Neuro Flashcards
- Describe the laminae and their contents
- Laminae I – VI: SENSORY
- Lamina VII: AUTONOMIC
- Laminae VIII & IX: MOTOR
- Lamina X: Gray commissure, contains small neurons and glia.
Neuronal Architecture – Laminae (Sensory)
- Lamina I
- pain neurons tend to be small and non-myelinated
- thus they are exhausted when they reach the spinal cord
- lamina I contains the posteromarginal nucleus, which receives pain and temperature inputs
- first order neurons begin to synapse and partially form the spinothalamic tract
- Lamina II – Substantia Gelatinosa:
- Extends the entire length of the spinal cord, contains small neurons that send excitatory and inhibitory synapses onto the STT ^[spinothalamic] primary cells (gating effect on sensory transmission).
- Rostrally, it continues into the spinal nucleus of V.
- Afferents: small-diameter sensory fibres carrying pain & temperature, larger mechanoreceptor nerves
- Small inhibitory interneurons in the lamina filter and modulate incoming sensory information
- Efferents: contralateral STT (together with cells from Laminae I, IV & V)
- Contains small neurons that send excitatory and inhibitory synapses onto the STT primary cells (gating effect on sensory transmission).
- Contains high concentration of Substance P (neuropeptide, plays a role in pathways modulating pain sensibility) and enkephalinergic internuncials (opioid inhibiting pain transmission)
- Laminae III & IV (V) – Nucleus Proprius ^[aka trigeminal nucleus which is responsible for pain and temperature]:
- Extends the entire length of the spinal cord
- afferent: large sensory fibres carrying PRIMARILY position & light touch, - project to dorsal column nuclei. ^[no efferents?]
- which project to dorsal column nuclei
- afferent: small diameter sensory fibres carrying noxious stimuli (pain and temperature) and interneurons from lamina II
- project to contralateral spinothalamic tract
Neuronal architecture - Laminae (Sensory)
- Lamina VI
- small interneurons
- afferent from muscle spindles (proprioception)
- efferents to motor neurons in laminae VIII and IX
- play a role in spinal reflex arc
- send information to brain via spinocerebellar pathways
Neuronal Architecture – Laminae (Visceral)
- Lamina VII:
- large heterogenous zone: autonomic nervous system and unconscious activity
- size varies through the length of the spinal cord
- afferents from viscera
- efferents: motor information to viscera
- gives rice to cells involved in autonomic system
- Includes
- Dorsal Nucleus (Clarke’s nucl; Posterior Thoracic Nucl) for unconscious proprioception
- extends from C8- L2/3
- major relay station for unconscious proprioception
- afferents: sensory nerves from muscle spindles and tendon organs
- efferent/projection: posterior spinocerebellar tract
- Intermediomedial nucleus
- at all spinal cord levels
- afferents: sensory information from viscera
- efferents to lateral horn
- Intermediolateral Nucleus
- extends T1-L2
- preganglionic sympathetic neurons.
- Sacral autonomic nuclei
- extend S2-4
- preganglionic parasympathetic neurons
##### Neuronal Architecture – Laminae (Motor)
- Motor Neuron Columns:
- α motor neurons: Large multipolar cells innervate extrafusal muscle fibres of skeletal muscles
- γ motor neurons: Small multipolar cells innervate intrafusal muscle fibres of neuromuscular spindles
- Medial (VIII): LMNs to axial and proximal appendicular musculature
- Lateral (IX): LMNs to distal appendicular musculature. Present in cervical and lumbosacral segments
- Shorter distinct columns:
- C1-6: spinal accessory nucleus
- C3-5: phrenic motor nucleus
- S1-3: Onuf’s nucleus (striated mm control of defecation and micturition, pudendal n.)
Neuronal architecture - Lamina X(visceral)
- grey commissure
- surrounds the central canal
- site of decussation of commissural fibres
![[Pasted image 20240221105714.png]]
- Describe the course of the conscious ascending tracts
The tracts associated with conscious sensation are:
- DCML
- spinothalamic tract/spinal lemniscus
Unconscious sensation:
- dorsal spinocerebellar
- cuneocerebellar
- ventral and rostral spinocerebellar
-
Spinothalamic Tract: Originates from C / A∂-type fibres in the lateral part of the dorsal root. Carries information about pain and temperature(lateral), and crude touch and pressure, to the thalamus (anterior). There is a high degree of somatic organisation, allowing for discrimination of location and intensity of pain
- (1) Nerve fibres entering the dorsal horn
- (2) either enter Lissauer’s Tract (LT) and ascend or descend one or two levels.
- (3) then enter the dorsal horn, terminate in laminae I, II, III, IV, where they synapse. Most in Substantia gelatinosa
- (4) After synapsing, 2°fibres cross the midline, ventral to the intermediate grey, then traverse the anterior horn to reach the antero-lateral funiculus.
- (5) They turn and ascend to thalamus (VPL) and the somatosensory cortex
Characterised by a sharp stabbing pain.
Note:
- Fibres that enter caudally are displaced laterally by more rostral fibres.
- Collaterals of these fibres enter the reticular formation in the lower brainstem.
-
Dorsal Column / Medial Lemniscus Pathway: Originates from large diameter, heavily myelinated A-type fibres (Aβ) in the medial part of the dorsal root. Carries conscious information about discriminative touch, 2-point discrimination, vibration, and conscious proprioception to the thalamus.
- (1) Large myelinated fibres enter medial to LT, turn rostrally and ascend in the posterior funiculus. Fibres from the lower limb form the gracile fasciculus, while fibres from the upper limb form the cuneate fasciculus.
- (2) Fibres from the lower limb synapse in the gracile nucleus; fibres from the upper limb synapse in cuneate nucleus in the closed medulla.
- (3) Secondary fibres take an arcuate course, cross the midline at the sensory decussation to form the medial lemniscus then again turn rostrally.
- (4) They turn and ascend to thalamus (VPL) and the sensory cortex
The next tracts carry unconscious sensory information to the cerebellum:
-
Dorsal Spino-cerebellar Tract: Carries unconscious proprioceptive information, concerning muscle force and stretch, from lower limb muscles and tendons to the cerebellum.
- (1) Information coded by Golgi tendon organs (strain) and muscle spindles (stretch) in lower limb muscles is carried in large diameter fibres (Aα) that pass through the dorsal horn and synapse on cells in Rexed’s lamina VII, Nucleus dorsalis / Clarke’s nucleus (C8-L2/3).
- (2) Secondary fibres enter the lateral funiculus, near the dorsal root, and turn rostrally, forming the Dorsal Spino-cerebellar Tract.
- (3) In the upper medulla, this tract enters the inferior cerebellar peduncle. and fibres terminate in the ipsilateral cerebellar cortex.
-
Cuneo-cerebellar Tract: Carries information from upper limb muscles and tendons about muscle force and stretch to the cerebellum. Upper limb equivalent of dorsal spino-cerebellar tract.
- (1) Information coded by Golgi tendon organs (strain) and muscle spindles (stretch) is carried in fibres that enter the dorsal horn then turn rostrally.
- (2) 1° fibres synapse in the Accessory cuneate nucleus, in the medulla (the Clarke’s column equivalent for the upper limb).
- (3) 2° fibres enter the inferior cerebellar peduncle, along with the Dorsal Spino-cerebellar fibres to terminate in the ipsilateral cerebellar cortex.
-
Ventral Spino-cerebellar Tract: Carries predominantly force information from lower limb muscles, to the ipsilateral cerebellum.
- (1) Information from Golgi tendon organs (strain) in the lower limb muscles is carried in fibres that enter the dorsal horn and synapse in the base of the dorsal horn (Rexed lamina VI).
- (2) 2°fibres cross the midline, enter the ventral part of the lateral funiculus, then turn rostrally in the Ventral spino- cerebellar tract.
- (3) In the pons/midbrain, these fibres enter the Superior Cerebellar Peduncle, then re-cross the midline to terminate in the ipsilateral cerebellar cortex
-
Rostral spino-cerebellar tract
Carries predominantly force information from upper limb muscles, to the ipsilateral cerebellum.
- (1): Information from Golgi tendon organs (strain) in the upper limb muscles is carried in fibres that enter the dorsal horn and synapse in the base of the dorsal horn (Rexed lamina VI).
- (2): 2°fibres ascend ipsilaterally
- (3):In the brainstem, fibres enter the cerebellum through the Inferior Cerebellar Peduncle
Other ascending pathways with role in pain sensation
Medial pain system: crude, not well-localised pain.
Medial tracts are usually more primitive.
Note also that tracts that go to the cerebellum do not decussate.
- spinoreticular
- old, multi-synaptic tract
- originates from dorsal horn neurons
- ipsilateral ascending fibres terminating in the reticular formation
- projects to intralaminar nuclei of thalamus
- important role in sensation of deep, burning chronic pain
- spinotectal
- originates from dorsal horn
- ascends contralaterally to superior colliculus & periaqueductal gray
- role in regulating pain
- Lissauer’s tract: a ‘bridge’
- Describe the course of the unconscious ascending tracts
The next tracts carry unconscious sensory information to the cerebellum:
-
Dorsal Spino-cerebellar Tract: Carries unconscious proprioceptive information, concerning muscle force and stretch, from lower limb muscles and tendons to the cerebellum.
- (1) Information coded by Golgi tendon organs (strain) and muscle spindles (stretch) in lower limb muscles is carried in large diameter fibres (Aα) that pass through the dorsal horn and synapse on cells in Rexed’s lamina VII, Nucleus dorsalis / Clarke’s nucleus (C8-L2/3).
- (2) Secondary fibres enter the lateral funiculus, near the dorsal root, and turn rostrally, forming the Dorsal Spino-cerebellar Tract.
- (3) In the upper medulla, this tract enters the inferior cerebellar peduncle. and fibres terminate in the ipsilateral cerebellar cortex.
-
Cuneo-cerebellar Tract: Carries information from upper limb muscles and tendons about muscle force and stretch to the cerebellum. Upper limb equivalent of dorsal spino-cerebellar tract.
- (1) Information coded by Golgi tendon organs (strain) and muscle spindles (stretch) is carried in fibres that enter the dorsal horn then turn rostrally.
- (2) 1° fibres synapse in the Accessory cuneate nucleus, in the medulla (the Clarke’s column equivalent for the upper limb).
- (3) 2° fibres enter the inferior cerebellar peduncle, along with the Dorsal Spino-cerebellar fibres to terminate in the ipsilateral cerebellar cortex.
-
Ventral Spino-cerebellar Tract: Carries predominantly force information from lower limb muscles, to the ipsilateral cerebellum.
- (1) Information from Golgi tendon organs (strain) in the lower limb muscles is carried in fibres that enter the dorsal horn and synapse in the base of the dorsal horn (Rexed lamina VI).
- (2) 2°fibres cross the midline, enter the ventral part of the lateral funiculus, then turn rostrally in the Ventral spino- cerebellar tract.
