Movement and Parkinson's Disease Flashcards
Area 6 of the brain contains which two areas which are important in planning motor movement?
Lateral premotor area and medial supplementary area
Movement originates in cortical layer 5 of the primary motor cortex in which pyramidal neuron cells?
Betz cells
The major subcortical input to the PMA and SMA arise from a nucleus of the dorsal thalamus - the ventrolateral nucleus. Where does input to this nucleus arise from?
The basal ganglia
What are the functions of the basal ganglia?
The voluntary selection and initiation of higher functions
scaling the output of motor responses
projects to frontal eye fields to control saccadic eye movements
may have a role in memory relating to body orientation
The caudate nucleus and putamen contain identical cell types. T/F?
True
The corpus striatum of the basal ganglia receives somatotropin information from…?
Motor, sensory, association and limbic areas and the intrealaminar nuclei of the thalamus
What is the name for the connection between the corpus striatum, internal Globus pallidus and thalamus?
Direct pathway
The corticostriate projection is topographically and functionally organised so that the putamen is chiefly concerned with motor control and the caudate nucleus with…?
Eye movements and cognition
There is a bidirectional communication between the sub thalamic nucleus and the internal Globus pallidus. T/F?
False - this bidirectional connection is between the sub thalamic nucleus and the external Globus pallidus
Which part of the substantia nigra projects to the thalamus (ventrolateral and ventroanterior nuclei) to promote thalamus projections to the cortex?
Pars reticulata
Which part fo the substantial nigra projects onto the corpus striatum?
Pars compacta
Describe the direct corticostrital loop?
The corpus striatum inhibits the internal Globus pallidus to reduce the ability of the GPi to inhibit the thalamus. This effectively encourages the thalamus to fire and stimulates the cortex
Describe the indirect corticostital loop?
Corpus striatum output inhibits the external Globus pallidus which reduces the inhibition of the sub thalamic nucleus which then excites the internal Globus pallidus and the pars reticulata of the substantial nigra to inhibit the thalamus. the cortex therefore gets less stimulation
Lesions of the basal ganglia produce extrapyramidal signs. Give examples of these types of signs
Tremor
Rigidity
Dyskinesia
From which amino acid are dopamine, noradrenaline and adrenaline synthesised?
Tyrosine
Which enzyme is involved in the first stage of dopamine synthesis, conversion of tyrosine to L-DOPA (L-dihydroxyphenylalanine)?
Tyrosine hydroxyls
In which areas of the brainstem are dopaminergic neurons located?
Substantia nigra
Ventral tegmentum area
The ventral tegmentum area uses dopaminergic signalling. What is the function of this area?
Circuitry involved in reward, motivation and emotion
The ventral tegmentum is involved in pathways for reward, motivation and emotion. As such, which structures does it project to?
Nucleus accumbens Ventral striatum prefrontal cortex amygdala hippocampus hypothalamus olfactory tubercle
Where in the brainstem are neurons which use noradrenaline as their principal neurotransmitter clustered?
Pons, fourth ventricle and lateral tegmentum
What is the main function of noradrenergic neurons in the CNS?
Modulate attention, arousal, mood and pain
What neurotransmitter is used by the raphe nuclei?
Serotonin
Which amino acid is serotonin produced form?
Tryptophan
What are the functions of serotogenic neurons in the CNS?
Regulation of mood, appetite and pain
modulation of pain, state of wakefulness, aggression and some cognitive functions such as memory and learning
Which enzyme converts L-DOPA to dopamine?
DOPA-decarboxylase
When dopamine is release, about 50% is taken up again and transported into vesicles for storage and release. The remaining dopamine enters the neural terminal and is destroyed by which enzyme?
Monoamine oxidase
When dopamine is released in the synaptic cleft some of the dopamine is taken up again by the pre-synaptic neuron (reuptake 1), some is destroyed by enzymes on the post-synaptic neural terminal and some is taken up by the effector cell (reuptake 2). What percentage of the dopamine released from the pre-syanptic neuron is taken up by the post-synaptic neuron (reuptake 2)?
