CNS Motor Control & Systems 🧠 Flashcards

1
Q

Motor control: Desc control of spinal circuits and motor cortex

What are the 3 components of the motor system?

A
  • cerebral cortex (and voluntary movement)
  • descending pathways
  • spinal cord
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2
Q

What is the brain part of the motor system?

A

the cerebral cortex

  • motor cortex
  • sensory input
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3
Q

What are the two non-brain components of the motor system?

A

descending pathways

  • lateral= volunatry
  • ventromedial (brainstem control)

spinal cord

  • motor neurons
  • sensory input
  • local reflexes
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4
Q

What neurones within the spinal cord are part of the motor system?

A

alpha motor neurones

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5
Q

Where in the spinal cord are these alpha motor neurones?

A

the ventral horn - they then directly synapse w muscles at neuromuscular junction to initiate movement

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6
Q

What can influence the motor neurone activity in the spinal cord?

A

sensory input

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7
Q

What type of local pathways can be activated in the spinal cord?

A

local reflexes

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8
Q

What are 3 key features of the spinal cord?

A
  • motor neurones
  • sensory input
  • local reflexes
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9
Q

What are the two types of descending motor pathways?

A
  • lateral

- ventromedial

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10
Q

What type of movement is the lateral pathway in charge of?

A

voluntary e.g. decision to stand up

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11
Q

What type of movement is the ventromedial pathway in charge of?
brainstem control

A

involuntary (e.g. maintaining posture)

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12
Q

What are the two key features/functions of the cerebral cortex as part of the motor system?

A
  • voluntary movement

- sensory input

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13
Q

What nuclei are under the cortex and what do they form?

A

subcortical nuclei, form the basal ganglia

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14
Q

What are the 3 key features of the motor system?

A
  • hierarchical organisation
  • feedback loops
  • somatotopic representation
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15
Q

Where does the spinal cord receive input from?

A
  • sensory receptors
  • brainstem
  • primary motor cortex
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16
Q

Where does the the spinal cord output to?

A
  • brainstem
  • sensory receptors
  • cerebellum
  • thalamus
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17
Q

Where does the brainstem receive input from?

A

primary motor cortex

cerebellum

SC

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18
Q

Where does the premotor and supplementary motor cortex receive input from?

A

thalamus

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19
Q

Where does the premotor and supplementary motor cortex output to?

A
  • basal ganglia
  • cerebellum
    blue
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20
Q

Where does the thalamus receive input from?

A
  • basal ganglia
  • cerebellum
  • spinal cord
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21
Q

Where does the thalamus output to?

A

premotor and supplementary motor cortex

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22
Q

Where does the primary cortex output to?

A
  • brainstem

- spinal cord

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23
Q

Where does the basal ganglia receive input from?

A

premotor and supplementary motor cortex

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24
Q

Where does the basal ganglia output to?