- (3) In the pons/midbrain, these fibres enter the Superior Cerebellar Peduncle, then re-cross the midline to terminate in the ipsilateral cerebellar cortex
-
Rostral spino-cerebellar tract
Carries predominantly force information from upper limb muscles, to the ipsilateral cerebellum.
- (1): Information from Golgi tendon organs (strain) in the upper limb muscles is carried in fibres that enter the dorsal horn and synapse in the base of the dorsal horn (Rexed lamina VI).
- (2): 2°fibres ascend ipsilaterally
- (3):In the brainstem, fibres enter the cerebellum through the Inferior Cerebellar Peduncle
- Describe the course of the conscious descending tracts
The corticospinal tracts
- Corticospinal fibres originate from both frontal and parietal cortices
- Cells of origin are large triangular or pyramidal cells in layer V of neocortex
- ![[Pasted image 20240313124535.png]]
- where things can go wrong: hemiparesis and failure to abduct eye; ptosis/dilation/down and out; tongue deviation
- ![[Pasted image 20240313124545.png]]
- Originate from cells in M1, SMA, PMA, S1 and descend through the corona radiata, then the internal capsule (posterior limb, posterior portion – CBT occupies anterior portion)
- Enter cerebral peduncles ~ middle 3/5; leg is most lateral
- Pass through the pons, crossed by the pontocerebellar fibres
- Enter the pyramids on the ventral aspect of the medulla
- 80% axons cross in the pyramidal decussation to formthe lateral corticospinal tract. ~10% do not cross andremain in the lateral CST (not shown); another ~10% also remain on the ipsilateral side and form the ventral/anterior corticospinal tract, the majority of these cross before entering the ventral horn
- Glutamatergic fibres terminate at all levels of the spinal cord
- Provide input to lower motor neurons of ventral horn that innervate skeletal muscles, especially flexors. Some send collaterals to thalamus, reticular formation dorsal column nucl,(sensory modulation) and interneurons in spinal cord (motor modulation)
The corticobulbar fibres
The corticobulbar fibres originate from cells in the head and face regions of the motor areas (lateral regions).
It controls both sides bilaterally.
Exceptions include lower part of CN VII and CN XII.
They descend through the corona radiata, then the middle (around the genu) part of the internal capsule.
They enter the cerebral pedncles medial to the CST fibres.
They synapse bilaterally on the motor nuclei of cranial nerves, directly and via interneurons (exc parts of VII and XII) and reticular formation.
They are glutamatergic/excitatory fibres.
![[Pasted image 20240314110956.png]]
Extrapyramidal tracts
There are four main extrapyramidal tracts.
- rubrospinal: important for quality of life, responsible for skilled movements, mainly terminate at cervical levels
- reticulospinal both medial and lateral, essential for life (posture, balance and gaze): modifies reflex control of extensors
- tectospinal: head orientation to external stimuli, mainly terminates at cervical levels
- vestibulospinal, both medial and lateral: responsible for posture and balance, medial tract terminates at cervical levels
### Rubrospinal
- controls flexion in upper limb e.g. involuntary arm movement to keep balance
- irginates from cells in red nucleus in the upper midbrain (level of superior colliculus)
- fibres cross midline in midbrain
- red nucleus receives input from motor areas that are somatotopically organised – output from nucleus is also somatotopic = “corticorubrospinal” pathway
- while it receives input from cortex it is not ITSELF involved in conscious control
- discrete bundle of fibres in the lateral medulla, and in the lateral SC adjacent to the corticospinal tract
- fibres terminate mainly in cervical levels, and mianly innervate flexor groups
- fibres are glutamatergic
### Reticulospinal
- pontine or medial – stimulate limb extensors and inhibit flexors
- does NOT cross
- originate from large cells in PRF
- terminate at all levels of spinal cord (VII, VIII) on ipsilateral alpha and gamma motor neurons
- activates spinal reflexes of antigravity muscles: stimulate limb extensors helping to maintain posture (enhances anti-gravity spinal reflexes that hold the body upright)
- stabilises in anticipation of other movements
- contains enkephalin, substance P as well as glutamate
- medullary/lateral tract
- stimulates limb flexors and inhibits axial and limb extensor muscles
- arises from large cells in the medial medulla
- fibres terminate at all levels of the spinal cord (8,9) on alpha and gamma motor neurons
- inhibits antigravity/axial muscles from relfex control, stimulate limb flexors (inhibits spinal reflexes that hold the body upright e.g. axial and limb extensors)
Tectospinal
- coordinates head and eye movement i.e. involuntary adjustment of head position on visual stimuli
- originate from cells in deep layers of superior colliculus
- SC gets direct input from retina, VC, somatosensory and auditory systems
- inputs are mapped
- fibres cross midline and midbrain
- descend in contralateral central medulla, close to medial lemniscus
- terminate in contralateral intermediate grey (laminae 6,7) in the cervical layers of sc
- primary role in orientation reflexes of the head, especially towards auditory, visual and somatosensory stimuli
### Vestibulospinal
- playa role in maintaining erect position by activation anti-gravity muscles i.e. control extension in extremities
- originate from cells in lateral and medial vestibular nuclei of CN VIII
- these are relay cells that get input from cells in the vestibular ggl (in IAM) and cerebellum
- fibres from the **medial vestibular nucleus descend bilaterallyin te MLF to lower medulla (spinal accessory nucleus) and upper cervical SC to innervate muscles controlling head position and orientation reflexes
- fibres from the **lateral nucleus project to all levels of the ipsilateral SC
- these pathways mainly innervate extensor groups and help maintain posture and balance
- Describe the course of the unconscious descending tracts
Extrapyramidal tracts
There are four main extrapyramidal tracts.
- rubrospinal: important for quality of life, responsible for skilled movements, mainly terminate at cervical levels
- reticulospinal both medial and lateral, essential for life (posture, balance and gaze): modifies reflex control of extensors
- tectospinal: head orientation to external stimuli, mainly terminates at cervical levels
- vestibulospinal, both medial and lateral: responsible for posture and balance, medial tract terminates at cervical levels
### Rubrospinal
- controls flexion in upper limb e.g. involuntary arm movement to keep balance
- irginates from cells in red nucleus in the upper midbrain (level of superior colliculus)
- fibres cross midline in midbrain
- red nucleus receives input from motor areas that are somatotopically organised – output from nucleus is also somatotopic = “corticorubrospinal” pathway
- while it receives input from cortex it is not ITSELF involved in conscious control
- discrete bundle of fibres in the lateral medulla, and in the lateral SC adjacent to the corticospinal tract
- fibres terminate mainly in cervical levels, and mianly innervate flexor groups
- fibres are glutamatergic
### Reticulospinal
- pontine or medial – stimulate limb extensors and inhibit flexors
- does NOT cross
- originate from large cells in PRF
- terminate at all levels of spinal cord (VII, VIII) on ipsilateral alpha and gamma motor neurons
- activates spinal reflexes of antigravity muscles: stimulate limb extensors helping to maintain posture (enhances anti-gravity spinal reflexes that hold the body upright)
- stabilises in anticipation of other movements
- contains enkephalin, substance P as well as glutamate
- medullary/lateral tract
- stimulates limb flexors and inhibits axial and limb extensor muscles
- arises from large cells in the medial medulla
- fibres terminate at all levels of the spinal cord (8,9) on alpha and gamma motor neurons
- inhibits antigravity/axial muscles from relfex control, stimulate limb flexors (inhibits spinal reflexes that hold the body upright e.g. axial and limb extensors)
Tectospinal
- coordinates head and eye movement i.e. involuntary adjustment of head position on visual stimuli
- originate from cells in deep layers of superior colliculus
- SC gets direct input from retina, VC, somatosensory and auditory systems
- inputs are mapped
- fibres cross midline and midbrain
- descend in contralateral central medulla, close to medial lemniscus
- terminate in contralateral intermediate grey (laminae 6,7) in the cervical layers of sc
- primary role in orientation reflexes of the head, especially towards auditory, visual and somatosensory stimuli
### Vestibulospinal
- playa role in maintaining erect position by activation anti-gravity muscles i.e. control extension in extremities
- originate from cells in lateral and medial vestibular nuclei of CN VIII
- these are relay cells that get input from cells in the vestibular ggl (in IAM) and cerebellum
- fibres from the **medial vestibular nucleus descend bilaterallyin te MLF to lower medulla (spinal accessory nucleus) and upper cervical SC to innervate muscles controlling head position and orientation reflexes
- fibres from the **lateral nucleus project to all levels of the ipsilateral SC
- these pathways mainly innervate extensor groups and help maintain posture and balance
- List the somatic motor cranial nerves: entry, exit, function, location in brainstem
Recall that 3, 4, 6 and 12 have pure somatic motor nuclei and sit medially.
Oculomotor
Motor nucleus
Superior colliculus
Edinger Westphal
Superior colliculus
Ciliary (parasympathetic)
Ciliary & pupillary muscles
Trochlea
Motor nucleus
Inferior colliculus
Superior oblique muscle
Trigeminal
Motor nucleus
Superior colliculus - pons
Principal V
Pons
Semilunar (sensory)
Spinal V
Medulla - upper spinal cord
Semilunar (sensory)
Mesencephalic
Superior colliculus - upper pons
VERY SPECIAL! Sensory cell bodies within the CNS
Sensation (proprioception) of face
Abducens
Motor nucleus
Pons
Lateral rectus muscle
Facial
Motor nucleus
Lower pons
Super salivatory
Lower pons
Pterygopalatine & Submandibular (parasympathetic)
Solitary nucleus (taste)
Open & closed medulla
Geniculate (sensory)
(Spinal V)
Medulla - upper spinal cord
Geniculate (sensory)
Somatic sensation around the ear
Glossopharyngeal
Solitary nucleus (rostral)
Open & closed medulla
Inferior ganglionof IX (in jugular foramen)
Solitary nucleus (caudal)
Open & closed medulla
Inferior ganglionof IX (in jugular foramen)
Spinal V
Medulla - upper spinal cord
Superior ganglionof IX (in jugular foramen)
Nucleus ambiguus
Open & closed medulla
Inferior salivatory
Openmedulla
Otic (parasympathetic)
Parotid gland
Vagus
Dorsal motor nucleus of X
Open & closed medulla
Walls of viscera (parasympathetic)
Spinal V
Medulla - upper spinal cord
Superiorganglionof X (in jugular foramen)
Solitary nucleus
Open & closed medulla
Inferior ganglionof X (in jugular foramen)
Taste (epiglottis); pharynx, larynx, trachea, esophagus, thoracic and abdominal viscera (visceral afferent)
Accessory (cranial)
Nucleus ambiguus
Open & closed medulla
Intrinsic muscles of thelarynx; spinal = scm, trapezius
Hypoglossal
XII motor nucleus
Open & closed medulla
Muscles of the tongue except palatoglossus
- List general sensory cranial nerves and their features
see C Brock table
- Describe visceral/branchial motor cranial nerves and their features
- Describe special sensory cranial nerves and their features
CN1 Olfactory Sensory Special Sensory: smell cribiform plate (ethmoid
bone)
Rostral to brain stem –
lies under frontal lobe
CN2 Optic
Retina ganglia optic
nerve optic chiasm Optic
tract thalamus (lateral
geniculate nucleus)
occipital lobe
Sensory Special Sensory: Sight
(joining of retinal ganglion cells)
Optic canal (sphenoid bone) Rostral to brainstem –
connects to occipital
lobe via thalamus
CN8 Vestibulocochlear
Travels through internal
acoustic meatus
(temporal bone) before
splitting into trochlear
and cochlear nerves
Sensory Special Sensory: Hearing (cochlear) and balance (vestibular) Internal acoustic meatus Pons (lateral and
caudal aspect
- Label a diagram of dorsal brainstem
- Label a diagram of ventral brainstem
- Describe the sensory territory of V1/2/3
- Ophthalmic branch or V1 - sensations from the nasal cavity, skin of forehead, upper eyelid, eyebrow and nose
- Maxillary branch or V2 - sensations from lower eyelid, upper lips and gums, teeth of the maxilla, cheek, nose, palate, and pharynx
- Mandibular branch or V3 - sensations from teeth of the mandible, lower gums and lips, palate and tongue
Describe innervation of facial nerve branches
Nerve reaches the muscles of facial expressions, reaches the parotid gland and split into five branches:
- temporal
- zygomatic
- buccal
- mandibular
- cervical
Nerve reaches the muscles of facial expressions, reaches the parotid gland and split into five branches:
- temporal
- zygomatic
- buccal
- mandibular
- cervical
- frontalis
- orbicularis oculi - circular, around the eye responsible for closing the eye
- levator labii superioris - elevating the upper lib
- zygomaticus
- buccinator - innervated by CN VII (drooling, big buccinator)
- risorius - smiling muscle
- procerus
- corrugator supercilli
- nasalis
- orbicularis oris - surrounds the lips and close your mouth
- depressor anguli oris - depressing angle of the mouth
- platysma - covers the neck
- depressor labii inferioris
- What relationship does sympathetic innervation of eye have to trigeminal nerve
Note: the trigeminal nerve does NOT have autonomic fibres BUT does have hitchhiking sympathetic and parasympathetic fibres.
