Neurology 1 Flashcards
What does the brain process?
Movement, seeing, hearing, feeling (touch, pain, temperature), tasting and smelling the world
Emotions - giving meaning to the world
Learning, behaviour, memory, executive function
How have the features of the brain be preserved in evolution?
Our brain is very different to that of our distant vertebrate ancestors but mainly in terms of the size and proportions of various parts.
The basic structure, anatomy and connectivity is incredibly well preserved.
What are the different mechanisms of defense that the brain uses?
Escape from pain - uses spinal cord e.g. withdrawal reflex to keep tissues safe, doesn’t require any complex processing
Avoidance from threat - uses sensorimotor
midbrain (outside conscious control)
Avoidance from learned threat - uses cortex and limbic system e.g. understanding that a gun is dangerous
More complex, sophisticated threat detection and avoidance behaviour requires additional or more complex processing capacity.
What is the CNS?
Made of the brain and the spinal cord
What is the PNS?
Outside the skull and spine.
Somatic Nervous System: part that interacts with the external environment.
Automatic Nervous System: part that regulates the body’s internal environment.
Sends sensory signals to the CNS (afferent)
CNS sends motor signals to the peripheries (efferent)
What are the unipolar sensory neurons?
Afferent neurons bringing sensory information via the dorsal roots to the CNS. They have their cell bodies grouped in the dorsal root ganglions. Each neuron has a peripheral process ending in the skin, a muscle or a joint (sensory receptor) and a central process ending in the dorsal horn of the spinal cord.
What are the mutlipolar motor neurons?
Efferent neurons sending motor information via the ventral roots to the muscles. They have their cell bodies in the ventral horn.
How can the brain be divided up?
FOREBRAIN
Telencephalon (cerebral cortex, basal ganglia and limbic system)
Diencephalon (thalamus, hypothalamus)
MIDBRAIN
Mesencephalon (tegmentum, tectum)
HINDBRAIN
Metencephalon (pons, cerebellum)
Myelencephalon (medulla)
What is the function of the medulla?
Contains tracts carrying signals between the rest of the brain and the body.
Contain caudal part of the reticular
formation (“little net”):
- Low level sensorimotor control e.g. balance
-Involved in variety of vital functions:
Sleep/Wakefulness
Motor Plant: movement, maintenance of muscle tone
Various cardiac, circulatory, respiratory, excretory
reflexes
What is the function of the pons?
Relay from cortex and midbrain to the cerebellum
Contains millions of neuronal fibers
Contains pontine reticular formation (pattern generators) e.g. for walking
What is the function of the cerebellum?
Smaller than the brain but contains as many neurons as all the rest of the CNS.
“Motor errors” between intended movement and actual movement – adjusts synaptic weights to eliminate error.
Correction can take place during the movement : motor learning.
Thought exclusive for motor coordination – recently implicated in cognitive and affective/emotional function.
What is the function of the tectum?
Visual/spatial and auditory frequency maps
Made up of the:
- Superior colliculus: Sensitive to sensory change – orienting/defensive movements
- Inferior Colliculus: Similar, but for auditory
events
What is the function of the tegmentum?
The Periaqueductal gray - role in defensive behaviour, analgesia, reproduction
Red nucleus - Target of cortex and cerebellum, projects
to spinal cord. Role in pre-cortical motor control (especially arms and legs).
Substantia nigra – made up of Substantia nigra pars compacta (Dopamine cells) which deals with basal ganglia input and Substantia nigra pars reticulata which deals with basal ganglia output.
What is the function of the thalamus?
Specific nuclei : relay signals to cortex/limbic system for all sensations (but smell…).
Non-specific nuclei : Role in regulating state of sleep and wakefulness and levels of arousal
Important relays from basal ganglia and cerebellum back to cortex
What is the function of the hypothalamus?
Regulates the pituitary gland which regulates hormonal secretion: interface between brain and hormones
Role in hormonal control of motivated behavior including hunger, thirst, temperature, pain, pleasure and sex
What is the function of the basal ganglia?
Subcortical structure
Group of structures
Loop organisation - central arbiter of function
These structures thought to be involved in motor function since involved in movement disorders
However: work from this department suggested fundamental role in action selection and reinforcement learning
What is the function of the limbic system?
Subcortical structures
Group of structures
These structures involved in emotion, motivation and emotional association with memory
The limbic system influences the formation of memory by integrating emotional states with stored memories of physical sensations
What are the structures found in the limbic system?
Amygdala Hippocampus Fornix Cingulate gyrus Septum Mamillary body
What is the function of the amygdala?
Involved in associating sensory stimuli with emotional impact
What is the function of the hippocampus?
Involved in memory (long term)
Involved in spatial memory
What is the function of the fornix?
C-shaped bundle of fibers
Carries signals from the hippocampus to the mammillary bodies and septal nucleus
What is the function of the cingulate gyrus?
Linking behavioural outcomes to motivation and autonomic control – atrophied in schizophrenia
What is the function of the septum?
Involved in defense and aggression
What is the function of the mamillary body?
Breast shaped Important for the formation of recollective memory – amnesia
What are the major features of the frontal lobe?
Contain the precentral gyrus from which motor instructions (particularly for fine motor control) that are sent to muscles controlling hands and feet.
- Primary motor cortex: contains many of the cells giving origin to the descending motor pathways - it is involved in the initiation of voluntary movements.
- Premotor and supplementary motor areas: higher level motor plans and initiation of voluntary movements.
What are the functions of the frontal lobe?
Executive” planning – generating models of the consequences of actions
Judgmental roles
Emotional modulation
Working memory: short-term information (rather than long-term factual data)
Control of behavior that depends upon context or setting
Prefrontal cortex: generating sophisticated behavioural options that are mindful of consequences
What are the major features of the parietal lobe?
Contains the postcentral gyrus which receives sensation from the rest of the body
- Primary somatosensory cortex
Maintains representations of the body’s and of the head’s position in space.
Permits complicated spatio-temporal predictions – e.g. catching something when you are moving
What are the major features of the temporal lobe?
Plays important roles in integrating sensory information from various parts of the body
Interface between cortex and limbic system – association of affect/emotion with things
Contains the primary auditiory cortex
Inferotemporal cortex: recognition faces and objects
What are the major streams of the occipital lobe?
