Reticular Formation and Hearing (2 lectures)

Question 1

What is the dorso-ventral organisation of the brainstem and what is contained in each part?

Answer 1

• Dorso-ventral organization
  o Dorsal part
   Cranial nerve nuclei and sensory reflex centers
  o Middle part (tegmentum) –
   Ascending pathways; Reticular formation (with integrating nuclei); descending sympathetic axons travel with reticulospinal tracts
  o Ventral part
   Descending motor pathways e.g., corticospinal & corticobulbar tracts; rubrospinal, reticulospinal and vestibulospinal tracts arising in brainstem

Question 2

What is the reticular formation and where is it located? What is its function and what does it consist of?

Answer 2

• The central core of the brainstem, the reticular formation is an evolutionarily ancient part of the brain that performs numerous integrative and modulatory functions
  o Consists of scattered clusters of neurons in between ascending and descending axons of the tegmentum
  o Usually, the clusters cannot be easily recognized as distinct nuclei
  o However functional groups are identified
  (see diagrams in lecture notes)

Question 3

What are the different functions of the reticular formation? What carries out these functions?

Answer 3

• Somatic motor control
  o Reticulospinal tracts
   Muscle tone, balance and posture
  o Relay’s eye and ear signals to cerebellum
  o Gaze centres
• Cardiovascular and respiratory control
  o Cardiac and vasomotor centres of medulla
  o Pneumotactic and apeustic centres in pons
• Pain modulation
  o Pain signals pass through on way from body to cortex
  o Origin of descending analgesic pathways
• Sleep and consciousness
  o Projections to thalamus and cerebral cortex - controls which sensory signals reach the cerebrum
• Habituation
  o Brain learns to ignore repetitive, meaningless stimuli while remaining sensitive to others (e.g. ignoring stimulation whilst asleep – female reticular formation is sensitive to baby crying nut male is less so)

Question 4

What is the reticular formation?

Answer 4

The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain.
(from wikipedia)

Question 5

What are the four principle functions of the reticular function?

Answer 5

1. Arousal responses
2. Autonomic nervous system control
3. Control of muscle tone and reflexes
4. Pain modulation

Question 6

What are the three regions of the reticular formation and what are their functions?

Answer 6

Lateral (sensory) = afferent (sensory and other) input from special senses (ascending and descending systems)
Medial (motor) = efferent output to midbrain, cerebellum, hypothalamus, thalamus and spinal cord
Midline (inhibitory) = faciliatory or inhibitory (e.g. pain filtering outputs)

Question 7

What type of organisation is there in the reticular formation and what is it similar to?

Answer 7

Medial-to-lateral organisation similar to that of cranial nerves

Question 8

What is the reticular formation made up of and where? What are the functional divisions?

Answer 8

• Grey matter in core of brainstem
  o Neurons form a network (reticulum) instead of well defined tracts
• Divisions (functional divided into):
  o Lateral reticular formation
   Contains small local circuit neurons forming “reflex centre” close to brainstem motor nuclei
   Swallowing, coughing, sneezing, vasomotor and vomiting centre (medulla)
   Centre for mastication co-ordination, lateral gaze movement and emotional facial expression (pons)
  o Medial reticular formation
   Neurons usually have long axons which either ascend or descend
• Ascending reticular formation (RAS)
  o Long sensory ascending tracts (STT, dorsal columns) give collaterals to RAS
  o Non-specific system activated by any sensation
  o Stimulation causes “sleep arousal”
   On arousal from sleep EEG pattern changes from high voltage slow δ-wave to high frequency low voltage β-wave activity
   Causes δ-block
• Descending reticular formation
  o Modulates pain
  o Controls motor function

(see diagrams in lecture notes)

Question 9

What does the reticular formation contain? What substances do diffuse reticular activating systems utilise?