The nasociliary nerve (off ophthalmic) carries sympathetic fibres, picked up in the cavernous sinus and distributes them:
- long ciliary branches (V1) to dilator pupillae muscles
- via branches of the ciliary ganglion (of III - oculomotor nerve), short ciliary nerves ^[post-ganglionic]
- sympathetic fibres to levator palpebrae superioris travel in upper division of oculomotor nerve (III)
- note that sympathetic fibres do NOT synapse, just pass through
- e.g. superior cervical ganglion—> internal carotid artery
- Name and describe the roles of the trigeminal nuclei
Motor nucleus of V
- located at mid pons,at level of entry of the nerve
- as it is a branchiomotor nucleus, we find it laterally, close to the sensory nucl.
- innervates mm connected to the embryonic mandibular arch: mm of mastication, mylohyoid, digastric (ant belly) + tensor veli palatini, tensor tympani
- receive bilateral corticobulbar input from motor cortices (contralateral more strongly)
#### Supratrigeminal nucleus
- part of the reticular formation
- acts as pattern generator for mastication
- in conscious person it is constantly active
- in erect position activates jaw closing
- in horizontal position activates the lateral pterygoid to prevent asphyxia
- general anaesthesia inactivates the nucleus ^[hence intubation is required]
Mesencephalic nucleus
- only sensory nucleus in the brain that acts as a ganglion within the CNS (ie it is equivalent to a dorsal root ganglion of the spinal cord, or the trigeminal ganglion, where cell bodies are found)
- dendrites of the pseudo-unipolar sensory cells originate at muscle spindles of the jaw mm (as well as TMJ itself?) (via V3) and as mechanoreceptors from periodontal ligaments in teeth and gums (via V2 and V3).
- these large,heavily myelinated fibres form the mesencephalic tract,which surrounds the nucleus
- axonal processes of some of these cells project directly to the Motor nucl V, most synapse in the supratrigeminal nucl before they reach Trigeminal Motor nucleus
ntine nucleus
otherwise known as principal nucleus.
It is located in the mid pons, at level of entry of the nerve, lateral to the motor n.
It is a homologue of the dorsal column nuclei - ie., relays
information about discriminative touch sensations from the face
and oronasal cavity.
Information is carried by fast-conducting, heavily myelinated fibres.
Where is the information projected to in the cortex?
Spinal trigeminal nucleus
The spinal trigeminal nucleus is a large nucleus extending from the caudal-pons to about C3 level of spinal cord.
It has smaller diameter fibres from V1,V2 andV3, turn caudally on entering the pons, forming
the spinal trigeminal tract on the lateral aspect of the nucleus.
The fibres only synapse once they reach the target level of the nucleus. Then they follow the spinothalamic tract up to the VPM of the thalamus.
Divided into 3 parts:
- pars/nucl oralis (medullary-pontine junction),
- pars/nucl interpolaris (open medulla),
- pars/nucl caudalis (closed medulla).
Oralis and Interpolaris are small, and receive afferents from the mouth
Caudalis is a homologue of substantia gelatinosa (Rexed II).
The nucleus processes information concerning pain and temperature from the territories of V1,V2
and V3. This nucleus blends into dorsal horn of the spinal cord and the lower tract
blends into Lissauer’s tract
There are three main afferents to the spinal nucleus:
- Trigeminal nociceptive fibres from cornea (V1), teeth (V2 & 3), temporomandibular joint (V3), dura mater of anterior and middle cranial fossae (V2 & 3)
- Facial (CNVII), Glossopharyngeal (CNIX) and Vagal (CNX) afferents from pharynx, larynx, pharyngotympanic tube, outer and middle ear (cell bodies in geniculate ggl, inf ggl of IX, or inf ggl of X)
- Cervical afferents from nociceptive fibres of posterior roots of C1-3 (note: C1 is usually absent) from dura mater of post cranial fossa, spinal dura, intervertebral joints and suboccipital mm
Note: taste fibres or chemoreceptors carried by these nerves (VII, IX, X) which hitchhike with the trigeminal nerve, synapsing in the solitary tract nucleus.
**Describe stroke syndromes
**
MCA- supploes motor cortex and sensory cortex (upper limb and face), temporal lobe (Wernicke), frontal lobe (Broca)
Symptoms of lesion:
- CL paralysis of upper limb and fae
- CL loss of sensation upper and lower limbs and face
- aphasia if in dominent hemisphere
- hemineglect is nondominant side
ACA
- motor and sensory cortices, lower limb
- CL paralysis and loss of sensation in lower limb; R ACA= anosmia; personality/attitude/memory= frotal lobe damage
ASA: supplies lateral CS tract, medial lemniscus and caudal medulla esp hypoglossal nerve nucleus, tectospinal tract.
LEsion: CL hemiparesis of U and L limbs, decreased CL proprioception and ipsilateral hypoglossal dysfunction – ie tongue deviates ipsilateral side. Note that stroke is most commonly bilateral. Pain and temperature intact because isSTT is lateral and supplied by VA
Note also this is @medial medulla syndrome@ caused by infarct of paramedian ASA branches and vertebral arteries.
PICA- lateral medulla, vestibular nuclei, lateral STT, spinal tg N, N ambiguus, sympathetic fibres and inferior cerebellar peduncle.
Lesion: vomiting, vertigo and nystagmus. Reduced pain and temperature sensation from ipsilateral face and contralateral body, dysphagia, hoarseness, reduced gag reflex, ipsilateral Horner, ataxia ipsilateral cerebellar signs. Dysmetria.
AICA: Latearl pons: CN nuclei- VIII, VII, spinal T g nucleus, cochlear nuclei, sympathetic fibres; middle and infeerior cerebellar peduncles. Vomiting, vertigo, nystagmus, paralysis of face– specific to aica aka latearl pontine syndrome- reduced lacrimation, salivation, taste 2/3, corneal reflex. Face reduced pain and temperature, ipsilateral hearing, Ipsilateral horner, ataxia, dysmetria.
PCA- occipital cortex esp visual cortex
CL hemianopia with macular sparing
—
Basilar: @locked in sydnrome’
pons medulla lower midbrain, CST, CBT, ocular CN nuclei, paramedian pontine reticular formation.
Note also:
- Amaurosis Fugax: Transient monocular blindness due to retinal (Ophthalmic) artery occlusion. A red flag for oncoming stroke.
- Carotid “T” Occlusion: Face-Arm-Leg weakness/numbness on contralateral side, global aphasia if dominant side affected, visual sparing.
- —
Pontine stroke syndromes typically a result of occluded perforations
- Foville/dorsal pons: ipsilateral lateral gaze palsy and LMN facial palsy
- Rymond’s/ventral pons: ipsilateral lateral rectus palsy and contralateral hemiplegia
- —
-
- Weber’s Syndrome
- I/L ophthalmoplegia and ptosis, dilation of pupil, no light response, no accommodation, C/L paralysis of arm and leg (CNIII nuclei &/or nerve fibres, corticospinal fibres)
- Benedikt’s Syndrome
- C/L involuntary limb movements, C/L loss of sensation (red nucleus and ascending SCP fibres, spinal and medial lemnisci)
- Compare and contrast Rinne and Weber hearing tests and explain findings if hearing loss is conductive or sensorineural
hearing loss can be described as
- Conductive - outer or middle ear damage
- Sensorineural - inner ear or vestibulcochlear (CNVIII) nerve, or pathway damage.
To distinguish between these hearing losses, two simple auditory examinations may be conducted:
Weber test:
Tuning fork (512 Hz) is placed in the midline of the forehead. In normal hearing, the vibration should be heard equally, on both sides. In conductive hearing loss, stronger vibration is localised on the damaged side. This is explained by the loss of the masking effect of ‘background noise’, normally coming through the tympanic membrane, on the bone conduction. In sensorineural hearing loss, the stronger vibration is felt on the healthy side.
Rinne test:
Compares air and bone conduction. Tuning fork is placed in front of the external auditory canal, and then on the mastoid process. Patient is asked which sound appears louder. In normal hearing, and sensorineural hearing loss, the air conduction will be heard louder. In conductive hearing loss, the sound from the skull (mastoid process) will be heard louder.
For more precise detection of hearing loss, audiometry is performed.
- Interpret audiometry graph
Audiometry measures hearing acuity using a variety in sound intensity and pitch by identifying the hearing thresholds at different frequencies of sounds.