Contains visual cortices
Dorsal stream - Vision for movement (Where is it in relation to us)
Ventral stream - Vision for identification (What does it mean to us)
What are the major milestones of development of the brain?
10w – cerebral expansion and commissures.
3m – basic structures established.
5m – CNS myelination begins. Continues to adolescence.
7m – lobed cerebrum.
9m – gyri and sulci.
What are the consequences of fetal alcohol syndrome?
Alcohol crosses placenta.
Fetus doesn’t clear alcohol well so fetal levels of alcohol are higher.
- Facial abnormalities
- Microcephaly - loss of cells, loss of fibres e.g. callosal agenesis, disturbed migration
- Irritability
- Motor and intellectual impairment
What are the effects of drugs of abuse on neuronal development of the fetus?
Opiates – neonatal withdrawal
Cocaine – neonatal hypoxia, abortion, withdrawal, decreased cognition
Ecstasy - long term effects on hippocampus
When do the senses of the fetus/baby develop?
Taste and smell - well developed at birth.
Hearing - responsive at birth.
Excellent discriminators of language sounds.
Locate sounds from 3 days.
Vision
Eyes open and sensitive from 7 months.
Vision least well developed at birth.
What are the major post-natal reflexes?
Moro (startle) reflex - the infant is held in the supine position with the head supported, the head is then suddenly allowed to drop. The infant will abduct and extend the arms, open the hands, and then adduct the arms and flex the elbows.
Stepping - hold up feet on a surface
Palmar grasp - supports own weight, goes by 3 - 4 months
Swimming - goes by 4-6 months
Babinski reflex - Neonates fan toes when sole stroked
When can babies achieve co-ordinated motor responses?
Significant development post-birth e.g. reaching begins at 5th month
Attain objects at 8-9m
By 2 years, show adult motor patterns
What do the neural crest cells give rise to?
Cartilage and bone in the skull or face.
Also give rise to schwann cells, adrenal medulla, meninges, sensory dorsal root ganglia of spinal cord and V, VII, IX and X.
What are the abnormalities of the spinal cord?
The neural tube usually closes at the end of embryonic week 4.
Failure to close cephalic region - anencephaly
Failure to close spinal regions - spina bifida
Collectively called neural tube defects.
What increases the risk of neural tube defects?
Environmental factors - folic acid and maternal diabetes
Genetic factors - 1 sibling 1%, 2 siblings 2%, parent 4%
Irish individuals have a greater risk of neural tube defect due to various genetic polymorphisms which activate folic acid.
What are the types of spina bifida?
Spina bifida occulta - opened posterior vertebral body
Meningocele - protrusion of the meninges (dura mater)
Myelomeningocele - protrusion and opened spinal cord
Lower motor neuron lesion - floppy (spina bifida patients are often incontenent)
Upper motor neuron lesion - stiffness
What is microcephaly and macrocephaly?
Microcephaly - reduced head circumference, brain size is too small, not enough neurons have been made, normally associated with some sort of intellectual disability
Macrocephaly - increased head circumference
Compared using a normal distribution
What is Periventricular nodular heterotopia?
Abnormal migrations of neurons
Gene that tells the neurons to migrate is abnormal. Often associated with learning problems and epilepsy.
How is CSF circulated?
CSF circulates through the subarachnoid spaces and through the vesicles
CSF cushions the brain and helps circulate metabolites
About 120mls
Produced as filtrate of blood at choroid plexuses in ventricles
Absorbed via arachnoid granulations in superior sagittal sinus.
What is obstructive hydrocephalus?
Lateral ventricles found in the cerebral hemispheres
Foramen of Monro connects lateral ventricles to the third ventricle
Aqueduct of Sylvius connects third ventricle to the fourth ventricle
These areas can get blocked by infection
Obstructive hydrocephalus - impaired consciousness and a headache
What is hydrocephalus?
Accumulation of CSF with increased intracranial pressure
Can cause macrocephaly in children
Obstructive (non-communicating) e.g. tumour, haemorrhage
Non-obstructive (communicating) e.g. increased CSF production
Try to treat the underlying cause or put in a shunt
What are the key processes that occur in the eye?
Transmission of light: tear film, cornea, aqueous, lens, vitreous, inner retina
Refraction of light: cornea and lens
Detection of light: photoreceptors and ganglion cells
The afferent pathway: optic nerve, chiasm, optic tracts, thalamus, optic radiations, visual cortex
The efferent pathway: brain stem nuclei, cranial nerves, ocular muscles
How are the orbits positioned in the head?
Conical or four-sided pyramidal cavities
Open into the midline of the face
Point back into the head
What are the bones surrounding the orbit?
Orbital margin - Frontal, Zygomatic, Maxilla
Walls - Lacrimal, Ethmoid, Sphenoid: body, lesser and greater wings
What are the holes present in the orbit?
Optic canal
Superior orbital fissure
Inferior orbital fissure
Nasolacrimal fossa
What is a blowout fracture?
A traumatic deformity of the orbital floor or medial wall, typically resulting from impact of a blunt object larger than the orbital aperture, or eye socket.
What is facial palsy and what causes it?
A loss of facial movement due to nerve damage. Facial muscles may appear to droop or become weak. It can happen on one or both sides of the face. Common causes of facial paralysis include:
- infection or inflammation of the facial nerve
- head trauma
- head or neck tumor
- stroke
What are the different layers of the tear film?
Surface layer contains the Meibomian glands
Middle layer is aqueous and contains lacrimal glands, lysozyme, lactoferrin, antibodies
Deep layer contains mucin: goblet cells
What is Sjogren’s syndrome?
A chronic inflammatory autoimmune disorder which may be primary or secondarily associated with connective tissue disease. Lymphatic infiltration and fibrosis of exocrine glands, especially lacrimal and salivary glands.
Dry mouth and dry eyes
What are the layers of the cornea?
Epithelium - Non-keratinising squamous
Stroma - Regular lamellae
Endothelium - Pumps fluid out of stroma
What is the sclera?
Very strong
Insertion of eye muscles
Holes for optic nerve and neurovascular bundle
What is keratoconus?
A disorder of the eye which results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, astigmatism, and light sensitivity. Usually both eyes are affected. In more severe cases a scarring or a circle may be seen within the cornea.
What makes up the uveal tract?
