Neurobiology of Consciousness

Question 1

What is the “content of consciousness”?

Answer 1

Arousal (level of consciousness)

Awareness of self/environment (content of consciousness)
+
Motivation to respond

Question 2

What is arousal?

Answer 2

Global state of wakefulness
(deep sleep to high vigilance)

Question 3

What is awareness?

Answer 3

Ability to perceive one or more specific stimuli:
Visual, Tactile, Auditory, Gustatory, Olfactory, Vestibular, Proprioceptive, Interoceptive

Question 4

Define motivation

Answer 4

Drive to act on internal or external stimuli that have entered conscious awareness

Question 5

What is the “modern day” ARAS (Ascending reticular activating system)?

Answer 5

Ascending arousal system

Question 6

What is the ascending arousal system?

Answer 6

Complex and diffuse network of neurons projecting from multiple brainstem source nuclei (within and adjacent of RF) to the cortex via thalamic and extrathalamic pathways

Question 7

What functions does the reticular formations have?

Answer 7

Wakefulness
Eye movements
Swallowing/vomiting
Posture/locomotion
Respiration
Blood pressure
Sensory awareness

Question 8

What are the two pathways of the ascending arousal system

Answer 8

Thalamic and extrathalamic
Two pathways provides redundancy!

Question 9

What is the general pathway of the thalamic branch?

Answer 9

Starting in the reticular formation
Projects to the thalamus
Then spreads to various cortical regions via what are known as thalamocortical projections

Question 10

What is the general pathway of the extrathalamic branch?

Answer 10

Starting in the brain stems reticular formation
A little bit of input to the thalamus, but by and large, the projections bypass the thalamus and go to the hypothalamus and the basal forebrain
Then continue to project on to other areas of the cerebral cortex.

Question 11

What are the nuclei for the thalamic pathway?

Answer 11

Cholinergic (pedunculopontine and laterodorsal tegmental nuclei)
(PPT/LDT)

Question 12

What are the nuclei for the extrathalamic pathway?

Answer 12

Serotonergic, some dopaminergic (dorsal and median raphe subnuclei)

Noradrenergic (locus coeruleus) (LC)

Dopaminergic (ventral tegmentum, ventral periaqueductal gray) (vPAG)

Glutamatergic (parabrachial complex in the rostral pons)

Histaminergic (tuberomamillary nucleus in hypothalamus) (TMN)

Orexin and melanin-concentrating hormone (lateral hypothalamus (LH)

Cholinergic and GABA-ergic (basal forebrain) (BF)

Question 13

How does one become aware of stimuli?

Answer 13

Conscious awareness and arousal states interact

Awareness requires interactions between the cortex and specific and nonspecific thalamic nuclei (e.g., reticular, intralaminar)

Question 14

What is the function of the thalamus?

Answer 14

Relay station and filters and modulates information

Coordinates activity in widespread areas
1. Cortico-striatopallidal-thalamocortical loops
2. Cortico-thalamocortical loops

Question 15

How do the thalamus and striatum interact?

Answer 15

Largest thalamic efference is to the striatum (caudate, putamen, nucleus accumbens)

Provide connections to large cerebral networks: potential mechanism for translating sensory/motor activity to awareness

Question 16

What role does the thalamus play with the cortical and subcortical regions?

Answer 16

Frontal/parietal system: Movement planning/execution

Brainstem attentional capture mechanisms: Redirect attention to peripheral sensory inputs

Question 17

What is a connectomes?

Answer 17

spontaneous resting brain activity, functionally connected brain regions

Question 18

What are some examples of resting state networks?

Answer 18

Default mode
Frontoparietal
Salience
Auditory
Sensorimotor
Visual

Question 19

What is the pathophysiology of a coma?

Answer 19

Global dysfunction of corticothalamic loops from diffuse cellular dysfunction, disconnection, or loss of upper brainstem arousal tone.
If the entire brain or brainstem is permanently nonfunctional, then diagnosis is brain death rather than coma

Question 20

What is the pathophysiology of vegetative state?

Answer 20

Same as coma, except that it implies some functioning of the upper brainstem

Question 21

What is the pathophysiology of minimally conscious state?

Answer 21

Diverse but typically diffuse injury to white matter and/or thalamus.
Varying degrees of cortical injury

Question 22

What is the pathophysiology of akinetic mutism (disorder of motivation)?

Answer 22

Dysfunction of prefrontal cortex or its subcortical connections or of white matter connecting these areas

Question 23

What is the pathophysiology of locked-in state?

Answer 23

Classically the loss of corticospinal tract in ventral pons, but can also be from diffuse white matter injury in the setting of trauma

Question 24

What pathophysiology presents as decorticate positioning?

Answer 24

Bilateral damage to the diencephalon-upper midbrain

Question 25

What pathophysiology presents as decerebrate positioning?

Answer 25

Bilateral damage to the upper midbrain

Question 26

What pathophysiology presents as localization?

Answer 26

Swelling in one hemisphere compression the diencephalon

Question 27

What is a potential mechanism to restore consciousness?

Answer 27

Amantadine hydrochloride - the gold standard medication for stimulation of arousal and subsequent awareness

Question 28

How does amantadine hydrochloride aid in restoring consciousness?

Answer 28

Increases the excitation of the striatum to the frontal cortex
This increase the inhibitory input to the globus pallidus, which then limits the amount of inhibitory influence it previously had on the thalamus

Restores the cyclical behavior of the thalamus - providing excitatory input to the cortices as well as the striatum