Ch. 9 Brain States

SLEEP

• Humans spend approximately (\frac{1}{3}) of their lives asleep (≈ 8 hours per 24‐hour day).
• Sleep is an active neurological process essential for:
  • Brain health and metabolism.
  • Memory consolidation.
  • Regulation of mood and attention.
• Chronic sleep deprivation elevates the risk of:
  • \text{Diabetes}, \text{obesity}, \text{high blood pressure}.
  • \text{Stress}, \text{anxiety}, \text{depression}, and \text{cognitive impairment}.
  • Driving performance decrements comparable to alcohol intoxication.

BRAIN ACTIVITY DURING SLEEP

• Measured by electroencephalography (EEG): electrodes record net extracellular ionic currents across hundreds of thousands of cortical neurons.
• EEG output = “brain waves” (cyclic voltage fluctuations).
• Two principal sleep states:
  1. Slow-Wave Sleep (SWS)
     • High-amplitude, low-frequency waves.
     • Reflect synchronized oscillation between depolarized & hyperpolarized states.
     • Amount of slow waves ↑ with prior wake time; ↓ across the night.
     • Awakening during SWS → fragmented thought, minimal dream recall.
  2. Rapid Eye-Movement (REM) Sleep
     • Low-amplitude, high-frequency EEG (resembles wakefulness).
     • Periodic rapid eye movements; profound atonia (skeletal muscle paralysis except respiratory & extra-ocular muscles).
     • Motor cortex fires as in wake movement (explains twitching paws in kittens).
• Nightly architecture: \approx75\text{–}80\ \text{min SWS} + 10\text{–}15\ \text{min REM} ⇒ 90-minute cycles that repeat, with REM periods becoming deeper & longer toward morning.
• Species contrast:
  • Humans: single \approx8-hour nocturnal episode.
  • Rodents: polyphasic, 3\text{–}30-min bouts, predominantly diurnal sleep.

SLEEP REGULATION (AROUSAL SYSTEMS)

• Key neurotransmitters sustaining wakefulness (mostly upper brainstem projections to forebrain):
  • \text{Acetylcholine (ACh)}.
  • \text{Norepinephrine (NE)}.
  • \text{Serotonin (5-HT)}.
  • \text{Glutamate}.
  • Orexin (hypocretin) neuropeptides (Orexin-A, Orexin-B) from lateral hypothalamus:
  – Excite other arousal systems; ↑ metabolic rate; activated by low blood glucose.
  – Loss of orexin neurons ⇒ narcolepsy (see later).
  • Orexin neurons stimulate histaminergic neurons in posterior hypothalamus (additional wake drive).
• REM generator: specialized brainstem neurons send signals → thalamus & neocortex (dreaming) + spinal inhibition (muscle atonia).
• VLPO (ventrolateral preoptic nucleus): hypothalamic GABA + galanin neurons that actively inhibit arousal systems during SWS; lesions cause irreversible insomnia.
• Neurochemical balance table:
  • Wake = high \text{ACh} + high \text{NE}.
  • SWS = low \text{ACh} + low \text{NE}.
  • REM = high \text{ACh} + low \text{NE}.

SLEEP–WAKE CYCLE DRIVERS

1. Circadian System
   • Master clock = suprachiasmatic nucleus (SCN) (hypothalamus).
   • SCN neurons express cyclic “clock proteins” ≈ 24-h biochemical loop.
   • Direct retinal input (light resets clock) → explains jet-lag adjustments.
   • SCN signals → VLPO & orexin neurons to orchestrate arousal.
2. Homeostatic System
   • Promotes sleep pressure proportional to time awake.
   • Mediator = adenosine:
   – Accumulates with prolonged wake; binds receptors on arousal neurons ⇒ ↓ firing.
   – ↑ adenosine ⇒ ↑ slow-wave density during SWS.
   – Sleep lowers adenosine; slow waves diminish.
   – Caffeine = competitive antagonist at adenosine receptors, thereby sustaining arousal.
   • Sleep loss → rebound: longer subsequent sleep & elevated SWS slow-wave power.

COMMON SLEEP DISORDERS

• Insomnia: difficulty initiating or maintaining sleep.
• Daytime Sleepiness (non-narcoleptic): often secondary to sleep apnea; heightens accident risk.
• Obstructive Sleep Apnea (OSA):
  • Pharyngeal muscle relaxation → airway collapse.
  • Leads to repeated arousals, hypertension, cardiovascular risk.
  • Management: weight loss, avoid sedatives/ alcohol, positional therapy, CPAP (continuous positive airway pressure), or surgery.
• REM Sleep Behavior Disorder (RBD):
  • Failure of REM atonia pathways; patients physically act out dreams.
  • Associated with neurodegenerative diseases (Parkinson’s, stroke, dementias).
  • Treated with clonazepam (benzodiazepine enhancing GABA) or Parkinsonian drugs.
• Narcolepsy:
  • Prevalence ≈ 1:2000.
  • Loss of orexin neurons in lateral hypothalamus.
  • Symptoms: daytime “sleep attacks,” rapid REM onset, hypnagogic hallucinations, cataplexy (emotion-triggered muscle paralysis).
  • Evidence: orexin-knockout mice → narcoleptic phenotype; humans show low orexin in CSF.
  • Optogenetic studies: activating neighboring melanin-concentrating hormone (MCH) neurons induces sleep, suggesting balance with orexin neurons governs state transitions.

