Neuroscience & Mental Health Flashcards
What are the 2 germinal layers from which the neural tube forms?
Endoderm
Mesoderm
Ectoderm
How does the neural tube form?
A strip of ectoderm proliferates and thickens to form the neural plate down the back of the embryo
The neural groove forms when the neural plate forms. The neural groove fuses at the midline to form the neural canal
What are neural crests?
Cells of the neural tube which do not fuse but instead form a separate source of neural tissue which are the neural crests
Which tissues form the CNS and PNS?
Neuroepithelium - CNS
Neural crests - PNS
Which types of principle cells does the neuroepithelium differentiate to form?
Neuroblasts - neural cells which form neurones with cell bodies in the CNS (motor
Glioblasts - supportive cells of the CNS
Ependymal cells - cells which line the ventricles and the central canal of the CNS
Give 2 examples of glioblasts
Astrocytes
Oligodendrocytes
Why are microglia not considered glioblasts?
They develop from the mesoderm and only then migrate to the CNS
Which principle cells does the neural crest cells form?
Sensory neurones
Post-ganglionic autonomic neurones
Schwann cells
Non-neuronal derivatives
What characteristic is shared by all neural crest cells?
Their ability to migrate long distances in order to reach their periphery
How does the neural tube differentiate into layers?
A cell contracts towards the inner membrane of the neuroepithelium and produces two daughter cells via mitosis
One daughter cells remains on the membrane and eventually returns to the cell cycle and forms the ependymal lining layer
The other daughter cell migrates from the membrane and begins to differentiate to form neuroblasts and glioblasts.
How is differentiation controlled?
By signalling molecules that surround the neural tube which interact with receptors on neuroblasts
They control migration and axonal growth by attraction and repulsion
What are the 3 layers of the neural tube?
Ependymal
Grey
White
With regards to the development of the spinal cord, what develops from the alar and basal plates?
Alar - neuroblasts develop into interneurons with sensory function
Basal - some neurons develop into interneurons and some into motor neurons
What are alar and basal plates called in the mature spinal cord?
Alar - dorsal horns
Basal - ventral horns
What is dorso-ventral patterning?
Signalling molecules derives fro the notochord spread out and induce neuroblasts in the ventral part to differentiate as motor neurons.
Signalling molecules from the ectoderm induce dorsal neuroblasts to develop into sensory cells
From where does the brain develop?
The most anterior tip of the neural tube
What are the 3 primary vesicles?
Prosencephalon - develops into the forebrain
Mesencephalon - develops into the midbrain
Rhombencephalon - develops into the hindbrain
At 5 weeks, what do the further divisions of the fore and hind brain form?
Forebrain:
Telencephalon - forms the two hemispheres
Diencephalon - consists of the thalamus and hypothalamus
Hind brain:
Pons
Medulla
What are the 3 folds during development of the brain?
Cephalic flexure
Pontine flexure
Cervical flexure
What folding of the neural tube occurs during development of the brain?
5 weeks - further differentiation and folding
8 weeks - cerebral hemispheres spread backwards to partially hide the diencephalon
Term- brain is recognisable as mature brain with ventricular system inside
When does myelination end?
Late teens
How does the 4th ventricle form?
Lateral proliferation of the roof plate enlarges the neural canal
How does the relationship of the basal and alar plates change when the 4th ventricle forms?
Basal plates now lie medially whilst alar plate lie laterally
How does the cerebral cortex develop?
A result of migration of neuroblasts towards the pial surface along radial glia
Successive waves of migration then form the cortical layers
What processes does normal neural development depend n?
Proliferation Differentiation Migration Axon growth Synapse formation
How can an understanding of developmental mechanisms lead to treatment of neurological disorders?
Use of stem cells to replace lost neurons
Use on axonal guidance mechanisms to induce regeneration in the CNS
What time of information do the dorsal horns receive?
Sensory information via spinal nerves and dorsal roots
What is the function of ventral horns?
Contain motor neurons whose axons control the muscles of the body via the ventral roots and spinal nerves
Describe the intermediate horns in the thoracic and upper lumbar region
They contain sympathetic preganglionic motorneurons whose axons control visceral function via the ventral roots and spinal nerves
What does the white matter of the spinal cord contain?
Short pathways which interconnect adjacent segments of the spinal cord
And longer pathways which convey information to and from the brain
What are the 3 meningeal coverings of spinal cord and brain?
Dura Mater
Arachnoid mater
Pia mater
How does the meningeal coverings of the spinal cord differ from the brain?
1) There is an extradural space which contains fat and a venous plexus
2) Lateral extensions of the pia mater called dentate ligaments extend to the dura which helps stabilise the spinal cord
3) The filum terminale (pial thread) anchors the low end of the spinal cord to the coccygeal vertebrae
4) The subarachnoid space below the end of the spinal cord is called the lumbar cisterns and contain lumbar and sacral spinal roots (cauda equina)
What does the degree of deficit following a spinal cord lesion depend on?
1) Loss of neural tissue eg. metastases, degenerative disease
2) Vertical level- the higher the level, the more severe the disability
3) Transverse plane- damage to the white matter tends to be more important that damage to the grey matter
What can damage to the ascending of descending spinal tracts produce?
Motor and/or sensor loss
eg. paralysis, anaesthesia
What can develop as a result of raised sensitivity of spinal motorneurons?
Hyperreflexia and/or spasticity
Why might there be functional improvement after damage to spinal cord tracts?
If the tracts are only compressed
What is syringomyelia?
A disorder in which a cyst of cavity forms within the spinal cord, usually occurs in the cervical region and so upper limbs are affected
What is the brainstem?
The part of the CNS, excluding the cerebellum that lies between the cerebrum and the spinal cord
What are the 2 major divisions of the brainstem?
Midbrain- most rostral & anterior
Pons- bulbous structure
Medulla- most caudal and posterior
How is the medulla connected to the spinal cord
Via to foramen magnum
What is the purpose of colliculi?
Super colliculi- important in head and neck reflexes related to vision
Inferior colliculi- involved in auditory reflexes
What does the trochlear nerve (IV) supply?
Superior oblique muscle of the eye
What are the main ascending pathways seen in the brainstem?
Dorsal columns (cuneate fasciculus & gracile fasciculus) to the thalamus, carrying fine touch and proprioceptive information to the brain
How is the cerebellum held onto the back of the brainstem?
Cerebellar peduncles
They are the superior, middle and inferior, connecting the cerebellum to the midbrain, pons and medulla respectively
Where does the optic nerve (II) originate?
Diencephalon
Where do 50% of optic nerve fibres from the retina cross over?
Optic chiasm
Why can the olfactory nerve (I) no be seen in the anterior view?
Its origin is in the cerebrum
Where does the occulumotor nerve (III) arise from?
Interpendicular fossa at the midbrain level
What does the oculumotor nerve (III) supply?
Most of the extrinsic muscles of the eye
Which nerve is responsible for the muscles of mastication?
Trigeminal nerve (V)
Which nerves arise from the pontine-medullaly junction?
Abducens nerve (VI) Facial nerve (VII) Vestibulocochlear nerve (VIII)
What are the pyramids of the medulla?
Motor fibres run down the corticospinal tract through the cerebral peduncle and disappear from view in the pons, then they reappear as the pyramids
What is pyramidal decussation?
95% of the pyramidal fibres cross over to the other side at the base of the medulla
Which cranial nerves arise from the medulla?
(Superior to inferior) Glossopharygeal nerve (IX) Vagus nerve (X) Accesory nerve (XI)
How can cranial nerves be classified by general functions?
1) General somatic afferent- fibres provide sensation from the skin and mucous membranes
2) General visceral afferent- fibres provide sensation from the GI tract, heart vessels and lungs
3) General somatic efferent- fibres supply muscles of the eye and tongue movements
4) General visceral efferent- fibres are preganglionic parasympathetic fibres
How can cranial nerves be classified by special functions?
1) Special somatic afferent- fibres are vision, hearing & equilibrium
2) Special visceral afferent- fibres are for smell and taste
3) Special visceral efferent- fibres supply the muscles involves in chewing, facial expression, swallowing, vocal sounds and turning the head
What are the characteristics of the midbrain level?
‘Mickey mouse’ shaped, defined by cerebral peduncles which are the main fibres coming down from the cortex, into the spinal cord and forming the corticospinal tract
Cerebral aqueduct
Inferior colliculi
Substansia niagra
What is the space between the two cerebral peduncles of the midbrain called?
Interpendicular fossa
What are the characteristics of the cerebral aqueduct, inferior colliculi and substantia nigra?
Cells are full of neuromelanin therefore appear to be black
Neuromelanin is a by-product of dopamine metabolism
What are the distinguishing features of the pons?
Transverse fibres which run between the two middle cerebellar peduncles
Pons forms floor of fourth ventricle
What are the distinguishing features of the upper medulla?
Inferior olivary nucleus (wiggly structure) is important in motor function
Re-emergence of the corticospinal tract as the pyramids
Hypoglossal nerve nucleus
What are the distinguishing features of the hypoglossal nerve?
Has a round shape nucleus
The gracilis and cuneatus dorsal columns are visible
Central canal
Pyramidal decussation
What is lateral medullary syndrome?
A set of symptoms seen where there is thrombosis of the vertebral artery or the posterior inferior cerebellar artery
What will a patient with lateral medullary syndrome present with?
Vertigo
Ipsilateral cerebellar ataxia
Ipsilateral loss of pain/thermal sense in the face
Signs of Horner’s syndrome (droopy eyelids, lack of sweating and miosis)
Hoarseness
Difficulty in swallowing
Contralateral loss of pain/thermal sense in the trunk and limbs
What are the sensory cranial nerve nuclei?
Midbrain: Mesencephalic trigeminal (V) Pons: Pontine trigeminal (V) Vestibulocochlear (VIII) Medulla: Spinal trigeminal (V) Solitarius (VII, IX, X)
What are the motor cranial nuclei?
Midbrain: Edinger-westphal (III) Oculomotor (III) Trochlear (IV) Pons: Trigeminal Motor (V) Abducens (VI) Facial (VII) Salivatory (VII) Medulla: Salivatory (IX) Dorsal Motor (X) Ambiguus (IX, X, XI) Hypoglossal (XII) Cervical spinal cord: Spinal accessory (XI)
What are the characteristics of the olfactory nerve (I)?
Component fibres: Sensory Structures innervated: Olfactory epithelium via olfactory bulb Function: Olfaction
What are the characteristics of the optic nerve (II)
Component fibres: Sensory Structures innervated: Retina Functions: Vision
What are the characteristics of the oculomotor nerve (III)?
Component fibres: Motor Structures innervated: Superior, inferior and medial rectus, inferior oblique, levator palpebrae muscles Functions: Movement of the eyeball
Component fibres Parasympathetic Structures innervated: Pupillary constrictor and cilliary muscle of the eyeball via cilliary ganglion Function: Pupillary constriction and accommodation
What are the characteristics of the trochlear nerve (IV)?
Component fibres: Motor Structures innervated: Superior oblique muscle Function: Movement of the eyeball
What are the characteristics of the trigeminal nerve (V)?
Component fibres: Sensory Structures innervated: Face, scalp, cornea, nasal and oral cavities, cranial, dura mater Function: General sensation
Component fibres: Motor Structures innervated: Muscles of mastication Tensor tympani muscle Functions: Opening and closing the mouth Tension of tympanic membrane
What are the characteristics of the abducens nerve (VI)?
Component fibres: Motor Structures innervated: Lateral rectus muscle Functions: Movement of the eyeball
What are the characteristics of the facial nerve (VII)?
Component fibres: Sensory Structures innervated: Anterior two-thirds of tongue Functions: Taste
Component fibres: Motor Structures innervated: Muscles of facial expression Stapedius muscle Functions: Tension on bones of middle ear
Component fibres: Parasympathetic Structures innervated: Salivary and lacrimal glands via submandibular and pteryglopalatine glanglia Functions: Salivation and lacrimation
What are the characteristics of the vestibulocochlear nerve (VIII)?
Component fibres: Sensory Structures innervated: Vestibular apparatus Cochlea Functions: Vestibular sensation Hearing
What are the characteristics of the glossopharygeal nerve (IX)?