- Label sagittal/axial/coronal diagrams of brain
- Label the following sections of the brainstem – rostral and caudal midbrain, rostral and caudal pons, open and closed medulla. Predict the effect of lesions
See doc- labelled brainstem
- Label the basal ganglia, describe the circuitry and relate to hypokinetic disorders
Basal ganglia:
- Striatum: caudate, putamen, (n accumbens)
- Pallidum: globus pallidus – medial (internal) and lateral (external) segments (includes substantia nigra ‘pars reticulata’ which may be considered functionally continuous with GPi. It is only separated by internal capsule fibres)
- putamen plus globus pallidus makes lentiform mucleus
- Sub-Thalamic Nucleus
- Substantia Nigra pars compacta
- Sub-thalamic nucleus and substantia nigra are regulators of the basal ganglia
-
Caudate
- Connected mainly to frontal and pre-frontal areas, and Posterior Parietal Cx.
- Influence on social/moral behaviours.
- More active during the acquisition of new motor skills and planning ahead during more complex motor intentions.
-
Putamen
- Mainly connected to somatic cortical areas.
- Has a mapped representation of the body.
- More involved in cognitive loops
Striatum = caudate + putamen
- Complex structure, but one functional unit with connections to the cortex (1000s:1) .
—
-
Cognitive Loop (Caudate):
- Planning ahead for motor intentions.
- Once learned → motor loop.
-
Limbic Loop (N. Accumbens):
- Involves reward/motivational behaviours, memory, and motor expression relevant to emotions (smiling/gesturing).
- In Parkinson’s Disease (PD), there are problems with expressions.
-
Oculomotor Loop (Caudate):
- In PD, there are problems with saccades.
-**
Motor loop (putamen)
- Scaling strength of muscle contractions
- in collaboration with SMA
- Putamen provides a reservoir of learned
programs
- Execution of motor programs involves decision/plan of what to do, integrating all cortical inputs to determine appropriate motor programs, with motor instructions sent to Motor Cx.
- decision or planning what to do occurs in frontal/parietal; temporal, insular and cingulate cortices —->
- basal ganglia integrates all cortical inputs to determine approporiate motor programs —>
- thalamic nuclei sends motor instuctions to motor cortex
- SMA and M1 execute motor programs
- enact action from M1
Cognitive Loop:
- e.g. for any learnt motor program
- Strong projection to caudate which becomes active during learning new motor skills – reinforcement learning.
- Thought to incorporate planning ahead during new motor tasks & action selection.
- Returns to prefrontal and premotor cortices via VA & MD nuclei of thalamus.
- When the new task is well practiced, the task comes under control of the motor loop.
Example loop:
- prefrontal and PPC
- Putamen, caudate and GP
- VA/MD thalamus
- SMA
Limbic Loop
- e.g., Memory, motivational behaviours, gesturing, facial expressions…
-
Nucleus Accumbens
- Anterior end of putamen/caudate
- Connected to inferior prefrontal Cx (limbic system)
- Returns signals to Cx via MD nuclei of thalamus
- Limbic Cx determines appropriate emotional status for the environmental conditions
- Important in gesturing and expression of affect
- Rich in dopaminergic input may explain loss of affect / ‘mask-like’ appearance of PD patients.
Example loop:
- Limbic Cx
- N. Accumbens
- MD Thalamus
- Inf. Prefrontal Cx
Oculomotor Loop
- e.g., Fixation
- Substantia Nigra pars reticularis (SNr)
- Connected to the ‘frontal eye fields’ and parietal association cortex
- Returns to Cx via VA & MD nuclei of thalamus
- During fixation, SNr tonically inhibits cells in the superior colliculus (SC)
- When a deliberate saccade is about to be made, SNr activity stops, to disinhibit SC.
Example loop
- frontal eye fields and PC to caudate and SNr (inhibits SC)
- VA/MD thalamus
- frontal eye fields
- frontal eye fields and PC directly to SC
-
Direct: Go!
- Direct pathway feeds information to the thalamus via striatum and GPi
- Results in an increase in muscle activity
-
Indirect: Stop!
- Indirect pathway includes a ‘side loop’ from GPe > STN > GPi
- Net effect is suppression of muscle activity
- This pathway dominates during inactivity
Parkinson’s Disease: Effect of DA Loss
- Dopaminergic cells in the SNc are lost; striatum neurons eventually die, leading to disengagement of the direct pathway and default prevalence of the indirect pathway.
- Increased excitation and decreased inhibition of GPi result in enhanced inhibition of the thalamus, leading to hypokinesia i.e. difficulty starting motor program.
- Symptoms include tremor, rigidity, poor facial expression, and saccades.
- tremor and rigidity of both flexors and extensors not explained by hypokinesia
![[Pasted image 20240314140120.png]]
Huntington’s Chorea
- Uncontrolled, abrupt, and jerky movements of distal muscles due to a chromosome 4 defect causing GABAergic cell death in the striatum.
- Early D2 MSNs and later D1 MSNs are affected, applying harder brakes to STN and reducing basal inhibition on the thalamus, leading to execution of otherwise suppressed motor behaviors.
- Results in dementia due to retrograde loss of cortical neurons as striatal targets die.
![[Pasted image 20240314140134.png]]
Movement Disorders
- Athetosis: Slow, involuntary convoluted writhing movements; symmetry maintenance is difficult.
- Chorea: Quick, involuntary “dance-like” movements, not repetitive or rhythmic.
- Hyperkinesia: Chorea and Huntington’s disease are examples.
- Ballism: A form of hyperkinesis.
- Describe the contents and location of the cavernous sinus, and describe the expected clinical signs and symptoms of cavernous sinus thrombosis
Contents of the cavernous sinus:
- trigeminal ganglion
- V1, V2; III, IV, VI
- internal carotid artery
- sympathetic nerves
Cavernous sinus syndrome is characterized by ophthalmoplegia and sensory deficits over the head due to combined deficits of the three cranial nerves (third, fourth, and sixth) responsible for eye movements and pupil function, and at least one branch of the trigeminal nerve.
may cause isolated or combined ophthalmoplegia, painful ophthalmoplegia, anesthesia in CNIII, unitemporal or bitemporal visual field defects, acromegaly, and galactorrhea
- A lesion in spinocerebellum would cause what signs? A lesion in cerebro? A lesion in…?
- spinocerebellum:
Ataxic Gait; Uncoordinated, Clumsy Movements of the Limbs; Stagger to Side of Lesion.
- cerebrocerebellum:
- Hypotonia & Intention Tremor- ipsilateral to cerebellar lesion
- Dysmetria - Overshooting Targets: a failure to provide cerebral cortex with information necessary to plan and execute the movement accurately
- Dysdiadochokinesia - Loss of Rhythmic Control, especially with alternate limb patterns
- Loss of Timing and Control of Speech
- vestibulocerebel:
- Ataxic Stance (Swaying – Like a Toddler)
- Nystagmus (Lateral, Fast-Slow Eye Movements)
- Which two CNs are responsible for the light reflex arc. Describe the arc. Describe how to test it
The pupillary response or pupil reflex constricts the pupil in response to light ^[https://www.ncbi.nlm.nih.gov/books/NBK537180/].
The afferent segment of the pupillary response are the ganglion cells that form the optic nerve. They project from the retina to the midbrain. travels to the pretectal olivary nuclei. It decussates in the nasal retina but not in the temporal retina.
The interneuron segment of the pupillary response are the cells of the pretectal nucleus. They project bilaterally to the parasympathetic nuclei of CNIII, known as Edinger-Westphal nuclei (preganglionic parasympathetic nuclei in the midbrain.)
The efferent segment runs from the Edinger- Westphal nuclei to the pupillary constrictor muscle to constrict the pupil, via the ciliary ganglion, which sends postganglionic axons to directly innervate the iris sphincter muscles ^[https://www.ncbi.nlm.nih.gov/books/NBK537180/].
First order pre ganglionic parasympathetic fibres exit the mifbrain in the oculomotor nerve, without crossing, synapsing in ciliary ganglion.
Second order post ganglionic neurons send axons from the ciliary ganglion to the sphincter pupillae via short ciliary branches.
The direct response is constriction of pupil in the ipsilateral eye; the consensual response is constriction of pupil in the contralateral eye.
It is tested by shining a light into one pupil and looking for a response in the other pupil (which constricts as well).
The swinging lamp sign: move light to the contralateral pupil; the ipsilateral pupil will then dilate after light has moved away from it (this is called an afferent pupillary defect) ^[https://www.derangedphysiology.com/files/cranial%20nerve%20exam.pdf]
The pupillary reflex exam is considered part of a neurological exam.
- Describe the MLF and its function. Describe lesions of MLF
- Axon bundles close to the midline from Interstitial nucl of Cajal (just above the aqueduct in midbrain) to the upper cervical spinal cord.
- Important in coordinating head-eye movement.
- Connects nucl III, IV, VI (internuclear fibres - must communicate to move together e.g. to look to right, left with both eyes).
- Has input from gaze centres (tectum), cerebellum, vestibular organs (CN VIII).
- Carries fibres of the tectospinal, med. vestibulospinal, and reticulospinal tracts.
- Innervates some neck & upper limb mm.
Lesion e.g. in MS results in RINO
presents as an inability to perform conjugate lateral gaze and ophthalmoplegia due to damage to the interneuron between two nuclei of cranial nerves (CN) VI and CN III (internuclear).[1] This interneuron is called the medial longitudinal fasciculus (MLF). The MLF can be damaged by any lesion (e.g., demyelinating, ischemic, neoplastic, inflammatory) in the pons or midbrain. The MLF is supplied by branches of the basilar artery and ischemia in the vertebrobasilar system can produce an ischemic INO.
- What is the origin of the sympathetic nervous system
T1-L2 : Paravertebral chain
- Label a sagittal diagram of the eye
- Label the inner/middle/outer ear
- Describe the circle of Willis
- There are 2 major arteries supplying blood to the brain - the Vertebral A. and the Internal Carotid A.
- The ‘communicating arteries’ (ant & post) form an anastomosis between these two systems - the Circle of Willlis.
Circle of Willis
- There are 2 major arteries supplying blood to the brain - the Vertebral A. and the Internal Carotid A.
- The Internal Carotid A:
- ascends within the carotid sheath
- enters the cranium through the carotid
note: no branches outside skull
- The Vertebral A:
- ascends the cervical vertebrae within the f. transversaria
- enters vertebral canal by penetrating the posterior atlanto‐occipital membrane
- enters the cranium via the f. magnum
- Describe the blood supply to the brainstem
The vertebral and basilar arteries supply the brainstem and cerebellum.
#### Vertebrobasilar System
- Vertebral artery
- Posterior inferior cerebellar artery
- Posterior spinal artery
- Anterior spinal artery
- Basilar artery
- Anterior inferior cerebral artery
- Superior cerebellar artery
- Posterior Cerebral artery
Vertebral Artery
- Branch of the 1st segment of the subclavian artery
- Runs within foramen transversarium of C1-6
- turns at C2 to enter C1 foramen
- Enters dura between C1 and foramen magnum
- Joins the contralateral partner to form the basilar artery in front of the pons
- Within the cranium, they are ventrolateral to the medulla.
- End adjacent to the upper medulla at the junction of the L and R Vertebral Aa –> Basilar A.
