05/05/2011
Outline • • • • •
Neuroanatomy Thought Senses Movement Neurological disorders and pathology
Neuroscience Created by Daniyal Daud, Christopher Taylor, Edward Tam & Lorna Caulfield ©
What we won’t cover • • • • •
Nerve physiology Detailed anatomy (especially head/neck) Psychiatry – affect/psychosis Detailed musculoskeletal anatomy/physiology Endocrinology – thyroid/parathyroid
NEUROANATOMY
Anatomy – quick overview
Cortex Longitudinal fissure
Pre-central gyrus Post-central gyrus Central sulcus
Left cerebral hemisphere
Right cerebral hemisphere
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Cortex Optic Chiasm
Histology of the cortex I: dendron-axon interactions II: Intracortical connections III: give rise to commissural/ association fibers IV: receive thalamic afferents V: project to subcortical structures VI: project to cortical/ subcortical areas
Olfactory bulb Olfactory tract
Mammillary bodies
Pituitary gland & infundibular stalk
Uncus Parahippocampal gyrus
Cerebral peduncles Pons
Medullary olives Medulla (pyramids)
Left cerebellar hemisphere
“Brainstem�
Spinal cord
Subcortical structures
Subcortical structures
Subcortical structures - brainstem
Cerebellum
Amygdala
Mammillary body
Crus Cerebri
Sup. cerebellar peduncle Sup. colliculus Midbrain
Thalamus
Inf. colliculus
Pons Middle cerebellar peduncle Pyramids Olives
CN IV Pons
Medullary olive Pyramid
Cerebellar peduncles
Primary Horizontal fissure fissure
Cerebellar hemisphere
Floor of 4th ventricle Flocculonodular Flocculus lobe Nodulus
Vermis Inferior view
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Brainstem and cerebellum
Cranial nerves
• Cortex attaches to brainstem at crus cerebri (cerebral peduncles) • Brainstem has
1 – Olfactory (bulb and tract) 2 - Optic
– nerve fibers (tracts) going to and from cerebrum/cerebellum – Cell bodies (nuclei) of ten cranial nerves: CN 3 – 12 – Reticular formation and respiratory center
• Cerebellum attaches to brainstem via three peduncles • Basal ganglia buried in the cortex, have connections
3 - Oculomotor 4 – Trochlear (dorsal) 7 - Facial
5 - Trigeminal
8 – Vestibulocochlear 6 - Abducens
9 - Glossopharyngeal
10 - Vagus 12 - Hypoglossal
11 - Accessory
C1 spinal nerve
Foramina of skull
What passes through • • • • • • • • • •
Superior orbital fissure
Jugular Foramen Hypoglossal canal
Blood supply • Two systems
ACA
– Vertebro-basilar (~posterior) Circle of Willis MCA – lateral and deep ACA/PCA – medial and deep Strokes are territorial
MCA
PCA
Optic chiasm Posterior comm. artery MCA
CN III Superior Cerebellar Artery
– Carotid (~anterior)
Optic nerve CN 3, 4, 5a, 6 Maxillary branch of 5 Mandibular branch of 5 Middle Meningeal Artery Internal Carotid Artery CN 7 and 8 Jugular vein, CN 9, 10, 11 CN 12 Spinal cord
Blood supply – circle of Willis
Lenticulo -striate Internal Carotid
• • • •
Optic canal Superior Orbital Fissure Foramen rotundum Foramen ovale Foramen spinosum Foramen lacerum Internal acoustic meatus Jugular foramen Hypoglossal canal Foramen Magnum
Communication between ‘anterior’ and ‘posterior’ systems • Ensures backup if one fails • Aneurysms can occur – Proximity to cranial nerves - implications?