Component fibres:
Sensory
Structures innervated:
Pharynx, posterior third of tongue, eustachian tube, middle ear, carotid body and carotid sinus
Functions:
General sensation and taste, Chemo- and baroreception
Component fibres: Motor Structures innervated: Stylopharygeus muscle Function: Swallowing
Component fibres: Parasympathetic Structures innervated: Parotid salivary gland via otic ganglion Function; Salivation
What are the characteristics of the vagus nerve (X)?
Component fibres: Sensory Structures innervated: Pharynx, larynx, oesophagus, external ear Aortic bodies, aortic arch Thoracic and abdominal viscera Function: General sensation Chemo-and barreception Visceral sensation
Component fibres: Motor Structures innervated: Soft palate, pharynx, larynx, upper oesophagus Function: Speech, swallowing
Component fibres:
Parasympathetic
Structures innervated: Thoracid and abdominal viscera
Function:
Control of cardiovascular system, respiratory and gastro-intestinal tracts
What are the characteristics of the accessory nerve (XI)?
Component fibres: Motor Structures innervated: Sternomastoid and trapezius muscles Function: Movement of head and shoulder
What are the characteristics of the hypoglossal nerve (XII)?
Component fibres: Motor Structures innervated: Intrinsic and extrinsic muscles of the tongue Function: Movement of the tongue
Which two sets of arteries form the circuit of the Circle of Willis?
Internal carotid arteries (anteriorly) Vertebral arteries (posteriorly)
With regards to the circle of Wills, how is impairment of the blood supply to the brain prevents?
3 main pairs of cerebral arteries from the Circle of Willis supply the anterior, middle and posterior cerebrum which allows for compensation if one of the arteries is occluded
What does the external carotid artery supply?
Structures of the face
What is the vertebral artery a branch of?
Subclavian artery
What do two vertebral arteries come together to form?
Basilar artery
Describe the branching of the Circle of Willis
Internal carotid- branches into a large middle cerebral artery and a smaller anterior cerebral artery
Basilar artery- bifurcates to form 2 posterior cerebral arteries
2 posterior communicating and one anterior communicating artery complete the circle
How are venous sinuses formed?
The folds of the dura mater
Where does most venous blood of the brain drain?
Into the superior saggital sinus via the cerebral veins
Venous blood then circulates to the back of the head and moves laterally through the lateral sinus and sigmoid sinus to become continuous with the internal jugular vein
What is a stroke?
A cerebrovascular accident
Definition: a rapidly developing focal disturbance of brain function of presumed vascular origin which lasts for more that 24 hours
What are the proportions of strokes caused by infarctions and haemorrhages?
Infarction (85%)
Haemorrhage (15%)
What is a transient ishaemic attack?
A rapidly developing focal disturbance of brain function of presumed vascular origin that resolves completely within 24 hours
What is an infarction?
Degenerative changed which occur in tissue following occlusion of an artery
What is cerebral ischaemia?
A lack of sufficient blood supply to nervous tissue resulting in permanent damage if blood flow is not restored quickly
What are the risk factors of stroke?
Age Hypertension Cardiac disease Smoking Diabetes mellitus
What does interruption of flow to the anterior cerebral artery present with?
Paralysis of the contralateral leg more than the arm and the face.
Frontal lobe affected so disturbance of intellect and judgement (abulia)
Loss of appropriate social behaviour
What does interruption of flow to the middle cerebral artery present with?
'a classic stroke' Contralateral hemiplegia in the arm more than the leg Hemisensory deficits Hemianopia Aphasia (left side lesion)
What does interruption of flow to the posterior cerebral artery present with?
Visual deficits
Homonymous hemianopia
Visual agnosia
What are the types of haemorrhagic stroke?
Extradural- trauma, immediate effects
Subdural- trauma, delayed effects
Subarachnoid- ruptured aneurysms
Intracerebral- spontaneous hypertensive
How long does cerebral blood flow need to be interrupted for in order for unconsciousness to result?
4 seconds
Irreversible damage results after a few minutes
Why is provision of glucose to the brain vital?
The brain cannot synthesise or utilise any other source of energy
Ketones can only be metabolised to a very limited extent
Under which glucose concentration will unconsciousness result?
2mM
How is cerebral blood flow regulated?
Systemically- mechanisms which affect the total cerebral blood flow
Locally- mechanism which relate activity or requirement in specific brain regions by altered localised blood flow
How is total cerebral blood flow autoregulated?
Between mean arterial blood pressures of 60 and 160 mmHg
What are the two mechanisms by which cerebral blood flow is regulated?
Neural control
Chemical control
Describe neural control of cerebral blood flow
When increased blood flow is required in active areas of the brain, neural control involved diverting blood flow to those active areas by means of vasoconstriction/vasodilation of the cerebral arteries
Parasympathetic innervation of which nerve produces slight vasodilation of the cerebral arteries?
Facial
What do central cortical neurones release?
A variety of vasoconstrictor neurotransmitters eg. Catecholamines
What effect do dopaminergic neurones produce?
Vasoconstriction
What do dopaminergic neurones innervate?
Penetrating arterioles and pericytes around capillaries
What are pericytes?
A form of brain macrophages with diverse activities eg. immune function, transport properties, contractile
With regards to chemical control of cerebral blood flow, what chemical factors are released which effect blood flow?
1) CO2 (indirect)
2) pH (i.e. H+, lactic acid)
3) nitric oxide
4) K+
5) adenosine
6) anoxia
7) kinine, prostaglandins, histamine, endothelins
Explain the relationship between increased carbon dioxide and cerebral blood flow
Sinusoidal relationship
Carbon dioxide itself is not responsible for the vasodilatory effect
Carbon dioxide diffuses across the blood brain barrier.
H+ ions are produced due to the presence of carbonic anhydrase in the neural tissue of the brain
The H+ ions lead to smooth muscle dilation
How does NO synthesis increase cerebral blood flow?
Nitric oxide conversion from arginine is catalysed by NO synthase
NO activates guanylyl cyclase
GTP is converted to cyclic GMP which leads to vasodilation of the cerebral arterioles
Where is cerebrospinal fluid found?
In intracerebral ventricles
What is the choroid plexus
Forms the cerebrospinal fluid
Is a collection of capillaries surrounded by ependymal cells with tight junctions between the cells
How much cerebrospinal fluid is formed by the choroid plexus?
80-150 ml
How does the choroid plexus secrete cerebrospinal fluid?
Into the ventricles
lateral ventricles > 3rd ventricle via intraventricular foramina > down cerebral aqueduct > into 4th ventricle > into subarachnoid space via medial and lateral apertures
What are the functions of cerebrospinal fluid?
Protection (physical and chemical)
Nutrition of neurones
Transport of molecules
What is the function of the blood-brain barrier?
Protects
- from certain toxins and circulating transmitters such as catecholamines
- from wide variations in ion concentrations
What is the structure of the blood-brain barrier?
- Mainly tight junctions between endothelial cells (capillaries ‘non-fenestrated’)
- Pericyte end-feet close to the capillary walls
What substances are allowed through the blood-brain barrier?
- Lipophilic molecules are allowed access to the brain CSF and ECF
- Certain hydrophilic substances can enter the brain CSF and ECF but only with the help of transport mechanisms e.g.
1) water via aquaporin (AQP1,AQP4) channels
2) glucose via GLUT1 proteins
3) amino acids via 3 different transporters
4) electrolytes via specific transporter systems
What are circumventricular organs?
Lie outside the blood brain barrier
Have fenestrated capillaries and respond directly to changes in the blood but have neural connections with the blood brain barrier
e.g.
- median eminence region of the hypothalamas
- subfornical organ (SFO)
- organum vasculosum of the lamina terminalis (OVLT)
Which has a high pH, plasma or cerebrospinal fluid?
Cerebrospinal fluid
What is the location of the thalamus?
Occupying most of the diencephalon
How is the thalamus organised?
It is divided into left and right thalamus by the third ventricle
Each is a collection of individual nuclei with separate functions and connections with ipsilateral forebrain structures
What is the function of the thalamus?
Acts as a relay centre between the cerebral cortex and other parts of the CNS
Integrates/modulates information en route
Integrates all functions except olfaction
Some nuclei form part of the Reticular Activating System
Which thalamic nuclei connect with the motor cortices?
Ventral lateral
Ventral anterior
Which thalamic nuclei connect with the body of the somatosensory cortex?
Ventral posterolateral
Which thalamic nuclei connect with the head of the somatosensory cortex?
Ventral posteromedial
Which thalamic nuclei connect with the visual cortex?
Lateral geniculate
Which thalamic nuclei connect with the auditory cortex?
Medial geniculate
What are specific nuclei?
Nuclei with reciprocal connections with a primary cortical area
What are association nuclei?
Thalamic nuclei with more diffuse reciprocal connections with association cortex
From where do the intralaminar nuclei receive inputs?
The Reticular Formation of the brainstem and project diffusely to all cortical areas
From where do the reticular nucleus receive inputs?
The Reticular Formation and projects to the other thalamic nuclei which regulated the flow of information through these to the cortex
What forms the Reticular Activating System?
Reticular Formation
Intralaminar Nuclei
Reticular Nuclei
What is the location of the hypothalamus?
In the diencephalon, below the thalamus
How is the hypothalamus organised?
Divided into the left and right hypothalamus by the third ventricle
Each is a collection of individual nuclei with separate functions and largely ipsilateral connection
What is the function of the hypothalamus?
It co-ordinated homeostatic mechanisms by:
- Regulating the autonomic nervous system via connections with the brainstem and spinal cord
- Acting as an endocrine organ, via the pituitary
- Controlling behaviour via connections with forebrain structures
In what instances is there hypothalamic involvement in the control of certain behaviours?
1) Eating and drinking
2) Expression of emotion
3) Sexual behaviour
4) Circadian rhythm
4) Memory
What structures are associated with the hypothalamus?
Olfactory system
Limbic system- hippocampus, amygdala, cingulate cortex, septal nuclei
Behaviour directed towards well-being triggers the reward system in the hypothalamic-limbic circuitry, leading to reinforcement of that behaviour
What is the somatosensory system?
It is concerned with sensory information coming from the skin, muscles, joints and ligaments
Touch and proprioception are carried via the dorsal columns/medial lemniscus pathway to the somatosensory cortex
What type of receptor are the receptors for touch and proprioception?
Mechanoreceptors
They are modified terminal of the peripheral axons of primary sensory neurones
What is the mechanism of touch and proprioception receptors?
They transduce a mechanical stimulus (deformation) into electrical signals
What does the function of mechanoreceptors depend on?
1) Degree of specialisation- from free nerve endings to elaborate accessory structures
2) Location- e.g. in various layers of skin, around hair shaft, in muscles, in tendons
3) Physiological properties- activation threshold determines sensitivity (all touch and proprioception receptors are low threshold) May be slow or fast adapting
Where are the cell bodies of sensory nurones?
In the PNS (DRG or trigeminal ganglia)
What types of axons do sensory neurones have?
Muscle spindles and tendon organs are innervated by type 1 axons.
Most other mechanoreceptors are innervated by type 2/alphabeta axons
All are fast conducting
Describe the receptive field of sensory neurones
It is the number of receptors that are innervated by one sensory neurone.
The larger the receptive field, the lower the resolution.
Density of receptive fields varies over the body
Describe the intensity of the stimulus from a sensory neurone
It is coded by the frequency of firing of the neurone.
Amplitude of action potential does NOT change.
If stimulus increases 10 fold, firing frequency doubles
Where does decussation of the central pathway occur?
In the brainstem
What enhances the difference between adjacent inputs in the central pathway?
Lateral inhibition
When do touch and proprioceptive stimuli become a conscious localised sensation?
When it reaches the cortex
What is the somatotopic arrangement of the somatosensory cortex known as?
The homunculus
Describe cortical analysis
Somatosensory I is where the body map is distorted according to relative density input from different parts of the body
The response of neurones in SI varies depending on stimulus or abstracted properties
Information is analysed by SI and goes to SII and the posterior parietal cortex for further analysis
What is the posterior parietal cortex necessary for?