Answer 9

Reticular formation contains groups of aminergic neurons
- Diffuse reticular activating systems utilise monoamines and acetylcholine
o Monoamines
 Dopamine
 Noradrenaline
 Serotonin (5HT)
- Widespread output to hypothalamus, cortex and limbic system, as well as descending projections

Question 10

Which areas/pathways is the monoamine dopamine used in? How many receptor subtypes and effects are there?

Answer 10

• Substantia Nigra (SN)
  o nigrostriatal pathway
  o Control of movement- initiation/ switching
  o Loss  Parkinson’s disease
• Ventral tegmental area (VTA)
  o Mesolimbic and mesocortical pathways
  o Organising behaviour; focusing & attention; reward & motivation
  o Disturbance: Schizophrenia; Addiction (brain is over-rewarding)
• At least 5 major receptor subtypes for DA so there are numerous, different effects

Question 11

Which areas/pathways is the monoamine noradrenaline used in? What are its effects?

Answer 11

• Locus ceruleus and other nuclei
  o Sympathetic NS control centre activated by the hypothalamus
  o Descending fibres carried in reticulospinal tract activate preganglionic sympathetics
  o Activates the motor system so our reflexes are faster.
   Don’t think about it – respond!
  o Inhibition of pain
  o Ascending fibres to the forebrain activate a central sympathetic system  behavioural alertness & arousal (esp. to stress/ stimuli evoking fear)

Question 12

Which areas/pathways is the monoamine serotonin (5-HT) used in? What are its effects and what is caused by a deficit of it?

Answer 12

• Raphe nuclei – midline nuclei
  o Rostrally Inhibits basal forebrain cholinergic GABA cells to produce arousal; gate sensory input to cortex; effects on cognition, mood
  o Caudally - modulates pain perception and facilitates muscle activity
• Numerous receptor types/ complex
• Deficits produce OCD, depression, anxiety, aggression
• Drugs that target 5HT receptors affect mood e.g. anti depressants, also anti-migraine, anxiolytics, hallucinogens, anti-psychotics

Question 13

What are the functions of noradrenaline, dopamine and serotonin? What are their similarities?

Answer 13

Noradrenaline = alertness and energy
Dopamine = attention, motivation, pleasure and reward
Serotonin = obsessions and compulsions
Both dopamine and serotonin affect anxiety
Both noradrenaline and dopamine affect mood

Question 14

Where and how is acetylcholine used in diffuse modulatory systems?

Answer 14

• Pedunculopontine & lateral dorsal tegmental nuclei of the brainstem
• Cortical arousal and sensory filtering (through thalamic projection), movement
• Basal forebrain- roles in arousal, learning and memory

Question 15

How are the upper motor neuron pathways organised?

Answer 15

See diagrams in lecture notes

• From – motor control lecture
• Anticipatory feed-forward postural control when planning a movement– moving biceps and stabilisation of posture with contraction of gastrocnemius– predicted by brain
• Input via cortical control

Question 16

What are the reticulospinal tracts? What do they influence? What are they formed from? How do axons descend into them and what are these responsible for? Where are the tracts located?

Answer 16

An extra pyramidal tract
- Influence voluntary movement and mainly of the axial and girdle muscles
- Formed from:
o Reticular formation of the pons and medulla
o Axons from pontine reticular formation descend ipsilaterally as the medial (pontine) reticulospinal tract
o Responsible for controlling axial and extensor motor neurons enabling extension of legs to maintain postural support (e.g. moving body weight between legs)
o Stimulation of midbrain locomotor centre can result in patterned movements (stepping)
- Axons from medulla descend bilaterally in the lateral (medullary) reticulospinal tracts
o Responsible for flexor motor neurons
o Inhibits medial reticulospinal tract (extensor enabling modulation of stretch reflex)
- Both tracts located in the ventral and lateral white matter columns respectively

Question 17

What functions are controlled/mediated/helped by the reticulospinal tracts?

Answer 17

• Control the activity of both alpha and gamma motor neurones
• Mediate pressor and depressor effects on the circulatory system
• Help to control breathing

Question 18

What can the interrelation between vestibulospinal and ipsilateral reticulospinal tracts result in, and what ability does this give us?