Basilar Artery Vertebral artery Posterior Cerebral Artery
Anterior Inferior Cerebellar Artery
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Spinal cord
Peripheral nervous system
Dorsal horn Dorsal roots
Central canal Lateral horn
Anterior fissure Ventral horn Ventral roots Pia mater Arachnoid mater Dura mater
Chemical Neurotransmission
THOUGHT
Noradrenergic pathways • Cell bodies of noradrenergic neurons: – Locus ceruleus (“blue spot”) – Lateral tegmental area
• Projections to – Cortex – Spinal cord – Hippocampus – Hypothalamus
• One way that neurons communicate (other: electrical synapse with gap junctions) • Precursors • Synthesis by enzymes • Stored in vesicles • Electrical signal arrives along membrane Ca++ channels open • Chemical release • Binds receptor • (Deactivated by enzymes) • Reuptake into presynaptic cell • Degraded by enzymes
Dopaminergic pathways • Cell bodies of dopaminergic neurons: – Substantia nigra compacta (“black stuff”) – Ventral tegmental area – Hypothalamus
• Projections to: – Striatum (nigrostriatal, mesolimbic) – Frontal lobe (mesocortical) – Anterior pituitary (tuberoinfundibular)
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5-HT pathways
Cholinergic pathways
• Cell bodies of serotonergic neurons:
• Cell bodies of cholinergic neurons:
– Raphe (“seam”) nuclei in pons, medulla, midbrain
• Projections to – Cortex – Hippocampus – Hypothalamus – Spinal cord (pain)
Explicit/ declarative Semantic
– Nucleus basalis of Meynert – Pedunculopontine nucleus – Medial septal nuclei
• Projections to – Cortex – Hippocampus – Thalamus
Memory
Memory Implicit
Episodic
Skills/ procedures
Priming
Classical conditioning
• Explicit memory – what you can describe – Episodic – events e.g. Memory of your 18th birthday – Semantic – facts/figures e.g. Capital of Bulgaria? – Hippocampus (“sea horse”) and mammillary bodies important
• Implicit memory – what you can’t describe (easily) – Learnt procedures e.g. Fastening a button – Conditioned responses e.g. Pavlov’s dogs
• Stored throughout cortex • Memory in one sensory modality stored in its association areas (e.g. tune of Lady Gaga’s Paparazzi) • Medial temporal lobe – hippocampus and parahippocampal regions – Crucial in forming new memories – anterograde amnesia (Memento)
• Long-term potentiation (LTP) – one mechanism of learning
Long-term potentiation • Regular coincidental activity at a synapse more efficient at doing said activity • Requires NMDA receptors (glutamate Ca++ entry) • Ca++ upregulates AMPA receptors – Now post-synaptic cell is stimulated more easily
SENSE Repeated stimulation
• Stimulus-response association formed • See also: long-term depression
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Sensory physiology - basics
• Peripheral receptors
– Concept of receptive field: “territory” of a neuron. A stimulus presented in the field changes the neuron’s firing rate
• Pathway from peripheral to central – – – –
Tracts (fibers) ~ road trip Nuclei (cell bodies) ~ rest stops along the way Convergence As order of neuron increases, receptive field gets larger & more complex
• Central representation: cortical area dedicated to the sense e.g. V1, S1, A1 • Cortical centers can also change what we sense (central peripheral pathway)
Somatosensation – dorsal columns
Somatosensation • Submodalities – Fine discriminatory touch, vibration, proprioception – Crude touch, pain, temperature
• Peripheral mechano-receptors, nociceptors, stretch receptors • Sensory fibers back to spinal cord – cell bodies in dorsal root ganglion
Somatosensation - spinothalamic
VPL thalamus
• First synapse in Lamina II • Immediate decussation • Go up in the crescent-shaped anterolateral pathway • VPL thalamus S1
