Neurology Flashcards
Name 2 common disorders of the basal ganglia.
Parkinsons
Huntingtons
What components make up the ‘corpus striatum’?
- caudate nucleus and lentiform nucleus
- substantia nigra
- subthalamic nucleus
Where does the head and body of the caudate nucleus lie?
Nestles into the curvature of the frontal horn of the lateral ventricles
Where does the tail of the caudate nucleus lie?
Lies in the roof of the temporal horn of the lateral ventricle. On top of the hippocampus.
What does the genu of the internal capsule wrap around?
How can you tell a slice shows the genu of internal capsule?
- wraps around apex of lentiform nucleus (g.pallidus)
- at the level of the interventicular foramen of Monro
What is the anterior limb of the internal capsule between?
Caudate nucleus and the lentiform nucleus
What is the posterior limb of the internal capsule between?
What does it contain?
The thalamus and the lentiform nucleus
Has corticospinal tract fibres
What is the striatum?
What is the pallidum?
Striatum = input = caudate and putamen Pallidum = output = internal and external pallidum
Basic basal ganglia loops go:
frontal - striatum - pallidum - thalamus - frontal
What are the 3 loops regulated by and how?
Dopamine
Caudate and putamen get it via nigro-striatal tract
Ventral striatum gets it via VTA of midbrain
Where do the 3 BG loops originate?
What do they pass through?
Cognition - prefrontal cx…(passes through caudate)
Movement - motor and premotor areas (via putamen)
Emotion - limbic lobe, hippocampus, amygdala (V.striatum)
Which part of the substantia nigra projects to the BG?
The pars compacta
What are D1 -like receptors and what is DA’s effect on them?
e.g. D1 & D5,
They are excited by DA
What type of DA receptors do the striatal neurones express in the direct pathway?
What about in the indirect pathway?
Direct pathway expresses D1-like receptors
vs indirect expresses D2-like
What effect does the internal pallidum projection to the ventral thalamus have?
How does the direct/indirect pathway affect this?
Inhibitory (supress unwanted movements/thoughts)
Direct-disinhibits this (so activity occurs)
Indirect pathway-reinforces this (strengthens brake)
Direct pathway is from striatum->int. pallidum
Where does the indirect pathway go?
Striatum –> ext pallidum –> sub.thalamic nucleus –>int pallidum
How does the indirect pathway increase the subT nucleus excitation to int pallidum, reinforcing the inhibitory action?
- striatum/putamen sends an inhibitory neurone to the ext. pallidum
- disinhibits subT nucleus (no longer inhibited by ext.p
- strong excitation from subT to internal pallidum
- int pallidum inhibits thalamus more
Where is the ventral striatum and what is it formed by?
Anteriorly the caudate and lentiform nuclei are fused inferior to the ant limb of internal capsule
This is the VS and has ^^ and the N.Accumbens
What is the Ventral/Limbic striatum involved in?
Reward based learing
What projects to the Ventral Striatum? Function?
Ant. Cingulate Cx and orbiomedial pre-frontal Cx - emotions, decisions, behavior
Hippocampus - spatial/temporal contextual info about reinforced behaviours. +Amydala
Why may DA dysregulation syndrome/addiction to Levodopa, hypersexuality, gambling.. occur in Parkinson’s.
Ventral striatum activity is increased
This area is rich in receptors for addictive behaviours/substances
How do DAT scans show DAergic levels?
- radioactive label binds to DA-Transporters
- if there’s v. low DA transmission, there will be a low signal as less DATs are active
What is hemiballismus?
- shooting fast movements of limbs from midline
- (involuntary)
What is Huntington’s Disease?
- AD
- loss of GABAergic neurones in striatum
- causes hyperkinesia and dementia
Braak Stages of Parkinson’s disease:
Stage 1&2-
Stage 3&4-
Stage 5&6-
1&2 - early degeneration, sleep and small changes
3&4 - 50-80% loss, motor symptoms
5&6 - lewy bodys, psychiatric symptoms
Why does Parkinson’s result in a tremor?
- other NT disturbances (Ach, NA, 5-HT, GABA)
- less DA = less Ach inhibition so hyperactive Ach
What was the effect of MPTP (heroin metabolite) in causing Parkinson’s?
