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How should the brain be studied?

- neuroscientists are usually seeking reductionist, causal mechanistic explanations of how system components interact to produced system behaviour
- a key part of neurological diagnosis is to localise the location of damage by examination of site-specific functions


What can be determined about brain function in a clinical setting?

- in addition to general observations and patient reports of nervous system dysfucntion (vital signs, consciousness, neuropathic pain) the neurological exam includes specific functional tests to localise the site of nervous system dysfunction

motor / sensory function:
- segmental reflexes
- primitive reflexes e.g. babinksy reflex
- strength, symmetry, palsy
- cranial nerves: fundamental part of medical neuroscience,
- balance, posture, gait

- pin prick, cotton ball

- language, orientation, memory


What are cranial nerves?

- corner stone of clinical examination
- 12 pairs
- left and right, symmetrical
- they are the connections of the peripheral nerves to the brain
- e.g. optic nerve, joins eyes to brain, II, huge, pure sensory, special sensory neuron
- olfactory nerve: from nasal epithelium, through the cribiform plate, runs into olfactory bulb, tricky
- III and IV innervate extrinsic muscles of the eye
- III has a parasympathetic component (e.g. pupil dialtion)
- trigerminal nerve: mixed motor and sensory nerve (sensory innervation of face, muscles of the face that we use for chewing )


What are the cranial nerves and their primary functions?

- olfactory nerve
- sensory
- sense of smell

- optic nerve
- sensory
- vision

- oculomotor nerve
- motor
- eye movements; papillary constriction and accommodation; muscles of eyelid

- trochlear nerve
- motor
- eye movements

- trigeminal nerve
- sensory and motor
- somatic sensation from face, mouth, corea; muscles of mastication

- abducens nerve
- motor
- eye movements

- facial nerve
- sensory and motor
- controls the muscles of facial expression; taste from anterior tongue; lacrimal and salivary glands

- vestivulocochlear (auditory) nerve
- sensory
- hearing; sense of balance

- glossopharyngeal nerve
- sensory and motor
- sensation from parynx; taste from posterior tongue; carotid baroreceptors

- vagus nerve
- sensory and motor
- autonomic functions of gut; sensation from pharynx; muscles of vocal cords; swallowing

- spinal accessory nerve
- motor
- shoulder and neck muscles

- hypoglossal nerve
- motor
- movements of tongue


What are the clinical tests of the different cranial nerves?

- nasal epithelium
- test sense of smell with standard odour

- retina
- measure acuity and integrity of visual field

- oculomotor nucleus in midbrain; Edinger-Westphal nucleus in midbrain
- test eye movements (patient can't look up, down or medially if nerve involved)
- look for ptosis
- pupillary dilation

- trochlear nucleus in midbrain
- can't look downward when eye abducted

- trigeminal motor nucleus in pons; trigeminal snensory ganglion (the gasserian ganglion)
- test sensation on face; palpate masseter muscles and temporal muscle

- abducens nucleus in midbrain
- can't look laterally

- facial motor nucleus; superior salivatory nuclei in pons; trigeminal (Gasserian) ganglion

- spiral ganglion
- vestibular (scarpa's ganglion)
- test audition with tuning fork
- vestibular function with caloric test

- nucleus ambigus; inferior salivatory
- test swallowing; pharyngeal gag reflex

- dorsal motor nucleus of vagus; vagal nerve ganglion
- test above plus hoarseness

- spinal accessory nucleus; nucleus ambiguus; intermediolateral column of spinal cord
- test sternocleidomastoid and trapezius muscles

- hypoglossal nucleus of nedulla
- test deviation of tongue during protrustion (points to side of lesion)


What sort of resolution could you get with a relatively simple set of tests?

- second optic nerve
- runs from retina to brain
- some of the fibres - the nasal fibres cross at the midline
- run to lateral geniculate where they run out to the visual cortex (conscious visual pathway)
- some retinal ganglion cells project to superior colliculus: posture and motor control, visual input to orienting and postural maintenance
- people that are cortically blind but can catch a ball rely on the projection to superior colliculus being intact

- driver of the parasympathetic control of pupil dilation and lens shape is a little nucleus: pretectum

- hypothalamus:
- regulation of circadian rhythms
- measures how much daylight we can see

- the presence or absence of certain functions can tell you a lot about the location of a lesion

- a lot of brain stem is used to move the muscles of the eye, so again specific absences of movement will indicate which part of the brain stem is affected


How can you tell between lower motor neuron and upper motor neuron damage in the face?

- if whole half of face e.g. eyebrow and lips = lower motor neuron
- if you can do some of those things = upper motor neuron


What is the most important sign in neurology?