Somatosensation - head Mesencephalic nucleus
Chief sensory nucleus
•
• • • •
Separate pathway for pain (similar to rest of body) Separate pathways for proprioception and touch (c.f. rest of body) Decussation of 2˚ neurons within brainstem Travel up to ventral-posterior-medial thalamus (lateral for rest of body) NB – tongue somatosensation carried by V3 (lingual nerve) & CN 9
Somatosensation - summary Trunk and limb • Fine touch, proprioception, vibration – Dorsal columns (gracile and cuneate fasciuli) to nuclei – Decussate and then up via medial lemniscus to thalamus
• Crude touch, pain, temperature – 2˚ neurons start in spinal cord gray matter & decussate immediately – Up to thalamus via spinothalamic (or anterolateral) tract
Spinal tract of V nucleus
Head: Trigeminal, Glossopharyngeal, Vagus nerves • Fine touch: Chief sensory nucleus • Pain/temperature: Spinal nucleus of V • Proprioception: Mesencephalic nucleus
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Vision - retina
Vision - retina
• Rhodopsin (orange blob) inactive in the dark. Associated Na+ channel open – “dark current” • Cell depolarized – continuous Glu release • Light changes conformation of the retinal in rhodopsin • Na+ channel closes • Cell HYPERPOLARIZES • Glutamate release stops • Therefore phototransduction occurs by hyperpolarization (c.f. normal excitation)
5 layers, 7 types of cells • Vertical connections relay signal Photoreceptor Bipolar cell Retinal ganglion cell
• Horizontal connections (amacrine, horizontal cells) modify signal
Light
Vision – optic nerve
• Nasal fibers from both eyes decussate at optic chiasm, temporal don’t • Lesion of chiasm - ?
Temporal Nasal
cGMP
Photoreceptor cell
Glutamate release
Light
• Optic tract – fibers looking at opposite side of world • Some go to superior colliculus (tectum – “roof”) & pretectum • Most synapse on to lateral geniculate (“knee-like”) nucleus of thalamus • LGN projects to visual cortex via optic radiation • V1 a.k.a ‘striate’ cortex • Topsy-turvy organization
Optic nerve Chiasm Optic tract
LGN Optic radiation Visual cortex V1
Vision - summary
Vision - cortex
• Retina: “phototransduction” – conversion of light signals to electrical impulses
• Visual processing in V1 • Signal passed on to related areas • Two ‘streams’ – Dorsal: perceives spatial aspects e.g. Motion, depth, orientation – occipitoparieto-temporal function – Ventral: perceives descriptive details of object e.g. Color, shape – E.g. driving
trans-retinal 11- cis-retinal
Vision – central pathway
• Each eye looks at both sides of the world – Nasal retina – outer half of world on same side as eye – Temporal – inner half on other side
Na+
Dorsal stream
– Importantly: rods/cones bipolar cells ganglion cells – Vertical relay signal, horizontal modify it
• Ganglion cell axons = optic nerve – Axons from nasal half of retina cross over at optic chiasm – After chiasm, the axons ‘looking’ at one side of space are all on the other side of the brain Ventral stream
• Axons synapse on Lateral Geniculate Nucleus (thalamus) • LGN sends fibers to V1 – visual processing • Dorsal & ventral streams for further processing
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Bony Labyrinth
Hearing REISSNER’S MEMBRANE
SCALA MEDIA
SCALA VESTIBULI
Hearing - Frequency analysis 1. Sound enters the cochlea
ORGAN OF CORTI
2. Basilar membrane vibrates SCALA SCALA TYMPANI TYMPANI
TECTORIAL MEMBRANE
BASILAR MEMBRANE
Hearing - Frequency analysis
Organ of Corti
3. Frequency of sound determines position of maximal displacement BASE •High sounds
APEX •Low sounds
4. Displacement excites hair cells
• Bend towards • Bend towards TALLEST stereocilia SHORTEST stereocilia + • Increased K inflow • Decreased K+ Inflow = = DEPOLARISATION HYPERPOLARISATION