Interpretation of spatial relationships
What can injury to the pathway anywhere from the periphery to the cortex result in?
Anaesthesia or paraesthesia
What is nociception?
Provides information about noxious (unpleasant or harmful) stimuli.
This information is processed by the brain but it is percieved as pain.
How is visceral pain carried?
It is carried peripherally by autonomic nerves and centrally in the spinothalamic and dorsal columns pathways.
How is somatic pain and temperature information carried?
By the spinothalamic tract to the brain from the skin, muscles, joints and ligaments
What are the features of nociceptors?
Polymodal (triggered by mechanical, thermal or chemical stimulus)
Free nerve endings
High threshold
Slow adapting
What are the types of axon for sensory neurones that are involved in nociception?
Aδ: mechano-or thermoreceptor, faster, produces sharp pain, leads to avoidance
C: chemoreceptor (eg. bradykinin, histamine) produces dull aching pain, leads to guarding to allow recovery
What are the features of sensory neurones that are involved in nociception?
Cell bodies are in PNS
Receptive fields usually large
Intensity coded by frequency of firing
Which pathway is responsible for carrying information about nociception and temperature?
Spinothalamic pathway
Via which structure does the basic pathway convey information about nociception and to which destination?
Via the VPL and VPM nuclei of the thalamus to the SI and SII cortex
The information is sent for analysis of localisation and intensity of the noxious stimulus
Which structures convey information to forebrain structures for perception of pain?
Collateral branches to the brainstem
affective pathway
What is the central inhibition pathway?
Collateral branches to the periaqueductal grey of the midbrain inhibit pain
Where does decussation of the central pathway for information coming from the body occur?
In the spinal cord
Where does decussation of the central pathway for information coming from the head occur?
In the brainstem
What is the affective pain pathway?
Where axons of the spinothalamic tract send collateral branches to the brainstem (reticular formation) thalamus (intralaminar nuclei) hypothalamus and and some cortex which triggers an increase in awareness and registered the unpleasantness of the stimulus such as pain
How does central (descending) inhibition work?
Cerebral activity triggers a descending pathway in the branstem which inhibits the nociceptive pathway in the dorsal horn
The pathway uses endogenous opioids and other transmitters
What is peripheral inhibition?
- Concerns the gate theory
- Takes place in superficial levels of the dorsal horn (substantia gelatinosa)
- Stimulation through non-nocioceptive inputs inhibits projection of nociceptive stimilus to spinothalamic tract
What is nociceptive dysfunction?
- Disruption of pathway may reduce pain but predisposes to increased injury
- Some changes may exacerbate pain. eg/ windup in dorsal horn, thalamic syndrome, phantom pain
What is volition?
Where the motor system produces movements that are adaptive and accomplish a certain goal
What is functional segregration?
How the motor system is organised in a number of different areas that controls different aspects of movement
What is hierarchal organisation?
High order areas are involves in more complex tasks (programme and decide on movements, coordinate muscle activity)
Lower level of hierarchy performs lower level tasks (execution of movement)
What do primary sensory areas include?
Primary visual cortex
Primary auditory cortex
Primary somatosensory cortex
What do principle motor areas of the cerebral cortex include?
Primary motor cortex (M1: executes voluntary movements)
Motor association cortex (selects voluntary movements)
What is the function of association areas within the cerebral cortex?
To produce a meaningful perceptual experience of the world.
Enable us to interact effectively and carry out abstract thinking and language
Where is the primary motor cortex located?
In the frontal lobe, on the precentral gyrus just anterior to the central sulcus
What does stimulation of the primary motor cortex result in?
Muscle movement at stimulus intensities far lower than any other part of the cerebral cortex
How is primary motor cortex control specific?
Small populations of cortical neurons in M1 control small groups of motor neurons in the spinal cord
This related to the most delicate and precise movements
How are the somatotopically related areas of each of the 3 motor areas of the cerebral cortex interconnected?
Via intracortical motor pathways
What is the function of the supplementary motor area?
It is involved in motor planning of internally driven voluntary movements
What is the result of stimulating the supplementary motor area neurons?
Complex movements involving many muscle groups as opposed to highly specific movements generated by M1 stimulation
Which type of scans show supplementary motor area activity?
PET scans
How much larger than the primary motor cortex is the premotor area?
6x larger
What is the purpose of the premotor area?
Prepares the primary motor cortex for an impending motor act
Under what circumstances will electrical stimulation of the premotor area produce muscle movement?
If the stimuli are much more intense than the effective stimuli for the primary motor cortex
What 3 stages are needed to achieve motor control?
Strategy
Tactics
Execution
What do the descending motor pathways consist of?
The corticospinal (pyramidal tracts The subcorticospinal (extrapyramidal) tracts: - Rubrospinal tracts - Reticulospinal tracts - Vestibulospinal tracts
What is the function of the descending motor pathways?
They act as a direct connection between neurons in the motor cortex and neurones in the spinal cord
What is the largest component of the descending motor pathway?
Corticospinal tract
From where does the corticospinal tract originate?
The pyramidal cells in layer V of the primary motor cortex (grey matter)
From where does the corticospinal tract recieve inputs from?
The somatosensory cortex & up to layer IV of the primary motor cortex
How do fibres of the corticospinal tract travel?
They travel via cerebral peduncles into the medulla
In the medulla they come together and form two column-like structures on the ventral surface of the medulla (pyramids)
How do the lateral corticospinal tracts and anterior corticospinal tracts form?
At the medulla 80% of the corticospinal tract fibres decussate and form the lateral corticospinal tracts
The remaining 20% uncrossed fibres form the anterior corticospinal tract
How is motor innervation for voluntary muscles provided?
In the corticospinal tract, axons of the upper motor neurones project to the ventral horns of the spinal cord.
Here, they connect with the lower motor neurones which provide the motor innervation
What is the function of subcortical (extrapyramidal) tracts?
Support voluntary movement and help control posture, locomotion and stereotypes automatic movements
From where do the subcortical (extrapyramidal) tracts receive inputs?
Brain stem nuclei & cerebellum
Indirect input comes from the basal ganglia
What is the purpose of the rubrospinal tract?
Provides information for supporting somatic motor & skeletal muscle control and regulation of muscle tone for posture
What is the vestibulospinal tract involved in?
Balance
What does the reticulospinal tract play a role in?
Involved in somatic motor control
Plays a roll in the control of autonomic functions
What are the clinical features of an upper motor neuron lesion?
Weakness
Hyperreflexia
Spasticity
Babinski Sign
What are the component structures of the basal ganglia?
Striatum
Globus pallidus
Subthalamic nucleus
Substantia nigra
What is the basal ganglia?
A group of nuclei situated deep in the white matter of the forebrain (cerebral cortex)
They are associated with a variety of functions which include motor control, procedural learning, eye movements, cognitive and emotional function
What is striatum?
2 distinct masses of grey matter which are separated by a large tract of white matter (the internal capsule)
The 2 masses are caudate nucleus and the lentiform nucleus
The lentiform nucleus is putamen and the globus pallidus
How is the globus pallidus divided?
GPe: receives input from the striatum and projects to the subthalmic nucleus
GPi: receives signals from the striatum via the direct pathway and the indirect pathway
Why does the globus pallidus have largely inhibitory effects on targets?
The segments it is composed of, primarily contain GABAergic neurons
What is the substantia nigra and how is it divided?
It is a mesencephalic grey matter portion of the basal ganglia
Divided into-
SNr (Reticulate): works with GPi to inhibit the thalamus
SNc (Compacta): produces dopamine, significant in the maintenance of striatal pathway balance
What is the largest component of the basal ganglia?
Striatum
What is the output of the globus pallidus?
Recieves most important inout from the striatum and sends inhibitory output to a number of motor-related areas
What is the pathway of the basal ganglia circuit
From the cerebral cortex (SMA, PMA, primary motor cortex, somatosensory and parietal cortex) projections to the striatum (caudate and putamen nuclei)
From the putamen, there are projections to
i) GPi and SNr (direct pathway)
ii) GPe (via SNT involving GABA)
From GPi and SNr, there are projections to the thalamus
From the thalamus back to the cortex - the SMA and PMS (two areas of motor cortex involved in the planning of movements)
How is the pathway of the basal ganglia circuit inhibited/excited?
GPi and SNr inhibit the thalamus (involves GABA)
The putamen inhibits GPi and SNr which releases the thalamus from inhibition
The thalamus released the selected movement through its projections to the cortex
How is the correct balance of excitation/inhibition of the thalamus maintained?
SNc which provides excitory inputs to the caudate and putamen
This involves dopamine
What is Parkinson’s disease?
A progressive degenerative disorder of the CNS
It is neuronal degeneration of dopaminergic cells in the substantia nigra which results in loss of dopaminergic terminals in the putamen and to a lesser extent- the caudate
What are the signs of Parkinsons disease?
Bradykinesia Hypomimic face Akinesia Tremor at rest Lead pipe rigidity Parkinson gait Stooped posture
Why are the initial symptoms of Parkinson’s disease movement related?
Due to the loss of dopamine to the striatum leads to less inhibition of GPiSNr which results in increased inhibitory output from GPi/SNr to the thalamus.
Too much inhibition of the thalamus produces a decreased facilitation to the motor cortex- especially the SMA
What is Huntington’s disease?
A neurodegenerative disorder which involves the degeneration of spiny GABA neurons in the striatum (mainly caudate)
What causes cognitive decline and dementia in Huntington’s disease?
The degeneration of spiny GABA neurons in the striatum results in reduced GABAergic inhibition of GPe and thus increased inhibitory output from GPe to STN
- The facilitatory output from STN to GPi/SNr is consequently reduced leading to less inhibitory output from GPi/SNr to the thalamus
- The lack of inhibitoru control of the thalamus on the motor cortex affects muscle coordination
What is chorea?
Rapid jerky movements most commonly caused by Huntington’s
The movements tend to affect the hands and face first
Gradually increase over time until a patient becomes totally incapacitated
Symptoms can be described as hyperkinesia
What is the cerebellum?
A region of the brain which plays an important role in motor control.
Contributes to coordination, precision and accurate timing
From where does the cerebellum receive inputs?
Sensory systems and other parts of the brain and spinal cord
These inputs are integrated into fine motor activity
How is the cerebellum separated from the overlying cerebrum?
A layer of the dura mater
What are the 3 layers of the cerebellum?
From top to bottom:
- A molecular layer
- A layer of Purkinje cells
- A granular cell layer
Within the layers of the cerebellum, what are the types of fibres?
Mossy fibres
Climbing fibres
What are the three highways into and out of the cerebellum?
Superior, middle and inferior cerebellar peduncle
What is the narrow midline zone between the two hemispheres of the cerebellum?
The vermis
What are the folds of grey matter on the surface of the cerebellum?
Folia
What are the three deep cerebellar nuclei embedded within the white matter?
Fastigial nucleus- involved in balance and has connections with the vestibular system and reticular nuclei
Interposed nucleus and Dentate nucleus- both involved with voluntary movement
What are the three sources of input into the cerebellar nuclei?
1) Mossy fibres from spinocerebellar pathways
2) Climbing fibres from inferior olive
3) Mossy fibres from pons bringing information from cerebral cortex
What are the 3 main divisions of the cerebellum?
1) Vestibulocerebellum
2) Spinocerebellum
3) Cerebrocerebellum
What is the function of the vestibulocerebellum?
Tunes balance (stance and gait) and vestibulo-oculo-reflex (VOR)
What are the disorders of the vestibulocerebellum?
1) Ataxic gait- wide based stance (looks drunk)
2) Imbalance when eyes closed (Romberg sign)
3) Nystagmus
What is the function of the spinocerebellum?
Tuns motor execution by adjusting movements and muscle tone
What is a disorder of the spinocerebellum?
Hypotonia
What is the function of the cerebrocerebellum?
Initiation of skilled movements
What are the disorders of the cerebrocerebellum?
1) Tremor and clumsy movements: movements overshoot or undershoot target (dysmetria)
2) Coordination problems (dysdiadochokinesia)
What are the contact ratios for synapses?
Ranges from 1:1 for muscles to 10,000:1 in the CNS
How can membrane potential of the post synaptic neurone be altered?
