Session 14 - Lecture 1 - Review Flashcards
1 - Review lecture 2
“GW: pathophysiology of selected conditions – some very important conditions like meningitis – included some rare conditions e.g. CJD and prion diseases,
DR: Can we detect structural differences between male and female brains – quantitative measurements of the brain in the DR – detect diff in size in corpus callosum between men and women – said in some sources than women have a bigger corpus callosum than men. And then finally – do a bit of stitching, put the brain back into skull, so first ever experience of doing some suturing.
Review topics: requests for basal ganglia again. A few qs on central cord syndromes – few misconceptions I want to sort out.”
2 - Basal ganglia
- Prefrontal cortex
- Motor cortex
- Sensory cortex
- Area 6
- Area 4
- Cortex
- Basal ganglia
- VLo
- VLo
- Pons, cerebellum
- Red nucleus
- Reticular nuclei
- Superior colliculus and vestibular nuclei
- Lateral motor system
- Ventromedial motor system
- Spinal cord
The basal ganglia take an ‘idea’ or motor plan provided by the prefrontal cortex and determine the MOST APPROPRIATE SET OF MOVEMENTS that will facilitate this plan. The direct pathway facilitates appropriate movements and the indirect pathway inhibits inappropriate movements. Dopamine from SNc can be thought of as a ‘kick starter’ and ‘fine tuner’
The cerebellum looks at the position of the limbs currently and determines an APPROPRIATE SEQUENCE to conduct the motor plan in
For example:
Motor plan – ‘pick up a cup of tea’
Basal ganglia say ‘you need to flex your fingers and
inhibit finger extension, flex your wrist and inhibit
wrist extension and flex your elbow and inhibit
elbow extension
Cerebellum says ‘you need to move the fingers first,
then the wrist and finally the elbow’
This stuff is not examinable. I am more interested in whether you understand the basic pathophysiology of Parkinsonian bradykinesia and can predict whether a given lesion in the basal ganglia is going to cause increased or decreased movement
“The normal function of the BG is v poorly understood - Latest edition of Grey’s Anatomy – Alan Crossman – a v well known neuroanatomist in Manc.
One thing we do know is they are important for the planning of movements. E.g. drinking a drink - the BG for any hidden things you want to do – they are involved in making the decision about which are the most appropriate movements to do out of all the ones which are available. What do I need to do? Grasp the drink with my hand. Need to flex my fingers, flex my elbow and flex my shoulders. So there’s a sequence of 3 movements there. But furthermore, they are 3 appropriate movements – in this case – extension is not an appropriate movement when I want to feed myself – I will not extend my fingers, wrist and elbow – I need to make sure I am choosing appropriate movements, i.e. flexions. Now, how do we facilitate these appropriate movements and inhibit these inappropriate movemetns. Now we know the mechanisms for that – direct pathway facilitates movement – indirect pathway inhibits movements – so in the case of flexion of this limb bringing the drink to my mouth – the direct pathway is stimulating the flexors and the indirect pathway is inhibiting the extensors: i.e. it’s selecting the appropriate movement. But it is all speculative and poorly understood – so not loads of detail bc it’s not going to be examined – if you’re interested – direct pathway stimulates appropriate movements, indirect inhibits inappropriate movements.
So what does the cerebellum do? Well the cerebellum here, is actually taking a large amount of input from the sensory parts of the brain – so the BG takes their input from pre-frontal cortex – where out motor plan is generated. Cerebellum takes most of it from the sensory cortex. What’s that got to do with function? Well cerebellum determines correct sequence of movements – based on position of limb at Time 0, if you like. The cerebellum sequences those movements, so the BG have just decided which movements are appropriate – first thing you need to do is flex your fingers, next thing you have to do is flex your elbow, next is your shoulders – so the cerebellum does the sequencing.
So once again, as it says in red – not going to ask you about the normal function of the BG except for broad thing of selecting appropriate movements – but you want to know how Parkinsonian develops and hyper and hypokinetic disorders.”
3 - Basal ganglia pathways
Don’t need to learn diagram - just understand it!
- Parkinson’s (hypokinetic) – Loss of dopamine from SNc
- Could treat by inhibiting STN
- Hemiballismus (hyperkinetic) – Damage to STN
- Could treat by stimulating GPi/SNr
- Huntington’s (hyperkinetic) – Loss of Inhibition of Gpe (early phase)
- Could treat by stimulating STN
- OCD – overactivity in direct pathway?
- Could treat by stimulating STN
“Diagram: edited version of a full circuit – and in an exam I will either highlight the bits of the circuit I want you to use or edit it like this.
