1. UofR: Neural Basis of Cognition
Lecture 4
Motor Control, Part II
Motor Disorders

2. Motor Disorders
As we saw in the last lecture, motor control is a complex system
There are many ways in which motor control can be disrupted or damaged
We will go over some of these ways
First, a brief review of basic synaptic transmission

3. Synaptic Transmission

4. Synaptic Transmission

5. Parkinson’s Disease
Damage to dopaminergic neurons of the substantia nigra
May result from
Encephalitis
Example: encephalitis lethargica (aka von Economo’s encephalitis) of the 1910s and 1920s
Toxins
Example: adults in their twenties and thirties in the mid 1980s developed Parkinson’s due to use of a synthetic heroin, MPTP, which the body converts into methylphenylpyridinum MPP+, which is toxic to dopaminergic neurons (“frozen addicts”)
Trauma
Neural degradation

6. Parkinson’s Disease

7. Parkinson’s Disease
Symptoms are not evident until 60% of nerve cells and 80% of dopamine has been lost
This is due to the brain’s high ability to compensate through upregulation of dopamine production and other mechanisms
Generally around years of age, compensation mechanisms fail and behavioral effects are observed

8. Parkinson’s Disease
Usually observed bilaterally (unilateral Parkinson’s is called “hemi-Parkisonism”)
Symptoms:
Tremors
Generally of the arms and hands, at rest (“pill rolling”)
Rarely seen during deliberate movements
Cogwheel rigidity
Increased muscle tone in the extensor and flexor muscles
Term refers to mechanical nature of movements

9. Parkinson’s Disease Symptoms: Akinesia or bradykinesia
Akinesia: poverty of movement
Bradykinesia: slowness of movement
“Parkinsonian mask”
Disturbances of posture
Affects muscle groups throughout the body
Occurs due to difficulty counteracting force of gravity
Walking, recovering from loss of balance, postural transitions, &c. become difficult
Patients tend to shuffle

10. Parkinson’s Disease
Not all symptoms are typically observed in each person
Rigid-bradykinetic-predominant form versus tremor predominant form
Forms also differ in degree of intellectual impairment and clinical course of disease
These may be less severe in patients with the tremor predominant form

11. Parkinson’s Disease
Overactivation of the cholinergic system is associated
How would one treat Parkinson’s?
First, dopamine synthesis

12. Dopamine Synthesis

13. Dopamine Synthesis

14. Parkinson’s Disease
DA cannot be administered orally because it does not pass the blood-brain barrier
Tyrosine is before the slow step in DA synthesis (and is already plentiful in a normal diet)
L-DOPA is therefore used
Anticholinergic compounds help alleviate overactivity of the cholinergic system

15. Parkinson’s Disease Experimental (and controversial) treatments:
Grafting of fetal tissue with dopamine-producing cells to the substantia nigra
Demonstrated in monkeys
Varying success in human trials
Pallidotomy (destruction of globus pallidus) to reduce tremors
Implantation of electrodes to artificially produce simulation in the subthalamic nuclei (which inhibit the GP)

16. Huntington’s Disease Caused by degeneration of the striatum Symptoms:
Difficulty initiating movements
Abnormal speed, initiation of voluntary eye movements
Abnormal movements (chorea)
Cognitive deficits (eventually dementia)
Psychiatric symptoms
Inherited
Gene remains dormant until years of age, followed by slow decline of years and ending in death
No cure or established treatment of symptoms

17. Huntington’s Disease
Degree of atrophy of caudate has been directly linked to eye-movement abnormalities, disruptions on tests requiring writing speed, tests of complex psychomotor processing, severity of cognitive empairment, but not with the severity of chorea
Starkstein, S. E., J. Brandt, et al. (1988). "Neuropsychological and neuroradiological correlates in Huntington's disease." J Neurol Neurosurg Psychiatry 51(10):

18. Tourette’s Syndrome Symptoms: More severe symptoms:
Tics: typically involve face and head, can affect limbs and the entire body
Complex movements such as touching, hitting, jumping, can occur
More severe symptoms:
Cries and vocalizations
Echolalia: repeating what was just said
Coprolalia: obscene speech
Seen in childhood, usually before age of 11

19. Tourette’s Syndrome Much more common in males
Also associated with obsessive-compulsive behavior (50% of children show some symptoms, 25% have full-blown OCD)
People with Tourette’s say that trying to suppress a tic makes the urge to do it become stronger and stronger until carried out
Some association with ADHD as well