1) Be made less negative
i. e. be brought closer to threshold for firing; excitory post synaptic potential (EPSP)
2) Be made more negative
i. e. be brought further away from threshold for firing; inhibitory post synaptic potential (IPSP)
What is a neuromuscular junction?
A specialised synapse between the motor neuron and motor end plate, the muscle fibre cell membrane
What occurs when a neuromuscular junction is activated?
Depolarisation leads to calcium ion channels opening and the influx of ions in the pre-synaptic terminal
Vesicle fusion occurs with the pre-synaptic membrane and Ach is released into the synaptic cleft
Ach binds to receptors on the motor end plate and sodium ion channels open.
There is a sodium ion influx leading to an action potential being generated
What are alpha motor neurons?
Lower motor neurons of the brainstem and spinal cord. They innervate the (extrafusal) muscle fibres of the skeletal muscles. Their activation causes muscle contraction. The motor neuron pool contains all alpha motor neurons innervating a single muscle
Where are alpha motor neurons situated?
In either side of the ventral horns (anterior grey matter)
What is the motor unit?
The name given to a single motor neuron, together with all the muscle fibres that it innervates. It is the smallest functional unit with which to produce force. Stimulation of one motor unit causes contraction of all muscle fibres in that unit
On average, how many muscle fibres does each motor neuron supply?
600
What are the different types of motor unit?
Type I: Slow twitch, low tension, fatigue resistant
Type IIa: Fast twitch, moderate tension, fatigue resistant
Type IIb: Fast twitch, high tension, high fatigue
What is recruitment?
When a motor neurone and its associated muscle fibres is activated, the motor unit is thought to have been recruited. They are recruited by an order dictated by the ‘Size principle’
- smaller units recruited first allowing for fine control
What is rate coding?
A second mechanism by which force is regulated
The change in the frequency in motor neuron firing.
Slow units fire at a lower frequency and as the the force needs to be increased, more motor units are recruited and the firing rate increases. The force produced by the unit increases as the firing rate increases
What are neurotrophic factors?
Growth factors which prevent neuronal death and promote growth of neurons after injury. Motor unit and fibre characteristics are dependent on the nerve which innervates them
What is a common change in muscle fibre properties following training?
Type IIb to IIa (fatigable to fatigue-resistant)
How may muscle fibre properties change in cases of severe spinal cord injury?
Type I to Type II (shift from slow to fast)
How do muscle fibre properties change with ageing?
Loss of type I and type II fibres
Preferentially, there is a loss of type II fibres, resulting in a larger proportion of type I fibres
Slower contraction is seen in elderly people
What is a reflex?
An automatic and often inborn response to a stimulus that involves a nerve impulse passing inward from a receptor to a nerve centre and then outward to an effector without reaching the level of consciousness
What happens in the monosynaptic (stretch) reflex?
- Tendon jerk
- The stretching stimulates sensory receptors which excites the sensory neurone
- The excited sensory neuron activates the motor neurone within an integrating centre of the spinal cord
- The motor neuron is excited, and the effector contracts to relieve the stretching. At the same time, the motor neuron to the antagonistic muscle is inhibited
What is the Hoffman reflex
The electrical equivalent of the tendon jerk reflex
What are the supraspinal influences on reflexes?
- Higher centres of the CNS exert inhibitory and excitatory regulation upon the stretch reflex
- Inhibitory control dominates in normal conditions
What is hyporeflexia?
When reflexes are below normal or absent.
Mostly associated with lower motor neuron (alpha motor neuron) diseases
What is hyper-reflexia?
Due to a loss of descending inhibition.
Is sometimes seen due to stroke
It can be seen at the platellar tendon, the biceps as well as in the Babinski sign
Describe the outer ear
Consists of the pinna (auricle) & external acoustic meatus (external auditor meatus/ auditory canal)
It collects and conducts sound waves towards tympanic membrane
Describe the middle ear
It is an air-filled chamber in bone, lying between tympanic membrane laterally, and oval and round windows medially
Describe the inner ear
Comprised of cochlear and the organs of balance (vestibular apparatus)
Hair cells transduce mechanical energy of sound into electrical signal in the cochlear nerve
What is sound?
A pressure wave in air- alternating areas of compressed and non-compressed air
What is frequency?
Cycles/sec (Hz), perceived as pitch
What is amplitude?
Intensity, perceived as loudness
What is the decibel range?
The log scale of loudness
0db is the threshold of hearing
How is sound amplified within the ear?
Conduction through the middle ear amplified sound by around 30 db which is achieved by the lever system of articulated ossicles and the ratio of area of tympanic membrane to oval window
Describe the lever system of articulated ossicles
When a soundwave travels down the external acoustic meatus, it vibrates the tympanic membrane.
The vibration is carried through the ossicles in a lever system, which is turn causes the membrane covering the oval window to vibrate which transfers sound waves into the inner ear
How does the ratio of the area of the tympanic membrane to the oval window (17:1) aid amplification?
The larger area of the tympanic membrane compared to the membrane covering the oval window acts to focus the energy of the sound wave which ultimately increases its intensity
What are the protective mechanisms of the inner ear?
- Reflex contraction of the tensor tympani and stapedius muscles reduces the amplitude of vibrations which pass through the ossicles.
- This protects against natural sounds (not necessariy man-made sounds)
- The auditory tube allows equilibration of air pressure on either side of the tympanic membrane
What is the eustachian tube?
The auditory tube
It connects the middle ear with the back of the nasopharynx. It is normally closed but on swallowing/chewing it temporarily opens.
On opening, if there is a pressure difference, it will immediately move in order to restore the equilibrium
What can cause sound being prevented from reaching the cochlea?
- Wax (build up in the outer ear stops vibration)
- Otitis media (infection of the middle ear leads to inflammation and fluid build up
- Otosclerosis of ossicles (bony extensions grow from the ossicle > damage to lever system of sound amplification)
- Perforated tympanic membrane (eardrum; caused by trauma of sound of very high intensity
- Congenital malformations
What is the structure of the cochlea?
- Hollow tube in bone, curled into spiral
- Divided longitudinally into 3 compartments, separated by 2 membranes
- Sound wave causes vestibular (Reissner’s) and basilar membranes to vibrate
- Cochlear hair cells are attached to basilar membrane
What are the finger-like projections on the apical surface of a cochlear hair cell?
Sterocilia
Movement of the stereocilia causes depolarisation of nerve endings and ultimately the generation of an impulse to the brain
In the cochlea, where does perilymph flow?
Through a small channel (the helicotrema) which connects the scala vestibuli and scala tympani and allows the fluid to mix
What is hyperacusis?
Painful sensitivity to low intensity sounds
This can occur following conidtions which lead flaccid paralysis of muscles involved in the auditory reflex
Give an example of hyperacusis
Bell’s Palsy
nerve VII
Describe the auditory reflex
Stapedius and tensor tympani muscles contract to reduce movement of the ossicles. The reflex has a 50-100ms latency and is a safety mechanism for loud noises and also suppressed internally generated sounds e.g. self-generated vocalisation
What are the three compartments of the inner ear?
Scala vestibuli
Scala tympani
Scala media (contains endolymph fluid)
How does the inner ear function?
1) The stapes vibrate and generate a pressure wave in the perilymph fluid
2) This vibrates the basilar membrane
3) The cochlear is made of bone and the fluid is incompressible, so the round window vibrates out when the oval window vibrates inwards
How is a ‘place code’ or tonotopic map’ generated?
Due to different parts of the membrane being sensitive to different frequencies.
A specific frequency is associated with a spatial position on the membrane and this arrangement is mirrored in higher levels of auditory processes
How is the basilar membrane sensitive to different frequencies?
Low frequencies = apex
High frequencies = base
What is the Organ of Corti?
The organ of the inner ear which contains the auditory sensory cells which lie on the basilar membrane, consisting of sensory hair cells, surrounded by supporting cells which are powered by the potential difference between the endolymph and perilymph
What contains endolymph?
Scala media
How does the Organ of Corti act as a sensor?
Acts as a sensor when the basilar membrane is deflected by a pressure wave (due to a sound and induced by the stapes)
What is the arrangement of hair cells within the Organ of Corti?
A single row of inner hair cells followed by 3 rows of outer hair cells
What is the function of the inner hair cells?
They send connections primarily back to the brain (afferent)
They have stereocilia which move in response to movement of the endolymph
They sense movements of the endolymph and this is presented to the brain as sound information
What is the function of the outer hair cells?
Receive input from the brain (efferent)
Have stereocilia which are in contact with the tectorial mebrane. They receive input from the brain
They move in response to information from the brain to amplify the signals from the inner hair cells
They constitute the ‘cochlear amplifier’
What can damage to the outer hair cells result in?
Sensorineural hearing loss
What effect do high amplitudes of sound have on stereocilia?
Higher amplitudes cause greater deflection of stereocilia and open the K channels to a greater extent
What are otoacoustic emissions?
Noises that the ear makes itself
Outer hair cells are responsible for these sounds
What happens when the hair cell moves due to movement of the endolymph?
1) Upward movement of the inner hair cell= basilar membrane displaces sterocilia away from modiolus > K+ channels open and K+ enters from the endolymph and the hair cell thus depolarises.
The outer hair cells can contract to enhance the movement of the basilar membrane towards the tectorial membrane
2) Downward movement of the inner hair cell= basilar membrane displaces stereocilia towars modiolus > K+ channels close and the hair cell hyperpolarises as a result
The outer hair cells elongate to reverse the movements of the basilar membrane and inner hair cells to hyperpolarise
What are the concentrations of K+ and Na+ in the endolymph and perilymph?
Scala media (endolymph) = high K+, low Na+ Scala tympani (perilymph)=high Na+, low K+
What gives rise to the endocochlear potential across the membrane of the stereocilia?
The scala media (endolymph) and scala tympani (perilymph) have different concentrations of K+ and Na+. The concentration is maintain by the scala vascularis
What causes depolarisation of the axon of the spiral ganglion cell?
Glutamate released from the base
What is tonotopy?
Spatial organisation of response to frequency is preserved throughout pathway
To where does the superior olivary nuclei project?
Backward to the cochlea
Forward to the central pathways
How do spiral ganglions from each cochlear project?
Via auditory vestibular nerve (VIII) to the ipsilateral cochlear nucleu (monoaural neurons)
All connections after this point are bilateral
What is affected in deafness in one ear that is due to central causes?
The cochlear nucleus
or
VIII nerve (rare)
What reflex is the inferior colliculus responsible for?
The turning of the head to loud sounds
To where are there collateral pathways?
The reticular formation and cerebellum
Which pathways provide feedback at all levels?
Descending pathways
Where do all ascending pathways converge?
The inferior colliculus
From where does the inferior colliculus receive input?
Both cochlear (binaural neurons)
How are auditory pathways bidirectional?
Feedback to outer hair cells
What is lateral inhibition?
A feature of many sensory systems.
Neuronal responses are ‘sharpened’ by suppressing the response of neighbouring neurons (similar frequencies)
This provides a mechanism to filter out noise from the auditory signal
How is the primary auditory cortex subdivided?
According to frequency response
How does the secondary cortex differ from the primary auditory cortex?
The neurones respond to more complex sound patterns
What is conductive hearing loss?
When diseases of the middle ear destroy ossicles or stiffen their joints, the amplification mechanism is eliminated resulting in a conductive hearing loss.
A heavily waxy ear can also block sound waves from the ear drum
What is senorineural hearing loss?
When the cochlear or the cochlear nerve is damaged, the signal transmitted to the auditory cortex is reduced or lost resulting in a sensorineural hearing los
In what instances are sensorineural hearing losses typically seen?
Schwanomma (tumour of the cochlear nerve)
Cerebellar tumours that expand and press on the cochlear nerve
Give examples of sensory causes of sensorineural deafness
Presbyacusis (normal ageing)
Exposure to loud noise
Ménière’s disease
Toxicity e.g. some antibiotics
Give examples of neural causes of sensorineural deafness
Acoustic neuroma
Viral infection
Give example of central (rare) causes of sensorineural deafness
Demyelination in MS
Injury to central auditory pathway (unlikely to cause serious deafness unless both auditory cortices affected)
What senses angular motion of the head?
