Cognitive Neuroscience of Sleep Flashcards
What forms the reticular activating system?
Nonspecific thalamic nuclei + nonspecific afferents to basal forebrain, which includes brainstem, hypothalamus, and basal forebrain groups.
Where does the RAS project? What does it regulate?
Broadly, to forebrain and spinal cord.
- Regulates phasic excitability of forebrain during waking = level of arousal, presence of salient stimuli
- Mediates the sleep-wake cycle
What are the five neurotransmitters of the RAS?
- Norepinephrine
- Acetylcholine
- Dopamine
- Serotonin
- Histamine
What is the function of norepinephrine in RAS?
Phasic + tonic excitability of cortex, maintains waking state
What is the function of histamine in the RAS and where is it produced?
Produced in tubomamillary nucleus of hypothalamus, functions to maintain tonic waking state
What is the function of serotonin in RAS?
Functions in waking
What are the major locations of acetylcholine in the reticular activating system?
- Basal forebrain
- Pontine lateral dorsal tegmentum (LDT)
- Pedunculopontine tegmental nucleus (PPT)
What is the function of acetylcholine in the RAS?
Controls excitability during both waking (basal forebrain) and REM sleep (LDT-PPT).
What is the role of tuberohypophysial dopamine release?
Inhibits prolactin release (PHIH)
What is the role of mesocortical dopamine?
Regulates frontal system activity, potential site of action of neuroleptics
What makes up the afferents to the LGN?
20% - retina
40% - cortical feedback from layer 6 of area 17
40% - extrinsic input
What are the “Extrinsic input” afferents to the LGN?
- Brainstem systems of reticular activating system - regulates relay and interneuron activity
- Thalamic reticular nucleus - regulates relay excitability
- Interneurons - regulate relay excitability, are inhibitory
What is the function of the thalamocortical network?
It is a complex machine which is devoted to generated an internal representation of reality and operates int he presence or absence of sensory input
What is the function of being awake to controlling our consciousness?
It allows sensory input which functions like a cookie cutter to stamp or mold a specific pattern in our awareness
What is the tonic mode of the thalamus? When is this seen?
Mode which conveys excitation of sensors to the cortex, occurs when thalamic relay cells are depolarized. This produces beta waves that are seen during REM and waking -> desynchronized
What is the burst mode of the thalamus?
Rhythmic bursting, spikes; plays a role in EEG synchronization. Occurs when thalamic relay cells are hyperpolarized. This is seen during stage 4 NREM (delta waves)
What is the function of the reticular nucleus of the thalamus in tonic vs burst mode?
These cells are inhibitory and hyperpolarize thalamic relay cells -> mediate the switching to burst mode
What is the function of the reticular activating system in tonic vs burst mode?
Acetylcholine will inhibit the reticular nucleus of the thalamus and activate thalamic relay cells. Thus, PPT-LDT will turn on tonic mode (seen in REM sleep)
What is NREM sleep also called?
Synchronized or slow wave
What is REM sleep also called?
Desynchronized or paradoxical -> looks like consciousness
What is the general sleep pattern during the night?
Early in the night -> more deep sleep and NREM. REM stages will not start until after the first deep sleep, and replaces stage 1 sleep seen at the beginning of the night. REM intervals get longer as the night goes on.
What marks stage 1 NREM?
Alpha waves -> decreased awareness of sensory stimuli with easy arousal
What marks stage 2 NREM?
- Spindles - short high frequency bursts
- K complexes - sudden, large amplitude waves.
This is where body temp starts to drop, and breathing + heart rate even out.
What marks stage 3 NREM?
- First appearance of delta waves
- Some spindles
Body temp further drops and breathing + blood pressure slow / fall
What marks stage 4 NREM, and what is released here? What causes this stage?
- EEG shows no spindles, mostly delta waves
- High arousal threshold
Growth hormone is released during this stage
Stage is caused by massive activation of thalamocortical burst mode
What waves are present in REM sleep? How does this happen?
Beta, alpha, and theta -> similar to waking
This occurs due to PPT inhibiting (via Ach) the thalamic reticular nucleus, which disinhibits thalamic relay neurons
What muscles are immune to the peripheral atonia of REM sleep?
Oculomotor muscles, middle ear muscles, and respiratory muscles
What is the mechanism of peripheral atonia during REM?
Perilocus ceruleus is stimulated by LDT-PPT to release glutamate on medullary relay center
Medullary relay center releases glycine onto alphamotoneurons in spinal cord to inhibit
Motor cortices are still active in REM, and if this pathway fails you will act out your dreams
What happens to autonomic behavior during REM?