- MPTP taken up by DAT and metabolised by MAO-B
- MPP+ (metabolite) generates free radicals
- mitochondrial and DA cell degeneration
Why is L-DOPA always given with peripheral DOPA-decarboxylase inhibitors e.g. Benserazide, carbidopa?
- So more L-DOPA reaches brain and isnt converted into DA peripherally
- (which cant cross BBB and has many SE.s)
Why may the DA antagonist Domperidone be given in Parkinson’s patients on L-DOPA?
- treat nausea/vom. as CTZ has many DA receptors
- this antiemetic doesnt cross the BBB it acts just outside on D2 and D3 receptors
How do MAO-B blockers like Selegiline help in Parkinson’s?
- less DA metabolised (+protects vs MPTP toxicity)
- only acts in brain so no peripheral SE.s
What type of drug is ‘Entacopone’ that may be given to treat Parkinson’s with L-DOPA?
COMT-inhibitor
-slows L-DOPA elimination by increasing its t 1/2
Bromocriptine, ropinerole, pramipexole and rotigiotine are examples of what class of drugs?
DA agonists
Why may antimuscarinics like ‘benzatropine’ be given in Parkinson’s?
-to decrease the tremor
What do the dorsal columns detect?
Fine touch
Proprioception
Vibration
What route does the corticospinal tract take?
- motor area, through corona radiata, post limb of internal capsule. Decussates at pyramids
- descends on contralateral side to muscles
Where is M1 located?
And pre-motor cx?
M1-precentral gyrus of frontal lobe, ant to central sulcus
Immediately infront = pre-motor cx
Where is S1 located?
S1-post central gyrus of parietal lobe
2/3rds fibres in corticospinal tract come from M1 and pre-motor cx, where does the other 1/3rd come from/function?
- from parietal lobe, project to dorsal horn of cord
- to “filter out” sensations generated by movement
Dorsal Collumn pathway: from low-threshold mechanoreceptors…-DRG, dorsal gracile/cuneate fasiculus
- reach nuclei, medulla, X, up as internal arcuate fibres
- become medial lemniscus
- limbs/trunk-VPL, head/neck-VPM
Name 4 types of movement
- voluntary
- rhythmic
- reflexive
- postural
In the Rexed laminae of the spinal cord, what would the a medial ventral part control (e.g. VIII)
-medial = proximal, ventral = extensors
so would supply proximal extensors
Touch and olfaction receptors are “all in 1” (receptor+afferent) so are resilient to injury. Name 2 receptors that are separate.
-auditory, -vestibuluar, -gustatory
These are delicate and irreplacable
Name 3 things that can damage photoreceptors.
- light
- vit A deficiency
- mutations, metabolic disease
Name 3 things that can cause auditory cell receptor damage.
- Noise trauma
- mutations
- ototoxicity (chemo, aminoglycoside antibiotics)
Give 2 ways sensory skin receptors increases their “dynamic range” and save the cost of unnecessary APs
- lack of 2 point discrimination by summing depolarisation over 1 receptive field
- limited temporal resolution (2 quick taps feels like 1)
What is the advantage of “adaptation” of receptors?
-damps down constant responses, allowing highlighting of salient stimuli without saturating receptor
What does lateral inhibition enhance?
Spatial discrimination
At what day in development do the neuroepithelial cells attach to the pial and luminal surface and proliferate? How?
Day 22
- drop down to luminal surface
- split perpendicular
After the NT closes, how do the neuroepithelial cells now proliferate? What is the resulting cell?
- drop to luminal surface and split parallel to surface
- upper daughter cells exposed to different intracellular signal, it becomes a ‘neuroblast’
Name two extracellular chemicals that act as morphogens which neuroblasts have receptors for.
- neuroregulins
- reelin (from Cajal-Retzus cells in marginal zone)
What do each of the 6 cortical layers become?
- deep 5&6
- middle (4)
- outer 2&3
- Glial layer (1)
- 5&6 - big pyramidal cells, axons to subcortex
- (4) - stellate cells
- 2&3 -small pyramidal cells, axons to cortex
- Glial layer (1) - neuroepithelial cells drop to luminal surface and become ependymal cells
Name a condition causing inappropriate formation of the brain/neurogenesis?