Inner hair cells Depolarisation Voltage gated Calcium Channels OPEN
RELEASE OF NEUROTRANSMITTER
Activation of Cochlear Nerve
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Information from Cochlear nerve
Outer Hair Cells • Shorten and lengthen in response to sound stimuli – PRESTIN
Medulla
• AMPLIFY Basilar Membrane movement
Midbrain
• Antibiotics • Aminoglycosides
Thalamus
DORSAL
3. INFERIOR COLLICULUS
3. INFERIOR COLLICULUS
4. MEDIAL GENICULATE BODY
Temporal lobe
Auditory pathway Transverse gyri of Heschl (A1)
2. SUPERIOR OLIVARY COMPLEX
2. SUPERIOR OLIVARY COMPLEX
4. MEDIAL GENICULATE BODY 5. AUDITORY CORTEX
Midline
• Change length when hairs bend
1. COCHLEAR NUCLEUS
5. AUDITORY CORTEX
Speech and language BROCA’S AREA
WERNICKE’S AREA UNDERSTANDING
PRODUCING LANGUAGE
LANGUAGE Thalamus
Medial geniculate nucleus Inferior colliculus
Midbrain
Pons Pons
Superior olivary nucleus
Cochlear nucleus
RECEPTIVE APHASIA
EXPRESSIVE APHASIA
Medulla
Summary • Cochlea • Frequency analysis: ‘where’ on basilar membrane = identity of frequency • Hair Cells: peripheral receptors of hearing • Auditory Pathway: brainstem, midbrain, thalamus and cortex • Speech: Broca’s & Wernicke’s
Smell • Olfactory receptor cells above superior turbinate in nose • Metabotropic receptors for shapes of chemicals • Signal goes up into olfactory bulb and via olfactory tract to cortex Olfactory receptor cell
Mitral cell (olfactory tract)
Thalamus Piriform cortex Amygdala
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Taste
• Receptor cell bears receptor for one kind of taste • Taste bud = all kinds of receptor cells • Some ionotropic (Na+, H+) some metabotropic • Chorda tympani (CN 7) & CN 9 carry impulses to solitary tract nucleus in brainstem • VPM thalamus • Cortical representation in insula/operculum (“lid”)
Movement What do I need to make a purposeful movement? • Will to move (Prefrontal cortex) • Plan and preparation (Pre-motor areas) • ‘Permission’ to move (Basal ganglia) • Raw command to muscles (Motor cortex) • Coordination & fine tuning (Cerebellum) • Final command to muscles (spinal cord) • Muscles(!) • Sensory feedback (vision, proprioception...)
MOVEMENT
Motor regions of the cortex
• Primary motor cortex (red)
– Represents contralateral half of body
• Premotor cortex & supplementary motor area (bright orange and yellow) – Planning movement, ‘getting into position’ for an action
• Frontal eye fields (brown) – Eye movements: complex & different from other movements
• Posterior parietal motor area (tan) – Sensory feedback: origin of majority of corticospinal fibers
Motor cortex - homunculus • Similar layout to somatosensory homunculus • Greater representation of hands & fingers – For dexterity/fine control
• Lower limbs medial – Not affected by MCA stroke, but ACA stroke would affect them
Corticobulbar tract
• Upper motor neuron fibers from cortex to cranial nerve nuclei • Bilateral innervation except – Lower facial nerve nucleus (only contralateral)
• Decussate BEFORE, not AT the pyramids! • Lesion - ? – Paresis (not total paralysis) of muscles: pseudobulbar palsy
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Lateral Corticospinal Tract
Corticospinal tracts
• Upper motor neuron fibers from cortex to trunk & limb lower motor neurons (LMNs) • Fibers to
Cortex Internal capsule
Sends signals for fine, delicate movements in distal muscles
Crus cerebri
– limb LMNs ≈ Lateral CSTs: dextrous movements – trunk LMNs ≈ Ventral CSTs: postural control
Basal pons Lower medulla
• VCST fibers from one hemisphere go bilaterally • LCST from one hemisphere goes only contralateral: pyramidal decussation