Answer 18

• Due to the interrelation between vestibulospinal and ipsilateral reticulospinal tracts, this can result in selective activation of many muscles at the same time. As they work through interneurons and long propriospinal neurons, they can enable co-ordinated, selective movements. In addition this pathway has the ability to code movements to select the appropriate level of force required for a muscle contraction

Question 19

What role does the relationship between the rubrospinal and crossed reticulospinal tracts have?

Answer 19

• The relationship between the rubrospinal and crossed reticulospinal tracts can result in a postural role within distal musculature. The pathways innervate motorneurons both directly and indirectly through interneurons and short propriospinal neurons (e.g. intrinsic muscles acting in a postural role for individual finger movement)

Question 20

In the corticospinal tract, what does the reticulospinal tract contribute to?

Answer 20

• In corticospinal tract lesions the reticulospinal tract is thought to contribute to upper limb recovery. Although the reticulospinal tract is thought to contract the hand weakly, these outputs can strengthen following lesions to the corticospinal tract

Question 21

What does the medial (pontine) reticulospinal do? What about the lateral (medullary) reticulospinal tract?

Answer 21

• Medial (pontine) reticulospinal
  o Posture
  o Steering of head and trunk in response to external stimuli
  o Crude, stereotyped movements of the limbs (stepping)
• Lateral (medullary) reticulospinal
  o Produces loss of muscle tone (atonia) associated with the atonia that occurs in REM sleep (under control of cholinergic neurons in pedunculopontine nucleus – stop you acting out your dreams)

(see flowchart in lecture notes)

Question 22

What are the functions of the visceral (autonomic) reflex control centres?

Answer 22

• Control of pupil size, respiration, cardiovascular function, swallowing and vomiting
  o Mediated by reticular formation centres
• Respiratory activities such as initiation and modulation of respiratory rhythm, coughing, hiccupping and sneezing
• Cardiovascular responses such as baroreceptor reflexes and responses to cerebral ischemia and hypoxia
• The reticulospinal tract carries the descending control to autonomic motor groups
• The nucleus of the solitary tract is the main visceral sensory processing site

See flowchart in lecture notes

Question 23

What do some reflexes also involve somatic control of? What other centres for control/reflexes are there? Which centres maintain breathing?

Answer 23

• Some reflexes involve somatic muscle control too
• Other centres for bladder control, sexual function reflexes
• Medullar respiratory centres maintain breathing. The dorsal respiratory group of the medulla is part of the nucleus of the solitary tract (nucleus tractus solitarius; NTS) It integrates inputs for respiration and controls outputs via the ventral respiratory group of the nucleus ambiguus (nAmb) and surrounding reticular formation
• Working together the pontine reticular formation centres modify and fine tune breathing rhythms during vocalisation, sleep and exercise
• Medullary pacemaker centres including the Pre-Bötzinger complex generate the breathing rhythm

Question 24

How does the reticulospinal tract achieve autonomic control? What happens if the tract is damaged?

Answer 24

• Reticulospinal tract projects to the preganglionic autonomic neurons (both sympathetic and parasympathetic)
• If the reticulospinal tract is damaged the autonomic output is lost leading to loss of blood pressure, temp regulation (sweating), bladder and bowel control

See diagrams in lecture notes

Question 25

How and where does the reticulospinal tract achieve respiratory control? What happens if the tract is damaged?

Answer 25

• The pneumotactic centre superior pons
  o Sends continual inhibitor impulses to inspiratory centre of medulla
   Projects to inspiratory centre in the ventrolateral part of the nucleus solitarius
  o Limits inspiration and facilitates expiration
  o When damaged prolonged deep inspiration (gasping breathing)
• The apneustic centre in inferior pons
  o Prolongs inspiration and reduces expiration
  o Increases depth of inspiration for 2 secs then inhibited by pneumotaxic centre
• Pneumotactic centre switches off inspiration
• Apneustic respirations deep gasping inspiration with a pause at full inspiration followed by a brief, insufficient release

See diagrams in lecture notes

Question 26

What is the role of the reticular formation pain modulation? Which monoamines are involved in this?