10%
Which enzyme in the post-synaptic cell degrades dopamine which has been taken up by the cell in reuptake 2?
Catchol-O-methyltransferase
Describe the tuberohypophyseal dopaminergic pathway?
Neurons from the ventral hypothalamus run to the median eminence and release dopamine to inhibit prolactin secretion by the anterior pituitary
Renal vasodilation and increased myocardial contractility in the periphery is mediated by what type of dopamine receptor?
D1
What type of dopamine receptor exists in the limbic system but not in the corpus striatum?
D3
What are the main features of Parkinson’s disease?
Bradykinesia
resting temor
rigidity
postural instability
What is often the first sign/symptom of Parkinson’s disease?
Anosmia
What genes are particularly associated with Parkinson’s disease?
Parkin
synuclein
PINK-1
LRRK2
What environmental factors are particularly associated with Parkinson’s disease?
Exposure to pesticides and herbicides
In Parkinson’s disease there is a loss of the nigrostriatal dopaminergic neurons in which part of the substantial nigra?
Pars compacta
What is the name of the intracytoplasmic eosinophilic inclusions seen in cells of patients with Parkinsons disease?
Lewy bodies
What protein are levy bodies and neuritis (present in Parkinson’s disease) composed of?
Synuclein
Explain how the loss of dopaminergic neurones in the pars compacta of the substantia nigra causes the symptoms of Parkinsons disease?
This causes decreased activity of the direct pathway and increased activity of the indirect pathway causing an increase in inhibitory activity from the internal Globus pallidus and zone reticulata of the substantial nigra to the thalamus which reduces output to the cortex
What are the non-motor symptoms which may be present in Parkinson’s disease?
Depression autonomic dysfunction sleep disorders pain anosmia
How is the face affected by Parkinson’s disease?
It is masked with reduced expression and reduced blink rate
How is the voice affected by Parkinson’s disease?
It is softened and poorly articulated
A finding of clockwork rigidity in an upper limb neurological exam is suggestive of which disease?
Parkinson’s disease
What exercises and activities have been shown to reduce motor symptoms and improve functional status in patients with Parkinson’s disease?
Progressive resistance exercise
Tai Chi
Dance
Why is L-DOPA (the dopamine precursor) rather than dopamine given to treat Parkinson’s disease?
L-DOPA can cross the blood brain barrier, dopamine cannot
L-DOPA rather than dopamine must be given to patients with Parkinsons disease in order to cross the blood brain barrier. How do you stop L-DOPA from being metabolised peripherally which causes side effects?
By co-prescribing carbidopa or benserazide which inhibit dopa decarboxylase (the enzyme which converts L-DOPA to dopamine) but cannot cross the blood brain barrier, so only work peripherally
What are the side effects of L-DOPA?
Nausea and vomiting
Reduced gastric emptying
Dyskinesias
Pyschiatric effects ([sychosis, depression, acute confusional state)
In long term treatment, tolerance to L-DOPA occurs. T/F?
True
Why might ACh antagonists be used in the treatment of Parkinsons disease?
ACh antagonises dopamine so using ACh antagonists may increase dopaminerergic transmission to reduce tremor and rigidity
What drugs are used in severe Parkinson’s disease when L-DOPA is beginning to lose its efficacy to reduce the rate at which dopamine is degraded and therefore potentiate the effects of L-DOPA?
Monoamine oxidase B inhibitors such as selegiline
Direct dopamine agonists can be used in Parkinsons disease as they mimic the effects of dopamine but do not mimic the normal conditions in which dopamine is release din the striatum. Give an example of this type of drug
Bromocriptine
In addition to standard treatments such as L-DOPA, ACh antagonists, MOBI inhibitors and dopamine agonists, what newer treatments may be used in Parkinson’s disease?