Semicircular canals
What do the otolith organs sense?
Acceleration of the head
Strength and direction of gravity
What are the signals from the semi circular canals and the otolith organs used for?
- Control balance reactions
- Provide spatial reference for other sensory motor co-ordinations
- Provide compensatory reflexes (VOR)
- Tune cardio-vascular function for re-orientations
- Serve perception of motion in space
What is the result when there is a problem with controlling balance reactions?
Ataxia
What is the result when the ability to provide compensatory ocular reflexes dysfunctions?
Total loss > Oscillopsia
Unilateral loss > nystagmus
What is the result when the ability to tune cardivascular function for re-orientations dysfunctions?
Hypotension
What is the result when the ability to serve perception of motion in space dysfunctions?
Dizziness
What does unusual stimulation of the balance organs result in?
Motion sickness
What is vertigo?
False perception of movement in space
What is vestibular ataxia?
Instability of gait and posture
What is vestibular nystagmus?
Inability to stabilise the eyes in unilateral lesions
What is oscillopsia?
Inability to stabilise the eyes during head movement in bilateral vestibular lesions
How is a structural vestibular disorder characterised?
Destructive or irritative disease
How is a functional vestibular disorder characterised?
Misinterpretation of sensory input
Maladaption
Loss of rules of correspondence between senses
Over awareness/magnification of sensory input?
How is a vestibular disorder which is both structural and functional characterised?
Structural disorder provoking chronic dysfunction
What causes vertigo that lasts seconds?
Benign positional vertigo (due to debris in canals)
Intense vertigo and nausea
Paroxysmia
What causes vertigo that lasts minutes?
Migraine
What causes vertigo that lasts hours?
Ménière’s syndrome
What causes vertigo which is fluctuating/continuous?
Uncompensated vestibular lesions
What causes silent vertigo?
Acoustic neuroma
To where do the otoliths send information?
Lateral and inferior nuclei
To where do the semi-circular canals send information?
Superior and medial nuclei
What are some projections of the vestibular nuclei?
Spinal cord
Nuclei of the extraocular muscles
Cortex via the thalamus
Various autonomic centres
To where do the superior and medial vestibular neurons project?
Motor nuclei supplying extraocular muscles
Where do the axons of the medial vestibular nucleus project and for what function?
They cross the midline and project to the contraleral abducens (VI) nucleus to abduct the eye (in the opposite direction to head rotation
Where do axons from VI cross and ascend?
Cross and ascend the medial longitudinal fasciculus (MLF)
They excite the contralateral occulomotor (III) nucleus which adducts the other eye
What is the vestibulo-ocular reflex?
When the head rotates to the left, the eye rotate to the right and saccade to the left
The vestibulo-ocular reflex operates to maintain the gaze on a selected target
What are the sensory receptors of the vestibular system?
Epithelial hair cells located in macula (utricle and saccule) and crista of ampulla (swellings of the vestibular ganglion)
What are vestibular hair cells?
Sensory receptors consisting of apical stereocilia and a single long kinocilium.
They act as mechanical transducers detecting static tilt and acceleration
Describe the transduction mechanism of the vestibular hair cells
Displacement towards to kinocilium > depolarisation > increased frequency of ganglion cell discharge Displacement away from the kinocilium > hyperpolarisation > reduced frequency of ganglion cell discharge
What are semi-circular canals?
Bone structures which enclose the hair cells which overly the sensory receptor crista.
Why are the hair cells which project from the ampulla in the wall of the semi-circular canals unidirectionally orientated?
So that the acceleration phase of head rotation to a particular side or direction preferentially stimulates the canals on that side.
E.g. rotation to the right stimulates the right canal. Rotation in the opposite direction inhibits the canal activity.
Which semi-circular canal is stimulated when head rotation decelerates to a stop?
The canal on the opposite side
E.g. Stopping a rightwards rotation stimulates the left canal
What allows the tonuses from the left and right canals to balance out?
Each canal has a tonic firing rate
What does the loss of canal function on one side result in?
Permanent partial impairment of sensitivity to rotation in the ‘on’ direction of the defunct canal
With regards to the otolith organs, what do both the saccule and utricle contain?
A sensory epithelium and macula, which consists of vestibular hair cells
What stimulates otolith hair cells?
The inertial resistance of the otoconial mass to linear head acceleration
(tends to stay still when the head moves- like people swaing on the bus when it accelerates or brakes)
How does the lateral vestibulo-spinal tract descend?
Ipsilaterally in ventral funiculus of spinal cord
Where do the axons of the lateral vestibulo-spinal tract terminate?
The lateral part of the ventral horn and influence motor neurons to limb muscles
How does the medial vestibulo-spinal tract descend?
Bilaterally in medidal longitudinal fasciculus (MLF) to cervical and upper thoracic spinal cord
Where do the axons of the medial vestibulo-spinal tract terminate?
In the medial part of the ventral horn and influence motor neurons to the neck and back muscles
What is the result of vestibular ataxia?
- Bilateral vestibular disorder causes a mild gait ataxia which worsens with speed, when negotiating rough ground or when vision is reduced.
- Unilateral vestibular disorder causes a tendency for the body and head to lean or fall to the lesioned side, which becomes pronounced in difficult balancing situations
How can the vestibular system cause hypotension and respiratory dysrhythmia?
- Vestibular projections affect heart rate, peripheral vasculature and respiratory muscles
- Loss of vestibular tone can provoke hypotensive episodes so that the patient feels faint as well as dizzy.
- Vestibular stimulation can affect respiratory rhythm
How can the vestibular system causes nausea and vomiting?
- Vestibular nuclei project to a wide range of autonomic structures in both the brainstem and the hypothalamus
- In the acute phase of a unilateral vestibular disorder, the unusual pattern of stimulation also provokes symptoms like motion sickness which is nausea and vomiting
How is benign, paroxysmal positional vertigo typified?
By transient attacks of vertigo provoked by head movement, especially rolling over in bed and tilting the head up or down.
Debris floating in the canal stimulates the ampulla causing false signals of head rotation-vertigo
How can benign, paroxysmal positional vertigo be cured?
By turning the head vigorously in the opposite direction to that which which provokes the vertigo
What is the diameter of the eye in adults?
24mm
What 3 layers coat the eye?
Sclera- hard and opaque
Choroid- pigmented and vascular
Retina- neurosensory tissue
What are the properties of the anterior chamber of the eye?
- Between the cornea and the lens
- Filled with clear aqueous fluid
- Supplies nutrients
What are the properties of the posterior chamber?
- Between the lens and the retina
- Filled with a jelly substance called the virteous
- Provides mechanical support
What are the problems associated with ageing vitreous?
The vitreous liquifies and collapses with age which results in posterior vitreous detachment
- Vitreous separates from the retina
- The patient experiences vitreous detachment as seeing floaters
- May be occasionally associated with retina tear
- Patients are advised to see and ophthalmologist for retina examination to exclude retinal tear
What is the ciliary body of the eye?
- A ring tissue between the anterior and poster segments
- Is behind the iris
What is the iris of the eye?
- Anterior to the ciliary body and eye
- Posterior layer- epithelial layer
- Anterior layer- stromal layer containing muscle fibres
What is the name given to the choroid ciliary body and iris collectively?
Uvea
From where is intracoular fluid secreted?
Ciliary body
What is the function of intraocular fluid?
- It flows anteriorly into the anterior hamber
- Supplies nutrient
- Normal pressure is 12-21mmHg
What drains intraocular fluid out of the eye?
Trabecular meshwork
What is glaucoma?
- Medical condition of sustained raised intraocular pressure
- Retinal ganglion cell death and englarged optic disc cupping
- Visual field loss, blindness
What is the most common type of glaucoma?
Primary open angle glaucoma (left)
- Trabecular meshwork dysfunction
What is closed angle glaucoma?
- Can be acute or chronic
- Due to increased pressure pushing the iris/lens complex forwards, the trabecular meshwork is blocked.
- Risk factors include small eye (hypermetropia) and narrow angle at trabecular meshwork
- May present with sudden painful red eye with acute drop in vision
- Can be treated with peripheral laser iridotomy to create a drainage hole on the iris
What is the structure of the lens?
- Outer acelluar capsule
- Regular inner elongates cell fibres- transparency
- May lose transparency with age - Cataract
What is the function of the lens?
- Transparency
- Refractive power (1/3 power)
- Accomodation (elasticity)
How is the lens suspended?
By a fibrous ring known as lens zonules, consists of passive connective tissue
What is the cornea of the eye?
- Front most part of the anterior segment
- Continuous with the scleral layer
- Transparent
- Refraction - 2/3 power (convex curvature)
- Physical barrier
- Infection barrier
What are the 5 layers of the cornea?
1) Epithelium
2) Bowman’s membrane
3) Stroma
- regularity contributes towards transparency
- Corneal nerve endings provide sensation and nutrients for healthy tissue
- No blood vessels in normal cornea
4) Descemet’s membrane
5) Endothelium
- pumps fluid out of cornea and prevents corneal oedema
- Only 1 layer of endothelial cell
- No regeneration power
- Endothelial cell density decreases with age
- Endothelial cell dysfunction
may result in corneal oedema and corneal cloudiness
What is the purpose of the tear film?
It is a thin layer of fluid
- Maintains a smooth cornea-to-air surface which is important for maintaining clear vision and removing surface debris during blinking
- Source of oxygen and nutrient supply to anterior segment (as normal cornea has no blood vessels)
- Bacteride
What are the three layers of the tear film?
- Superficial oily layer to reduce tear film evaporation (produced by a row of Meibomian Glands along the lid margins)
- Aqueous tear film (tear gland) - forms main bulk of tear film
- Mucinous layer on the cornea surface to maintain surface wetting
How does mucinous layer of the corneal surface render the surface of the eye ‘wettable’?
The mucin molecules act by binding water molecules to the hydrophobic corneal epithelial cell surface
Where is the lacrimal gland located?
Within the orbit, latero-superior to the globe
What are basal tears?
Tears produced at a constant level even in the absence of irritation or stimulation
What are reflex tears?
Tears produced in response to irritation
What is the tear reflex pathway?
- Afferent pathway - Cornea -CN V1 (Ophthalmic branch of the trigeminal nerve)
- Efferent pathway- Parasympathetic
- Neurotransmitter - Acetylcholine
Lacrimal gland
What is the lacrimal system?
= Tear is produced by the lacrimal gland
- The tear drains through the two puncta, opening on medial lid margin
- Tear glows through the superior and the inferior canaliculi
- Tear gathers in the tear sac
- Tear exits the tear sac through the tear duct into the nose cavity
How does the cornea and lens act to form a clear image in the eye?
Focuses incoming light ray onto retina by refraction
What is the purpose of the retina?
Converts image into nerve impulses which are then transmitted to the brain via the optic nerve
What is the purpose of the pigment in the iris, ciliary body and choroid?
Serves to shield out excess scattered light
What is the purpose of the iris?
Regulates the amount of light with enters the eye by varying the size of the pupil
What maintains the shape of the eye?
- Scleral coat
- Maintenance of intraocular pressure (ciliar body, trabecular meshwork)
What is refractive power?
The ability to focus and incoming light ray to form a clear image on the retina
What is Emmetropia?
Parallel rays (image from distance) converge exactly on the retinal surface (fovea) to form a clear imagine on the retina which allows a person to see clearly at a distance without glasses
What is Hypermetropia? (long sighted)
Parallel rays (distant image) focus behind the retinal surface as the eye does not have sufficient power to focus a clear image on the retina.
What causes hypermetropia?
Short eyeball
Flat corneal surface
How is hypermetropia corrected?
Glasses with convex lenses to provide additional converging power
What is myopia (short sighted)?
The light ray from distance objects focuses in front of the retinal surface due to the cornea or lens having excessive refractive power
What causes myopia?
Long eyeball or occasionally highly curved cornea
How is myopia corrected?
Glasses with concave lenses to take away excessive refractive power to see clearly at a distance
What is astigmatism?
- When the cornea is oval rather than spherical shaped
The refractive power varies along different meridians or planes - Distant objects are seen as blurred ellipses
- Can be optically corrected with astigmatic glasses with variable correction for every plane or meridian
What is accommodation?