Iris - Pupil and Sphincter and dilator muscles to control pupil reflexes
The ciliary body - made up of ciliary epithelium: aqueous and ciliary muscle: accommodation and pars plana
The choroid - Highly vascular and highly pigmented
What is coloboma?
A hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc.
What the layers of the retina?
INNER RETINA: Internal limiting membrane Nerve fibre layer Ganglion cell layer Inner plexiform layer Inner nuclear layer Outer plexiform layer Outer nuclear layer Outer limiting membrane OUTER RETINA: Photoreceptors Retinal pigment epithelium
What makes up the peripheral and central retina?
CENTRAL RETINA Macula (lutea) Fovea (centralis) Cone photoreceptors - Fine visual resolution - Colour vision - Photopic vision PERIPHERAL RETINA Rod photoreceptors - Peripheral visual field - Motion detection - Scotopic vision
What is Central retina artery occlusion?
A disease of the eye where the flow of blood through the central retinal artery is blocked (occluded). There are several different causes of this occlusion; the most common is carotid artery atherosclerosis.
What are the major features of the lens?
Continues to grow Contained within elastic capsule Natural shape is almost spherical Shape controlled by ciliary muscle in the ciliary body via zonules Allows for accommodation Fades with age
What is cataract surgery?
A procedure to remove the lens of your eye and, in most cases, replace it with an artificial lens. Normally, the lens of your eye is clear. A cataract causes the lens to become cloudy, which eventually affects your vision
What are the anterior and posterior segments of the globe?
Anterior segment contains the anterior chamber (AC), cornea, angle, iris, pupil/lens and aqueous humour which circulates from ciliary body, via pupil, into AC and leaves via the trabecular meshwork in the ‘angle’
Small posterior chamber behind iris
Posterior segment contains vitreous humour
Supportive but largely redundant from birth
What is angle-closure glaucoma?
Acute angle-closure glaucoma occurs when the flow of aqueous humour out of the eye is blocked and pressure inside the eye becomes too high very quickly. It is an emergency because if it is not treated quickly, it can lead to permanent loss of vision
What are the humours of the eye?
Aqueous (humour):
Produced by ciliary epithelium in ciliary body
Maintains intraocular pressure between 12 and 20 mmHg above atmospheric pressure
Circulates around lens
Low protein ‘plasma’
High vitamin C (antioxidant)
Nourishment for avascular structures
Vitreous (humour):
Collagen matrix
Hyaluronic acid and water
What happens in retinal tear & detachment?
As the vitreous separates or peels off the retina, it may tug on the retina with enough force to create a retinal tear. Left untreated, the liquid vitreous can pass through the tear into the space behind the retina, causing the retina to become detached.
What are the extraocular muscles and their nerve supply?
Rectus muscles: Horizontal (lateral and medial) Vertical (superior and inferior) Oblique muscles: Superior and inferior Arise from orbital apex Insert anteriorly into sclera Nerve supply CNIII: medial rectus, inferior rectus, superior rectus, inferior oblique CNIV: superior oblique CNVI: lateral rectus
What are the actions of the extraocular muscles?
Horizontal recti: abduction and adduction
Vertical recti: mostly elevation and depression
other actions depending on globe position in orbit
Obliques:
Mostly intorsion and extorsion
other actions depending on globe position in orbit
What is 3rd nerve palsy?
Third cranial nerve disorders can impair ocular motility, pupillary function, or both. Symptoms and signs include diplopia, ptosis, and paresis of eye adduction and of upward and downward gaze. If the pupil is affected, it is dilated, and light reflexes are impaired.
What is needed for normal light transmission in the eye and the potential problems?
Wavelength - UV absorbed Eyelids separated - ptosis Normal tear film - dry eye Transparent cornea - scarring, swelling Clear aqueous - inflammation, blood Normal pupil - too large, too small, incorrect position, occluded Clear lens - cataract Clear vitreous - blood, inflammation Normal inner retina - swelling, blood
What is refractive error?
Refractive error, also known as refraction error, is a problem with focusing light accurately onto the retina due to the shape of the eye. The most common types of refractive error are near-sightedness, far-sightedness, astigmatism, and presbyopia.
How does light detection (transduction) occur in the visual system?
Photoreceptor outer segments
Discs contain rhodopsins which respond to different wavelengths
Change in structure of retinal opens Na/K channels
Hyperpolarisation of membrane closes Ca channels
Reduces glutamate release- bipolar cells respond
What is dyschromatopsia?
A rare acquired inability to discriminate colors by hue. Dyschromatopsia is most often associated with damage to the inferior part of the occipital lobes, in the fusiform gyrus.
Where does vision from each eye end up?
Images temporal to midline fall on nasal retina
Images nasal to midline fall on temporal retina
Optic nerves transmit from each eye but maintain orientation
Splits at chiasm:
Nasal fibres (temporal field) cross
Tracts now have information from opposite field but from each eye
How does light affect pupillary constiction?
Pupillary reflexes to light Light sensitive ganglion cells Optic nerve, chiasm, tract Synapse in midbrain (3rd n) 3rd n to ciliary ganglion (orbit) Fibres to sphincter muscle Light stimulus in one eye therefor causes both pupils to constrict (direct and consensual response)
What is a visual field defect?
A visual field defect is a loss of part of the usual field of vision, so it does not include severe visual impairment of either one eye or both. The lesion may be anywhere along the optic pathway; retina to occipital cortex.
What is Horner syndrome?
Horner syndrome is characterized by drooping of the upper eyelid (ptosis) on the affected side, a constricted pupil in the affected eye (miosis) resulting in unequal pupil size (anisocoria), and absent sweating (anhidrosis) on the affected side of the face.
What are the cell types of the CNS?
Neurons
Differentiated glia: Oligodendrocytes, Microglia, Astrocytes
Others - glial stem cells, oligodendrocyte precursors, ependymal cells, etc.
What is a neuron?
Specialized for intercellular electrical signalling via synapses
Dendrites receive inputs (dendritic spines), transmit to cell body (soma)
Action potentials propagate along axon from axon hillock
Mainly, but not exclusively, formed during brain development
What is the Neuropil?
Any area in the nervous system composed of mostly unmyelinated axons, dendrites and glial cell processes that forms a synaptically dense region containing a relatively low number of cell bodies.
What are the 2 types of synapses?