DCX-loss of doublecortin protein
X-linked condition
How do simultaneous deplolarisations of an effective circuit cause long term potentiation. AMPA is stimulated by a little glutamate..
- If AMPA is sufficiently stimulated, the Mg ion blocking NMDA receptors is diplaced so Glutamate binds here
- opens Ca2+C, Ca2+ strengthens synapse
- grows, makes more NT and more AMPA Rs
Describe A-delta fibres. NT..respond to…feels like…
- thin, myelinated, NT used is glutamate
- respond to mechanical trauma/noxious heat
- immediate sharp pain
Describe C fibres. NT..respond to…feels like…
- thin, unmyelinated, NT is glutamate, sub P
- report ongoing pain/pressure/heat/inflammation
- long, throbbing/aching pain until injury heals
How does damage and prostoglandins activate C fibres?
Damage-K+/H+, hist, bradykinin…depolarise C fibres
Prostoglandins increase C fibre sensitivity
What is sub P’s role in injury?
Sub P increases inflammation causing loss of function
So promotes healing
What is the lateral pain pathway responsible for?
What areas of thalamus/cx involved
- perception and sensation of pain
- VPN - sharp localised pain
- SS cortex - localised pain
What is the medial pain pathway responsible for?
What areas of thalamus/cx involved
- emotional response to pain (fear/aversion)
- midline thalamic nuclei (unpleasant sensation)
- ant. cingualte cx (mood/links to hypothal and limbic)
- insula cx (whole body map, increases alertness)
How can pain overrun CNS via medial pain pathways?
- ruin sleep
- disrupt concentration
- switch attention/salient stimulus
Descending modulatory pathways project from the RV medulla and DL pontine tegmentum to spinal cord releasing what? To do what? When?
- release NA/5HT onto interneruones
- to decrease activity in the 2dry pain afferents
- always at a backgound level, more with opiods/anti-depressants
What is allodynia?
When normal touch becomes painful
What 3 things characterise drug addiction?
- compulsion to take drug
- loss of control limiting intake
- emergence of a negative emotional state
What is the timeline leading to drug addiction?
social drugs - escalating use - dependence - withdrawal - protracted withdrawal - recovery (+/-relapse)
Where do the mesolimbic DAergic systems project to?
- VTA and Nuc Accumbens
- mediate drug use and positive reinforcement
What areas of the brain are involved in negative reinforcement e.g. bad emotional state –> drug taking?
NTs?
Amygdala, hypothalamus, hippocampus, Nuc Accumbens (orbiofrontal, prefrontal and ant.cingulate Cx)
Releasing NA, GABA and CRH.
When your awake, impulses from thalamus and modulatory input fires, but when asleep….and REM sleep…
…modulatory inputs stop, thalamic cells fire spontaneously/synchronous firing.
-REM sleep cortex active, thalamus desynchronised, EO and ear muscle active, skeletal muscle paralysis
As you drop down the 3 levels of sleep what happens in relation to thalamus?
Firing becomes more and more synchronous
deep sleep 4Hz/sec vs 20Hz/sec awake
From where does ACh modulatory input originate?
- Pontomesencephalic Tegmentum - (to thalamus)
- Basal Forebrain - (to hippocamp. increases cx response strength and selectivity, attentiveness)
From where does NA modulatory input originate?
Effect?
- Locus coeruleus in brainstem - (to everywhere)
- increase cx response amplitude&selectivity, vigilant
From where does DA modulatory input originate?
Effect?
-Substantia Nigra (to basal ganglia)
-VTA (to frontal cx, limbic lobe, n. Accum, amygdala
Alert, adaptive motivational behaviour
From where does Histamine modulatory input originate?
Effect?
- Tuberomammilary Nucleus in hypothal
- excites wake promoting circuits -> alert to stimuli
From where does Orexin modulatory input originate?
Effect? Pathology?
-Hypothal
Switch on wake-promoting centres
Narcolepsy, fragmented sleep, REM while awake
From where does Seratonin modulatory input originate?
Effect?
- Raphe Nuclei (to brainstem, cerebellum and Cx)
- active in quite wakefullness, normal stress response
What processes are involved in waking up?
- Hypothal orexigenic cells switch on histamine cells
- they both activate 5Ht/NA/Ach brainstem ARAS centre
- basal forebrain Ach to whole brain starts activity
What processes are involved in falling asleep?
