The document discusses the neurophysiological mechanisms and neurobehavioral model of insomnia. It begins by outlining the two main systems that regulate sleep and wakefulness - the homeostatic system and circadian system, as well as the arousal system. It then presents a neurobehavioral model of insomnia which involves interactions between these physiological systems and psychological/behavioral factors. The model posits that insomnia may stem from imbalances or dysfunctions in the homeostatic system, circadian system and/or arousal system, as well as maladaptive sleep-related cognitions and behaviors. Clinical implications and studies on insomnia patients are discussed to support this neurobehavioral conceptualization of insomnia.

1. SLEEP
S 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

2. 睡 Outline
 Neurophysiological Mechanisms of
Sleep/Wake Regulation
 Neurobehavioral Model of Insomnia
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 Clinical Implications

3. 睡
NEUROPHYSIOLOGICAL MECHNISMS
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OF SLEEP/WAKE REGULATION

4. Brain Systems
睡 for Sleep/Wake Regulation
“Sleep is of the brain, by the brain and for the brain.”
~ Allan Hobson, 2005, Nature
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5. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
Two- System
process
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model
of sleep
Sleep
regulation
Circadian vs.
System Wake/Arousal
Arousal
System

6. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
System
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Sleep
Circadian vs.
System Wake/Arousal
Arousal
System

7. 睡 Homeostatic Regulation
of Sleep
 The homeostatic sleep drive is determined by the
amount of prior sleep and waking/activities.
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8. SLEEP 睡

9. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
System
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Sleep
Circadian vs.
System Wake/Arousal
Arousal
System

10. 睡
Free Running
Study
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11. Forced
睡
SLEEP Desynchrony
Protocol
20 hours/”day”
Core body
temperature &
Melatonin rhythms
= 24 hrs 15 mins
(Czeisler, 2000)

12. 睡 Intrinsic Circadian Period
(Forced desynchrony protocol)
8
Number of subjects 7
6
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5
4 Young (n = 11)
3 Older (n = 13)
2
1
0
23.8 23.9 24 24.1 24.2 24.3 24.4 24.5 24.6
Intrinsic circadian period (hours)

13. 睡
SLEEP Circadian Regulation of Sleep

14. 睡 Light & Circadian Rhythms
 Neural pathway
- Melanopsin in ganglion cells of retina
- Retinohypothalamic tract
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- SCN
 PRC of light on phase shifting

15. 睡
SLEEP PRC Curve of Light

16. 睡 Circadian Regulation of Sleep
 Genetic control of circadian process
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17. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
System
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Sleep
Circadian vs.
System Wake/Arousal
Arousal
System

18. 睡 Arousal System
 The arousal system does not regulate
sleep directly, but may inhibit sleep by
promoting waking and arousal.
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 Factors that may trigger arousal:
- Sensory stimulus
- Emotion and motivation

19. SLEEP 睡

20. 睡
NEUROBEHAVIORAL MODEL
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OF INSOMNIA

21. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
System
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Sleep
Circadian vs.
System Wake/Arousal
Arousal
System

22. Homeostatic Regulation
睡 in Insomnia
 Neurophysiological findings
- Reduced EEG slow wave activity (Merica & Gaillard,
1992)
- Reduced brain GABA measured by Proton
Magnetic Resonance Spectroscopy (Winkelman et al.,
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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

23. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
System
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Sleep
Circadian vs.
System Wake/Arousal
Arousal
System

24. Circadian Regulation
睡 in Insomnia
 Neurophysiological findings
- Shifting in circadian phase: Circadian
Rhythm Sleep Disorders
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- 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)

25. 睡
SLEEP A Case of Young Adults
Complaining of Insomnia

26. 睡 週末晚睡晚起的影響研究
延後實驗情境 基準實驗情境
pm am pm am
*8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00 *8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00
週一至
週四
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週五
週六
週日 SSS SSS SSS SSS
VAMS VAMS VAMS VAMS
Sleep Log Sleep Log
Cognitive Tests Cognitive Tests
Wake Sleep * The timing indicated is for subjects whose habitual
bedtime is 11:00 pm and wake-up time is 7:00 am.