Chemical - majority
Electrical – less abundant, enable synchronized electrical activity in brainstem neurons (breathing) and hypothalamus (hormone secretion)
What is synaptic plasticity?
Synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.
Basis of learning & memory
Highly relevant to disease – e.g. neuro-developmental disorders & Alzheimer’s
How do neurons express heterogeneity?
Size
Morphology
Electrical properties
Neurotransmitters
What are oligodendrocytes?
Myelinating cells of the CNS
Unique to vertebrates
Myelin insulates axon segments, enables rapid nerve conduction
Myelin sheath segments interrupted by nodes of Ranvier – saltatory conduction
Provide metabolic support for axons
What is the myelin sheath?
Formed by wrapping of axons by oligodendrocyte processes (membranes)
Highly compacted – 70% lipid, 30% protein
Myelin specific proteins, e.g. MBP, PLP, etc. involved in compaction, excellent “markers”
What are the microglia?
Resident immune cells of the CNS
“Resting” state, highly ramified, motile processes survey environment (2-3 µm/min)
Upon activation (e.g. by ATP), retract processes, become “amoeboid” & motile
Proliferate at sites of injury - phagocytic
What are the functions of the microglia?
Immune surveillance
Phagocytosis – clearing up debris/microbes
Synaptic plasticity – pruning during development, refining of the circuitry
What are astrocytes?
“Star-like cells”
Most numerous glial cells in the CNS
Highly heterogeneous – not all star-shaped
Common “marker” glial fibrillary acidic protein (GFAP)
What are the 2 major morphologies of astrocytes?
Fibrous – white matter, contact blood vessels, pia & nodes of Ranvier
Protoplasmic – grey matter, contact blood vessels & pia
What are the functions of astrocytes?
Developmental – will give rise to radial glia
Structural - define brain micro-architecture
Envelope synapses – “tripartite synapse”
Homeostatic – buffer K+, glutamate, etc.
Metabolic support - Glutamate-Glutamine shuttle, lactate shuttle, etc.
Disease – gliosis/astrocytosis
Neurovascular coupling
What are some of the specialised glia?
Radial glia –important for braindevelopment Müller cells (in retina) Bergmann glia (in cerebellum)
How does motor neuron disease affects the cells of the CNS?
MND symptoms are due to loss of motor neurons.
MND spinal cord shows pathological changes in motor neurons, microglia and astrocytes.
Pathological CNS lesions in MS involve neurons, oligodendrocytes and T lymphocytes (demyelinating disease).
Acute symptoms of MS reflect dysfunction of neurons.
What are nuclei? Tracts? Commissures? White and grey matter?
Abundance of neuronal cell bodies in nuclei
Axons gathered into tracts
Tracts that cross midline = commissures
Grey matter abundant in neural cell bodies & processes – neuropil contains few cell bodies
White matter contains abundance of myelinated tracts & commissures
What are ganglia? Nerves? Schwann cells?
Cell bodies & supporting cells located in ganglia – e.g. dorsal root ganglia (DRGs)
Axons bundled into nerves
Many PNS axons are enveloped by Schwann cells (myelinating cellsof the PNS – neural crest derived)
What are the features of the blood-brain barrier?
Endothelial tight junctions
Astrocyte end feet
Pericytes
Continuous basement membrane, lacks fenestrations
Need specific transporters for glucose, water, essential ions etc.
What is the Area postrema?
Paired structure in the medulla oblongata of the brainstem, is a circumventricular organ having permeable capillaries and sensory neurons that enable its dual role to detect circulating chemical messengers in the blood and transduce them into neural signals and networks.
What are the Ependymal cells?
Epithelial-like, line ventricles & central canal of spinal cord
CSF production, flow & absorption
Ciliated – facilitates flow of CSF
Allow solute exchange between nervous tissue & CSF
What is the choroid plexus?
Frond-like projections in ventricles
Formed from modified ependymal cells, villi form around network of capillaries → large surface area
Main site CSF production by plasma filtration (driven by solute secretion)
Gap junctions between cells form blood-CSF barrier
What are the main features of a neuron?
Basic cellular unit of the nervous system
Huge range - specialised for different functions
All have same basic components: dendrites, cell body/soma, axon, presynaptic terminals.
Axon transmits the action potential from the cell body, to axon via axon hillock to the synapse.
What are the different types of neurons?
Unipolar - one structure extending from the soma
Bipolar - one axon and one dendrite extending from the soma
Multipolar - one axon and many dendrites; Pseudounipolar - single structure that extends from the soma, which later branches into two distinct structures.
What’s the difference between axonal and synaptic transmission?
Axonal transmission: Transmission of information from location A to location B
Synaptic transmission: Integration/processing of information
What are the main symptoms of multiple sclerosis?
Eye movements – uncontrolled, seeing double
Speech – slurred
Paralysis – partial/complete, any part of body
Tremor
Co-ordination – lost
Weakness – tired
Sensory – numbness, prickling, pain
Who gets multiple sclerosis?
Young adults 20-40
Slightly more women than men
Temperate zones
Areas with high standards of sanitation
What is the diagnosis/prognosis for multiple sclerosis?
Initial symptoms – slight with remission
Episodes become more numerous, frequent and severe and become chronic
Difficult to diagnose because:
Early symptoms slight – person doesn’t go to doctor
Other diseases have similar symptoms
No definitive current lab-test – diagnosis based on repeated presentation of symptoms combined with an MRI
What is the nerve impulse?
The signal used by neurones to transmit information between different spatial locations
What is the neuronal membrane permeable to?
Some substances which are electrically charged (+ve or –ve) and cross readily – potassium (K+) and chloride (Cl-)
Some cross with difficulty – sodium (Na+)
Some not at all – large organic proteins (-ve charge)
What are the forces that determine the distribution of charged ions?
Diffusion – the force driving molecules to move to areas of lower concentration
Electrostatic pressure - ions (like magnets) move according to charge, like ions repel and unlike attract
Why is the membrane potential at rest -70mV?
More K on the inside than the outside – diffusion wants to push them out, electrostatic pressure wants to pull them in (balanced).
More Cl on the outside than the inside - diffusion wants to pull them in, electrostatic pressure wants to keep them out (balanced).
Na are drawn towards the inside due to diffusion and the electrostatic forces but they can’t get in because the membrane isn’t very permeable to them.