A

thalamus

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25
Where is the cerebellum receiving input from?
- precentral and supplementary motor cortex | - spinal cord
26
Where is the cerebellum outputting to?
thalamus
27
What is meant by 'somatotopic representation'?
sensory info reaches a specific group of neurones in the cortex that expects input from a specific part of the body
28
What are the 3 types of movement?
- reflex - rhythmic motor patterns - voluntary
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How are reflexes generated? | protective e.g. limb withdrawal
by closed loop motor patterns in the SC
30
What are examples of rhythmic motor patterns? 3
- walking - breathing - chewing
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What are rhythmic motor patterns a combination of?
- voluntary and reflex movements | - e.g. walking is a reflex, but can be sped up or slowed down (voluntary)
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What is the nature of voluntary movement?
purposeful, goal directed
33
Where does command originate for voluntary movement?
higher centres
34
Are voluntary movements open or closed loop?
open - they can be modulated as they're happening
35
Lower motor neurones What types of motor neurones are known as the 'final common pathway' of motor control? Why?
alpha neurones - these are the only ones making direct contact with muscle
36
What are lower motor neurones also known as?
alpha motor neurones | a-MNs
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Input from what governs spinal motor neurone activity?
REFLEXES: - sensory input (dorsal roots) - spinal interneurones - upper motor neurones
38
Why are spinal interneurones known as "inter"?
connections these neurones make are all located within the spinal cord
39
What of the inputs to spinal motor neurone activity control reflexes?
- sensory input (dorsal roots) | - spinal interneurones
40
Where are the upper MN located? What does this mean for their function?
- cerebral cortex | - in charge of initiating and controlling voluntary
41
What does the saying "see the headless chickens running" tell us about spinal cord circuits?
- even if input from descending tracts are severed, the spinal cord can generate coordinated movement - hence brain influence is not necessary
42
What are the circuits generated within the spinal cord sufficient to cause coordinated movement called?
central pattern generators
43
descending inputs from the upper motoneurons? causes... superimposed upon what?
- causes sophisticated, adaptable, patterns of movement - This is voluntary or otherwise involves input descending from the brain - superimposed upon the intrinsic circuitry of the spinal cord
44
what is an upper motoneuron?
- confined to the CNS - initiates voluntary movement - maintenance muscle tone for support of the body against gravity - regulates posture to provide a stable background upon which to initiate
45
What is fine motor control? | innervated by...
- ability to make movements using the small muscles (hands / wrists / toes) - innervated by lateral motoneurons
46
What is posture?
- movements made by larger muscles (elbow/knee/trunk) | - innervated by medial motoneurons
47
what do MEDIAL motorneurons innervate?
axial: trunk muscles proximal: elbow, knee
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what do LATERAL motorneurons innervate?
distal: hands, feet, digits
49
What are the 2 lateral descending pathways?
- Direct motor cortex -> SC - Indirect motor cortex -> red nucleus -> SC
50
How many ventromedial descending pathways are there?
2 indirect pathways... motor cortex > brainstem (Vestibular Nuclei) > SC or motor cortex > Reticular Nuclei > spinal cord
51
How many Lateral descending pathways are there?
2: 1 direct, 1 indirect, through red nucleus
52
lateral pathways are...
VOLUNTARY | distal muscle flexors
53
ventromedial pathways govern...
POSTURE | proximal/axial muscles extensors
54
What are the 2 lateral descending motor pathways?
- Corticospinal (pyrimidal/ direct) Tract | - Rubrospinal Tract (indirect)
55
What is the corticospinal (pyrimidal) tract? lateral pathway
direct line contralateral projection from cortex -> lateral spinal motor neurones
56
corticospinal (pyrimidal) tract has what kind of contact with aMNs?
monosynaptic
57
corticospinal (pyrimidal) tract- where are majority of axons, and what does it innervate?
... from neurons w cell bodies in motor cortex (areas 4-6) aMNs (a interneurons a bit) controlling distal muscles and esp flexors
58
What is the Rubrospinal Tract?
contralateral projections from red nucleus running down lateral column of SC similar role to corticospinal tract, but smaller component of lat pathway less important in humans
59
4 ventromedial descending pathways? | pic on p607 too