Answer 26

• Serotonergic raphe magnus nucleus in the midline of rostral medulla
• Noradrenergic cell groups in the pons
  o Locus ceruleus
• Activation of either of these inhibit the transmission of nociceptive information
• Endogenous opiates released from enkephalinergic neurons in the periaqueductal grey matter activate the descending modulatory pathway
• LC source of most Noradrenaline in the CNS involved in attention and pain inhibition
• Noradrenaline via the cerebrospinal endings in dorsal horn inhibit the spinothalamic tract and supresses substance P
• Inactive during sleep and highest activity when attentive watchfulness is needed

See diagrams in lecture notes

Question 27

What is the reticular activating system (RAS) and what is its role in sleep regulation? Which substances can affect this system? How can this activity be depicted?

Answer 27

• Neurons in reticular formation can set the pace of activity in neurons throughout the brain
• Ascending arousal system
  o Modify and potentiate thalamic and cortical function such that EEG desynchronisation happens
• During alert wakefulness
  o Low voltage, fast (>12 Hz) electrical activity (desynchronised)
• During deep sleep
  o High voltage, slow (<3 Hz) electrical activity (synchronised)
   Pattern indicating that the thalamus is unable to relay sensory information to the cortex
• Sleep wake cycle
• Damage to the RAS can produce
  o Reduced attention, confusional state or coma
• Stimulants and depressants have an effect on this system
• see graphs on lecture notes*
• Electroencephalographs (EEG) rhythms during different stages of sleep. (A) Graph depicts the extent to which different stages of sleep are present throughout the night, beginning at 11:00 p.m. when sleep began. Initially, there were deeper periods of non-REM (rapid eye movement) sleep, which were eventually replaced by longer periods of REM sleep. The sleep cycles tended to be repeated, with the REM sleep becoming more prominent. (B) The four stages of sleep are characterized by the presence of different EEG rhythms. For example, theta rhythms are present during stage 1, sleep spindles are present in stage 2, and delta rhythms are present in stages 3 and 4. Note that, during REM sleep, the EEG displays a beta rhythm, which is characteristic of the waking state.

Question 28

What are the two opposing systems of sleep-wake control? How do they work?

Answer 28

Two opposing systems of sleep- wake control: reticular formation is essential for wakefulness
- Sleep-promoting:
o Anterior hypothalamus
 Lesion = insomnia
o Ventrolateral preoptic (VLPO) area
o GABA/ galanin
o Inhibit wake promoting neurons
- Ascending arousal systems (1)- increase firing in anticipation of waking and in arousal
o Brainstem reticular formation (RF)
 Damage can lead to coma
o locus ceruleus (NA) and raphe n (5HT) Posterior hypothalamus
 Lesion = hypersomnia
o Tuberomammillary nucleus (TMN) of the hypothalamus – Histamine
- Ascending Arousal systems(2) Brainstem RF
o ACh promotes forebrain activation in both waking and REM sleep (via thalamus + basal forebrain)
- Shown by lesion and stimulation studies

• see diagram in lecture notes*
• Noradrenergic neurons in locus ceruleus
• Serotonergic neurons in dorsal raphe of brainstem
• Histaminergic neurons in tuberomammillary nucleus of hypothalamus
• Dopaminergic neurons in ventral tegmental area, substantia nigra and ventral periaqueductal area

Question 29

How is wakefulness maintained? What areas allow for this? What is sleep initiated and maintained by? What can disruption lead to?