Membrane and pump resists Na+ inward movement - some sodium leaks back in but is expelled by the pump.
Anions are restricted to the inside of the cell.
What does the sodium potassium pump do?
Active process to transport Na+ ions out of neuron & K+ in
Three Na+ for every two K+
Require energy supplied by ATP
What is the action potential?
Neuron fires – a sudden pulse where the negative resting potential is temporarily reversed (becomes briefly positive)
Transmits information i.e. the message [digitally/all or none/0 or 1]
1) Depolarization & threshold
2) Reversal of membrane potential
3) Repolarisation to resting potential
4) Refractory period
How is an action potential triggered?
The membrane potential remains in this resting ‘stable’ state until something disturbs the balance.
Membrane permeability changes.
Neurotransmitters initiate such changes at the dendrites of neurons.
Neurotransmitters activate receptors on dendrites/soma
Receptors open ion channels
Ions cross plasma membrane, changing the membrane potential
The potential changes spread through the cell
If the potential changes felt at the axon hillock are positive (+mV), and large enough, an action potential is triggered
What is the EPSP and IPSP?
Excitatory neurotransmitters depolarise the cell membrane, increases probability of an action potential being elicited. This causes an Excitatory Post Synaptic Potential (EPSP).
Inhibitory neurotransmitters hyperpolarise the cell membrane, decreases probability of an action potential being elicited. This causes an Inhibitory Post Synaptic Potential (IPSP).
What is temporal and spatial summation?
Spatial summation occurs when multiple presynaptic neurones together release enough neurotransmitter to exceed the threshold of the postsynaptic neuron.
Temporal summation occurs when one presynaptic neurone releases neurotransmitter many times over a period of time. The total amount of neurotransmitter released may exceed the threshold value of the postsynaptic neurone. The higher the frequency of the action potential the more quickly the threshold may be exceeded.
What happens during depolarisation and repolarisation?
EPSPs begin to depolarise cell membrane
When the threshold (-60mV) is reached Na+ channels open and polarity reverses to +30 inside
Membrane potential reverses with the inside going positive at which point voltage-gated Na+ channels close and K+ channels open which restores resting membrane potential
How is the action potential self-perpetuating?
The voltage changes are caused by the opening or closing of ion channels.
In the cell membrane there are channels which are opened by detecting opposite polarity in an adjacent bit of membrane, i.e. voltage gated thus voltage changes control the ion channels which control the voltage changes meaning that the action potential is self-perpetuating.
How does saltatory conduction increase speed of transmission?
Without myelination, signal loss due to lack of insulation and transmission is slow due to the time needed to activate each channel. Saltatory Conduction (jumping between nodes of Ranvier) means that decremental conduction occurs between nodes (but ‘re-boosted’ each time). Myelin insulates sections of the axon leading to faster and more accurate transmission.
Why does the breakdown of myelin affect the transmission of messages?
Degeneration of myelin and development of scar tissue disrupts and eventually blocks neurotransmission along myelinated axons.
What are the 5 fundamental processes of synaptic transmission?
Manufacture – intracellular biochemical processes
Storage – vesicles
Release – by action potential
Interact with post-synaptic receptors – diffusion across the synapse
Inactivation – break down or re-uptake
What occurs during synaptic transmission?
Calcium ion channels open when action potential reaches pre-synaptic terminal
Ca++ ions cause vesicles to move to release sites – fuse with the cell membrane – and discharge their contents
Transmitter substance diffuses across synaptic cleft
Attach to receptor sites on post-synaptic membrane
The neurotransmitter would remain active in the synapse if it wasn’t for various mechanisms such as enzyme degradation e.g. acetylcholinesterase breaks down acetylcholine.
What are some of the common neurotransmitters?
- Fast neurotransmitters – short lasting effects Acetylcholine (ACh) Glutamate (GLU) Gamma-aminobutyric acid (GABA) - Neuromodulators – can be targeted with drugs Dopamine (DA) Noradrenalin (NA) (norepenephrine) Serotonin (5HT) (5-hydroxytryptamine)
What membrane changes occur post-synaptically?
Transmitter-gated ion channels on post synaptic membrane are sensitive to specific neurotransmitter substances.
Results in depolarization or hyperpolarization depending on channel type:
- Depolarization - excitatory - EPSP (excitatory post-synaptic potential)
- Hyperpolarization - inhibitory - IPSP (inhibitory postsynaptic potential)
How do local anesthetics work?
Procaine and lignocaine Na+ channels blockers-particularly well Can be absorbed through mucous membranes - ’EMLA cream’ Blocks progress of action potential Used in medicine and dentistry
What is Acetylcholine (ACh) and what is it affected by?
Transmitter at the neuromuscular junction, also used widely in brain and spinal cord. Affected by: Cigarettes (nicotine - agonist) Poison arrows (curare - antagonist) Spider toxins (black widow - release) Nerve gas (WW-I – blocks break-down)
What is Noradrenaline and what is it affected by?
Transmitter in peripheral (heart) and central nervous systems – diverging architecture in brain
Affected by:
Antidepressant drugs (Imipramine – blocks re-uptake)
Antidepressant drugs (MAO inhibitors – block break-down)
Stimulants (Amphetamine – increases release and blocks re-uptake)
What is Dopamine and what is it affected by?
Important transmitter in basal ganglia – diverging architecture
Affected by:
Antipsychotic drugs (Chlorpromazine – receptor blocker)
Stimulants (Amphetamine/cocaine – increase release and block re-uptake)
Anti-Parkinson drugs (L-DOPA increases manufacture)
What is Serotonin and what is it affected by?
Diverging projections in the brain – innervating many structures
Affected by:
Antidepressant drugs (Prozac – serotonin re-uptake inhibitor – SSRI)
Hallucinogens (LSD –5HT receptor agonist)
Ecstasy
What is GABA and what is it affected by?
Main inhibitory transmitter
Affected by:
Anti-anxiety drugs (benzodiazepines - valium – inhibitory effect at GABA receptors
Anticonvulsant drugs (benzodiazepines)
Anaesthetics (Barbiturates – potentiate the effect of GABA)
What are the problems with designing drugs for the brain?
A region of the brain engaged in a particular function uses several neurotransmission systems e.g. basal ganglia.