- What neurones, where, controlled by?
- what else activates these neurones?
- GABAergic neurones in venerolateral preoptic nucleus (VLPN) of hypothal inhibit the orexin/Hist/ARAS
- GABAergic cells are under the control of SCN
- also adenosine increases with wake time which activates GABA cells so do immune byproducrs
What might a VLPN lesion cause?
Intractable insomnia
What causes REM sleep? (which NT, where)
Cholinergic centre in pontomesencephalic tegmentum
axons desynchronise thalamus so cortical neurones in BG wake up an higher Cx activity
Where is Broca’s area? Responsible for?
- pars triangularis and pars opercularis of inferior frontal gyrus on the left hemisphere
- for motor/producing speech
What is the pars orbitalis of inferior frontal gyrus responsible for?
-behavioural inhibition/restraint
What does the dorsolateral part of the pre-frontal cortex do?
In what patients is it abnormally active?
- executive cognition (organising planning) via basal ganglia loops involving the caudate nucleus
- (+frontal eye fields controlling attention/gaze)
- in OCD patients
What does the ventromedial part of the pre-frontal cortex do?
What would a lesion here lead to?
- regulation of behaviour, personality and social conduct
- lesion –> rude, inappropriate, lack of insight
What is the sensory association Cx involved in? What important projection does it receive?
- visuospatial representation of objects in space
- ‘where’/dorasl visual stream from occipital cortex
- where x is, speed, trajectory, object interaction
Where is the sensory association cx?
Just behind S1 in the parietal lobe
The posterior parietal region is also involved in what?
A post. parietal lesion therefore causes what?
- attention/gaze
- hemineglect (sometimes anosognia-unaware their deficit exists)
The parietal lobe does praxes. What is this? What may a parietal/frontal/white matter connection lesion cause?
- semi automatic motor sequences stored in the pre-frontal cx but selected by the post. parietal lobe
- lesion -> apraxia
What is the dominant (L) inferior parietal lobe involved in? Lesion causes what - name of syndrome?
- symbolic representation, number concepts, physics. reading and writing
- lesion Gerstmann syndrome - L/R confusion, maths difficulty, cannot name fingers
What is the medial parietal lobe/tne pre-cuneus involved in?
active in day dreaming
episodic memory recall
object visualisation
Where does visual info relating to form/colour project to? What is it called if you can’t integrate this info?
- ‘what’ pathway to lateral and inferior temporal cx to identify and categorise objects
- failure to recognise objects = agnosia
What does the auditory association cortex do in the language dominant cx? Wernicke’s is here, where exactly?
- recognition of speech sounds
- Wernicke’s - post 1/3rd of superior temporal gyrus
What do areas in the inferior parietal lobe, adjacent to Wernicke’s area do?
-understanding of written language ie. reading
What do you get with a lesion to
- arcuate fasiculus
- broca’s
- Wernicke’s
Arc. Fasiculus - conduction aphasia
Broca’s - non-fluent aphasia
Wernicke’s - fluent aphasia
What is the main function of the spinocerebellum?
-modulates descending motor systems in brainstem via reticular formation and vestibular nuclei
What is the main function of the vestibulocerebellum?
-regulates balance and eye movements via vestibular nuclei
What is the main function of the cerebrocerebellum?
- high level planning movement.
- regulates cortical motor programs (via thalamus)
Cerebellar output is via what cells? What NT? Project where?
Purkinje cells. GABAergic
- to deep cerebellar nuclei (excitatory) -> to thalamus -> Cerebral Cx
- (also to vestibular nuclei, reticular formation)
What are the 2 excitatory inputs to a Purkinje cell? Where do they come from?
- Climbing fibres from cerebral cortex to inf olive
- Mossy fibres from brainstem nuclei –> parallel fibres from granule cells
Name 2 local cerebellar inhibitory interneurones.
- basket cells
- stellate cells
- golgi cells
How is “cerebellar learning” brought about?
- long term changes in responsiveness to parallel fibre inputs
- synaptic strengthening in successful circuits
Where does the trochlear nerve exit the brainstem?
-DORSALLY. lateral to the frenulum below the inferior colliculi and cruciform sulcus.