Answer 29

• Wakefulness is maintained by the combined excitatory influence of:
  o Forebrain-projecting noradrenergic (locus ceruleus)
  o Histaminergic (tuberomammillary nucleus)
  o Serotoninergic (dorsal raphe), and
  o Cholinergic (not shown) cell groups located at or near mesopontine junction
• Sleep, is initiated and maintained by neurons in:
  o Median preoptic (MnPO) and
  o Ventrolateral preoptic (VLPO) nuclei
   Via inhibitory projections to more rostrally situated wakefulness-promoting cell groups
  o Hypocretin (orexin) neurons located in lateral hypothalamus reinforce activity in brainstem arousal pathways and also stabilize both sleep and wakefulness.
   Disruption of the hypocretin system leads to narcolepsy
  o Suprachiasmatic nuclei (SCN) determine timing of sleep-wake cycle and help “consolidate” these behavioural states
  o Pineal gland, located in epithalamus, produces melatonin - functions as a hypnotic signal
  o Cerebral cortex and medullary brainstem also contain subpopulations of γ-amino butyric acid (GABA)-ergic sleep-active neurons

See diagram in lecture notes

Question 30

What are the 2 main functions of the auditory system?

Answer 30

-	Hearing
o	Distinguishing different sounds
o	Localisation
-	Language
o	Production
o	Comprehension

Question 31

What are the four divisions of the auditory system?

Answer 31

Outer ear
Middle ear
Inner ear
Central auditory nervous system

Question 32

What is the mode of operation and function of the outer ear?

Answer 32

MOA = air vibration
Function = protection, localisation, amplification

Question 33

What is the mode of operation and function of the middle ear?

Answer 33

MOA = mechanical vibration
Function = impedance matching, pressure equalisation, inner ear stimulation

Question 34

What is the mode of operation and function of the inner ear?

Answer 34

MOA = mechanical, hydrodynamic and electrochemical
Function = sound filtering, signal transduction

Question 35

What is the mode of operation and function of the central auditory nervous system?

Answer 35

MOA = electrochemical
Function = information processing

Question 36

What is the anatomy of the middle ear?

Answer 36

See diagram in lecture notes

Question 37

What are the functions of the middle ear?

Answer 37

• Impedance matching – difference in area between ear drum and oval window compensates for impedance mismatch between air and cochlea fluid. Vibrational energy collected over 55mm2 in air transferred to 3.2 mm2
• Pressure equalisation – Eustachian tube prevents a standing pressure difference on either side of the eardrum that would compromise function
• Inner ear stimulation – the arrangement of ossicles transmits vibrational energy to the oval window, preventing it from being reflected away from the surface of the inner ear

Question 38

What are the two functions of the auditory reflexes? What are two examples of auditory reflexes?

Answer 38

• Two functions:
  o Prevent damage to the person and to the ear
  o To distinguish important sounds from background
• Attenuation reflex (40-80 ms) – relies on activation of middle ear muscles
  o Activated by own voice or loud sounds
  o Dampens out low frequency sound – allowing better discernment of speech
  o If damaged person has hyperacuisis
• Startle reflex (10 ms) ducking down to protect the back of the neck (whole-body startle) and closing the eyes (blink)

Question 39

What is the cochlea like? What three canals are located within it? What do these contain?

Answer 39

See diagram for anatomy in lecture notes

• The cochlea resembles a snail shell and spirals for about 2.75 turns (humans) around a bony column
• Vibrational displacement pass into the cochlear fluids at the oval window
• Within the cochlea are three canals:
  o Scala Vestibuli
  o Scala Tympani
  o Scala Media (cochlear duct)
• Scalar vestibuli and scalar tympani both contain perilymph (secretion similar to ECF – high in sodium and low in potassium)
• Basilar and vestibular membranes form the limits of scalar media – fluid in here is high in potassium – more similar to intracellular fluid – allows organ of corti to transduce sound according to changes in cellular membrane potential

Question 40

What is sound transduction? What can amplify low-level sound?

Answer 40

• Converts mechanical signals into electrical signals#
• Cilia can amplify low-level sound – supplied by efferent axons
• When sound enters cochlea, there is a sound-induced vibration (as shown above)
• Causes upward and downward deflection of tectorial membrane
• Causes change in forces that stereocilia are subjected to
• Ion channels in cilia opened by deformation from these mechanical changes

See diagrams in lecture notes

Question 41

How is loudness measured?