The process of the human lens being able to alter its lens- as it is elastic- in order to increase refractive power when focusing on a near objects
What is the mechanism of accommodation?
- Contraction of the circular ciliary muscle inside the ciliary body
- This relaxes the zonules that are normally stretched between the ciliary body attachment and the lens capsule attachment
- The zonules are passive elastic bands with no active contractilemuscle
- In the absense of zonular tension, the lens returns to its natural convex shape due to its innate elasticity
- This increases the refractive power of the lens
- It is mediated by the efferent third cranial nerve
What is the near response triad?
In humans, near vision is mediated by three separate but simultaneous pathways
- Pupillary miosis (Spincter pupillae) to increase depth of field
- Convergence (medial recti from both eyes) to align both eyes towards a near object
- Accomodation (circular ciliar muscle) to increase the refractive power of the lens for near vision
Why is the near response triad important for near vision?
Eyes with shallow depth of field lose focus easily, even with the slightest objects movement when viewing a near object
What is presbyopia?
Naturally occurring loss of accommodation (focus for near objects)
- Onset from age 40 years
- Distant vision is intact
- It is corrected by reading glasses (convex lenses) to increase refractive power of the eye
What is the head of the optic nerve?
The optic disc, where all retinal ganglion nerve fibres converge ad exit out of the eye towards the brain
Why does the optic disc correspond to the physiological blind spot?
There are no photo-receptors present in this region
What is the macula?
Responsible for central fine vision
Has the highest concentration of photo-receptors
What are the most important landmarks when examining the retina?
Optic disc
The macula
The four branches of vessel archades
What are the four branches of vessel arcades radiating from the optic disc?
The superior-temporal branch
The inferior-temporal branch
The superior-nasal branch
The inferior nasal branch
The retinal arteries and veins from the arcades radiating from the optic disc supply circulation to where?
The inner two thirds of the retina
What provides the circulation for the outer one third of the retina?
The Choroid
What is the difference between central vision ad peripheral vision?
Central vision is responsible for detailed central fine vision and daytime colour vision
Peripheral vision specialised in detecting shape and movement in the environment
How are central vision and peripheral vision assessed?
Central vision = Visual acuity assessment
Peripheral vision= Visual field assessment
What is the result of patients with loss of central vision?
Problems with reading and recognising faces
Loss of foveal vision = poor visual acuity
What is the result of patients with loss of peripheral vision?
Problems navigating the world
Patient may need white stick even with perfect visual acuity
What does the retina consist of?
The retina forms the innermost layer of the coat of the eye in the posterior segment
It consists of an outer thin layer of Retinal Pigment Epithelium - situated in front of the Choroid
An inner thicker layer called the Neuroretina
What is the purpose of the Retinal Pigment Epithelium layer of the retina?
Transports nutrient from the choroid to the photo-receptor cells, and removes metabolic waste from the retina
What are the layers of the Neuroretina?
Outer layer = Photoreceptors (1st order Neuron) - detection of light
Middle layer= Bipolar cells (2nd order neurons) - local signal processing to improve contrast sensitivity, regulate sensitivity
Inner layer= Retinal ganglion cells (3rd order neurons) - transmission of signal from the eye to the brain
What is the macula? (macula Lutea)
- The central region of retina
- 6mm in diameter
- Yellow patch due to yellow pigment
What is the fovea?
- Forms the pit at the centre of the macula as a result of the absence of the overlying ganglion cell layer
- Has the highest concentration of photorecptors for fine vision
What are the 2 main classes of photoreceptors in the retina?
Rods:
- Longer outer segment with photo-sensitive pigment
- 100x more sensitive to light than cones
- Slow response to light
- Responsible for night vision (scotopic vision)
- 120 million rods
Cones:
- Less sensitive to light, but faster response
- Responsible for day light fine vision and colour vision (Photopic vision)
- 6 million cones
Where are photopigments synthesised?
Synthesised in the inner photoreceptor segment and are then transported to the outer segment
How are distal discs shedded in photoreceptors?
They are shedded from the tips and then absorbed by retinal pigment epithelium cells by phagocytosis
Where are deactivated photopigments from photoreceptors regenerated?
Inside retinal epithelial cells and transported back to photoreceptors
What is rhodopsin?
- photopigment found in Rod photoreceptors
- Opson (transmembrane protein) located in outer segment of photoreceptor
How is a nerve action potential generated due to rhodopsin?
The cofactor is 11 cis-retinal (vitamin A derived)
The cofactor reacts to photon resulting in conformal changes to Rhodopsin activating the G-protein pathway
This results in the closure of ion channels and hyper-polarisation leading to an action potential
How may different cone photopigments are there?
3 subtypes of photospin which react to 3 different light frequencies
How does the distribution of rods and cones differ?
Rods= distributed all over the retina with the highest density just outside the macula, the density gently tails off towards the periphery. They are absent within the macula. Cones= distributed only within the retina
How far does normal visual field in each eye extend?
60 degrees nasally
100 degrees temporally
60 degrees above
70 degrees below
What is the single peak light sensitivity for Rod photopigments?
498nm
What are the wavelengths for Cone photopigments?
S-Cone 420-440nm (blue)
M-Cone 534-545m (green)
L-Cone 564-580nm (red)
What is the commonest form of colour vision deficiency?
When the M cone peak is shifted to the L cone peak as they are close to each other.
This results in red-green confusion (Deuteranomaly)
Which cones are stimulated with Yellow light?
M-cones and L-cones equally as yellow light has a wavelength between the peak sensitivity wavelengths of those two cones
What is the prevalence of colour vision deficiencies?
8% males
0.5% females
What is anomalous trichromatism?
When colour vision deficits are caused by a shift in the photo-pigment peak sensitivity
What is dichromatism?
A colour vision deficit which is the result of only two cone photo-pigment sub-types being present
What is monochromatism?
When there is complete absence of colour vision
It can be caused by blue cone monochromatism with the presence of only blue L-cones- these patients have normal day light visual activity
Or by Rod monochromatism where there is a total absence of all cone photo-receptors- these patients have no functional day vision
What test is used to identify red-green colour perception deficiencies?
The Ishihara Colour Perception Test
- Consists of plates of circle of dots appearing randomly in size
- Subjects with normal red-green vision will recognise the correct pattern in the form of a 2-digit number
- Patients with colour vision deficiencies will not recognise the wrong pattern
What is dark adaption?
Where the retina increases its light sensitivity when moving from a light to a dark environment
It is a biphasic process during which rod and cone photopigments regenerate.
Cone photoreceptors take 7 minutes to react the maximum level of dark adaption
Rod photoreceptors take 30 minutes to regenerate rhodopsin
Retina switches from photopic vision to scotopic vision
What is light adaption?
The suppression of light sensitivity when moving from a dark to a light environment
- Mediated by photopigment bleaching by bright light and neuro-adaption which inhibits rod and cone function
- Rod function is greatly suppressed and the cone function takes over
- Occurs over 5 minutes
What is pupil adaption?
Where the pupil provides a minor degree of light and dark adaption by acting as an adjustable aperture, regulating the amount of light into the eye.
The pupil constricts in the presence of light and dilates in darkness
What is the visual pathway?
The neurological pathway whereby vision is converted into neurological impulses to be transmitted from the eye to the visual cortex, the posterior part of the brain
What connects the eye to the brain?
Optic nerve
CN II
What makes up the optic nerve?
Myelinated ganglion nerve fibres with cell bodies originated within the retina
Where do the optic nerves from both eyes converge?
At the optic chiasma, at a location just in front and above the brainstem
What happens to the optic nerve ganglion nerve fibres at the optic chiasm?
Half of the nerve fibres cross here and exit along the contra-lateral optic tract while the remaining ganglion nerve fibres exit along the optic tract on the same side.
What is the lateral geniculate nucleus?
Optic nerve ganglion nerve fibres originate within the retina and synapse upon the next order neurons- at the Lateral Geniculate Nucleus
It is a relay centre situated within the Thalamus
What is Optic Radiation?
Forms the fourth order neuron, relaying signal from the Lateral Geniculate Ganglion, to the Primary Visual Cortex within the occipital love for lower visual processing
What is the Primary Visual Cortex? (Striate Cortex)
Within the occipital lobe
Relays visual information to the extra-striate cortex, a region adjacent to the primary visual cortex for further higher visual processing
What are examples of first order neurons within the visual pathway?
Rod and Cone retinal photoreceptors
What are examples of second order neurons within the visual pathway?
Retinal bipolar cells where photoreceptors synapse
What is the purpose of third order retinal ganglion nerve fibres?
Relay visual information out of the eye, to the brain along the optic nerve
Where does decussation of half of the retinal ganglion nerve fibres occur?
Optic chiasma
What happens to retinal ganglion fibres to improve signal transmission?
They become myelinated after entering the optic nerve
Where do retinal ganglion fibres terminate and synapse?
Lateral geniculate ganglion
They synapse upon the fourth order neurons, or Optic Radiation
What is the receptive field of a neuron?
The retinal space within which incoming light can alter the firing pattern of a neuron
The receptive field of ganglion cells covers a much larger area than that of a single photoreceptor
What is convergence?
Number of lower order neurons field synapsing on the same higher order neuron
The cone system has a lower convergence than that of the rod system
What are the characteristics of a system with low and high convergence?
Low convergence:
- Small receptive field
- Fine visual acuity
- Low light sensitivity
High convergence:
- Large receptive field
- Coarse visual acuity
What is the purpose of retinal ganglion cells having on-centre and off-centre sub types?
Plays an important role in contrast sensitivity and enhanced edge detection in vision
How are the on-centre and off-centre sub-types of retinal ganglion cells stimulated and inhibited?
On-centre ganglion:
- Stimulated by light at the centre of the receptive field
- Inhibited by light on the edge of the receptive field
Off-centre ganglion:
- Stimulated by light on the edge of the receptive field
- Inhibited by light at the centre of the receptive field
How do lesions anterior and posterior to the Optic Chiasma affect visual field?
Anterior: Visual field affected in one eye only
Posterior: Visual field affected in both eyes because of the fibres crossing at the chiasma
Where do the ganglion fibres which cross at the Optic Chiasma originate?
Originate from the nasal retina
Responsible for the temporal half of the visual field in each eye
Where do the ganglion fibres which do NOT cross at the Optic Chiasma originate?
Originate from the temporal retina
Responsible for the nasal half of the visual field in each eye
What is bitemporal hemianopia?
A temporal visual field loss in both eyes
How does a lesion at the optic chiasma cause bitemporal hemianopia?
The cross ganglion fibres originating from the nasal retina are damaged. The uncrossed fibres originating from the temporal retina are spared.
What is homonymous hemianopia?
Hemi-field loss in both eyes
N.B:
A right sided lesion posterior to the optic chiasma will cause left homonymous hemianopia in both eyes
A left sided lesion posterior to the optic chiasma will cause right homonymous hemianopia in both eyes
What typically causes bitemporal hemianopia?
Enlargement of pituitary gland tumour which presses on the optic chiasma from below.
What typically causes homonymous hemianopia?
Stroke or cerebrovascular accidents in the brain
Where is the primary visual corte situated?
Along the Calcarine Sulcus within the Occipital Lobe
Characterised by a distinct stripe derived from the myelinated fibre of the Optic Radiation projecting into the Visual Cortex
What is the function of the Primary Visual Cortex?
Specialised in processing visual information of static and moving objects
Where do the left and right hemi-fields project onto the primary visual cortex?
Left: Right Primary Visual Cortex
Right: Left Primary Visual Cortex
How is the primary visual cortex organised?
Organised as functional columns, with each column sensitive to a visual stimuli of a particular orientation
The right eye and left eye dominant columns intersperse each other
Why does damage to the primary visual cortex leading to homonymous hemianopia of the contralateral side characteristically present with sparing of the macula central vision?
The area within the Primary Visual Cortex representing the macula is well protected, as it receives dual blood supply from both right and left posterior cerebral arteries
What is the extra-striate cortex?
The area around the Primary Visual Cortex within the Occipital Love
- It converts basic visual information such as position and orientation, into complex human precepts like motion and object representation
What is the dorsal pathway?