What cranial nerve comes of the pons at the juction of pons base and middle cerebellar peducle?
CNV - Trigeminal Nerve
Where do the olives in the medulla project to? For..?
To the contralateral cerebellar hemisphere via inf. peduncle (decussate at raphe nucleus)
For motor learning
Which cerebellar peduncle runs up the lateral medulla like a rope and turns posteriorly sharply to enter the cerebellum?
Inferior cerebellum peduncle (restiform body)
The upper 1/3 of medulla opens like a flower posteriorly, the point of transition between closed/open is called what? What is here?
The transition = the “obex”
This is where the CTZ is
CN nuclei are arranged in discontinous vertical columns from medial to lateral what are the columns and their CNs?
- somatic motor group (EO & tongue CNIII, IV, VI, XII)
- visceral motor (E.West. CNIII, VII, IX, X-parasymp)
- branchiomotor (V, VII, nuc, ambiguus IX, X, XI)
What is the function of the Nucleus Ambiguus? (IX, X, XI) in the branchiomotor column derived from fish gill arches.
Muscles of speech and swallowing
muscles of soft palate, larynx and pharynx and parasymp to heart
What muscle do the fibers of the glossopharyngeal nerve (CN IX) innervate?
Stylopharyngeus muscle
What is the main sensory nerve of the head and neck for general fine touch/2 point discrimination? Where does this nerve emerge?
Trigeminal sensory root
-lateral to motor root (think embryo) at pons/MCP junction
What does the motor root of the trigeminal nerve supply?
Muscles of mastication
The trigeminal nucleus runs the whole length of the brainstem, what is the superior part in the midbrain responsible for? And the inferior part in medulla and C-spine?
- Superior does proprioception e.g. jaw muscles
- Inferior part does pain/temp sensation via trigeminothalamic tract
Where does the vestibulocochlear CNVIII arise from?
Fibres enter brainstem via?
And terminate at their nuclei….
- cochlear+vestibular apparatus in the petrous portion of the temporal bone.
- enter brainstem via internal auditory meatus at the CPA-cerebellopontine angle
- nuclei in lateral recess of floor of 4th ventricle
How many cochlear nuclei are there? How many vestibular nuclei?
2 cochlear (dorsal and ventral) 4 vestibular (3 in medulla, the superior one in the midbrain)
The V-shaped visceral afferent nucleus in the medulla is aka the solitary tract / nucleus tractus solitarius. What CN come to which part?
- Top part: fibres from taste buds (CN VII, IX, X)
- Middle: fibres from heart and lungs (CN IX, X)
- Bottom: sensation from GIT/abdo viscera (CN X)
V1 and V2 pass through the cavernous sinus. V3 does not. Name 3 muscles the trigeminal nerve innervates.
- mylohyoid
- ant belly of digastric
- tensor tympani
- tensor veli palatini
What muscles other than facial expression muscles does CNVII innervate?
- post. belly digastric
- stylohyoid
- stapedius
What CN carries visceral afferents from the carotid sinus? (this nerve also does ear drum sensation)
-CN IX - Glossopharyngeal
Where does the vagus nerve do pain and temperature sensation?
- infratentorial dura
- larynx
- external ear
CNXII innervates all the muscles of the tongue except….Which nerve innervates this?
Palatoglossus (innervated by vagus)
What is the effect of the following on the HPAxis: amygdala, hippocamppus. How is this different in depressed individuals?
-Amygdala stimulates HPA (–> CRH –> more cortisol)
-Hippocampus negatively feeds back on HPA (less C)
In depressed you have less cortisol receptors in the hippocampus so less neg. feedback
The motor loop of basal ganglia from motor cx to putamen goes to which part of pallidum and which part of thalamus?
Motor: …–> Internal segment of globus pallidus (lateral)
and to the VL nucleus of thalamus
The cognitive loop of basal ganglia from dorsolateral pre-frontal cx to DL caudate goes to which part of pallidum and which part of thalamus?
Cognitive…-> Internal segment of globus pallidus (medial)
and to MD and ventral anterior nuclei
The limbic loop of basal ganglia from Ant cingulate cx to ventral striatum goes to which part of pallidum and which part of thalamus?
- Ventral pallidum
- MD nucleus of thalamus