AND
Regions of the brain engaged in different functions use the same neurotransmission systems.
What are some of the potential side-effects when targeting neurotransmitters?
GABA agonists - anti-anxiety, anti-convulsant, anaesthetic
L-DOPA - Anti-parkinson, causes psychosis at high doses
Dopamine blockers - Anti-psychotic, causes Parkinson-symptoms at high doses
What are the main neuroimaging techniques?
Plain X rays CT scans Magnetic Resonance Imaging Cerebral Angiography Myelography Nuclear medicine – looking at functional status e.g. cerebral blood flow, receptor binding
What are the features of CT scanning?
X-ray source which constantly rotates around a series of detectors. Patient goes through the scanner.
Dose of radiation: 1 CT head = 100 chest X rays
Limited anatomical detail
Requires iodinated contrast media – potential for allergic reaction
Better than MRI for demonstrating bone and calcification (e.g. craniopharyngioma)
Quicker scan times than MRI
Can use a CT to create a 3D reconstruction, can model the bones and the intracranial circulation
What are the features of MRI scanning?
If you are scanning the head, it needs to be in the middle of the magnet. Can be very claustrophobic.
No ionising radiation.
Multiple planes possible
Excellent anatomical detail
Contrast injection may be required
Strong magnetic field – in some patients, MRI is contraindicated (metallic implants)
Noisy and claustrophobic
Longer scan times than CT
MRI can be used to look at the fibre bundles of the brain – visualised by looking at the way water diffuses.
What are the different types of intracranial hemorrhage?
Epidural hematoma - bleeding occurs between the dura mater and the skull
Subdural hematoma - bleeding occurs between the inner layer of the dura mater and the arachnoid mater
Subarachnoid hemorrhage - bleeding within the subarachnoid space
Intracerebral hemorrhage - bleeding within the brain tissue itself
What are cerebral contusions?
Cerebral contusions are bruises of the brain, usually caused by a direct, strong blow to the head. Cerebral lacerations are tears in brain tissue, caused by a foreign object or pushed-in bone fragment from a skull fracture.
What is diffuse axonal injury?
Diffuse Axonal Injury (DAI) is considered one of the most common and detrimental forms of traumatic brain injury (TBI).
The resistant inertia that occurs to the brain at the time of injury, preceding and following its sudden acceleration against the solid skull, causes shearing of the axonal tracts of the white matter.
What is sensation?
A mental process resulting from the immediate external stimulation from a sense organ
Sight, sound, taste, touch, hearing
What is perception?
The ability to become aware of something or understand something following sensory stimulation
Tactile, olfactory, gustatory, visual, auditory
What is the perceptual set?
We all have a very unique perceptual set - the psychological factors that determine how you perceive your environment. What we believe influences what we see. Context Culture Expectations Mood and motivation
How does the limbic system work with the visual and auditory cortex?
In the visual cortex in the occipital lobe, the nerve impulses are converted into a visual picture.
In the primary auditory cortex, the nerve impulses initiated by the vibrations are converted into an understandable auditory input.
The limbic system helps us to interrupt the visual and auditory input - do we like or dislike it?
What are the Gestalt principles?
Proximity, common fate, continuity, similarity, closure, common region, symmetry
What is an illusion?
The instance of a wrong or misinterpreted perception of a sensory experience
Can happen in any sensory modality
What is a hallucination?
Experiences involving the apparent perception of something not present
1 in 20 people will at some point in their lifetime will experience a hallucination.
Unique hallucinations because each person has a different perceptual set.
Not all down to mental illness
Causes:
Delirium
Drugs
Acute stress
Psychiatric conditions
How to treat hallucinations?
Bio-psycho-social model
Medication
Psychology - helping people to understand and reduce the distress they are experiencing
Social circumstances
What are the major fissures/sulci of the brain?
The cerebral hemispheres are paired structures separated from each other by the longitudinal fissure along the midline.
Examination of the lateral surface of the brain will reveal the lateral sulcus (the Sylvian fissure). This groove separates the temporal lobe from the parietal lobe.
The central sulcus (the Rolandic Sulcus), may be found by looking for two parallel gyri extending from the superior margin of the cerebrum down to the lateral fissure. The sulcus separates these parallel gyri and also demarcates the boundary between the frontal and parietal lobes.
The parieto-occipital sulcus separates the occipital lobe from the rest of the brain.
How does systole/diastole affect the CSF?
Contains CSF - a pulsatile fluid
In systole CSF is forced into the spinal cord
In diastole CSF is pushed back into the ventricular system
What is the corona radiata?
A white matter sheet that continues ventrally as the internal capsule and dorsally as the centrum semiovale. This sheet of both ascending and descending axons carries most of the neural traffic from and to the cerebral cortex.
What are the cisterns of the subarachnoid?
Compartments within the subarachnoid space where the pia mater and arachnoid membrane are not in close approximation and cerebrospinal fluid (CSF) forms pools
What is the cisterna magna?
Located between the cerebellum and the dorsal surface of the medulla oblongata at and above the level of the foramen magnum. CSF produced in the ventricular system drains into the cisterna magna from the fourth ventricle via the median aperture (of Magendie) and the lateral apertures (of Luschka)
What is the insular cortex?
A portion of the cerebral cortex folded deep within the lateral sulcus (the fissure separating the temporal lobe from the parietal and frontal lobes).
Folded within itself.
What is Psychological stress?
Mental or emotional strain or tension resulting from adverse or demanding circumstances.
What is Physiological stress?
Sensory, emotional and subjective experience associated with potential damage of body tissue and bodily threat.
Can psychological and physiological stress be separated?
Difficult to separate in practice as the mind/body dichotomy is false: ‘experiences’ and ‘perceptions’ may not be conscious – we may not be completely aware of the emotional stress response.
What is eustress?
Positive stress which is beneficial and motivating; typically the experience of striving for a goal which is within reach. Eustress is motivating. “I can do that”
What is distress?
Negative stress which is damaging and harmful. Typically occurs when a challenge (or threat) is not resolved by coping or adaptation. “I don’t think I can manage that”
What determines whether something is eustress or distress?
Type of stressor less important than how it is experienced, ie negative (threat) or positive (challenge), and how bearable.
What is the trajectory for good and bad stress?
Good stress increases motivation and leads to increasing attention and interest.
