Tutorial 05

Question 1

What does the thalamic-mediated Synchronisation mechanisms do?

Answer 1

They give rise to large-scale integration of information across cortical circuits

Question 2

Which sleep stage is the alpha waves?

Answer 2

Awake

Question 3

Which sleep stage are theta waves?

Answer 3

REM and Non REM1

Question 4

Which sleep stage are delta waves?

Answer 4

Non REM 3 – deep sleep

Question 5

Which sleep stage are spindles and K-complexes?

Answer 5

Non REM 2

Question 6

Sleep is a state of consciousness characterised by …

Answer 6

… low awareness and alertness with a higher threshold for sensory perception

Question 7

The sleep stage is a function of …

Answer 7

… neural integration, with seemingly special role played by the gap junctions

Question 8

What can we characterize to figure out the different Stages of sleep and how many sleep stages are there?

Answer 8

We can identify brain wave features, which characterize the 4 stages of sleep

Question 9

Where is a competing balance in the brain to initiate nREM and REM sleep?

Answer 9

There is a competing balance between the front and back of the brain to initiate nREM and REM sleep

Question 10

Is CR self sustained or entrained?

Answer 10

Both, CR is self-sustained; continues without external time-giving cues
CR is also entrained: synchronized by external time-giving cues

Question 11

What is the circadian rhythm coordinated by?

Answer 11

CR is coordinated by Suprachiasmic Nuclei (SCN), lesion studies demonstrate their importance for sleep-wake patterns

Question 12

What are the primary circadian photoreceptors? And where do they project to?

Answer 12

Melanopsin-containing retinal ganglion cells and they project to the SCN via a direct and an indirect pathway

Question 13

Where does the suprachiasmatic nuclei signal to?

Answer 13

SCN signals to pineal gland to inhibit melatonin production

Question 14

What happens to the pineal gland by an absence of light exposure?

Answer 14

Absent of light exposure, inhibition is removed and pineal gland releases melatonin
-> melatonin feeds back to SCN: permits sleep drive

Question 15

Circadian rhythm sleep disorder?

Answer 15

A chronic recurring pattern of sleep and wake disturbances due to a) a dysfunction of the internal circadian clock system
B) a misalignment between timing of internal CR and externally imposed sleep wake cycles

Question 16

Examples of circadian rhythm sleep disorders

Answer 16

Delayed sleep phase disorder
Non 24-hour sleep wake disorder
Advanced phase sleep disorder
Irregular sleep-wake rhythm disorder
Jet lag (chronic)

Question 17

ICD-11 definition of insomnia

Answer 17

○ Disorder is characterized by difficulty in falling asleep and/or remaining asleep
○ Subjectively causes difficulties with daytime functioning or well-being
○ Experience sleep problems at least three times a week for at least three months
○ Even if circumstances/opportunities for sleep are ideal

Question 18

Insomnia Disorder (Primary Insomnia)

Answer 18

constitutes an exclusionary diagnosis of poor sleep, ruling out
psychiatric, medical, substance, and other sleep-related pathology

Question 19

Nighttime symptoms of insomnia

Answer 19

Difficulty initiating sleep, frequent awakenings, early morning awakening, reduced
sleep efficiency

Question 20

Cognitive impairments

Answer 20

Memory and Attention Deficits, Impaired Executive Function, Emotional
Dysregulation

Question 21

Sleep and stress

Answer 21

● Literature presents a dynamic and complex
relationship between stress and sleep
● Exposure to stress and even to insomnia itself causes
changes in the regulation of stress and sleep
● As a result, the conditions under which the initial
episode of insomnia develops may differ from the
conditions that perpetuate its course or give rise to
recurrent episodes

Question 22

Restless REM sleep

Answer 22

Sound REM sleep is the only state during which the brain has a “time-out” of noradrenaline (NA): the
locus coeruleus (LC) is silenced
● Restless REM sleep, however, indicates insufficient LC silencing
→ The resulting lack of a NA-free REM sleep period disrupts synaptic plasticity

Question 23

Hyperarousal

Answer 23

● Hyperarousal resembles the state of acute
anxiety or other emotional distress
● Hyperarousal in insomnia involves
imbalances in neurotransmitters like
noradrenaline, GABA, and glutamate