- according to Kingsley
- monosynaptic stretch reflex


What is the locomotor pattern generator

- like the monosynaptic stretch reflex (MSR), the locomotor pattern generator is a spinal circuit that normally functions in the context of the entire motor control system
- like the MSR, observations of the expression of the pattern generator can reveal much about the functional status of the supra-spinal nervous system


What are some abnormal gait patterns associated with CNS disorders?

- ataxic gait (cerebellar disease)
- choreaform gait (huntingon's disease)
- hemiparetic gait (stroke)
- circumducting gait (stroke)
- parkinsonian gait


What is the earliest technique of direct measurement of brain function?

- electroencephalographic leads (EEG)
- tells you globally what state the brain is in
- has become more sophisticated
- poor spatial resolution
- activity diffuses
- wouldn't work were it not for the fact that a lot of activity in the brain is geometrically organised and temporally synchronised
- nice arrangement of pyramidal cells --> dipoles


What are EEG states of consciousness?

- awake: high frequency low amplitude noise, alpha and beta rhythms
- REM sleep: almost the same as awake, a state of conciousness, dreaming,
- lose all muscle tone except in the eye during REM sleep

conscious brain activity: characterised by uncoupled, desynchronised behaviour, one burst/continuous noise

increasing coherence in deeper sleep
- Stage 1 non-REM sleep: theta rhythms
- Stage 2 non-REM sleep: spindle, K complex
- Stage 3 non-REM sleep: delta rhythms
- Stage 4 non-REM sleep: delta rhythms
more and more high amplitude, low frequency stuff

- don't understand the importance of these brain rhythms
- what is the role of synchronous activity?


What is magnetoephalography?

- measuring the normal (tiny) magnetic fields associated with brain activity
- measures magnetic potential
- all electrical activity is actually electromagnetic
- can measure magnetic flux
- not great in terms of spatial resolution
- good temporal resolution
- has advantages in terms of resoultion
- can be combined with other technologies
- e.g. MEG/MRI
- rely incredibly heavily on computer analysis of the data


How is electromagnetic radiation related to these techniques?

- use different parts of the electromagnetic spectrum
- e.g. visible light ~10^15
- this sets the resolution limit when using light microscopy
- electrons have smaller wavelength
- MRI - using radiofrequency, harmless

- x-ray+ are destructive because they ionise molecules
- can get higher resolution
- can't expose yourself
- CAT scan has same as 3 months of walking around

- gamma rays can only have three a year


What is tomography?

- imaging technique that will allow us to get a slice of the brain
- e.g. MRI
- CAT scan: computer assisted tomography, slices of xrays put together, taken at different angles, accounts for bone of skull through different angles
- structure

- PET scan: positron emission tomography, source of radiation is a chemical you ingest e.g. oxygen or glucose
- positrons which annihalate with electrons: get two gamma energy photons shooting off
- where was the source?
- which functional areas are happening
- low in terms of spatial and temporal resolution
- limited due to gamma radiation

- uses harmless radiowaves
- variety of waves
- e.g. T1 weighted: good definition, grey matter and white matter, discolouration and distortion, high resolution
- changing the setting: T2 is sensitive to fluid
- can do every slice to create 3D brain


How does MRI work?

- hydrogen is paramagnetic
- it's like a spinning magnet
- because of all the water, tissues have lots of protons spinning around, but with random orientations of the spin axis
- radiowaves disrupt this alighmnet, when they realign they give off radiowaves
- radiowaves used as a measure of where protons are in a volume
- so, colleccted it (antennae), and reconstruct (computer) the spatial distribution of the source


Can MRI only provide structural information?

- no
- MRI can provide structural and functional information
- can tell you which parts of the brain are more active
- relies on the fact that haemoglobin is paramagnetic, so areas with more blood/higher brain activity will give off more


BOLD = blood oxygen level detection = fMRI

- not super high resolution but can combine it with higher resolution images


What are the limits of fMRI?

- it doesn't measure neuronal activity directly and it is blind to details such as how many neurons are firing, or whether firing in one region amplifies or dampens activity in neighbouring areas

- the signal: a boost in blood flow in response to a stimulus - can be difficult to extract from the 'noise' of routine changes in blood flow, and the statistical techniques involved are easy to misunderstand and misuse


What is MR tractography?

- looking at brain tracts
- water behaves differently depending on its location e.g. a tube with lots of axons
- can look at how constricted water is to map tractography

- still catching on in experimental neuroscience
- growth is in looking at connections in the brain

- create huge public database