- ‘How Pathway’
- Relays information from the Primary Visual Cortex to the Posterior Parietal Lobe
- Motion Detection
- Visually- Guided action
- Damage to the pathway may result in ability to perceive motion - “Motion Blindness”
What is the ventral pathway?
- ‘What Pathway’
- Relays visual information from the primary visual cortex to the temporal visual cortex
- Object representation, face recognition
- Detailed fine central vision and colour vision
- Damage may result in Cerebral Achromatopsia which is the inability to perceive colour despite functioning cone receptors
What is the significance of pupillary function in the light?
- The iris circular muscle contracts and constricts the pupillary aperture
- Increases the depth of field
- Small pupil reduces amount of light entering into the eye
- The rate of photo-pigment bleaching is reduced
- Pupillary constriction mediated by parasympathetic nerve within CN III
What is the significance of pupillary function in the dark?
- Pupil dilates in dark environment
- Increases light sensitivity in the dark by allowing more light into the eye
- Mediated by the sympathetic nerve, activating the iris radial muscle
Describe the afferent pathway of the Pupillary Reflex
- Rod and cone photoreceptors synapse on bipolar cells which synapse on retinal ganglion cells
- Pupil-specific ganglion cells exit at the posterior third of the optic tract before entering the Lateral Geniculate Nucleus
- The ganglion cells then synapse at the Dorsal Brain Stem
- The afferent pathways from each eye synapse on the Edinger-Westphal nuclei on both sides in the brainstem
Describe the efferent pathway in the Pupillary Reflex
- Provided by parasympathetic nerve arising from brainstem
- Edinger-Westphal nucleus > Occulomotor Nerve Efferent
- The nerve synapses at the Ciliary Ganglion upon the Short Posterior Ciliary Nerve
- The Short Posterior Ciliary Nerve innervates directly on the iris pupillary sphincter
Why does only one eye need to be stimulated with light in order to elicit a pupillary constriction response in both eyes?
The afferent pathway in the pupillary reflex from either eye stimulates the efferent pathway on both eyes
What is the direct light reflex and consensual light reflex?
Direct light reflex: Constriction of pupil in the light-stimulated eye
Consensual light reflex: Constriction of pupil of the fellow (other) eye
What is the result of a right afferent defect in the pupillary reflex?
- E.g. damage to the optic nerve
- No pupil constriction in both eyes when the right eye is stimulated with light
- Normal pupil constriction in both eyes when left eye is stimulated with light
What is the result of a right efferent defect in the pupillary reflex?
- E.g. damage to the right 3rd nerve
- No right pupil constriction whether right or left eye is stimulated with light
- Left pupil constricts whether right or left eye is stimulated with light
What is the purpose of the swinging torch test?
Damage to the afferent pathway is usually incomplete with some degree of pupillary constriction, albeit weaker.
The test demonstrates the weakened response by stimulated one eye at a time, alternating between right and left
What is eye movement?
- Refers to voluntary or involuntary movement of eyes
- Necessary for acquiring and tracking visual stimuli
What is duction?
Eye movement in one eye
What is version?
Simultaneous movement of both eyes in the same direction
What is vergence?
Simultaneous movement of both eyes in the opposite direction
What is convergence?
Simultaneous adduction (inward) movement in both eyes when viewing a near object
What is supraversion and supraduction?
Supraversion= elevation of both eyes Supraduction= elevation of one eye
What is infraversion and infraduction?
Infraversion= depression of both eyes Infraduction= depression of one eye
What is abduction and adduction?
Abduction= duction movement of one eye, moving away from the nose Adduction= duction movement of one eye moving towards the nose
What is dextroversion?
Right gaze
Involves simultaneous right eye abduction and left eye adduction
What is levoversion?
Left gaze
Involves simultaneous left eye abduction and right eye adduction
What is torsion?
Rotation of the eye around the anterior-posterior axis of the eye
What is saccade?
Refers to short fast burst eye movement, up to 900 degrees per second
- Can be voluntary or involuntary
- It is useful for acquiring a new external target, scanning text when reading a book, tracking objects in predictive saccades
- Can perform eye movements guided by memory in the absence of external stimuli
What is smooth pursuit?
A slow sustain movement, up to 60 degrees per second
- Involuntary movement
- Driven by motion of a moving target across the retina
What is optokinetic nystagmus?
A form a physiological nystagmus which is triggered by the presentation of a constantly moving grating pattern
Presents as cycles of smooth pursuit which alternates with fast phase reset saccade in the opposite direction
What is the optokinetic nystagmus reflex usefel in testing?
Testing visual acuity in pre-verbal children by observing the presence of nystagmus movement in response to moving grating patterns of various spatial frequencies
- The presence of the reflex in resposne to moving grating signifies that the subject has sufficient visual acuity to perceive the grating pattern
Which extra-ocular muscles responsible for eye movements originate from the orbital apex?
Superior rectus
Medial rectus
Inferior rectus
Lateral rectus
How do the rectus muscles act to move the eye?
They insert onto the anterior sclera of the eye and act by pulling the eye backwards
How do the superior oblique and inferior oblique muscles act to move the eye?
They insert onto the posterior sclera of the eye and act by pulling the eye forwards
Which muscle adducts the eye?
Medial rectus
Which muscle abducts the eye?
Lateral rectus
Which muscle aids in maximal elevation when the eye is in the abducted position?
Superior rectus
Which muscle aids in maximal depression when the eye is in the abducted position?
Inferior rectus
Which muscle aids in maximal depression when the eye is in the adducted position?
Superior oblique
When muscle aids in maximal elevation when the eye is in the adducted position?
Inferior oblique
Where do the vertical rectus muscles attach and what is their action?
Attach anterior to the globe equator and pull backwards and nasally.
What is the action of the vertical rectus muscles when the eye is adducted and abducted?
Adducted = anterior-posterior axis of the eye is no longer aligned with the vertical rectus muscle therefore the muscles produce torsion motion
Abducted= the anterior-posterior axis of the eye is aligned with the insertion of the vertical rectus muscles.
Here the superior rectus muscle elevates the eye maximally and the inferior rectus muscle depresses the eye maximally
Where do oblique muscles attach and what is their action?
Attach behind the globe equator
What is the action of the oblique muscles when the eye is adducted and abducted?
Adducted= the anterior-posterior axis of the eye is aligned with the oblique muscle action. Here, the oblique muscle pull forwards
Abducted= the anterior-posterior axis is not aligned with the oblique muscle action and the oblique muscles produce torsion eye motion
What is the innervation of the lateral rectus muscle?
Sixth Cranial Nerve
Abducens nerve
What is the innervation of the superior oblique muscle?
Fourth Cranial Nerve
Trochlear nerve
What is the innervation of the extra-ocular muscles excluding the lateral rectus and superior oblique muscles?
Third Cranial Nerve
Occulomotor nerve
What are the branches of the third cranial nerve to innervate the eye?
Superior branch:
- Superior rectus (elevates the eye)
- Lid levator (raises eyelid)
Inferior branch:
- Inferior rectus (depresses the eye)
- Medial rectus (adducts the eye)
- Inferior oblique (elevates the eye)
- Parasympathetic nerve (constricts pupil)
How is the action of the extraocular muscles tested?
The muscle to be tested is isolated by maximising its action and minimising the action of all the other muscles.
The muscles are best tested in different position. E.g.
Lateral rectus= abducted position
Medial rectus= adducted position
Superior rectus= elevated and abducted position
Inferior rectus= depressed and abducted position
Inferior oblique= elevated and adducted position
Superior oblique= depressed and adducted position
What does third nerve palsy present as?
- Affected eye down and out
- Droopy eyelid (upper lid levator muscle is innervated by superior branch of the occulomotor nerve)
- Unopposed superior oblique action innervated by fourth nerve (down)
- Unopposed lateral rectus action innervated by sixth nerve (out)
What does sixth nerve palsy present as?
- Affected eye is unable to abduct and deviates inwards
- Double vision worsens on gazing to the side of the affected eye
What is Hering’s Law of equal innervation?
Muscles from both eye in conjugate eye movement receive equal innervation
E.g. In dextroversion, there is simultaneous right abduction and left eye adduction.
According to Hering’s Law there is equal innervation to the right eye lateral rectus muscle which is innervated by the sixth nerve and to the left eye medial rectus muscle which is innervated by the third nerve
What acts as a link, synchronising the sixth nerve nucleus on the right side and the third nerve nucleus on the left side?
The medial longitudinal fasciculus within the brainstem
The MLF is responsible for coordinating eye movements in both eyes during right and left gaze
What does damage to thethe medial longitudinal fasciculus result in?
Internuclear Ophtalmophlegia
How can the MLF be damaged in multiple sclerosis?
Plaques from in the brain tissues.
On rare occasion, these may damage the MLF within the brainstem
How does internuclear Ophthalmophlegia present with?
- Right eye abduction not accompanied by left eye adduction
- Accompanies by nystagmus on right gaze
- Hering’s law of equal innervation is violated
What is Sherrington’s Law of Reciprocal Innervation?
Agonist muscles contract while antagonist muscles relax
E.g. In dextroversion, the right eye lateral rectus and left eye medial rectus contract, while right eye medial rectus and left lateral rectus relax
What is Duane’s Syndrome?
There is a congenital absence of the sixth nerve innervating the lateral rectus in one eye at birth.
Instead, the third nerve innervates both the opposing medial rectus and the lateral rectus which results in no abduction and limited adduction in the affected eye.
When a patient tries to adduct the eye, the third cranial nerve will cause the opposing medial and lateral rectus to co-contract at the same time which results in limited adduction.
The characteristic eye backwards retraction is seen.
What is the definition of dizziness?
An illusion of self and/or environmental motion
How does oscillopsia differ from vertigo?
Vertigo is present even with one’s eyes shut
What are the commonest emergency room vertigo diagnoses?
BPPV - 35% Vestibular neuritis - 15% Migrainous vertigo - 15% Stroke - 5% Mixed (syncope, anxiety) - 30% Meniere's
What are the three types of cerebral white matter fibres?
1) Association fibres- connects areas within the same hemisphere
2) Commissural fibres
- connects left hemisphere to the right hemisphere
- corpus callosum interconnects frontal, parietal, occipital and some temporal cortex
- anterior commisure provides additional temporal links
3) Projection fibres
- connects the cortex with the lower brain structures (e.g. thalamus), brain stem and spinal cord
- incoming fibres mainly from the thalamus but also from hypothalamus & brainstem
- outgoing fibres to corpus striatum, thalamus, brainstem, spinal cord most go through corona radiata and internal capsule
Why do posterior limb lesions result in motor deficits?
Corticospinal and corticobulbar fibres past through the posterior limb
Which projection fibres pass through both limbs?
Thalamocortical
Corticothalamic
Cortico-pontine
What does the cortical structure consist of?
Neocortex: largest and most complex
Archicortex & paleocortex: phylogenetically older and part of the limbic system
What are the characteristics of the cortical layers of grey matter in the neocortex?
Layers 1-3: mainly cortico-cortical connections
Layers 4: Inputs from the thalamus
Layers 5&6: connections with subcortical, brain stem and spinal cord
From where do all the layers of the neocortex receive inputs?
Reticular activating system (RAS)
Brainstem monoaminergic nuclei
What are the main functions of the occipital lobe?
- Visual association cortex analyses different attributes of visual image in different places
- Form and colour analysed along ventral pathway; spatial relationships and movement along dorsal pathway
- Lesions affect specific aspects of visual perception
What are the main functions of the parietal lobe?
- Posterior parietal association cortex creates spatial map of body in surroundings, from multi-modality information
What are the main functions of the temporal lobe?
- Language, object recognition, memory, emotion
What are the main functions of the frontal lobe?
- Judgement, foresight, personality, appreciation of self in relation to the world
What are the differences between the right and left hemispheres?
Left hemisphere= more concerned with language and sequential analysis
Right hemisphere= more concerned with shape, spatial relationships and music
What is prosopagnosia?
The inability to recognise familiar faces or learn new faces.
Can result from lesions of the visual posterior association area (fusiform gryus)
How are front cortex lesions characterised?