- Branches supply the medulla and most of the inferior surface of the cerebellum
Branches
- Posterior spinal arteries are paired branches and occupy the posterolateral sulcus
- Anterior spinal arteries form a single vessel that occupies the anterior median sulcus
- Run down the full extent of the cord, reinforced by segmental branches at each level
- Posterior Inferior Cerebellar Artery (PICA)
Anterior and Posterior Spinal Arteries
- Branches of V4 (intercranial) segments of the vertebral artery
- Anterior spinal artery supplies the anterior part of the medulla before meeting its partner at the foramen magnum to supply the anterior cord
- occlusion can have neural consequences because it supplies medulla
- Posterior spinal arteries do not meet
- Supply posterior 1/3 of the spinal cord (Posterior spinal arteries)
- Supply anterior 2/3 of the spinal cord (Anterior spinal artery)
Basilar Artery
- Formed by the union of vertebral arteries at the pontomedullary junction
- Unpaired
- Major branches: anterior inferior cerebellar artery, superior cerebellar artery, brainstem perforators (short, long, circumflex), posterior cerebral artery
- note that there are other unnamed branches e.g. perforators and circumflex to pons
3 Cerebellar Arteries
Three in total to supply hemispheres and deep nuclei:
- Superior
- Anterior inferior
- Posterior inferior
![[Pasted image 20240311195049.png]]
### Posterior Inferior Cerebellar Artery (PICA)
- Branch of V4 (intracranial) segment of the vertebral artery
- Courses between the medulla and cerebellum then passes to the inferior cerebellar surface
- Supplies lateral medulla and inferior cerebellum
- also supplies some of pons
### Anterior Inferior Cerebellar Artery
- also supplies some of pons
- The 1st branch of the basilar artery arises anterior to the pons
- Branches supply the anterior inferior cerebellum, lateral pons, cranial nerves VII and VIII
Superior Cerebellar Artery
- Branches of the distal basilar artery, immediately proximal to PCA
- May be duplicated
- Supplies superior cerebellum, cerebellar nuclei, cranial nerves III and IV
Brainstem Territories Supplied by Branches of Vertebral and Basilar Aa
![[Pasted image 20240311195124.png]]
- Vascular lesions of these branches result in specific symptoms.
- Lower Medulla:
- Branches of the anterior spinal arteries and direct branches of the vertebral artery supply territories that include lower, spinal V nucleus and tract, arcuate fibers, and medial lemniscus, pyramids, spinothalamic tracts.
- Posterior spinal artery territory includes both the gracile and cuneate nuclei of the dorsal column system.
Posterior Cerebral Artery
- Curves laterally and posteriorly around the midbrain (above the tentorium cerebelli).
- Superior Cerebellar Artery does a similar thing (below the tentorium cerebelli).
- Supplies tectum, most of the cerebral peduncle (except the most medial part) via perforators, oculomotor (III) nucleus, and Edinger Westphal nucleus.
- The proximal part is joined by the Posterior Communicating Artery.
- Runs posteriorly along the medial/inferior margin of the temporal lobe, then dorsally along the parieto-occipital sulcus.
- Central branches supply the thalamus, pineal, midbrain, posterior parts of the putamen, and globus pallidus.
- Cortical branches supply the entire inferior surface of the temporal lobe, lateral and medial surfaces of the occipital lobe (including V1, V2, and V3).
- Describe the blood supply to Broca and Wernicke
The middle cerebral artery supplies blood to Wernicke’s and Broca’s regions in the brain. Damage to the superior division, which supplies the lateroinferior frontal lobe, damages Broca’s area and affects language expression.
- An intention tremor is related to which part of the cerebellum?
The most common site for cerebellar lesions that lead to intention tremors has been
reported to be the superior cerebellar peduncle,in cereberocerebellum.
dEFICITS of spinocerebellum - dysmetria, dysdiadochokinesia, scanning speech, hypotonia
vestibulo - nystagmus, ataxicstance
spino - gait ataxia
- Label the layers of the meninges
Meninges
The brain and spinal cord are surrounded by three membranes, which are collectively called the meninges. The three membranes are called the dura mater, arachnoid mater, and pia mater.
Dura mater
The dura mater is the external membrane;that is, the outermost membrane of the three meningeal layers. The dura mater itself consists of two layers:
- The periosteal layer covers the skull’s inner surface.
- The meningeal layer is technically the true dura mater, as this covers the brain [+].
The meningeal layer of the dura mater extends inward in four places formingdural folds or septa. These foldsdivide the cranial cavity, which createsthe subdivisions of the brain. The dural folds act to restrict movement of the brain.
The falx cerebri divides the 2 cerebral hemispheres as it descends from midline of the roof of the skull (appr parallel to sagittal suture) to the corpus callosum.
The tentorium cerebelli separates the brain and the cerebellum.
Note the blue lines between the layers of the dura. These are the dural venous sinuses that drain the blood from the brain to the internal jugular vein.
Although the dura attached to the bone of the skull, head injury that may damage dural vessels may lead to the pooling of blood between the dura and the skull, described as epidural bleed—> epidural haematoma.
Arachnoid mater
The arachnoid mater is the middle membrane of the meninges. This membrane is elastic and can be described as loose fitting. This is because the membrane doesn’t follow the bumpy surface (formed from the grooves)of the brain. The space between the arachnoid mater and the dura mater is called the subdural space. This is a thin, space which is spanned by veins draining blood from the brain to the dural sinuses, which deliver the deoxygenated blood to the heart via the internal jugular vein.
The space between the arachnoid mater and the pia mater is called the subarachnoid space. This space is filled by cerebrospinal fluid (CSF), and is significantly wider than the subdural space. The subarachnoid space also contains the largest blood vessels that supply the brain. The arachnoid mater and subarachnoid space are named due to the spiderweb-like extensions that extend from the arachnoid mater to the pia mater. These extensions holdthe two layers together.
Pia mater
The pia mater is the internal membrane(that is, the innermost membrane of the meninges). This membrane is attached firmly to the brain by astrocytes, and so follows every curve formed by the grooves (unlike the arachnoid mater). The pia mater is the most delicate of the three membranes. Due to its close relationship with the brain tissue, there is no subpial space.
- What cells surround the cranial nerves?
Schwann cells
Can develop neoplasm : considered extra-axial
- What are the functional roles of the brainstem
- mapping internal environment
- mapping external environment
- vital processes regulation
- modulate brain activity in response to multiple inputs
- mapping body surface’
- pattern generator e.g. for vital functions
Describe inputs and outputs of the cerebellum
- cerebropontocerebellar:C/L - MCP –> cerebrocerebellum–>
- cerebroreticulocerebellar–> MCP ICP –> I/L -> cerebrocerebellum –>
- CEREBROOLIVO (input also from red)CEREBELLAR –> ICP (CLIMBING) C/L –> cerebrocerebullum –>
- spinocerebellar all to I/L, all but ventral via ICP (SCP) -> spinocerebellum
- vestibuloceebellar -> ICP -> I/L -> vestibulocerebellum
Projections from cortices to deep nuclei:
- dentate
- modifies I/L motor activity via SCP
- progects to CST via VL thalamus to modulate conscious descending activity
- glose emboliform rubral
- I/L
- via SCP to red nucleus -> rubrospinal
- influence proximal flexor UL muscles
- fastigial vestibula
- ICP
- LMNS of spinal cord - extensor muscle tone - posture
- also contributes to MLF – coordinating eye movement
- fastigial reticular – ICP medial and lateral RSTs
fastigial uses ICP, rest use SCP. cerebro uses MCP except cerebroolivo
lateral zone –> fastigial nucleus
paramedial –> GE
median -> F
Note also re vestibulocerebellar pathway – direct afferent input via SCP from SC and primary VC
- What is the function of the reticular activating system? What are the three basic areas?
Reticular Activating System:
- Arouses the cortex
- Maintains wakefulness
- Interacts with the limbic system, autonomic nervous system, and reticular activating system in the physiological processing of emotion.
Brainstem reticular nuclei:
- Modulates intentional and reflexive motor activity e.g. reticulospinal tract projections to spinal cord, and cerebellum
- Modulates pain transmission (PAG to raphe nuclei, medullary reticular formation to posterior horn of spinal cord)
- Controls ANS functions (viscera to autonomic nuclei)
- Controls arousal and consciousness (ARAS)
three basic areas:
In the medial column – the raphe nuclei.- mood and PAG
In the paramedian column – gigantocellular nuclei (because of larger size of the cells)- RST
In the lateral column – parvocellular nuclei (because of smaller size of the cells)- arousal
- Describe somatotopy of sensory and motor cortices
‘The brain cannot see’ - therefore, it uses maps to identify . process incoming information.
Primary centres are the first port of call for information coming into the cortex. They represent a single modality i.e. vision, somatosensory, auditory etc.
Associative areas cross-reference all information coming into the brain so that it can be interpreted. These are multi-modal-
Note
- spinocerebellum
- medial lemniscus
- What structures comprise the limbic system? What is the function of the components?
The limbic system categorises human emotional experiences as pleasant or unpleasant mental states
- amygdala in the archistriatum of the archicortex or hippocampus
- located within the inferior horn of the lateral ventricle. Below it, seen on the inferior surface of the brain, is the parahippocampal gyrus.
- The ‘_uncus’_is the most medial part of the temporal lobe
- GP of paleostriatum of paleocortex or entorhinal cortex
- receives input from all areas of cortex, especially the high order association areas of neocortex, amygdala
- holds representations of emotion and pain
- where the interoceptive meets the exteroceptive self
- outputs to hippocampus
- together these two comprise the limbic cortex
Limbic
The limbic lobe is an evolutionarily old cortical area. Hippocampus and the parahippocampal gyri form the floor of the inferior limb of the lateral ventricle. The limbic cortices receive information from the amygdala and olfactory cortical areas. Memory formation is linked to the hippocampus. Information from the hippocampus travels through the fornix to terminate in the mammillary bodies, nuclei of the hypothalamus. From here, the information is sent to the the anterior nuclei of thalamus, and to the frontal lobe, through the cingulate cortex.
Due to its central position and inputs from a cortical centres, the limbic system links the conscious, intellectual cortical functions with the unconscious, autonomic functions of the brain stem and diencephalon. It also facilitates memory storage and retrieval, establish emotional states, and expressing emotional states through gesturing.
The amygdala
- is the brain’s alarm system
- responds maximally to threatening stimulithat are relayed there from areas of neocortex (especially face recognition, auditory, olfactory and somatosensory areas, as well asprefrontal areas)
- also gets input from solitary nucleus, cardiorespiratory areas, hypothalamus and brainstem reticular formation.
Hippocampus
The major INPUT to the hippocampus is from higher order, multi-sensory areas of neocortex via the entorhinal cortex.
In addition, the hippocampus receives some direct inputs from pre-frontal cortex, the anterior cingulate gyrus and from the brainstem reticular formation.
The major OUTPUT from the hippocampus is the fornix. The fornix is a distinct bundle of fibres that arises from the surface of the hippocampal gyrus, passing posteriorly, then upwards and anteriorly; the two fornices join as they pass forwards attached to the lower margin of the septum pellucidum, then separate and dive through the hypothalamus to terminate in the mammillary bodies (part of the hypothalamus).