Answer 41

• dB (decibel) = 20log P/Pr
• P = Pressure of incoming sound
• Pr = Pressure of reference (20 microN/m2 ) (= pressure of a just audible sound)

Question 42

What is the shape of the minimum audibility curve mainly determined by? Why is there such a high threshold?

Answer 42

• The shape of the curve is mainly determined by the transmission resonances of the outer and middle ear
• The high threshold for very low and very high frequency sounds is due to the fact that the sound energy never makes it into the cochlea

Question 43

What auditory pathways are present in the brain?

Answer 43

• Superior olivary nucleus: spatial localisation
• Cochlea nucleus
  o Ventral: intensity and location
  o Dorsal: pitch and quality

Question 44

What is the role of the superior olivary nucleus in localisation by timing and loudness? What is interaural time difference (ITD) and when is it useful?

Answer 44

• The superior olivary nuclei use interaural time differences (ITD) and interaural level differences (ILD) to localise sound cues
• Interaural time difference (ITD) is the difference between the times sounds reach the two ears. Useful at low frequencies.

Question 45

What is the interaural level difference (ILD) and when is it useful?

Answer 45

• Interaural level difference (ILD) is the difference in sound pressure level reaching the two ears
  o Reduction in sound level occurs for high frequency sounds for the far ear. The head casts an acoustic shadow.
  Useful at high frequencies.

Question 46

What ways are there to determine location through hearing?

Answer 46

Location through timing
Location through sound intensity

See diagrams in lecture notes for the processes

Question 47

How can you test for damage to the auditory pathway?

Answer 47

-	Tuning fork tests
o	Rinne’s Test
o	Weber’s Test
-	Deafness
o	Conduction
o	Sensorineural
-	Some examples of pathologies affecting the auditory system

Question 48

What is Rinne’s test and what does it test for?

Answer 48

Method: Vibrating tuning fork placed on the mastoid process. Compares air to bone conduction and determines their relative sensitivity in each ear separately.
Normal response: Sound is heard louder and longer (>15s) by air conduction as sound energy dissipates quickly when travelling through bone. If sound ceases within 15 sec it suggests a middle ear problem.
Conduction deafness: Bone conduction is better than air conduction on AFFECTED side.
Sensorineural deafness: Air conduction is better than bone conduction in affected ear. Sound is loudest in UNAFFECTED ear.

Cannot determine the relative sensitivity of the 2 ears or if there partial deafness.

Question 49

What is Weber’s test and what does it test for?

Answer 49

Method: Place tuning fork middle of forehead and ask patient in which ear tone is heard.
Normal response: Sound heard equally well on both sides.
Conduction deafness: Sound is louder in AFFECTED ear, due to fact that vibrations reach cochlea by both air and bone but these are slightly out of phase and so interfere with each other in the more sensitive ear.
Sensorineural deafness: Sound is louder in UNAFFECTED ear.

Weber’s test cannot interpreted in isolation, as it only detects the relative difference between the 2 years.

Question 50

What is are examples of disorders of the middle ear?

Answer 50

• Otosclerosis
• Perforation of tympanic membrane
• Otitis media “glue ear”
• Failure of impedance matching mechanism can cause 40dB hearing loss

Question 51

What are the functions of the auditory complex (Primary auditory cortex: Brodmann’s area 41)?

Answer 51

• To identify complex auditory sounds
• To detect changes in auditory environment
• To learn about behaviourally relevant sounds
• To integrate attention with auditory processing
• Higher functions: language and musical appreciation

Question 52

What are the effects of damage to the language areas of the brain?

Answer 52

• Wernicke: fluent meaningless speech
  o Severely impaired speech understanding
• Broca: abbreviated, ungrammatical but meaningful speech
  o Speech understanding impaired where syntax conveys meaning
• Arcuate fasciculus: conduction aphasia
• Angular gyrus: Alexia (can’t read) with agraphia (can’t write) but can comprehend speech and speak
  o This area is abnormal in dyslexia