Neurosurgery to ablate the hyperactive internal Globus pallidus
placement of electrodes for deep brain stimulation to depress the function of the internal Globus pallidus and pars reticulata of the substantial nigra
implantation of dopamine rich material from foetal tissue
What is declarative memory?
Responsible for factual information and life events, is available to consciousness
What is non-declarative memory?
Involved in motor skills, not available to consciousness
Ballistic movements are based on a set of pre-programmed instructions. Why are these movements rapid but not always accurate?
There is little opportunity for compensation for unexpected changes
Give an example of a ballistic movement
Returning a tennis serve
Swatting a fly
What allows pursuit movements to be more accurate than ballistic movements?
Motor commands are continually updated according to sensory (usually visual) feedback
Imaging studies show activity in the SMA, M1 and S1 during a finger movement but only activity in which area when the movement is mentally rehearsed without actual movement?
SMA
What is the function of the basal ganglia?
Initiating movement
Planning voluntary movement
Motor learning
What are the symptoms of Huntington’s disease?
Chorea
Difficulty speaking and swallowing
Progressive general cognitive decline
Huntington’s disease is an inherited disease of the basal ganglia. What kind of genetic mutation causes this?
Triple repeat
What is the function of the cerebellum?
Coordinate and smoothly execute movements
Motor learning
Error detection
What type of motoneuron innervates skeletal muscle fibres?
Alpha motoneuron
What is a motor unit?
A motoneuron and the muscle fibres which it innervates
How is the strength of muscle contraction graded?
By the recruitment of motoneurons
Which part of the cerebellum projects to the fastigial nucleus?
Vermis
Which part of the cerebellum projects to the dentate nucleus?
Lateral hemispheres / cerebrocerebellum
Which part of the cerebellum projects to the interposed nucleus?
Medial hemispheres
The cerebellum consists of the cerebellar cortex and the three deep cerebellar nuclei. Name these nuclei?
Dentate nucleus
Interposed nucleus
Fastigial nucleus
Which part of the cerebellum is extensively connected with the vestibular system?
Flocculonodular lobe
What is the function of the cerebrocerebellum?
To plan the details of movements
What is the function of the medial hemispheres of the cerebellum?
To compare planned movements to actual movements and initiate corrective signals
How does information form the cerebral cortex travel to the cerebrocerebellum?
Pathway from the cerebral cortex descends through the internal capsule, accompanies corticospinal tract in the cerebral peduncles to the pontine nuclei. Pontocerebellar fibres then cross the midline and reach the cerebral cortex via the middle cerebellar peduncle where they are relays to the dentate nucleus of the cerebrocerebellum
Through which cerebral peduncle do dentothalamic fibres (from the cerebrocerebellum travelling to the thalamus) leave the cerebellum?
Superior cerebellar peduncle
The dentothalamic fibres sometimes give off collaterals to which nucleus?
red nucleus
Describe the input to the medial hemispheres of the cerebellum and how this allows the cerebellum to compare intended movement to actual movement?
Receives input from the cerebral cortex via the pontine nuclei and also from the limb areas of the primary motor cortex which it uses to form a somatotopic map
superimposed on this map is input from the spinal cord via the spinocerebellar tracts which convey proprioceptive info
this allows comparison of intended and actual movement
Describe the pathway by which corrective signals are issued from the medial hemispheres of the cerebellum.
Corrective feedback travels from the interposed nucleus back to the thalamus through the superior cerebellar peduncle. Along the way some fibres give off collaterals to the red nucleus which gives rise to the rubrospinal tract
What is the function of the vermis of the cerebellum?
Automatic postural adjustments made before and during limb movements
Input to the vermis of the cerebellum is via the pontine nuclei and spinocerebellar inputs to form a somatotropin map. How is output from the vermis arranged?
Outputs project from fastigial nucleus bilaterally to the vestibular nuclei and reticular formation