Question 24

Manifestations of hyperarousal

Answer 24

somatic, emotional,
cognitive, cortical

Question 25

Sleep reactivity

Answer 25

● Is the trait-like degree to which stress
exposure disrupts sleep, resulting in difficulty
falling and staying asleep
→ more susceptible to hyperarousal
● Sleep reactivity is a normal phenomenon

Question 26

Neurobiological underpinnings for sleep
reactivity

Answer 26

involve disrupted cortical networks
and dysregulation in the autonomic nervous
system and hypothalamic-pituitary-adrenal
axis

Question 27

Rumination

Answer 27

is a form of preservative cognition that
focuses on negative content, and results in emotional
distress

Question 28

Hyperarousal concept

Answer 28

subjects who tend to focus on the
insomnia and start to ruminate about their sleep complaint
are prone to develop ‘learned sleep- preventing
associations’ which may explain the chronicity of the
disorder

Question 29

most classical form of treatment for insomnia?

Answer 29

CBT-I, non-pharmacological approaches, pharmacotherapy,
(multimodal approach)

Question 30

Cognitive (Behavioral) Therapy (CBT-I)

Answer 30

= combination of cognitive therapy with other
techniques, multi-component approach
goal: change the patient’s misconceptions, beliefs,
and attitudes that hinder sleep
short-term treatment that includes 4 to 8 sessions
(25 min every 14 days)
e.g. sleep diary, psychoeducation

Question 31

Name non-pharmacological treatments of insomnia

Answer 31

Paradox intervention, sleep hygiene, (Physical) daytime activation, sleep restriction, Relaxation Training, stimulus control

Question 32

Hypnotics

Answer 32

= heterogenous group of substances with sedative, hypnotic, anxiolytic and sleep inducing effects
- different forms of application: spray, tablets, sublingual forms

Question 33

Common side effects of hypnotics

Answer 33

• anterograde amnesia, working memory impairment, attention
• distortion of sleep architecture (less REM, phase 3&4)
• daytime somnolence and dizziness
• potential for addiction (!)

Question 34

Examples of hypnotics

Answer 34

Non-Benzodiazepines “Z-Drugs”, Orexin Receptor Antagonists, Benzodiazepines, Melatonin Receptor Agonists, Antidepressants, Antipsychotics, Anticonvulsants, Antihistamines

Question 35

How do benzodiazepines work?

Answer 35

• positive modulation / activation GABAa-receptors
• ligand-gated ion channel (GABA)
• open: Influx of Cl- (cell becomes more
  negative)
• BZD/Non-BZD bind to α-γ / α unit of GABAa-
  receptors and induce a change of conformation
• dependent on presence of GABA
• overall inhibitory effect in the nervous system
• high risk for dependency in BZD, withdrawal needs to be
  under medical observation! → short period

Question 36

Melatonin

Answer 36

hormone, produced in pineal gland under control of
circadian system in hypothalamic suprachiasmatic
nucleus (SCN)
- key role in regulating the sleep-wake cycle
- synthesis modulated by presence of light

Question 37

Mechanism of melatonin receptor agonists

Answer 37

• Melatonin Receptor Agonists activate Mt1 and Mt2
  receptors and simulate the presence of Melatonin
• different onset possible (release)

Question 38

Orexin (Hypocretin)

Answer 38

= neuropeptide (protein made from genome) in two
forms
- bind to receptor OX1R and OX2R and leads in
cascades to opening of Ca2+-Channel (influx of
Ca2+)
- effects: promote wakefulness + suppress REM
sleep via excitatory projections from
hypothalamus (Flip-Flop)
- clinical implications in Narcolepsy

Question 39

How do Orexin Receptor Antagonists work?

Answer 39

Orexin Receptor Antagonists bind to OX1R and OX2R receptors and block Orexin from activating the receptors → promote sleep

Question 40

Stimulation therapy – results

Answer 40

• NIBS have potential in managing insomnia symptoms
• yet, “no brain-stimulation protocol exists that could claim relevant therapeutic benefits”
  →“understanding how the cortex contributes to sleep regulation and which
  patterns of cortical activity are altered in patients with insomnia will be essential
  when optimizing stimulation targets and protocols”
• need for further research, well established protocols, sham control group, double-blinded studies (minimizing methodological limitations