Some fibres from the fornix cross in the midline; others terminate in the septal area.
*note also the cingulate gyrus which registers pain and the emotional experiences, and septal area which has a key role in bonding experiences: trust, empathy and pro-social feelings. Also regulates theta rhyhtms in hipppocampal neurons. Afferents from hippocampus, reticular formation, hypothalamus and amygdala; output to PFC, anterior cingulate gyrus, medial hypothalamus, mamillary bodies, medial thalamus
Postero-medial cortex and self
- Postero-medial Cx (PMC) occupies a very high place in the functional hierarchy
- It mediates awareness of the environment and therefore consciousness
- Its main constituents are the
- posterrio cingulate cortex
- precuneus
- medial prefrontal cortex
- angular gyrus
- It hasnoconnections with primary areas
- Its afferent inputs include:
- parietal and temporal association areas: to make sense of self and surroundings
- premotor regions and frontal eye fields: motor planning areas; controls eye movement and visual attention
- anterior cingulate gyrus: part of limbic, regulates emotions and regulate behaviour
- claustrum, basal forebrain and amygdala: forebrain has roles in sleep, thermoregulation, learning and memory
- dorsal thalamus
- Efferents:
- are largely reciprocalbut also include neostriatum and periaqueductal grey
- Is the most highly metabolically active cortical region, consuming 35% more glucose than other areas of Cx
- note it has dense connections with entorhinal cortex (hippocampus and neocortex) - has memory retrieval role
- Describe the systems implicated in in anxiety and depression?
Changes in Function of Brain Regions
- Increased connectivity in depression of parts of the Default Mode Network including the medial prefrontal cortex, posterior cingulate and hippocampus thought to be related to rumination or preoccupation
- Reduced connectivity in depression of parts of the Cognitive Control i.e. to suppress rumination
-
Hypothalamic-Pituitary-Adrenal Axis Changes
- Elevated HPA axis activity is associated with the stress response
- 40-60% of depressed inpatients show hypercortisolism (evidence of increased HPA activity), especially older patients with melancholic or psychotic depression. However, this test has poor specificity and is therefore not used in clinical practice.
- Dexamethasone suppression test
- In normal subjects: administration of dexamethasone suppresses cortisol secretion for 24 hours
- In those with hypercortisolism: cortisol secretion is not suppressed
Changes in Sleep
- Mania is associated with decreased need for sleep:
- i.e. waking from little or no sleep with an excess of energy
- Depression is associated with:
- Decreased deep (slow wave) sleep
- Increased nocturnal arousal
- Increased nocturnal awakenings
- Reduction in total sleep time
- Increased time in REM sleep
- Increased core body temperature
- Most antidepressants suppress REM sleep
- Agomelatine (a melatonin receptor agonist) normalizes sleep without suppressing REM sleep
Kindling Theory in Bipolar Disorder
- Anticonvulsants may work by reducing the ‘kindling’ of neurons in bipolar disorder
- Brain cells that are involved in an episode are thought to be more likely to be involved in subsequent episodes
- With each episode more and more cells are thus sensitized
- If untreated, the inter-episode period becomes shorter and each subsequent episode’s severity worsens (which is a common observation)
- Describe the production and flow of CSF
- formed in choroid plexus in lateral, 3rd and 4th ventricles
- formed in lateral ventricles
- passes through to 3rd via foramen of munro
- from 3rd ventricle, to 4th ventricle via cerebral aqueduct
- some from 4th to central canal (spinal cord)
- majority of CSF passes through foramina of Magendie and Luschka into cistrna magna, cerebellopontine cisterns
- CSF then enters the subarachnoid space and is absorbed into the venous circulation, by the arachnoid granules
- Name the three deep nuclei of the cerebellum and their function
fastigial, globose, emboliform, and dentate
Fastigial nuclei
- receive spinocerebellar and labyrinthine afferents
- project to the spinal cord and ventral thalamic nucleus
Globose & Emboliform nuclei (interposed nucleus)
- sends i nterpositiorubrothalamic tract to the lateral thalamic nucleus and red nuclus
Dentate nucleus
- receives corticopontocerebellar fibers
- sends dentatorubrothalamic and dentatoolivary tracts
Mnemonic: Don’t Eat Greasy Food (Dentate, Embolform, Globose, Fastigial)
- Name the two types of fibres which input to cerebellum and their origin
Climbing Fibres
- Cell bodies in ION.
- Receive input from cerebral motor cortex and cerebellum via Red nucleus.
- Excite single Purkinje (Pj) cells (1:1 ratio).
- Send collaterals to the deep nuclei.
- Slow rate of activity.
- Provide motor error feedback for appropriate motor timing.
- Most active during learning/training.
- thought to encode sensory input independently of attention/awareness.
Mossy Fibres
- From all areas that provide excitatory input to the cerebellum, except ION.
- A single mossy fibre activates many granule cells, which in turn activate ~200,000s Purkinje cells.
- Have collateral branches to deep nuclei.
- cuneo, spino, ponto, vestibule
- Outline signs of cerebellar dysfunction
Lesions and cerebellar signs:
- D: dysdiadochokinesia () and dysmetria (failure to provide Cer Cx with adequate information needed to plan and execute the movement accurately)
- Ataxia
- Nystagmus
- Intention tremor
- Slurred speech/scanning (loss of timing and control)
- Hypotonia
- Describe the process of transducing a light to electrical signal
- In the outer segment of the photoreceptor light is ‘transduced’ into an electrical signal, through a G-protein-mediated interaction with light sensitive ‘opsins’. Photoreceptors are the most highly metabolically active cells in the body (ie., they are very oxygen hungry).
- bipolar cell: Bipolar cells are located in the middle layer of the retina (INL). Theyget synaptic input from photoreceptor dendrites (in the OPL) and pass information onto ganglion cells.In primates there are around 11 different types of bipolar cell, which process the inputs from photoreceptors in different ways.They play a critical role in ‘managing’ theinformation that is passed on from photoreceptors to ganglion cells.As far as we knowthere are no diseases that stem from problems with bipolar cells.
- ganglion cells: Ganglion cells pass visual information to the brain. This information is a distillation of data from various ganglion cell types that encodecolour, position/acuity or contrast.
- Theyhave long axons that form the innermost layer of the retina, the Nerve Fibre Layer, as they course across the retina, in a stereotypical pattern, towards the optic disc. There they make a 90° turn and leave the eye as the optic nerve (CNII). Their functional characteristics are determined largely by the way they wire up to bipolar cells, although ‘amacrine cells’ also interconnect the GC-bipolar synapses to modulate signal transmission.
The ‘vertical meridian’ is a virtual line that passes through the macula, and divides the retina (almost) in half.
GC axons from retina temporal to the vertical meridian project to the same side of the brain
GC axons from retina nasal to the vertical meridian cross the midline in the optic chiasm.
Step 2: This pattern of GC projections means that the left visual hemifield projects to the right side of the brain (and vice versa)
When you attend to an object each eye sees the object (represented by the white circle in the middle) in the centre of its visual field - so in the diagram, each retina sees both the green and red parts of the visual field (indicated by colouring on the ‘retinas’).
![[Pasted image 20240307093139.png]]
When both eyes are open, the 2 visual fields merge into one (Note the blending of green and red towards the centre of the visual field strip). This field is made up of two ‘hemifields’, on either side of the spot, shown here as green (right visual hemifield) and red (left hemifield).
Because of the pattern of retinal projections at the optic chiasma, the visual hemmifields are represented in the opposite cerebral hemisphere(ie.the right/green hemifield projects through the leftoptic tract, and on to the left cerebral hemisphere).
Step 3 : input from GC to brain
There are four key destinations for projections from the retina.
Suprachiasmatic nucleus
Part of the hypothalamus that regulates circadian rhythms or sleep/wake cycle. Further projections include the pineal gland, to regulate melatonin. The ganglion cells that project to the SCN are distinct from the 3 most commontypes of cells (midget, parasol, bistratified). Rather they expresstheir own photosensitive opsin, melanopsin, and do not rely solely on photoreceptors for excitation.
Pretectal area
This projection provides the input for the circuits that control the pupillary reflex and islargely derived from melanopsin-containing ganglion cells.Cells in the pretectal area project bilaterally to the Edinger-Westphal nucleus (CN III), which sends parasympathetic output to the ciliary ganglion, and thence the constrictor pupillae muscle.
Superior colliculus
These inputs are mapped onto the superficial SC, which receives corresponding, mapped inputs from the visual cortex. SC also receives mapped inputs from the auditory system, and somatosensory system. SC co-ordinates ‘saccadic’ eye movements towards novel stimuli (auditory / somatosensory) for rapid (self-preserving) responses.
dorsal LGN
All information destined for conscious perception must pass through the thalamus, before going to neocortex. the dLGN is the ‘visual nucleus’ of the thalamus, and projects directly to primary visual cortex / V1, also known as ‘striate cortex’.
Projections to the SC and dLGN are mapped
This means that adjacent points in the visual field are represented in adjacent parts of the brain target, preserving the relationship between points. Inthe dLGN there is a map of the visual field in each layer, in an approximately alternating (left eye/right eye) pattern.
Step 5: ### The dLGN sends a mapped projection to primary visual cortex - V1 / Striate cortex / Area 17
- Describe the transduction of sound
Waves travelling to the ear are interpreted as sound. To initiate the sensation of hearing, two physical processes are involved:
Pressure - air particles press against the ear drum and cause it to vibrate and initiate the mechanical part of hearing. The amplitude of the pressure determines the intensity of sound.
Auditory receptors (hair cells) in the cochlea initiate the auditory transduction. The denomination of ‘inner’ and ‘outer’ is in relation to the cochlear axis. Inner hair cells are the primary auditory sensory cells.
- sound waves arrive to the tympanic membrane
- tympanic membrane vibrates
- auditory ossicles vibrate
- displacement of fluid molecules in the membranous labyrinth and basilar membrane
- vibration of basilar membrane
- vibration of organ of Corti
- bending of cilia on hair cells
- change in K+ conductance of hair cell membrane
- oscillating receptor potential (Cochlear microphonic)
- intermittent glutamate release
- intermittent action potentials in afferent cochlear nerves
**Bending of stereocilia depolarises the cell and sends a signal to the auditory nerve
*Opening of mechano-electrical transduction channels (METs) by sound vibration causes entry of K+ and depolarization of the inner hair cell.
*Depolarization opens voltage-dependent calcium channels in the inner hair cell membrane.
*Calcium entry causes transmitter release (glutamate) at the inner hair cell–spiral ganglion cell synapse.
*Released glutamate activates receptors in the spiral ganglion cell, which depolarises and fires an action potential
*Action potentials propagate along the auditory nerve to the brain.
Action potentials in the spiral ganglion cells are collected in the cochlear nerve (CNVIII) that leaves the inner ear (petrous part of temporal bone) through the internal acoustic meatus to reach the pontomedullary junction, where it enters the brainstem.