LCST
Descending Pathways
Corticoreticulospinal tract - Muscle tone specific for movement - Breathing
Basal Ganglia VL nucleus of Thalamus
Caudate Putamen
Corpus Striatum – “striped body”
Globus pallidus externa
Subthalamic nucleus
Basal ganglia - loops Direct loop
Direct & Indirect Loops
Premotor & motor Cortex Striatum
Striatum
D2
D1 VPL Thalamus GPi / SNr
Similar structure & function
Indirect loop
Premotor & motor Cortex
SNc
Substantia nigra pars compacta
Globus pallidus interna Substantia nigra pars reticulata
SNc
VPL Thalamus
GPe STN
GPi / SNr
excitatory inhibitory
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Cerebellum
Cerebellum – connections • Superior peduncle:
– Afferent: spinocerebellar – Efferent to basal ganglia & thalamus
• Middle peduncle – Afferent only: olivo/pontocerebellar
Evolution
Anatomy
Afferents
Function
Archicerebellum
Flocculonodular lobe
Vestibulocerebellum
Stability
Paleocerebellum
Vermis & paravermal areas
Spinocerebellum
Muscle tone & posture
Neocerebellum
Cerebellar hemispheres
Cerebro-cerebellum
Motor coordination
• Inferior peduncle – Afferent: vestibulocerebellar – Efferent: Cerebellovesitublar
Cerebellum – basic physiology Mossy fiber
Gray matter
Granule cells Parallel fiber
White matter
Input
Climbing fiber
Purkinje cell
Cerebellar nucleus
Brainstem & thalamus
Cerebellar nuclei
• Mossy:
– Spinocerebellar – Vestibulocerebellar – Pontocerebellar
• Climbing: olivocerebellar • Purkinje cells coordinate input and output • Output to 3 groups of deep nuclei: – Fastigial – Interposed (globose & emboliform) – Dentate
DIAGRAM KEY: PMC = premotor cortex M – I = primary motor cortex VLp = posterior division of ventral lateral nucleus of thalamus CC = cerebrocerebellum SC = spinocerebellum VC = vestibulocerebellum D = dentate nucleus G/E = interposed nuclei (globose and emboliform nuclei) F = fastigial nucleus RetN = reticular nucleus VN = vestibular nucleus
Locomotion
• Multi-step process (pun intended) • Central pattern generators • Stance: lower limb in contact with ground (60%) – Heel strike – Mid-stance – Push off
• Swing: lower limb not in contact with ground (40%)
NEUROLOGICAL DISORDERS & PATHOLOGY
– Acceleration – Deceleration
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Parkinson’s Disease (PD)
Parkinson’s Disease • • • •
100 per 100,000 population affected Male > Female Age - Risk 2nd commonest neuro-degenerative condition – 1st = Alzheimer’s
• Cause(s) unknown! • Possibly: – Genetic – Environmental (pesticides)
Pathophysiology
Pathophysiology
• Protein misfolding & aggregation in SNc – α-synuclein – Blocks normal function – Build-up of cellular debris (‘rubbish’) – Puts stress on mitochondria – Finally: cell death
• Similar pathophys. in other neurodegenerative conditions
Basal ganglia loops in disease Premotor & motor Cortex Striatum D2 Lewy body in dopaminergic neurons in the nigrostriatal pathway
• Hypokinetic disorder: – Bradykinesia – “slow movement” – Resting tremor – ‘Lead-pipe’ rigidity
• Symptomatic when 80% of dopaminergic neurons lost – Unilateral onset
• Progressive deterioration
VPL Thalamus
SNc GPe
– Alzheimer’s – amyloid-ß – Huntington’s - huntingtin – Fronto-temporal Dementia - tau
Clinical features
D1
STN
GPi / SNr
Other features Motor • Gait disorder: – Short, shuffling steps – ‘Broken’ turn – Loss of arm swing
• Postural instability • Balance • Micrographia – “small handwriting”
Non-Motor • Neuropsychiatric – Depression – Dementia – Visual hallucinations
• Sleep disturbance • Anosmia
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Treatment
Headaches
• Increase dopamine levels in brain – L-DOPA – Dopamine agonists – Stimulation of dopamine production – Stop breakdown of dopamine