vestibulospinal tract tectospinal tract pontine reticulospinal tract medullary reticulospinal tract
60
What are the consequences of damage to the lateral ASCENDING spinal sensory pathway?
- can lead to motor deficit | - slower voluntary movements
61
What is the effect of damage to the lateral ASCENDING spinal sensory pathway on POSTURE?
no effect | - no damage to ventromedial tract
62
Are there any compensatory mechanisms if there is damage to the corticospinal tract? (selective corticospinal tract legion)
- rubrospinal tract can compensate almost entirely for loss of corticospinal (except fine digit control) - Re-routing of cortical output via the rubrospinal tract
63
Where do the ventromedial (extra-pyramidal tract) motor pathways originate?
- brainstem nuclei | - carry motor fibres to the spinal cord
64
What are the ventromedial pathways responsible for?
involuntary and automatic control of all musculature, such as muscle tone, balance, posture and locomotion
65
What do extra-pyramidal side effects mean and " of dopaminergic drugs affect what??
- occur when using anti-psychotics - symptoms include an inability to sit still, involuntary muscle contraction, tremors, stiff muscles, and involuntary facial movements. trunk muscles
66
What are the 2 pairs of ventromedial pathways?
reticular nuclei - Pontine reticulo-spinal - Medullary reticulo-spinal superior colliculus and vestibular nuclei - Vestibulo-spinal - Tecto-spinal
67
What is the importance of the 4 ventromedial pathways? 2 pairs
controlling balance, body position, visual input | -> modulate spinal reflexes and maintain body balance/posture
68
What is the Pontine reticulo-spinal tract roles? 2
- Enhances anti-gravity reflexes of SC | - Facilitates leg extensors to maintain standing posture
69
What is the Medullary reticulo-spinal tract roles?
opposing effect to Pontine reticulo-spinal tract - Frees antigravity muscles from reflex control - Allows voluntary override
70
What is the Vestibulospinal tract- what info does it relay from inner ear and axial muscles?
- Relays gravitational sensory info from vestibular labyrinth (inner ear) and stretch receptors in axial muscles - Maintains head and neck position and also legs
71
What is the tectospinal tract roles? 2
- Relays visual sensory information from retina and visual cortex - Orientates head & eyes to visual and auditory stimuli
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Cerebral cortex and voluntary movement what do cortical motor areas control?
voluntary movement, involves almost all of neocortex
73
other than execution, what 4 things does movement involve?
- sensory input - planning - deciding appropriate action - holding plan in memory
74
What is the primary motor cortex also called... and where located?
M1/ Area 4 in the precentral gyrus near primary sensory cortex
75
where is the pre-motor area (PMA)?
next to the primary motor cortex and the supplementary motor area (SMA) - SMA and PMA combine to form AREA 6
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Which 2 areas make up up the motor area of the brain?
Area 4: Primary motor cortex and Area 6: Pre-motor area and supplementary area
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which area in motor cortex= lowest stimulus threshold= strong synaptic link?
area 4- M1 prim motor area 6=more complex movement
78
What is a homonculus?
- map along the cerebral cortex of where each part of the body is processed - sensations occur all along the body. - Larger areas on the homunculus represent the greater supply to these areas of the body
79
Roles of cortical motor areas: | 1. primary motor cortex (M1; area 4)
control distal musculature (fine motor control)
80
Roles of cortical motor areas: | 2. premotor cortex (area 6; lateral) controls...
proximal musculature (posture, balance) movement sequencing prep for movement, initiation (planning + movement)
81
Roles of cortical motor areas: | 3. supplementary motor area (area 6; fronto/medial)
role in planning + initiation | bi-manual co-ordination
82
Which kind of movement is evoked when Area 6 is stimulated?
- complex movement | - some movement can be stored for use once stimulated
83
What are upper motor neurons?
- ~50% of corticospinal tract axons - neuronal cell bodies originate in the 5th cortical layer - Somatotopically organised - Activate small groups of muscles rather than single ones - Individually encode the force OR direction of movement
84
How can upper motor neurons be damaged? 3
- tumours - stroke - infection
85
What are symptoms of damage to upper motor neurons?
Eventual spasticity (⬆ resistance to passive movement) o ⬆ muscle tone (hypertonia) o ⬆ reflex responses (hyperreflexia)
86
Which side of the body is affect by damage to upper motor neurons?
opposite side to damage
87
Is recovery possible from damaged upper motor neurons?
yes. Primary motor cortex shows adaptive alterations