It synapses in the cochlear nuclei (ventral & dorsal) to form central auditory pathways. Observing the image on the right, you may notice that there are multiple relays on both sides of the brainstem for each ear. We will follow the main central auditory pathway (red):
After synapsing in the ventral cochlear nucl, the axons ascend to the pons to synapse in the superior olivary nucleus bilaterally. Once synapsing in the olivary nucleus, axons form the lateral lemniscus, which ascend to the inferior colliculus of the midbrain. After synapsing in the inferior colliculus, it ascends further to the medial geniculate nucleus of the thalamus, which relays the auditory information to the primary auditory cortex, in the Heschl’s gyrus of the temporal lobe. ^[at lip of lateral fissure, oriented perpendicular to surface of brain in a lateral-medial direction].
- What is prefrontal? Wernicke? PMC?
Areas in the prefrontal cortex are involved in “executive functioning”. This includes abstract thought, planning, consequences of actions, and learned social behaviors. It is thought the prefrontal cortexplays a significant role in working memory.
Broca’s area is involved in language expression. Lesions of Broca’s area are associated with difficulty in speaking in complete sentences, however, language comprehensive is unimpaired. This this type of aphasia is called expressive.
Wernicke’s area is involved in understanding language.
A lesion in Wernicke’s area is associated with an inability to understand both spoken and written language. Patients speak with normal fluency (i.e. rhythm and syntax) but sentences may be meaningless. This is known as receptive or fluent aphasia.
Postero-medial cortex and self
- Postero-medial Cx (PMC) occupies a very high place in the functional hierarchy
- It mediates awareness of the environment and therefore consciousness
- Its main constituents are the
- posterrio cingulate cortex
- precuneus
- medial prefrontal cortex
- angular gyrus
- It hasnoconnections with primary areas
- Its afferent inputs include:
- parietal and temporal association areas: to make sense of self and surroundings
- premotor regions and frontal eye fields: motor planning areas; controls eye movement and visual attention
- anterior cingulate gyrus: part of limbic, regulates emotions and regulate behaviour
- claustrum, basal forebrain and amygdala: forebrain has roles in sleep, thermoregulation, learning and memory
- dorsal thalamus
- Efferents:
- are largely reciprocalbut also include neostriatum and periaqueductal grey
- Is the most highly metabolically active cortical region, consuming 35% more glucose than other areas of Cx
- note it has dense connections with entorhinal cortex (hippocampus and neocortex) - has memory retrieval role
- What are primary and secondary cortical areas?
-
‘Primary’ / 1° areas have a single function, and do not interconnect with each other.
- ‘Secondary’ / 2° areas deal with specific aspects of a modality (eg colour). They may also ‘share’ some information.
- ‘Association’ areas_associate_information across modalities.
-
‘Higher order’ areas are sometimes referred to as ‘hubs’ and extract information across a wide range of modalities, as required for example, when understanding the rhythm, cadences, and meaning of speech. This is a fundamental feature of cognition.
Recall that projection, commissural and association fibres connect regions of the brain.
key- What are higher associational fibres?
Key association fibres include:
- arcuate fasciculus: connects Broca with Wernicke’s (see also [[Neurology - Lecture 4]])
- superior occipitofrontal fasciculus connects the posterior parietal cortex and premotor cortex
- uncinate fasciculus connects orbital cortex with anterior temporal lobe
- Provide differential diagnoses for double vision
- diplopia as muscular= NMJ, myasthenia gravis
- MS
- CN palsy 346
- Honer- symp n injury
- List the structures of eye, their innervation, type of innervation and broad function
- cornea
- innervated by long ciliary branches of V1
- sensory innervation (for light touch as well as pain)
- function: helps to protectthe corneal surface from damage from accumulation of particulate matter
- conjunctiva
- long ciliary branches of V1
- sensory i.e. light touch
- protection - helps detect particulate matter
- upper eyelid
- long ciliary branches of V1
- sensory (light touch )
- sweeps the tear film across the corneal surface
- lower eyelid
- V2 Maxillary (Infraorbital N)
- sensory (light touch )
- retina
- Optic nerve
- special sensory
- Transmits sensory information to cortex
- lacrimal gland
- V1 and facial nerve
- touch and pain fibres/secretomotor (parasympathetic)
- tears secreted and swept over surface for lubrication and cleaning
- levator palpebrae superioris
- Upper division of Oculomotor nerve, T1-4 fibres carried by V1 branches to Upper division of III
- somatic motor and sympathetic
- dilator of the orbit; elevates the upper eyelid / tarsal plate; mediates ‘eyes wide open’ in a stress response; provides tone to the resting, open position
- orbicularis oculi
- facial (orbital branches)
- somatic motor
- sphincter of orbit
- lateral rectus
- abducens
- somatic motor
- abducts eye
- superior oblique
- trochlear
- somatic motor
- works with inferior rectus when looking downwards
- superior inferior and medial rectus
- oculomotor inferior division
- somatic motor
- various movements:
- ciliary
- oculomotor via ciliary ganglion
- parasympathetic
- Draws the lens and lens capsule forward, allowing the lens to bulge and bend light more, during near vision = Accommodation
- sphincter pupillae
- oculomotor via ciliary ganglion
- parasympathetic
- reduce light by constricting pupil and during accommodation
- dilator pupillae
- T1-4. Could be via Long Ciliary brs of V1, OR from symp branches that pass through ciliary ganglion (with III)
- sympathetic
- increase light in sympathetic response allows maximum light to reach posterior chamber
- Describe photoreceptors, and distinguish between rods and cones
Humans have 4 types ofphotoreceptors.
RODS:named as such as based on their narrow, rod-like appearance.
Note the inner and outer segments of the photoreceptors. The inner segments are responsible for providing energy and the replenishment of proteins important for cell function. Indeed, photoreceptor inner segments have the highest concentration of mitochondria in the human body, indicating the high energy demand of these cells. The outer segment of the photoreceptors contain light sensing photopigments. The light sensitive pigment expressed by rods is rhodopsin. Rods respond in low levels of light in the 425-575 nm range.
CONES:respond in bright light across the entire ‘visible spectrum’ (indeed the cone responses determine what the visible spectrum is).
Each human cone expresses one of threephotopigments / cone opsins that is sensitive to light:
- Short wavelengths (~400-500 nm), which we see as (or call)blue - hence ‘blue / S-cones’
- Medium wavelengths (430-650 nm),which we see as (or call)green - hence ‘green / M-cones’
- Longwavelengths (450-675nm),which we see as (or call)red - hence ‘red / L-cones’
Note that the peaks of the curves (below) indicate the frequency where each of the cone types _responds at maximum strength_ (peak sensitivity).
In daylight, perceived colour is determined by the relative activation of the 3 cone types
Genes that encode the M- and L-opsins are both on the X-chromosome, leading to a higher incidence of red-green colour vision defects in males, compared with females.
The nucleotide sequences coding the M- and L- ospins are almost identical: L-opsin has arisen as a mutation of the M-opsin gene. The S-opsin gene is on a different chromosome.
- Describe macula
- macula lutea
- The high density of yellow xanthophyll pigment, filters damaging blue wavelengths of light, and has anti-oxidative qualities. Macula (=spot) lutea (=yellow).
- It is the part of the retina used in most of your minute-to-minute activities. It is approximately in the centre of the retina, and has a very high density of cells in all layers, and a relative absence of large retinal vessels coursing across it. Rather, retinal vessels tend to arch around the macula (as do the axons of ganglion cells).
- fovea centralis
- The ‘fovea’ (dip/depression) is in the centre of the macula (centralis) and is the part of the retina that has the highest capacity for resolving fine details (‘acuity’). The presence of a shallow depression is its most distinctive feature, but the depression itself does not contribute to acuity.
- At the location of the fovea there is the highest density of cone photoreceptors (no rods), and the least amount of neural convergence of signals from photoreceptors through to GC. That means that a single GC can get a signal from a single cone, at the fovea (but nowhere else in the retina).
- There are no retinal vessels at the fovea, and the depression itself it likely secondary to that important adaptation.
- Macula is responsible for almost all our ‘useful’ vision – reading, recognising faces, discriminating details
- it has high levels of vitamin A derivatives that filter damaging short wavelength light = hence macula lutea
- Reduced vascularity of macula and absence of retinal vessels from the fovea is of key importance to optical quality because it prevents shadowing of the photoreceptors by vessels and blood cells
- Describe retina and its components
Cross section through the retina.
The retinais made up of 2 layers of connections/synapses (inner and outer plexiform layers), and 3 layers of cells (ganglion cell layer, inner and outer nuclear layers) including the photoreceptors and theoutmost layer of light transducing elements, the photoreceptor outer and inner segments (PRS).
The transducing elements (PRS) are extensions of the ONL cells (photoreceptors)and are intimately related to the retinal pigmented epithelium (RPE).
![[Pasted image 20240307091119.png]]
![[s182_9_002i.jpg]]
![[EE020b.jpg]]
Note also the presence of blood vessels (small red dots).
Key cells of the retina:
- photoreceptor
- Both rods and cones have cell bodies in the outer nuclear layer, and axonal processes in the outer plexiform layer. The outer segments of photoreceptors are intimately associated with the retinal pigmented epithelial (RPE) cells. Light entering the retina passes though 5 layers of cells and connections before entering the outer segment of a photoreceptor.
- In the outer segment of the photoreceptor light is ‘transduced’ into an electrical signal, through a G-protein-mediated interaction with light sensitive ‘opsins’. Photoreceptors are the most highly metabolically active cells in the body (ie., they are very oxygen hungry).
- Disorders and diseases affecting photoreceptors:
- Retinal detachment.The molecular processes involved in visual transduction include reactions that take place in the RPE. In addition, the outer retina receives its nutrients (O2 and glucose) by diffusion, from the underlying choroid. During detachment, the distance between the outer retina and choroid increase, therefore nutrient delivery reduces (Fick’s law). Thus, detachment of the retina from the RPE (retinal detachment) results in vision loss. Photoreceptors can survive only for about 24 hours if detached from the RPE; therefore the condition of ‘retinal detachment’ requires urgent attention.
- Photoreceptor dystrophies are inheritable/genetic disorders that lead to progressivephotoreceptor death, and are a significant cause of vision loss in teenagers and young adults, who were normally sighted at birth (“retinitis pigmentosa”).
- bipolar cell: Bipolar cells are located in the middle layer of the retina (INL). Theyget synaptic input from photoreceptor dendrites (in the OPL) and pass information onto ganglion cells.In primates there are around 11 different types of bipolar cell, which process the inputs from photoreceptors in different ways.They play a critical role in ‘managing’ theinformation that is passed on from photoreceptors to ganglion cells.As far as we knowthere are no diseases that stem from problems with bipolar cells.
- ganglion cells: Ganglion cells pass visual information to the brain. This information is a distillation of data from various ganglion cell types that encodecolour, position/acuity or contrast.