• Stop indirect loop overactivity – Deep brain stimulation of subthalamic nucleus
Drowsiness/ coma
‘Thunderclap headache’ Collapse
Alcohol Smoking
Hypertension
CN palsy
Risk Factors
Clinical Features
Hemiplegia
Subarachnoid Haemorrhage
Neck stiffness
CT scan (bleed)
Spontaneous bleeding in subarachnoid space
Migraine
all over
unilateral
Quality
pressure
throbbing
Triggers
no
yes
no
yes
usually not
yes
Clinical Features
Photo/phono phobia
Photophobia
usually not
yes
Phonophobia
usually not
yes
no effect
aggravated
Mechanism
Prophylaxis Pizotifen (5-HT anatagonist)
Vomiting
•Bending •Coughing/ sneezing •waking
Subdural haematoma
Causes
Clinical Features
Drowsiness
Cerebral oligaemia from arteriole constriction
Propranolol
Papilloedema Focal neurology
Seizures
Changes in plasma 5-HT
Migraine
unilateral
Headache on:
Movement
Cheese
Triggers Nausea +/vomiting
Irritation of meninges
Tension headache
Nausea
Alcohol
Caffeine
Aura Bleeding Disorders
Location
Aura
Sensory e.g. spreading parasthesia
Mechanism
Investigations Lumbar puncture (bloody or yellow)
Visual e.g. dots+spots/ zig-zag lines
Space Occupying Lesion NOT Lumbar puncture ( herniation through foramen magnum)
Primary or Secondary tumour
CT scan
Investigations
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Petechial rash
N. meningitidis S. pneumoniae
Decreased conscious level
Seizures
•Opthalmic artery obstruction
Cause
Organisms
Clinical Features Photophobia
Age>55
Temporal Artery Inflammation
Hx proximal limb pain (polymyalgia rheumatica)
H. influenzae
Meningitis
Amaurosis fugax
L. monocytogenes
Clinical Features
Jaw claudication
Neck Stiffness
Treatment
Scalp tenderness
Giant Cell Arteritis
Temporal artery biopsy
Investigations Treatment
Broad spectrum antibiotics
Epilepsy
ESR + CRP Steroids
Epilepsy • Tendency to have seizures • Seizure = transient abnormal activity due to synchronous firing of brain neurons • Classification of seizures – Generalized: Entire cerebral cortex involved loss of consciousness – Partial: Focused in one area – Partial with secondary generalization – Functional
Epilepsy - generalized Grand mal (tonic-clonic) seizure • Aura/prodromal symptoms before • Shaking, frothing at the mouth • Loss of consciousness • Hyper excitable neurons: – Structural lesion – ion channel dysfunction – Infection – Trauma
Epilepsy Petit mal epilepsy (‘typical absence’) • More common in kids • Stop talking mid-sentence and stare into space • Eye twitch, muscle jerk (myoclonus) • Lasts ~ seconds • 3 Hz EEG waves during attack • Dysfunctional thalamic control of cortex • May go on to develop grand mal epilepsy in adulthood
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Epilepsy
Epilepsy
Simple partial epilepsy • Restricted to one cortical area e.g. motor cortex • Symptoms reflect function of the affected area – Jacksonian epilepsy: electrical activity spreads across homunculus contralateral limb jerking – Occipital lobe seizures: lights/colors, visual hallucinations
• Cause: often a structural lesion or abnormal neurodevelopment
Complex partial epilepsy • Usually temporal lobe affected – “Absence attack” – unaware of surroundings – Aura/prodrome of déjà vu – Stereotypical movements e.g. lip smacking
• Cause – structural lesion e.g. arterio-venous malformation – CNS inflammation
• DO NOT CONFUSE WITH ‘typical absences’ i.e. petit mal seizures
Epilepsy - summary • Brain neurons sensitive to agitation – Infection, inflammation, injury, malignancy, scar tissue…
• Classification of epilepsy:
THANKS FOR LISTENING!
Epilepsy Generalized Grand mal
Petit mal
Partial Partial with 2° generalization
Simple partial
Complex partial
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