88
Cerebellum What is the cerebellum?
part of the brain associated with voluntary responses. doesn't project outside the brain
89
What are the functions of the cerebellum?
· Closely involved with brainstem mechanisms · Control of muscle tone and body posture · Sensorimotor coordination · Motor learning
90
What are the 3 anatomical regions of the cerebellum?
- Spino-cerebellum (medial region) - Vestibulo-cerebellum (caudal region) - Cerebro- (ponto-) cerebellum (lateral hemispheres)
91
Characteristics of the 1. spino-cerebellum? - sensory input? - output? - controls?
- receives sensory input from SC - output -> reticular formation + red nucleus - from reticular formation/ red nucleus, info sent back to SC via motor cortex - this is involved in coordination of motor movements and maintenance of muscular tone.
92
Characteristics of the vestibulo-cerebellum? - sensory imput? - output? - controls?
- receives input from + output to: vestibular nucleus via ventromedial pathway - control over posture/ balance and eye movement
93
Characteristics of the cerebro-cerebellum?
intracerebral motor loop cortex -> cerebellum -> back to cortex (M1) - Instructs primary motor cortex (M1): movement direction, timing, and force - Compares intended movements with actual movements sends compensatory instructions to M1
94
damage to cerebullum 1: | What is ataxia and what functional component of the cerebellum does this affect?
- causes staggering and slurred speech | - affects all functional areas of the cerebellum
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damage to cerebullum 2: | What is dysmetria and what functional component of the cerebellum does this affect?
- causes inability to control distance/ force of movements | - affects spino-cerebellum and cerebro-cerebellum
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damage to cerebullum 3: | What is hypotonia and what functional component of the cerebellum does this affect?
- causes reduced muscle tone (over-relaxation of muscle) | - affects spino-cerebellum
97
damage to cerebullum 4: | What is slow saccades/ nystagmus and what functional component of the cerebellum does this affect?
- causes impaired eye movemnt | - affects vestibulo-cerebellum
98
damage to cerebullum 5: | What is Dysarthria and what functional component of the cerebellum does this affect?
- causes slurred speach (weakened speech msucles) | - affects cerebro-cerebellum
99
What are the 2 inputs to the cerebellar cortex (deep cerebellar nuclei)?
- climbing fibers - directly excite Purkinje cells | - mossy fibers - indirectly excite Purkinje cells (via parallel fibres of Granule cells)
100
Where do climbing fibers originate?
inferior olivary nucleus in medulla
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Where do mossy fibers originate?
Brainstem nuclei
102
What are the outputs from the cerebellar cortex?
- ONLY purkinje cells - project to deep cerebellar nuclei - inhibitory output
103
What is the deep cerebellar nuclei (DCN) cells role??
compare input from mossy and climbing afferent input BEFORE: via collaterals from axons to P cell- EXCitatory AFTER: cerebellar processing via INHIB P cell output comparison can -> error signal
104
``` ****************** cerebellar function summary: - whats it regulate? - act as... - role in.... ```
regulates: posture indirectky: adjusting output of major desc motor pathways acts as - COMPARATOR: identify + correct discrep in intented movement and actual - TIMER: sequencing motor activation-> smooth performance role in motor memory and learned motor seq when appr. not required for perception/muscle activation
105
BASAL GANGLIA what is it? what happpens here?
group of associated subcortical nuclei 'dark basements of brain' integrates sensory + motor info from cortex... relays back to cortex via thalamus. loop selection and initiation of voluntary movement
106
does basal ganglia project outside the brain?
no
107
what happens if basal ganglia gets damaged?
movement disorderes
108
What are the functions of the basal ganglia? 2 distinct
· Responsible for the Integration of sensory and motor information · Selection and initiation of voluntary movement
109
What is the cortico-basal ganglia-cortical loop?
· Integrates motor and sensory information from the cortex · Relays back to the cortex via thalamus · Motor loop circuit output to PMA/SMA cortex · Involved in selection and initiation of voluntary movement
110
What is the motor loop at rest?
- Cortex sends info to the basal ganglia (excita) - Basal ganglia sends outflows to the thalamus (inhibitory) - Thalamus is unable to send info to the cortex to cause movement
111
whys inhibi BG outflow paused?
to allow thalamus to be free to stimulate cortex= initiate movement
112
What is the motor loop when we want to move?
