

#17

#19

Average

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Neurophysiological Aspectsof Sleep/Wake Regulation

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

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Arousal Systemin Insomnia

Physiological hyperarousal, as measured by- CNS activities: e.g. EEG, PET, ……

- ANS indices: e.g. heart rate, HRV, VO2, ……

- Stress related hormones

Psychological/Behavioral Factors- Stress

- Emotional disturbances

- Cognitive hyperarousal

- Conditioning of arousal

- Use of stimulants

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ERPs in the first 5 min S2 sleep

(Yang & Lo, 2007)

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Neurobehavioral Model

of Insomnia

Sleep

vs.

Wake/Arousal

Homeostatic

System

Circadian

System

Arousal

System

Behavioral

Practices

Sleep

Cognition

Emotional

Arousal

Psychological/Behavioral

Facotrs

Neurophysiological

Systems

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Cognitive Model of Insomnia (Harvey, 2002)

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Dysfunctional Sleep Beliefs

in Young Adults (19.7±1.5 years old)

Table 1. Group comparisons between subjects with frequent sleep disturbance (WSD) and without frequent sleep disturbance

(NSD) of the scores on the FIRST and the DBAS-10

WSD group NSD group

Effect

Size*(N = 383) (N = 145)

Mean SD Mean SD F p

FIRST 22.6 4.75 18.88 4.76 64.17 < .001 0.78

DBAS-10

Total Score 60.91 14.4 53.29 15.01 28.76 < .001 0.52

Factor I 32.81 8.78 30.27 9.29 8.55 0.004 0.29

Factor II 16.43 5.17 13.72 5.04 29.35 < .001 0.53

Factor III 11.67 4.08 9.3 4.1 35.29 < .001 0.58

* Cohen's d effect size for the mean difference.

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Dysfunctional Beliefs vs. Vulnerability to

Insomnia in Non-insomniac Young Adults

Table II. Correlations between the FIRST score and the DBAS-10 factor and item scores in the subjects

without frequent sleep disturbance (N = 145)

Factor/Item ContentCorrelation with

the FIRST score

DBAS Factor I Beliefs about the immediate negative consequences of insomnia 0.27**

DBAS Factor IIBeliefs about the long-term negative consequences of insomnia

0.33**

DBAS Factor III Beliefs about the need for control over insomnia 0.35 **

DBAS-10 01 Need 8 hours of sleep to function 0.15**

DBAS-10 02 Need to catch up on poor sleep 0.12**

DBAS-10 03 Insomnia seriously affects health 0.18**

DBAS-10 04Should stay in bed and try harder when having sleep problems

0.10*

DBAS-10 05 Worried may lose control of sleep 0.22**

DBAS-10 06 Poor sleep will interfere with daytime activities 0.22**

DBAS-10 07 Poor sleep disturbs daytime mood 0.25**

DBAS-10 08 Poor night’s sleep affects the whole week 0.29**

DBAS-10 09 Lack of energy due to poor sleep 0.22**

DBAS-10 10 No control over racing mind 0.43**

DBAS-10 Total

Score 0.38**

*p<0.05; ** p<0.01

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Maladaptive Sleep-Related Behaviors

Normal young adults: Sleep hygiene practices correlated significantly with subjective sleep quality as well as with daytime sleepiness (Brown et al., 2002; Mastin et al., 2006).

Insomnia patients: They were found to engaged in poorer sleep hygiene practices in some studies (Lacks & Rotert, 1986; Kohn & Espie, 2005; Jefferson, 2005), but not in the other studies (Harvey, 2000; McCrae et al., 2006).

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Maladaptive Sleep Hygiene Practice

Insomniac Good Sleeper

t-value pGlass’s

ΔSHPS Scores Mean SD Mean SD

Sleep Schedule 22.64 5.43 21.17 5.79 1.83 .069 .253

Arousal-related

Behavior28.61 6.55 19.39 4.92 11.21 <.001 1.874

Drinking / Eating11.55 4.28 12.29 4.29 -1.21 .228 -.172

Sleep

Environment 18.92 6.24 17.33 5.62 1.87 .064 .283

Total Score 81.73 15.08 70.18 16.45 5.11 <.001 .702

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Maladaptive Sleep Hygiene Practice

ISI PSQI

Insomniacs Control Insomniacs Control

Sleep Schedule .007 .377** .176 .318**

Arousal-related Behavior .326** .610** .248* .533**

Drinking/Eating Habits -.092 .323** -.035 .117

Sleep Environment -.022 .511** -.038 .321**

Total Score .110 .576** .144 .412**

Correlations between sleep hygiene practices and insomnia severity

and sleep quality

* p < .05; ** p < .01

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Psychosocial Factors in

Transient vs. Chronic Insomniacs

假設一

假設二

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假設一結果摘要表

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病因模式路徑圖：慢性失眠

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CLINICAL IMPLICATIONS

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Pathological Model of Insomnia: An Example

人格特質

生理

亢奮 不當的因應/認知

壓力原 暫時性失眠 長期失眠

認知

亢奮

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Pathological Model of Insomnia: An Example

人格特質

生理

亢奮 不當的因應/認知

壓力原 暫時性失眠 長期失眠

認知

亢奮

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NIH 2005 State of the Science Conference Statement

“Behavioral and CBTs have demonstrated efficacy in

RCTs.”

“there are indications that the beneficial effects of CBT,

in contrast to those produced by medications, may last

well beyond the termination of treatment.”

“There is no evidence that such treatment produces

adverse effects, but thus far, there has been little, if

any, study of this possibility.”

“However, because few clinicians are experts in the

use of CBT for the treatment of chronic insomnia,

these techniques are not in widespread use.”

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CBT vs. Hypnotic for Sleep Maintenance Insomnia in Elderly

Morin et al. JAMA 1999; 281:991-999.

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CBT vs. Hypnotic for

Sleep-Onset Insomnia

0

10

20

30

40

50

60

Cha

nges

in

Sle

ep L

aten

cy, %

CBT Combination

Therapy

Pharmacotherapy Placebo

Treatment Condition

Mid-Tx

Post-Tx

(Jacobs, G.D., et al. Ach Intern Medicine 2004;164: 1888-1896)

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CBT for Insomnia

Understanding

the Pathological

Model of Insomnia

Changes of

Sleep Cognition

Changes of

Sleep Behaviors

Stress Management

& Relaxation

Training

Stabilization &

Adjustment of

Circadian Rhythms

Better

Sleep!!

Hypnotics

Tapering

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Treatment Outcome: ISI

Treatment effect: F = 56.8, p < .001

Group effect: F = .27, p = .77

Interaction: F = 18.15, p < .001

0

5

10

15

20

25

CBT COMB PT

ISI-pre ISI-post

***

***

*** p < .001

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Questions and Comments?