Arousal, Sleep, Attention and Selective Engagement Stephen E. Nadeau, M.D.

Midbrain Reticular Activating System: Arousal Projects to intralaminar nuclei of thalamus, which send diffuse projections to cerebral cortex. Projects to relay neurons throughout thalamus. Projects to nucleus reticularis, which regulates the thalamic gate.

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Nadeau SE, Crosson B. Subcortical aphasia. Brain Lang 1997;58: ,

Major Structures Implicated in Sleep

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Disorders of Sleep Architecture Narcolepsy (narcolepsy, cataplexy, sleep paralysis, hypnogogic/hypnopompic hallucinations) –Dissociation of REM, dreams, loss of muscle tone from normal context REM Sleep Behavior Disorder –No loss of muscle tone during REM Night terrors, somnambulism –REM sleep in wrong context; no loss of muscle tone Non-REM deep sleep deprivation (PLMS, sleep apnea): daytime somnolence, loss of concentration Fatal familial insomnia: persistent wakefulness –Presumed damage to pre-hypothalamic hypnogenic center Locked-in state: persistent wakefulness –Damage to caudal pontine hypnogenic center

Attention: Behavior Definition: focus of sensory resources on a particular stimulus Reactive –Superior colliculus (deep layers) –Temporal and parietal cortex Intentional –Prefrontal cortex Orienting response –Superior colliculus (superficial layers) –Frontal eye fields (BA 8)

Hemispatial Neglect No response to any left sided stimulus L homonymous hemianopia and hemisensory loss –Hemianopia corrects on right gaze Will not look to the left of midline Fails to eat from left side of plate or clean left side of mouth Left hemiparesis in left hemispace

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Attention Mechanisms: Selective Engagement Production of specific patterns of activity or neural membrane depolarization in selected frontal, temporal, parietal and limbic cortices Disengagement of other cortices

Moran J, Desimone R. Selective attention gates visual processing in extrastriate cortex. Science 1985;229:

Nadeau SE, Crosson B. Subcortical aphasia. Brain Lang 1997;58: ,

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Functions of Biogenic Amines Acetylcholine: declarative and procedural memory Dopamine –Putamenal function: regulation of balance between direct and indirect basal ganglia pathways –N accumbens: regulation of limbic “tone” –Other — unknown Norepinephrine –Arousal systems — the thalamic gate –? Regulation of balance between cortico-cortical activity and corticobulbar/corticospinal activity –? Regulation of balance between intentional and reactive attention –Other — unknown Serotonin –Regulation of balance between orbitofrontal-limbic and dorsolateral prefrontal systems –Other — unknown

Pharmacologic Manipulation of Biogenic Amine Systems Acetylcholine –Augmentation: Acetyl cholinesterase inhibitors –Blockade: scopolamine, Artane, Cogentin, Benadryl, tricyclic antidepressants Dopamine –Augmentation: levodopa, D2 agonists, cocaine, amphetamine –Blockade: neuroleptics Norepinephrine –Augmentation: d-amphetamine, methylphenidate, tricyclic antidepressants, venlafaxine, cocaine, methamphetamine Serotonin (5-HT) –Augmentation: tricyclic antidepressants, SSRIs, venlafaxine, mirtazapine DA, NE, 5-HT –Depletion: reserpine

Summary Arousal — MRF Sleep –5 stages –Hypnogenic centers (ventral preoptic n., caudal pontine reticular formation) –Arousal centers (MRF [ACh]; tuberomamillary n. [histamine]) –REM sleep architecture (rostral pontine tegmentum) –Muscle tone (peri-locus ceruleus) –Disorders of sleep architecture (narcolepsy; REM sleep behavior disorder; night terrors/somnambulism; fatal familial insomnia; locked in state)

Summary (cont.) Attention –Focus of sensory resources on one particular stimulus –Reactive –Intentional –The orienting response –Hemispatial neglect: a focal disorder of attention Attention as selective engagement –Moran and Desimone experiment Selective engagement by thalamic & biogenic amine systems