So I’ve just given you some examples of how you might treat them, using brain stimulation, but I suspect as you start to practice you’ll see them more and more – brain stimulation.
1a. Characterised by the deficit of movement (hypokinetic) – not enough movement – and we know this is caused by loss of dopamine from substantia nigra pars compacta (SNc). So - take away the pars compacta, and we lose a source of excitation on the putamen – therefore, we’re not inhibiting the globus pallidus internal segment (GPi) and substantia nigra pars reticulata (SNr) as much, which means they are able to inhibit the thalamus more – so takeaway dopamine from here and thalamic inhibition increases. Now let’s look at indirect pathway – take away dopamine, takeaway inhibitory influence on putamen, so activity will increase, so will inhibit globus pallidus external segment (GPe) more, so activity levels will drop, so will inhibit subthalamic nucleus (STN) more, so its level of activity will increase, so will stimulate these more, leading to more net inhibition on the thalamus. 1b. We could try inhibiting the subthalamic nucleus – could try jamming it with an electrical signal or burning it out. If you look here – here’s the STN – if you’re interpreting the effect of a lesion within a circuity, you can ignore everything upstream of it (ignore GPe and putamen). So here, destroy it in a pt with Parkinson’s disease. If we destroy that, means it’s not activity GPi and SNr as much – levels will drop, not inhibiting thalamus as much, so activity level will increase, facilitating corticoactivation and increase in movement. 2a. Let’s look at another example – hemiballismus – occur in certain strokes – damage to subthalamic nucleus – this is destroyed in hemiballismus. If we destroy thrat we remove stimulation on GPi and SNr so activity level will drop, therefore won’t inhbiti thalamus as much, so thalamic hence cortical activity will increase. Happy? Are you happy or do you want a little bit of time to just think about it again. How could we treat this? Well why not try stimulating GPi or SNr, by destroying STN we’ve lost a source fs timulation, so if we stuff an electrode in them and increase inhibition on thalamus, inhibit cortex and have fewer inapporpiate movements. Do you want to og through the other two? Who wants to, who really doesn’t want to. So huntington’s disease – what’s happening there? Hyperkinetic condition – excess movement at least in initial pahses of the disaes e- in Huntington’s believed ot be caused by loss of these inhibitory projections from the putamen to the GPe – so in Huntington’s we’ve lost inhibition of GPe – lost its inhibition therefore activity level increases – inhbitis subthalamic nucleus more, so ultimately thalamus is inhbitied less – thalamic activity increases, cortical activity increases. How could we treat it? Loss connection here, why not stimulate STN – stimulate that, inhibit thalamus and maybe decrease inapprorpaite movements. So that’s Huntington’s, not restricted to movement disorders. It also has an important role in a number of psychiatric conditions as well – been known or hypothesised for about 20 years – in OCD direct pathway is overactive. But this isn’t movement we’re talking about – we’re talking now about thoughts – so here’s the cortex, it has a “thought” gors down into basal ganglia, and if you have OCD goes back up to cortex – wash your hands ewash your hands wash your hands. So in OCD this circuit is believe to be hyperactive , meaning the thoughts can re enter the cortex. So how mgith we treat it – give it deep brain stimulation? Subthalamic nucleus stimulation – think agbout this – ogot loop, going round and round. One problem we’ve ogt here is that the thalamus is hyperactivity – too much activity going through thalamus. So why not, let’s stimulate STN – nice small area of grey matter deep in the brain – can get an electrode in there quite easily – sitmulate this and inhibit thalamus by GPi and SNr – break that cycle of OCD – that’s the feeling behind neurosurgical procedure that you saw in the video. So covered actually quite a lot of the permeations – last lecture almost veeyr permeation gave you to try out yourselves- effects on movement. So any questions on this bit? Any issues on this bit? Yeah – “not an issue, but just wondering if you asked us this q in exam would you give us the pathway – I will always give you the pathway – I don’t think it’s real to life if I didn’t give you the pathway – a neurosurgeon would have the pathway in front of them, so why should I expect you to memorise this pathway? So in the exam – I will give you a diagram almost identical to this – and I will probably highlight a given region to explain why we get so and so. So I might highlight, might just highlight the direct pathway – use the direct pathway to explain why loss of dopamine from SNc cause bradykinesia from dopamine disease – less dopamine from putamen blab la bla means lress cortical activation – I will give yo uteh diagram and highlight region I want you to use – bc it’s complex and v easy to get distracted in there, so I’ll highlight it for you.”
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