AROUSAL (GENERAL)

• Definition: heightened physiological & cognitive state promoting motivated action (teaching, escaping danger, social interactions, reproduction).
• Spectrum: low (drowsiness) → high (anxiety). Exceedingly high arousal prevents sleep threshold.
• Neurotransmitter map:
  • \text{Dopamine}: facilitates movement & reward.
  • \text{NE}: increases alertness.
  • \text{5-HT}: modulates emotion.
  • \text{ACh} & \text{Histamine}: cortical activation & body–brain communication.
• Sensory contribution:
  • Thalamus = central sensory “clearing house,” channels visual, auditory, tactile inputs to cortex, modulating arousal.
• Reticular Activating System (RAS) in brainstem:
  • Integrates neurotransmitter & sensory signals.
  • Controls autonomic nervous system ⇒ adjusts heart rate, blood pressure, respiration, delivering oxygen & nutrients to meet demand.

SEXUAL AROUSAL

• Shares circuitry with general arousal but uniquely requires sex hormones (estrogen, testosterone).
• Hormone–neurotransmitter interplay: estrogen/progesterone interact with dopamine, serotonin, GABA, glutamate.
• Key brain regions with dense sex-hormone receptors: hypothalamus, amygdala, hippocampus, plus reward circuitry (nucleus accumbens).
• Emotional & pleasure centers motivate sexual behavior; thus hormones are the defining feature of the “sexual arousal” state.

ATTENTION

• Depends on physiological arousal (heart rate, respiration, blood flow changes) to facilitate environmental processing.
• Evolutionary advantage: filters overwhelming sensory data; speeds reaction when goals (e.g., escaping a bear) demand focus.

Focus Mechanics

• Brain can attend to one line on a page though whole page is visible; can shift temporally (past/future thoughts) or categorically (searching for loved one in crowd).
• Two distinct attentional systems:
  1. Voluntary (Endogenous) Attention
     • Goal-directed; selects objects/locations.
     • Brain regions: frontal & parietal cortices (dorsal frontoparietal network).
  2. Involuntary (Exogenous) Attention
     • Stimulus-driven; sudden sights, sounds act as distractors.
     • Brain regions: ventral frontoparietal network (right hemisphere).
• Experimental “distractor” paradigms (emotional pictures, salient shapes) probe attention circuitry; findings inform vision science, learning, and developmental studies.

Disorders of Attention

• ADHD, schizophrenia, prosopagnosia (face blindness), hemineglect syndrome.
• Hemineglect syndrome (spatial/unilateral neglect):
  • Cause: right parietal cortex damage (often stroke).
  • Incidence: 50\text{–}82\% of right-hemisphere stroke patients.
  • Symptoms: ignore left visual field, left body, or left side of objects.
  • Diagnosis: pen-and-paper copying tasks (e.g., draw only right half of butterfly).
  • Clinical value: informs rehabilitation strategies & elucidates parietal role in attention/perception.

RESTING STATE – DEFAULT MODE NETWORK (DMN)

• Active during quiet rest, daydreaming, self-reflection; deactivates when performing demanding tasks.
• Identified via fMRI & PET imaging.
• Core nodes:
  • Frontal: ventromedial PFC, dorsomedial PFC, anterior cingulate cortex.
  • Posterior: posterior cingulate cortex, lateral parietal cortex, precuneus.
• Functional hints:
  • Ventromedial PFC activity correlates with subjective anxiety.
  • Dorsomedial PFC ↔ introspection, autobiographical self, stream of consciousness.
  • Posterior regions link with hippocampus; greater evening activity suggests role in consolidating daily memories.
• Diurnal pattern: DMN & hippocampus ↑ active at night rest, ↓ upon morning waking.
• Future directions: intracranial EEG + fMRI to map DMN coordination during tasks engaging emotion, memory, self-projection.

ETHICAL, PRACTICAL & REAL-WORLD IMPLICATIONS

• Understanding sleep architecture guides scheduling for healthcare workers, pilots, shift personnel → safety.
• Sleep disorder treatments (CPAP, pharmacology) improve cardiovascular & cognitive health.
• Insights into attention networks support educational strategies & rehabilitation after brain injury.
• Narcolepsy research (orexin system) is leading to targeted therapeutics (e.g., orexin agonists/antagonists).
• DMN studies inform mental health (anxiety, depression) and consciousness research.