- prefrontal cortex thinks about this and sends EXCITATORY info to the basal ganglia - Excitatory outflow to the basal ganglia REMOVES the inhibitory outflow to the thalamus - Thalamus Dis-inhibition allows for excitatory outflow to be passed to the cortex (causing movement)
113
What are the structures of the Basal Ganglia?
STRIATUM (STR) - Caudate nucleus - Putamen - Nucleus accumbens - Subthalamic nucleus (STN) - Globus pallidus (2 segments - internal/external) - Substantia nigra (2 segments - regulata/ pars compacta)
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What is the collective term for the Caudate nucleus, Nucleus accumbens and Putamen? and is it input/outflow?
Striatum STR input from cortex
115
What is the INTERNAL segment of the Globus pallidus responsible for?
- sending Inhibitory Outflow to the Thalamus | - uses GABA as a neurotransmitter
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What is the RETICULATA segment of the Substantia Nigra responsible for?
- sending Inhibitory Outflow to the Thalamus | - uses GABA as a neurotransmitter
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At rest what is the effect of the basal ganglia output on the excitatory drive to the cortex?
- output inhibits the excitatory drive of the thalamus to the cortex circuit pic p628
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What are the pathways of the basal ganglia? and role of each?
- direct: promote movement | - indirect: suppress movement
119
What is the (Dopamine +) direct pathway of the basal ganglia?
Striatum --> Substantia Nigra Regulata OR Globus palidus internal --> Thalamus --> cortex
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How is movement generated via the DIRECT pathway?
cortex STIMULATES inhbitory effects of striatum on the Substantia Nigra Regulata (SNr) - Inhibitory effects of SNr on the thalamus are stopped (stimulates thalamus) - Thalamus sends EXCITATORY information to Cortex
121
What is the effect of dopamine in the Direct pathway of the basal ganglia?
- acts on D1 receptors on the Striatum - increases the inhibitory effects of striatum on the substantia nigra reticulata DEC BG output facilitates movement
122
How is movement suppressed via the INDIRECT pathway?
- cortex sends excitatory signals to striatum which inhibits Globus palidus external (GPe) - Inhibitory signals from GPe to Subthalamic nucleus (STN) are stopped - Dis-Inhibition of STN, increases excitatory signals from STN to Substantia Nigra regulata/ SNr (inhibitory) - Increased stimulation of SNR increases inhibitory signals to thalamus - inhibition of the thalamus inhibits excitatory signals to cortex (stops movement)
123
What is the effect of dopamine in the Indirect pathway of the basal ganglia?
- Dopamine acts on inhibitory D2 receptors on the striatum - inhibiting the striatum - Inhibiting the striatum stops the inhibitory effect on the Globus palidus external (GPe) - Dis-inhibition of the GPE increases the inhibition of the excitatory Subthalamic nucleus (STN) - Inhibition of the STN decreases the inhibitory effect on the Substantia Nigra regulata/ SNr on the thalamus - Dis-inhibition of the thalamus allows for excitatory effects on the cortex (stimulating movement) pic p 629
124
what is dopamines role in both direct and indirect pathways? BG same end result
direct: act on excitatory D1 rec on striato- Gpi/SNr neurons...⬇ BG output.. movement ☺ indirect: act on inhibitory D2 rec on striato- GPe neurons... ⬇ STN activity ⬇ BG output... movement ☺ - less activity
125
What is the consequence of imbalance between the indirect and direct pathways?
motor disfunction - hypokinetic disorders (Parkinson's Disease) - hyperkinetic disorders (Huntington's Disease)
126
What is Parkinson's disease?
Movement disorder caused by the death of cells that generate dopamine in the basal ganglia and substantial nigra pars compacta.
127
What are 4 symptoms of Parkinson's Disease?
1) Resting tremor (shaking) 2) Bradykinesia: Slowed movement 3) Rigidity of movements of the face 4) Akinesia (the absence or reduction of movement)
128
What is the primary pathology of Parkinson's Disease?
- Progressive degenerative loss (> 80%) of nigro-striatal dopaminergic pathway - -> excessive inhibition of thalamo-cortical pathway
129
What is the rational for treating Parkinson's Disease?
Dopamine loss in basal ganglia-> excessive inhibition of thalamo-cortical pathway driven by ⬆ activity in subthalamic nucleus STN - stimulates Substantia nigra Regulata - inhibits thalamus
130
How can we treat Parkinson's disease?
need to boost dopamine in brain Dopamine boosting agents - L-DOPA - Drugs that slow Dopamine Metabolism (MAO-B inhibitors) - Deep brain stimulation
131
What is Huntington's disease?
A degenerative disease of the nervous system. uncontrollable, rel rapid motor patterns disrupts normal motor activity autosomal dominant disorder