- Lack of planning
- Behaviour becomes disorganised
- Attention span and concentration diminish
- Self control is hugely impaired
What can injury to the parietal cortex cause?
- Disorientation
- Inability to read maps
- Inability to understand spatial relationships
- Apraxia
- Hemispatial neglet
What are the characteristics of temporal cortex lesions?
- Language
- Object recognition
- Memory
- Emotion
- Injury leads to agnosia
- Receptive aphasia
What is diffusion tensor imaging?
A form of structural imaging that can be used to measure the effect of lesions in white matter.
The movement of water molecules in the brain can be used to infer the underlying structure of white matter.
This information can be used to estimate the location and connection between different white matter pathways
What is transcranial magnetic stimulation (TMS)?
- A brief magnetic pulse induces action potentials through electromagnetic conduction
- It can be used to induces brief bursts of activity in focal areas
- Prolonged bursts can be used to suppress cortical function
What is transcranial direct/ alternating current stimulation (TDCS/TACS)?
- A small positive or negative current (1-2mA) is appliedover a short period of time (10 – 30 minutes)
- The positive (anode) electrodes are associated with facilitatory action on excitability
- The negative (cathode) electrodes are associated with inhibitory effects
- Effects can last 1-2 hours following a single session
- Prolonged application is associated with longer term changes
What is evoked potential (EP) or event-related potential (ERP)?
- It is a refine form of EEG recording- a direct measure of neuronal activity
- Computer analysis reveals waveforms which are time-locked to particular events
- It is non-invasive
- It has very good temporal resolution (measured in msec)
- It has poor spatial resolution (measured in cms)
What is magnetoencephalography?
- It measures changes in magnetic fields which are induced by electrical currents in the cortex
- Non-invasive
- Very good temporal resolution
- The magnetic fields are not affected by artefacts in the way as EEG
- Very expensive
What is functional magnetic resonance imaging?
- It measured neuronal activity indirectly
- Minimally invasive
- Better spatial resolution than EEG/MEG (measured in mms)
- Minimally invasive
- Poor temporal resolution (measured in secs)
What is positron emission tomography (PET)?
- It is invasive as patients are injected with a radioactive tracer
- The PET then measured the radioactivity which is emitted by the tracer
- Different types of receptor can be mapped by attaching the tracer to different molecules e.g. glucose
- Expensive as the radionuclides must be produced using a clycotron
- Allows imagine of specific receptor populations
- Sometimes combined with a CT scan
What is diffusion tensor imagine (DTI)?
- It provides an index of the arrangement of white matter in the brain
- It can be used to visualise white matter pathways
- Computational techniques can be used to estimate connectivity between cortical and subcortical regions e.g. thalamo-cortical loops
What are the differences between the primary cortical areas and the associated cortex?
Primary cortical areas= function predictable, organised topographically, left-right symmetry
Association cortex= function less predictable, not organised topographically, left-right symmetry weak or absent
How many different odours are there?
2000-4000
What different cells make up the olfactory epithelium?
Bipolar olfactory neurons
Sustentacular cells
Basal cells
What is anosmia?
The loss of smell.
The main cause is trauma to the front of the face resulting in the fracture of the ethmoid bone and cribiform plate. This leads of shearing of olfactory neurones.
This is one of the early signs of Parkinson’s and Alzheimer’s
What is the limbic system?
The system responsible for the processes aimed at the survival of the individual:
- Maintenance of homeostasis
- Agnostic (defence/attack) behaviour
- Sexual and reproductive behaviour
- Memory
What are the key structures of the limbic system?
- Hippocampus, parahippocampal gyrus, fimbria of hippocampus
- Fornix (body and crux)
- Septal nuclei
- Cingulate gyrus
- Hypothalamus
- Amygdala
- Mammillary bodies
- The thalamus
What is the Papaz Circuit?
The emotional input circuit of the limbic system. It modulates the output of emotional expression
What plays an important function in acute memory and new learning?
The hippocampus
What is most likely responsible for long-term memories?
The parietal neocortex
How can the progression of Alzheimer’s symptoms be identified?
Early stage= loss of short term memory - hippocampus and entorhinal cortex
Moderate/middle stage= dressing apraxia - parietal lobe involvement
Late stage= disinhibition, loss of executive skills and personality- involvement of frontal lobe
What is the amygdala?
A small clump of nuclei in the uncus of the temporal lobe, which is involved in fear, anxiety, aggression and the fight/flight response
What are the main connections of the hippocampus?
Afferent= Perforant pathway Efferent= Fimbria/fornix
What are the main connections of the amygdala?
Afferent= olfactory cortex, septum, temporal neocortex, hippocampus, brainstem Efferent= Stria terminalis
What can damage to the amygdala result in?
Kluver-Bucy syndrome
What does Kluver-Bucy syndrome result in?
Hyperorality (insertion of inappropriate objects in the mouth)
Loss of fear
Visual agnosia
Hypersexuality
Which structures are experimentally shown to be associated with aggression?
Hypothalamus
Brainstem (periaqueductal grey)
Amygdala
5-HT in raphe nuclei
What are the main connection of the septum?
Afferent= Amygdala, olfactory tract, hippocampus, brainstem Efferent= Stria medularis thalami, hippocampus, hypothalamus
What are the functions of the septum
Reinforcement of knowledge and reward
Which pathway is involved in drug dependance?
Dopaminergic mesolimbic pathway
What does the mesolimbic pathway (dopamine) involve?
The midbrain stimulates the median forebrain bundle which projects to the prefrontal cortex, nucleus accumbens and the amygdala
How do drugs of dependence activate the dopaminergic mesolimbic pathway?
- Opioids, nicotine and amphetamines, ethanol and cocaine all increase dopamine release in the nucleus accumbens
- The midbrain neurons are stimulated which promote dopamine release or inhibit dopamine reuptake
What is consciousness?
The brain state than enables us to experience the world and us and within one self
What is the difference between levels and contents of consciousness?
Levels= alertness Contents= subjective experience & metacognition
How does the reticular formation affect consciousness?
The degree of activity in the reticular system is associated with alertness/levels of consciousness
Where does the reticular formation project?
To the thalamus and the cortex, thus allowing sensory signals to reach cortical sites of conscious awareness such as the frontoparietal cortex
Which neurons boost the level of activity in the cerebral cortex?
Cholinergic neurons in the reticular formation via the thalamus
What can a persistent vegetative state be due to?
Disconnection of the cortex from the brainstem or widespread cortical damage
What are the metabolic causes of coma?
Hypoxia
Hypoglycaemia
Intoxication
What can damage to the reticular formation/thalamus and massive bilateral cortical insult lead to?
Coma
Which sensory pathways does the reticular formation receive information from?
- Touch and pain from ascending tracts
- Vestibular from medial vestibular nucleus
- Auditory from inferior colliculus
- Visual from superior colliculus
- Olfactory via medial forebrain bundle
Via which mechanisms does the thalamus affect the cortex?
1) Cholinergic projections excite individual thalamic relay nuclei which leads to activation of the cortex
2) Cholinergic projections to intralaminar nuclei, which in turn project to all areas of cortex
3) Cholinergic projections to the reticular nucleus, which regulates flow of information through other thalamic nuclei to the cortex
Which four basic rhythms can be recognised on an EEG to present different levels of arousal?
1) Delta (0.5-4 Hz) present during sleep
2) Theta (4-8 Hz) associated with drowsiness
3) Alpha (8-13 Hz) subject relaxed with eyes closed
4) Beta (13-20 Hz) indicates mental activity and attention
What is confusion?
A sustained disturbance of consciousness and mental processes are slowed.
May be inattentive, disorientated have have difficulty carrying out simple commands or speaking
What is stupor?
A profound disturbance of consciousness.
Can only be roused by strong sensory stimuli
What is a coma?
A disturbance of consciousness where one cannot be roused even by strong sensory stimuli.
Different from sleep as metabolic activity of the brain is depressed and there is total amnesia for the period in a coma
What can produce a coma?
1) Metabolic alteration eg. hypoglycaemia, hypoxia, intoxication
2) Lesions in cerebral hemispheres - only if massive and bilateral- leads to flat EEG
3) Lesions in thalamus or brainstem eg. due to raised intracranial pressure- EEG looks like a slow wave sleep
What is brainstem?
An irreversible coma due to brainstem death, but the body is kept alive artificially.
An EEG is not diagnostic
Spinal reflexes and some postural movements may still be present
What does the decision to cease treatment in a patient who is brain dead depend on?
Demonstration of absence of brainstem reflexes & response to hypercapnia
What is a persistent vegetative state?
An irreversible coma due to the disconnection of the cortex from the brainstem or widespread disease in cerebral hemispheres
In this state, the brainstem is still functioning therefore reflexes, postural movements & sleep-wake cycle may be present.
What is blindsight?
Patients who are perceptually ‘blind’ of their visual field due to occipital damage but can however respond to visual stimuli
What is the behavioural criteria for sleep?
- Stereotypical or species specific posture
- Minimal movement
- Reduced responsiveness to external stimulation
- Reversible
What is the electrophysiological criteria for sleep?
- EEG rhythm
- Eye movements
- General muscle tone
What are the changes during non-REM sleep (stages 1-4)?
- State changes gradually from drowsiness, through light sleep to deep sleep
- The EEG rhythm gradually slows from theta (4-8 Hz) to delta (0.5-5 Hz)
- General muscle tone decreases gradually
- There are relatively few eye movements
What are the characteristics of REM sleep (stage 5)?
- The EEG rhythm speeds up to Beta (13-30 Hz)
- General muscle tone becomes very low
- Rapid eye movements occur
During which stage of sleep are dreams most prominent?
REM sleep
What occurs in the limbic system and frontal cortex during sleep?
Limbic system is more active
Frontal cortex is less active
What is the duration of a single sleep cycle?
Approx 1.5 hours
What nuclei in the brainstem does the reticular activating system consist of?
Raphe nuclei
Nucleus coeruleus
Cholinergic nuclei
They project directly or indirectly via the thalamus to all areas of the cerebral cortex
What maintains arousal?
The reticular activating system
How do hypothalamic nuclei control the activity of the reticular activating system?
1) Lateral hypothalamus promotes arousal
2) Ventrolateral preoptic nucleus promotes sleep
What is the purpose of the caudal pontine reticular formation during REM sleep?
It suppresses general muscle tone and activates rapid eye movements
How does the suprachiasmatic nucleus affect circadian control?
- Special cells in the retina detect a decrease in light level and activate the suprachiasmatic nucleus of the hypothalamus
- The suprachiasmatic nucleus modulates sleep-wake circuits and stimulates the pineal gland to secrete melatonin
- Melatonin synchronises physiological processes with day length
What evidence is there to suggest that sleep is necessary?
- Sleep has been highly conserved during evolution
- Sleep deprivation results in detrimental effects on life
- Sleep is regulated very accurately
What are the possible functions of sleep?
- Restoration and recovery
- Energy conservation
- Predator avoidance
- Memory consolidation
- Other effects on brain function
What are the effects of sleep deprivation?
- Sleepiness, irritability
- Performance decrements/ increased risk of errors and accidents
- Concentration/ learning difficulties
- Glucose intolerance
- Reduced leptin/ increased appetite
- Hallucinations (after long sleep deprivation)
- Death: rats (14-40 days), humans (fatal familial insomnia)
What is seen after sleep loss?
- A reduced latency to sleep onset (want to sleep earlier)
- Increase of slow wave sleep (non-REM)
- Increase of REM sleep (after selective REM sleep deprivation)
What are the causes of chronic cases of insomnia?
Physiological: eg. sleep apnea, chronic pain
Brain dysfunction: eg. depression, fatal familial insomnia, night working
What are treatments for chronic cases of insomnia?
Most hypnotics enhance GABAergic circuits
What is narcolepsy?
Too much sleep
It is defined by entering REM sleep directly and repeatedly throughout the day
Can also present with cataplexy (the sudden temporary inability to move)
Caused by orexin deficiency
Why can night working lead to sleep disorders?
Night working causes physiological processes to become desynchronised
This leads to sleep disorders, fatigue and an increased risk for some conditions such as obesity, diabetes and cancer