It is very erratic
- Loss of thermoregulation
- Blood pressure rises
- Increased respiration frequency and irregularity
- Penile erection
What are the three critical hypothalamic nuclei for the sleep-wake cycle?
- Tuberomamillary nucleus (TMN) - histamine concentrations regulated the same as 5-HT and NE
- Lateral hypothalamus
- Ventrolateral preoptic nucleus (VLPO)
What is the function of the lateral hypothalamus in the sleep-wake cycle?
Releases a peptide neurotransmitter called orexin which is the “conductor” in continued release of neurotransmitters from locus ceruleus, dorsal raphe, and tuberomamillary nuclei. PRO-WAKE
What is the function of the ventrolateral preoptic nucleus in the sleep-wake cycle?
Pro-sleep -> inhibits TMN, LC, and DR to disinhibit the PPT-LDT. Also inhibits orexin release from LH.
What is the function of the basal forebrain during waking?
Releases acetylcholine and inhibits the VLPO nucleus, preventing sleep
How does the basal forebrain become deactivated during the day?
Adenosine accumulates from ATP consumption during the day, which is a “somnogen” inhibiting the basal forebrain. This allows activation of VLPO, and onset of NREM sleep
What marks the shift between NREM and REM sleep? How does the system return to NREM sleep?
VLPO finally causes the complete inactivation of the DR and LC, which allow the PPT & LDT to turn on. PPT-LDT will activate DR and LC, which will inhibit the PPT-LDT once more and shift back to NREM.
How is the sleep cycle ultimately stopped?
The cycle is ultimately stopped with adenosine is depleted and inhibition of VLPO is restored. This allows all pro-wake nuclei to reactivate. Circadian rhythms from the hypothalamus are a major modulatory factor
What is hypnagogia and what stage of sleep is it associated with?
Vivid perceptions, which are usually visual, but may be auditory or tactile. I.e. isolated visual images in a black field
Seen in stage 2 NREM
When does sleep paralysis occur and what is it?
Occurs at REM to waking transition
Person thinks they are awake but cannot move, associated with strong sense of fear. REM atonia intrudes into waking, however conscious perceptions are all hallucinatory
What causes sleep terrors? When are they?
Occur during NREM sleep, usually not associated with dreaming, characterized by nonspecific feelings of terror from raw amygdala activation
What is NREM mentation? What is going on in the brain at this time?
No perception of sensory environment, but patient reports that they were “laying there thinking”. Thought is repetitive or nonsensical
At this time, the thalamus is in burst mode so there is no communication with senses
All mentation in NREM is “highly discrete” aspects of psychological function
What commonly causes sleep paralysis and lucid dreaming?
Narcoleptic drugs - i.e. dopamine-producing
What is the most common form of REM mentation?
Nonlucid dreams - characterized by bizareness and high incidence of anxiety provoking content
80% occur in REM awakenings, 25% in NREM -> appear to have same content
Electrical stimulation of what lobe introduces a dreamy state?
Temporal
What is the definition of a hallucination? What is one strange example of this?
Conscious awareness of something not presented to the brain by the senses
Dreams are considered hallucinations
What is the primary difference between dreaming and wakefulness? How does lucid dreaming tear this apart?
During dreaming, access to long-term declarative memories is massively decreased. Recovering declarative memory access is the basis of lucid dreaming
What causes obstructive sleep apnea?
Loss of muscle tone during REM sleep causes blockage, common in overweight people
What is the most common stage for nocturnal enuresis?
Stage 4 sleep -> not felt till subsequent REM period
When does sleep walking occur?
During NREM sleep (there is no atonia). It has a higher incidence in children who have underdeveloped sleep patterns
What is the etiology of narcolepsy?
Has both genetic and nongenetic factures, and appears to be autoimmune related. Most are orexin-deficient and cannot maintain wakefulness (Lateral hypothalamus deficiency)
What is the most common symptom of narcolepsy?
Random cataplexy (loss of muscle tone, onset of REM sleep). Lasts 5-30 minutes, and the patient may experience hypnagogia and constant passing between consciousness and unconsciousness.
What is REM sleep behavior disorder? When does it occur and how does it treated?
intermittent loss of REM sleep atonia, appearance of elaborate motor activity associated with dream mentation.
Often occurs in brainstem lesions or neurodegenerative disorders / dementia / Parkinson’s. It is treated with benzodiazepine sedatives
What are the types of insomnia and what is it a major risk factor for?
Trouble falling asleep (long sleep-latency)
Trouble staying asleep
Feeling nonrestored from sleep
Affects 5-10% of population, is a major risk factor for major depression
What is primary insomnia?
Insomnia caused by a psychophysiological hyperarousal process