Reaches at peak at optimal arousal and interest.
When a threat is acute and sudden or if it’s going on for a long time (unresolved), it becomes bad stress and we are less able and less effective - impaired performance because of anxiety.
Different kinds of stresses will have different trajectories.
Different people will move along at different rate – how quickly people become overwhelmed.
What are the features of distress/psychological stress?
“Any uncomfortable emotional experience accompanied by predictable biochemical, physiological and behavioral changes.”
“Psychological and physical responses that occurs whenever we must adapt to changing conditions, whether those conditions be real or perceived, positive or negative.
Psychological stress occurs when an individual perceives that environmental demands tax or exceed his or her adaptive capacity”
What is acute stress?
Short-lived response to a novel situation experienced by the body as a danger (usually without conscious processing). Healthy & adaptive.
e.g. noise, short-term danger, brief illness, brief physiological challenge
What is chronic stress?
Arises from repeated or continued exposure to threatening or dangerous situations, especially those that cannot be controlled.
Give some examples of chronic stressors?
Physical illness, disability & pain
Physical or sexual abuse
Poverty including poor housing, hunger, cold or damp, debt
Unemployment
Bullying or discrimination – social exclusion
Caregiving
What are the stages of the stress response?
Alarm - Threat or stressor identified or realised; body’s response is state of alarm
Adaptation – stress goes on for a while and body engages defensive countermeasures
Exhaustion - body runs out of defences, resources depleted (can lead to illness as a result)
What are the 5 elements of the human stress response?
Biochemical Physiological Behavioural Cognitive Emotional
What mediated the human stress response?
Stress responses are primarily mediated via the autonomic nervous system (sympathetic-adrenal-medullary (SAM) system) & the hypothalamo-pituitary (HPA) axis.
These responses lead to changes that influence future responses to stress, also reflecting brain plasticity – connections alter over time. We can develop responses specific to us. Influenced very early in life (parental care).
How is stress mediated by the sympathomedullary pathway?
Hypothalamus activates the adrenal medulla
Adrenal medulla (controlled by the ANS) releases adrenaline and noradrenaline into the bloodstream
Body prepares for fight or flight
Adrenaline and noradrenaline reinforces the pattern of sympathetic activation e.g. increased heart rate and blood pressure
Energy to the muscles
How is stress mediated by the pituitary-adrenal system?
Higher brain centres activate hypothalamus
Hypothalamus releases corticotrophin (CSF)
Pituitary gland releases adrenocorticotrophic (ACTH)
Adrenal cortex releases corticosteroids
Corticosteroids cause changes - liver releases energy and the immune system is suppressed.
What hormones are involved in stress?
Glucocorticoids (cortisol) – main stress hormone
Catecholamines (adrenaline & noradrenaline)
The so-called ‘fight-or-flight’ chemicals
What happens to the immune system in stress?
Inflammation and immune response are important but complex.
Acute stress: immune suppression
Chronic stress: partial immune suppression + low-grade chronic inflammatory response
Potential effects on gene expression
What are the physiological stress responses?
Breathing more rapid to increase oxygen
Blood flow increases by up to 400% & directed to heart and muscles
Increased heart rate & blood pressure
Muscles tense
Glucose released, insulin levels fall: boost energy to muscles
Red blood cells discharged from the spleen
Mouth becomes dry (saliva and mucus dry up)
Sweating
White blood cell redistributed where injury may occur i.e. bone marrow, skin, lymph nodes; less available elsewhere
What are some of the physiological stress responses that occur later?
Headache Chest pain Stomach ache Musculoskeletal pain Low energy Loss of libido More prone to colds & infections (immunosuppression) Cold hands & feet Clenched jaw & grinding teeth
What are some of the behavioural responses to stress?
Easily startled & hypervigilant Change in appetite – both directions Weight gain (obesity) or weight loss Procrastinating and avoiding responsibilities Increased use of alcohol, drugs & smoking Nail biting, fidgeting and pacing Sleep disturbances especially insomnia Withdrawal
What are some of the cognitive responses to stress?
Constant worrying Racing thoughts Forgetfulness and disorganisation Inability to focus Poor judgement Being pessimistic or seeing only the negative side ‘what if’ Learning
What are some of the emotional responses to stress?
Depression & sadness Tearfulness Mood swings Irritability Restlessness Aggression Low self-esteem and worthlessness Boredom & apathy Feeling overwhelmed Rumination, anticipation & avoidance – triggering memories of previous experiences
How does stress affect us?
Different parts of the brain mediate responses to different types of stressor (but amygdala and hippocampus are key).
Context, appraisal, vulnerability and learning (past experience) may modify perception of threat and hence the stress response. For example, people who experience adversity in early life are more sensitive to stress later on.
Stress mechanisms alter affect (mood, anxiety levels). This is likely to mediate the effects of stress on other bodily systems.
What is allostasis?
Allostasis refers to how multiple & complex systems adapt collectively (e.g. via ANS and HPA axis) in changing environments through dynamic change.
Allostatic states are inherently fragile and decompensation can happen quickly (positive feedback loops).
What is allostatic load?
Allostatic load refers to cumulative exposure to stressors (and cost to the body of allostasis), which if unrelieved leads to systems ‘wearing out’.
The body’s continued attempts to restore balance take a long-term toll on physiological systems, including plastic changes to the brain itself.
How does anticipation of stress and recovery from stress vary between different people?
For some people, because of their repeated exposure, they have a particular fine-tuning to stress, so the physiological response will be quicker, more extreme, and longer lasting. The point at which you return to baseline may also be different for people (taking longer to recover).
What’s the link between stress and illness?
Stress thought to be related to a host of illnesses, esp of cardiovascular and GI systems, ie those with strong ANS connections.
Stress undoubtedly exacerbates physical illnesses and slows recovery.
Strong evidence of association between depression and mortality following an MI.
But the evidence of causal association between stress and physical illness is still limited.
Give some examples of illnesses that may be linked to stress?
Cancer: stress linked to survival rather than incidence
Cardiovascular disease: high blood pressure, abnormal heart rhythms, MI and stroke
Obesity & eating disorders
Infertility, recurrent miscarriage & menstrual problems
Sexual dysfunction
Rheumatoid arthritis
Skin & hair problems eg acne, psoriasis, eczema
Gastrointestinal problems: inflammatory bowel disease, irritable bowel syndrome.