27. 睡 SSS ratings on Sunday night
6
5
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4
Baseline Week
SSS Rating
3 Delayed Week
2
1
0
BT-3h BT-2h BT-1h BT-1/2h* BT* BT = bedtime; * p< .05
Time

28. 睡 Sunday Night Sleep Logs
Baseline Delayed
Item Mean SD Mean SD t p
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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

29. Cognitive Tests
睡 on Monday Morning
Controlled Oral Word-list
Word Association Memory Test
30 12
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Number 25 10
of 20 8
Words
Baseline Week
15 6
Delayed Week
10 4
5 2
0 0
t = -3.49, p = .002 t = -2.71, p = .011

30. 睡 Monday Morning
Mood 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
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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

31. 睡 Salivary DLMO: After delayed
weekend schedule
24.00
#1
23.00 #2
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#4
Time
22.00 #5
#7
21.00 #11
#12
#16
20.00
#17
#19
19.00 Average
Friday Monday

32. 睡 Neurophysiological Aspects
of Sleep/Wake Regulation
Homeostatic
System
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Sleep
Circadian vs.
System Wake/Arousal
Arousal
System

33. Arousal System
睡 in Insomnia
 Physiological hyperarousal, as measured by
- CNS activities: e.g. EEG, PET, ……
- ANS indices: e.g. heart rate, HRV, VO2, ……
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- Stress related hormones
 Psychological/Behavioral Factors
- Stress
- Emotional disturbances
- Cognitive hyperarousal
- Conditioning of arousal
- Use of stimulants

34. 睡
SLEEP ERPs in the first 5 min S2 sleep
(Yang & Lo, 2007)

35. 睡 Neurobehavioral Model
of Insomnia
Psychological/Behavioral Neurophysiological
Facotrs Systems
Homeostatic
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Behavioral
Practices System
Sleep
Sleep Circadian vs.
Cognition System Wake/Arousal
Emotional
Arousal Arousal
System

36. Cognitive Model of Insomnia
睡
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37. 睡 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
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Effect
(N = 383) (N = 145) Size*
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.

38. 睡 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)
Correlation with
Factor/Item Content
the FIRST score
DBAS Factor I Beliefs about the immediate negative consequences of insomnia 0.27**
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Beliefs about the long-term negative consequences of insomnia
DBAS Factor II 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**
Should stay in bed and try harder when having sleep problems
DBAS-10 04 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

39. 睡 Maladaptive Sleep-Related Behaviors
 Normal young adults: Sleep hygiene practices
correlated significantly with subjective sleep
quality as well as with daytime sleepiness
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(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).

40. 睡 Maladaptive Sleep Hygiene Practice
Insomniac Good Sleeper
Glass’s
SHPS Scores Mean SD Mean SD t-value p Δ
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Sleep Schedule 22.64 5.43 21.17 5.79 1.83 .069 .253
Arousal-related
28.61 6.55 19.39 4.92 11.21 <.001 1.874
Behavior
Drinking / Eating
11.55 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

41. 睡 Maladaptive Sleep Hygiene Practice
Correlations between sleep hygiene practices and insomnia severity
and sleep quality
ISI PSQI
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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**
* p < .05; ** p < .01

42. 睡 Psychosocial Factors in
Transient vs. Chronic Insomniacs
假設一
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假設二

43. 睡
SLEEP 假設一結果摘要表

44. 睡
SLEEP 病因模式路徑圖：慢性失眠

45. 睡
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CLINICAL IMPLICATIONS

46. Pathological Model of Insomnia:
睡 An Example
人格特質
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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

47. 睡 Pathological Model of Insomnia:
An Example
人格特質
SLEEP
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

48. NIH 2005 State of the Science
睡 Conference Statement
 “Behavioral and CBTs have demonstrated efficacy in
RCTs.”
 “there are indications that the beneficial effects of CBT,
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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.”

49. CBT vs. Hypnotic for Sleep
睡
SLEEP Maintenance Insomnia in Elderly
Morin et al. JAMA 1999; 281:991-999.

50. 睡 CBT vs. Hypnotic for
Sleep-Onset Insomnia
60
Changes in Sleep Latency, %
50
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40
30
Mid-Tx
20 Post-Tx
10
0
CBT Combination Pharmacotherapy Placebo
Therapy
Treatment Condition
(Jacobs, G.D., et al. Ach Intern Medicine 2004;164: 1888-1896)

51. 睡 CBT for Insomnia
Changes of
Sleep Cognition
Changes of
Sleep Behaviors
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Understanding Stabilization &
Adjustment of
Better
the Pathological
Model of Insomnia Circadian Rhythms Sleep!!
Stress Management
& Relaxation
Training
Hypnotics
Tapering

52. 睡 Treatment Outcome: ISI
 Treatment effect: F = 56.8, p < .001
 Group effect: F = .27, p = .77
 Interaction: F = 18.15, p < .001
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25
***
20 ***
15
ISI-pre ISI-post
10
5
0
CBT COMB PT
*** p < .001

53. 睡
SLEEP Questions and Comments?