132
What is the primary pathology of Huntington's Disease?
loss of striatal output neurons in indirect pathway
133
What is the rational for treating Huntington's Disease?
· Loss of striatal cells in indirect pathway leads to the suppression of STN · This leads to the dominance of the direct pathway, leading to decreased Basal Ganglia output and an overactive thalamocortical pathway · Overactive thalamocortical pathway leads to excessive involuntary movemnt
134
How can we treat Huntington's Disease?
Symptomatic treatments only: · Tetrabenazine = VMAT inhibitor - decreases Dopamine storage and release · Chlorpromazine – Dopamine receptor antagonists (antipsychotic) Baclofen – GABA-B agonist, decreases spinal reflexes
134
What are other Hyperkinetic disorders of the Basal Ganglia origin? 2
- Hemiballismus | - Tardive Dyskinesia
135
cause and effect of.. - Hemiballismus - Tardive Dyskinesia
- Hemiballismus damage to subthalmic nucleus (from stroke) violent flailing movement of limbs - Tardive Dyskinesia long term exp to antipsychotics (DRAnt.. inc sensitivity?) uncontrolled movement esp facial, trunk muscles
136
dopamine therapy in PD can also ->?
acute dyskinesia | uncontrolled movement esp face + trunk muscles
137
what does deep brain stimulation for PD target?
subthalmic nucleus... - neurosurgical procedure involving the placement of a medical device called a neurostimulator.
138
L: Drugs used in movement disorders What drugs can be used to treat Parkinson's Disease? 3
- Dopamine replacement agents (L-DOPA) - Dopamine agonists - Dopamine breakdown inhibitors (MAO-B inhibitors) Non of these treatments · address the underlying degeneration of dopamine
139
How can L-DOPA cause an increase in (Nor)adrenaline production
L-DOPA is metabolised -> Dopamine via DOPA-carboxylase in the dopaminergic neuron Dopamine metabolised -> NAd via Dopamine-Beta-hydroxylase enzyme NAd then broken down into adrenaline
140
What is the function of carbidopa/ benserazide?
- coadministered for inhibition of DOPA-decraboxylase - stops conversion to dopamine in the periphery - Lack of dopamine slows the production of Noradrenaline from that dopamine
141
how does an enzyme inhibitor (carbidopa/ benserazide) restore normal movements?
inhibits LDOPA-> dopamine (DOPA decarboxylase allow brain to pick up LDOPA + make more dopamine ☺ p638
142
What is a Disadvantage of L-DOPA as a treatment for Parkinson's?
- effectiveness ⬇ over 2-5 years ⬆ dose frequency can cause: - ON-OFF effect (sudden transitions between symptom relief and hypokinesia) - dyskinesias (involuntary writhing movements)
143
Why does the effectiveness of L-DOPA decrease over time?
⬇ in dopaminergic nerve terminals therefore ⬇ capacity to convert L-DOPA to Dopamine
144
When using Dopamine Agonists, which receptors should we target ideally? 2 examples
- D2 recepetors | - examples are Pramipexole / Ropinirole
145
What is apomorphine and when is it used?
- a dopamine agonist | - reserved for advanced stage PD and ‘OFF’ L-DOPA episode treatment
146
What are some drawbacks of Dopamine agonists?
- Nausea/emetic effects (especially apomorphine) - Psychotomimetic effects (schizophrenic symptoms)
147
What are the other alternatives to Dopamine Agonists/ L-DOPA? - MAO-B inhibitor - dopamine releaser - Muscarinic ACh Receptor antagonists
- Selegiline = MAO-B inhibitor selectively elevates [DA] - Amantadine = dopamine releaser - Benzhexol = Muscarinic ACh Receptor antagonists (offsets local circuit consequences of DA deficiency on cholinergic striatal interneuron)
148
Can alternatives be used with L-DOPA?
yes or alone
149
How does deep brain stimulation work?
- sends electrical impulses, through implanted electrodes, to specific targets in the brain (the Subthalamic nucleus). - This makes the STN overactive and shuts it down – Increased stimulation of the STN increases the inhibitory outflow from the Substantia nigra Regulata on the thalamus - This is used for treatment of movement disorders (Parkinson's disease) p640
150
What are the symptoms of Huntington's Disease
- Tremors - clumsiness - memory loss - mood changes - poor concentration
151
What are the treatments for Huntington's Disease?
- There are no known drugs available for treating this disease - there is only symptomatic treatment o Tetrabenazine = VMAT inhibitor - decreases Dopamine storage and release o Chlorpromazine – Dopamine receptor antagonists (antipsychotic) o Baclofen – GABA-B agonist, decreases spinal reflexes
152
What are the treatments for Huntington's Disease?
no known drugs available, only symptomatic treatment o Tetrabenazine = VMAT inhibitor - decreases Dopamine storage and release o Chlorpromazine – Dopamine receptor antagonists (antipsychotic).. ⬇ DA influence on motor circuits, good for symptoms o Baclofen – GABA-B agonist, ⬇ spinal reflexes