Medically unexplained symptoms (MUS)
How does PSTD present?
Vivid flashbacks & nightmares Intrusive thoughts and images Sweating Nausea Trembling Hypervigilance & increased startle response Agoraphobia Insomnia Irritability Impaired concentration
What helps manage stress?
Shiatsu, T'ai Chi, Yoga Mindfulness Meditation Exercise Sleep hygiene Friends and family Healthy diet Exposure to natural environments Aromatherapy Self help support Cognitive Behavioural Therapy
What is natural selection?
The differential survival and reproduction of individuals due to differences in phenotype.
What is fitness?
How successful a organism at reproducing
What is sexual selection?
Competition for mates
What is Darwin’s theory of evolution?
More offspring are produced than can possibly survive.
Traits vary among individuals with respect to morphology, physiology and behaviour (phenotypic variation).
Different traits confer different rates of survival and reproduction (differential fitness in a given environment).
Traits can be passed from generation to generation (heritability of fitness).
What is evolutionary psychiatry?
EP considers the human social brain evolution. It proposes that some human psychiatric mechanisms, defences and traits, are consequences of adaptations to reproductive problems frequently encountered in Pleistocene environments (known as the Environment of Evolutionary Adaptation (EEA)).
Proposes theories to account for the widespread existence of substance misuse, borderline states and schizophrenia, bipolar disorder, the dementias and affective disorders as well as other defences, childhood and neurodevelopmental disorders
What are Tinbergen’s questions?
- Mechanism – how does this behaviour occur in an individual?
- Development – how does this behaviour arise in an individual?
- Evolution – how does this behaviour arise in the species?
- Adaptive value – why is this behaviour adaptive for the species?
What are the two types of causation?
Proximate causation – how? By what mechanism?
Answers would lie in biochemistry, anatomy, neuroscience, physiology
Ultimate causation – Why was trait selected for?
How does evolution help explain our disease vulnerability?
Mismatch: exposure to evolutionarily mismatched or novel environment e.g culture, alcohol, drugs and diet
Life History factors: e.g. reproduction, ageing, menopause, senescence
Excessive defence mechanisms
Co-evolutionary considerations: losing the arms race against pathogens e.g. HIV, parasites, antibiotic resistance
Constraints: imposed by evolutionary history e.g. eyes, backache and brain size
How does evolution help explain our defence mechanisms against disease?
Evolution has selected adaptations (defence mechanisms) that help protect against injuries and infections Pain, sickness, illness behaviour Anxiety, depression, OCD Fever, lethargy, fatigue Nausea Itching Sneezing, vomiting, coughing
What is Dunbar’s number?
Cognitive limit to the number of people with whom one can maintain stable social relationships
What is the Outgroup Intolerance Hypothesis in schizophrenia?
The social brain evolved to deal with the demands of living in hunter-gatherer environments surrounded by kin with a clear delineation between ingroup and outgroup members.
New social systems emerged blurring the demarcation between ingroup and outgroups eg towns and cities.
Led to a mismatch between the design of the social brain and the novel social environment.
Stress caused by this mismatch is what leads to schizophrenia in genetically vulnerable individuals.
What is the Compassion Focused Therapy?
Therapy rooted in evolutionary and neuroscience approach to psychological processes.
Our brains are designed to function in certain ways, motives, emotions are products of evolution.
3 types of emotion regulation system:
- Threat and protection
- Drive and excitement
- Contentment, soothing and social safeness
Compassion focused therapy aimed at facilitating development of soothing and social safeness system
What are the components of the outer ear?
PINNA - cartilaginous structure
Formed from pharyngeal arches 1 and 2 (6 Hillocks of His)
Forms between 10th and 18th week in utero
Directs soundwaves towards ear canal
High pitch > Low pitch
AUDITORY CANAL - ⅓ cartilage and ⅔ bone
Transmits sound from the pinna to the ear drum
TYMPANIC MEMBRANE
A connective tissue structure, covered with skin on the outside and a mucous membrane on the inside.
Pars flaccida - from endoderm and ectoderm
Pars tensa - fibrous layer runs through (from mesoderm)
What are the components of the middle ear?
The bones of the middle ear are the auditory ossicles – the malleus, incus and stapes. Sound vibrations cause a movement in the tympanic membrane creating oscillation in the auditory ossicles, transmitting sound.
MALLEUS: attaches to the tympanic membrane, via the handle of malleus and then articulates with the incus.
INCUS: consists of a body and two limbs, articulates with the malleus and stapes.
STAPES: It joins the incus to the oval window of the inner ear.
What is the role of the middle ear?
Acoustic impedance match between air and fluid-filled inner ear
Transfer from air to fluid (99.9% loss of energy)
Little movement at the tympanic membrane should translate into a big movement to the stapes footplate due to the ratio area and angle
Amplification of the airborne sound vibration - 200 fold increase boost in pressure from tympanic membrane to inner ear
What are the components of the inner ear?
VESTIBULE: separated from the middle ear by the oval window, and communicates anteriorly with the cochlea and posterioly with the semi-circular canals. Contains saccule and urtricle.
COCHLEA: houses the cochlea duct which twists upon itself around a central portion of bone called the modiolus, producing a cone shape.
SCALA VESTIBULI: Located superiorly to the cochlear duct, continuous with the vestibule
SCALA TYMPANI: Located inferiorly to the cochlear duct. Terminates at the round window.
SEMICIRCULAR CANALS: contain the semi-circular ducts, which are responsible for balance (along with the utricle and saccule).
SACCULE: larger of the two, receiving the three semi-circular ducts.
UTRICLE: globular in shape and receives the cochlear duct.
What is the role of the inner ear?
To convert mechanical signals from the middle ear into electrical signals, which can transfer information to the auditory pathway in the brain.
To maintain balance by detecting position and motion.
What are the cochlear fluids?
Endolymph - fills scala media, high K
Perilymph - fills scala tympani and scala vestibuli, like ECF and CSF, Na rich
Gradients maintained by Na-K ATPase, NKCC1, CIC-K chlorine channels
Channel abnormalities can lead to deafness
What does the helicotrema do?
A semilunar opening at the apex of the cochlea through which the fluid in the scala vestibuli and the scala tympani communicate so that sound vibrations can pass to the round window.