- Theyhave long axons that form the innermost layer of the retina, the Nerve Fibre Layer, as they course across the retina, in a stereotypical pattern, towards the optic disc. There they make a 90° turn and leave the eye as the optic nerve (CNII). Their functional characteristics are determined largely by the way they wire up to bipolar cells, although ‘amacrine cells’ also interconnect the GC-bipolar synapses to modulate signal transmission.
- Diseases of GC: In glaucoma ganglion cell axons become compressed at the optic disc, which results in ganglion cell death, usually in the periphery, and in distinct patches of the retina.
- Peak GC density is about 30,000 cells / mm sq, at 1 mm eccentricity. This is 30x greater than the average GC density across the retina.
- Each GC represents a line of direct communication to the brain. There are about 100,000 direct lines of information coming out of the foveal region and going to the brain; in peripheral retina there would be <5,000. Thus, the brain gets more information, of better ‘quality’, from the fovea / macula, than it does from other parts of the retina.
Note:
##### The retina is not uniformly effective at the 3 key elements of vision (colour, acuity and contrast / motion)
Different regions of the retina are specialised for different functions. These functions are determined by
- Differences in photoreceptor distribution e.g. photoreceptor topography: there is a 1mm region where cones outnumber rods ^[note rods and cones generated in utero and do not regenerate]
- Differences in the components of the neuralcircuits that process the information coming from photoreceptors, and the way they are ‘wired’. - gnaglion cell topography (there is a 400 um region of the fovea where ganglion cells and rods are absent)
Macula layers
![[Pasted image 20240307091745.png]]
- macula lutea
- The high density of yellow xanthophyll pigment, filters damaging blue wavelengths of light, and has anti-oxidative qualities. Macula (=spot) lutea (=yellow).
- It is the part of the retina used in most of your minute-to-minute activities. It is approximately in the centre of the retina, and has a very high density of cells in all layers, and a relative absence of large retinal vessels coursing across it. Rather, retinal vessels tend to arch around the macula (as do the axons of ganglion cells).
- fovea centralis
- The ‘fovea’ (dip/depression) is in the centre of the macula (centralis) and is the part of the retina that has the highest capacity for resolving fine details (‘acuity’). The presence of a shallow depression is its most distinctive feature, but the depression itself does not contribute to acuity.
- At the location of the fovea there is the highest density of cone photoreceptors (no rods), and the least amount of neural convergence of signals from photoreceptors through to GC. That means that a single GC can get a signal from a single cone, at the fovea (but nowhere else in the retina).
- There are no retinal vessels at the fovea, and the depression itself it likely secondary to that important adaptation.
- Describe/label fundoscope
The optic nerve is 4 mm away from the fovea.
The retina is transparent, allowing you to view the vessels of the choroid (orange streaks) which form a layer on the outerside of the retina.
The region in the centre of the image which has no retinal vessels running across it is the macula. We use the maculafor all of our ‘most useful’ vision - that is, reading and writing, recognizing faces, seeing colours, seeing details.
![[Pasted image 20240307092031.png]]
- Macula is responsible for almost all our ‘useful’ vision – reading, recognising faces, discriminating details
- it has high levels of vitamin A derivatives that filter damaging short wavelength light = hence macula lutea
- Reduced vascularity of macula and absence of retinal vessels from the fovea is of key importance to optical quality because it prevents shadowing of the photoreceptors by vessels and blood cells
- the optic disc or blindspot is the site for sensory fibres e.g. ganglion cell axons to exit the eye to go to the brain. These fibres constitute the optic nerve - CN II
- There are about 1.3 million ganglion cell axons that enter the opti nerve
- 25% of the fibres come from the central 2 mm of the retina, including the fovea
- Describe meningism and how to investigate for it
Is there meningism?
- ‘Meningism’ refers to a cluster of signs and symptoms indicating meningeal irritation or inflammation
- Neck rigidity is the hallmark
- Photophobia is common
- Pain may be increased with stretch of meninges
- Kernig’s sign (pain on straightening legs with hips flexed)
- Brudzinksi’s sign (active flexion of hips/knees on passive flexion of neck)
- Always a serious symptom, demands further investigation
- Important causes are:
- Subarachnoid blood
- Meningitis (bacterial, viral)
- Mild cases may be confused with migraine or cervicogenic headache
Blood cultures. A blood sample is placed in a special dish to see if it grows microorganisms such as bacteria. ... Imaging. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans of the head may show swelling or inflammation. ... Spinal tap.
- Describe the differences between UMN and LMN lesions
Upper Motor Neuron - spastic weakness
- Increased tone
- Pyramidal pattern of weakness (relative preservation of upper limb flexors and lower limb extensors)
- Hyper-reflexia
- Exacerbated deep tendon reflexes / Clonus
- Babinski sign +ve
- Hoffman’s Sign +ve
- Superficial abdominal reflexes are absent
- Cremasteric reflex (L1) is absent
- Minimal muscle atrophy secondary to disuse
- Difficulty placing foot on edge
Lower motor neuron – flaccid weakness
- Decreased tone
- Non pyramidal weakness
- Diminished or loss of deep tendon reflexes
- Babinski sign -ve
- Hoffman’s sign -ve
- Marked muscle atrophy
- Muscular fasciculations present (When there is slow destruction of LMN cell)
- Muscular contracture (shortening of the paralysed muscles)
- Compare and contrast Broca’s and Wernicke’s aphasias, especially presentation
- Define the following: ; first pass clearance; absorption and bioavailability; first pass clearance; metabolism
What is first pass metabolism?
- Orally administered drugs that are absorbed travel through the portal system and the liver before entering systemic circulation
- If a percentage of the drug is metabolised by the liver only the remainder of that drug will be able to enter systemic circulation to exert its effect (reduced bioavailability)
- requires a larger dose orally than parenterally
Metabolism
- The process of chemical modification of a drug
- Mainly via enzymes
- Liver primary site of metabolism
- other sites include: kidneys, lungs, intestines
- For the majority of drugs metabolism results in the formation of a more water-soluble compound or metabolite that can be more readily excreted
- clears the parent compound from circulation and promotes excretion
Prodrug - drugs that require activation (metabolism) to elicit a therapeutic action
**CYP enzymes
- CYP enzymes responsible for Phase 1 (functionalisation) metabolism
- CYP enzymes found in the smooth endoplasmic reticulum
- Abundant in hepatocytes
- More than 50 varieties. Three main families
- Genetic polymorphisms occur altering clearance of particular medications
- Responsible for many drug interactions
- Liver disease can effect the performance of these enzymes
Hepatic clearance
- Depends on hepatic blood flow (Q) and extraction ratio (EH)
- Hepatic extraction ratio (EH):
- the fraction of drug entering the liver in the blood that is irreversibly removed by metabolism on each pass through the liver. (0.7 = 70% removed)
- Hepatic clearance (Cl)= Q. EH
- Hepatic clearance can be:
- low extraction:
- clearance capacity by limited by liver enzymes to clear drug (clearance is independent of blood flow)
- high extraction
- clearance capacity limited by delivery of drug to the liver (blood flow)
- low extraction:
Absorption
Before a drug can be distributed to its site of action it must be absorbed
Drugs need to be able to cross biological membrane(s) to reach systemic circulation.
Lipid soluble drugs readily pass through lipid membranes Ionised drugs have difficulty crossing cell membranes Aquaporins in cell membranes allow the passage of small uncharged water soluble substances
Passive diffusion and carrier-mediated transport allow movement of drugs through the body
Variables that affect drug absorption:
Blood flow
Rich blood supply enhances absorption
Solubility
A drug must be in solution to be absorbed
Ionisation
Many drugs are weak acids or bases
Ionised form does not diffuse readily through cell membranes; unionised form is usually more lipid soluble and more capable of crossing cell membranes (Extent of ionisation is dependent on the pH of the environment)
Formulation
Drug formulations can be manipulated to achieve desirable absorption characteristics (eg slow release or enteric formulations)
Route of administration can affect both onset and magnitude of drug action.
A drug can enter systemic circulation by being injected there (IV) or absorbed from extravascular sites
Distribution
The process of reversible transfer of a drug between one location and another (one is usually blood) in the body. After a drug enters systemic circulation it can be distributed to various compartments of the body.
Some drugs remain exclusively in the blood
Distribution will depend on
Permeability across tissue barriers
Binding within the compartments
pH partitioning
Fat:water partitioning
- Provide examples of drugs on each ladder of analgesia
These classes of medications are used for pain and inflammation.
They appear on the first step of the WHO ladder and are considered ‘simple analgesia’. When used with paracetamol a lower dose is required of the NSAID is required.
They are a mainstay of analgesic therapy, but because of their mechanism of action do have side effects and precautions that must be considered before prescribing.
The COX enzymes
COX-1
Expressed in most tissue
Also found in blood platelets
Primarily involved in tissue homeostasis
Responsible for production of prostaglandins involved in:
Gastric cytoprotection Platelet aggregation Renal blood flow autoregulation Initiation of parturition
COX-2
Induced in many inflammatory cells
Responsible for prostinoid mediators of inflammation
Activated by:
Inflammatory cytokines Interleukin-1 Tumour necrosis factor-⍺ Antipyretic effects: Temperature balance is regulated by hypothalamus, NSAIDs rest this control returning it to normal point when fever is present Do not alter normal temperature Achieved by inhibition of prostaglandin production in the hypothalamus
Analgesic effects:
Used for mild to moderate pain caused my inflammation or tissue damage
Peripherally ↓ prostaglandin production that sensitise receptors to inflammatory mediators
Paracetamol (acetaminophen):
First line therapy in most pain managment strategies (first rung on the WHO ladder)
Mechanism of action is not fully understood
Inhibition of central prostaglandin synthesis
Paracetamol has negligible anti-inflammatory effects.
Does not have gastric or platelet adverse effects associated with NSAIDs
Although generally less effective than NSAIDs for musculoskeletal pain, its favourable safety profile in therapeutic doses justifies a trial of paracetamol first line for mild to moderate pain in most indications.
Often reduces doses needed of other agents (NSAID and opiod sparing)
Paracetamol may also be used to reduce the use of NSAIDs and thus the risk of NSAID adverse effects.
Indications:
Mild-to-moderate pain Fever Adjunct to moderate-severe pain
Adverse Effects:
Uncommon Occasionally skin reactions Opioids Considered 'strong' analgesics and occupy the top rung of the WHO ladder An opioid is any substance that produces morphine like effects All receptors are G protein coupled receptors There are many opioid receptors but the mu receptor is the one MOST responsible for analgesia and all opioids act on this receptor (but many act on others too - which mostly contribute to the side effect profile)
Opioids promote opening of potassium channels and inhibit opening of voltage-gated calcium channels
↓ neuronal excitability ↓ transmitter release Inhibition at a cellular level
Majority of receptors located in the brain and spinal cord
OPIOIDS HAVE VERY LIMITED ROLE IN MUSCULOSKELETAL CONDITIONS