20. Tourette’s Syndrome Cause isn’t known Evidence:
Linked to ADHD and OCD
Drugs that increase DA levels aggravate symptoms
Drugs that block DA receptors ameliorate symptoms
Homovanillic acid (HVA), a metabolite of DA, found at lower levels
Therefore it is believed that Tourette’s is caused by dysfunction of the dopaminergic system, largely comprised of the basal ganglia, specifically by hypersensitivity to DA
Treatment usually involves blocking of D2 receptors with drugs such as haloperidol, which reduces vocal tics in 85% of patients
Few patients stay on haloperidol due to unpleasant side effects
Treatments:
Leckman, J. F. and M. A. Riddle (2000). "Tourette's syndrome: when habit-forming systems form habits of their own?" Neuron 28(2):

21. Tourette’s Syndrome

22. Tourette’s Syndome

23. Tardive Dyskinesia
Occurs in 20-40% of long-term conventional antipsychotic drugs that act to block dopamine
Symptoms: Increased motor movements that affect the face, especially the mouth and lips, sometimes the trunk and limbs, including:
Chorea
Tics
Akathisia (compulsive, hyperactive, “fidgety” movements of the legs)
Dystonia (painful, sustained muscle spasms of the same muscle groups, frequently causing twisting and repetitive movements or abnormal postures)

24. Tardive Dyskinesia
Identifying which individuals on anti-psychotic medications will exhibit tardive dyskinesia is nearly impossible because the symptoms appear after at least three months of drug use
Lowering dosage completely eliminates the problem in only ~30% of patients (and lower dosages may not be enough to treat psychotic behavior)
New antipsychotic treatments that do not block D2 receptors like traditional antipsychotics

25. Cortical Motor Disorders
Most subcortical disorders involve bradykinesia , akinesia, or some form in increased movement
Cortical motor disorders have a different effect, tending to disrupt the ability to pursue specific plans of motor action or to relate motor action to meaning

26. Alien Limb Syndrome Symptoms: For more examples:
Patients feel as if one of their limbs is “alien” –it seems to move on its own, seems as though it doesn’t “belong” to its owner, or seems to have its own “personality”
Patients commonly complain that their limbs do not obey them or that they make involuntaryand complex movements, typically groping and grasping
Competition between hands or difficulty in bimanual control
For more examples:
Leckman, J. F. and M. A. Riddle (2000). "Tourette's syndrome: when habit-forming systems form habits of their own?" Neuron 28(2):
In almost all cases, only one limb, contralateral to a site of lesion, is affected

27. Alien Limb Syndrome
No consensus on what type of damage causes alien limb syndrome
Usually observed after infarction (blockage of blood vessel) in territory of the anterior cerebral artery, the anterior two thirds of the corpus callosum, and the anterior cingulate cortex
Damaged areas of the frontal cortex tend to invlude the SMA

28. Alien Limb Syndrome No cure Treatments:
Keeping the limb “busy” with repetitive action or with holding an object
Muscle relaxation
Warm water to “calm” the limb
Issuing verbal commands to the limb

29. Apraxia
Apraxia: an inability to perform a skilled, sequential, purposeful movement, that cannot be accounted for by disruptions in more basic motor processes such as muscle weakness, abnormal posture or tone, or movement disorders
Evidence that apraxias are a higher-order motor deficit:
Usually bilateral
Low-level motor processes are intact
Complex movements can be performed spontaneously but not purposefully
Classification of apraxias is a subject of debate; one approach is by the part of the body affected

30. Apraxia Oral apraxia Limb apraxia
difficulty performing voluntary movements with the tongue, lips, cheek, larynx (clearing one’s throat, yawning, sticking out one’s tongue, sucking on a straw can be impaired)
Limb apraxia
Difficulty manipulating items and tools
When asked to imitate manipulation of an object, a patient may use a limb to represent that object, e.g. stirring a cup of water with a finger when asked to imitate using a spoon

31. Apraxia Alternative classification scheme, due to Lipemann in 1905:
Ideational (conceptual) apraxia: inability to form an “idea” of a movement, so a person cannot determine which actions would be necessary and in what order they should occur.
Example: cannot light a candle due to inability to sequence the necessary events
Ideomotor apraxia: disconnection between the idea of a movement and its execution
Abstract though simple actions such as waving “hello” would be impaired
Complex sequences of moves can still be performed
There is debate on how, exactly to differentiate between these two classifications

32. Apraxia Underlying cause is unclear Sequencing of motor acts?
Understanding of abstract meanings of motor acts?
Linkage between visual/kinesthetic cues with motor plan?

33. Apraxia Other varieties of apraxia, related to spatial understanding
Constructional apraxia: items cannot be correctly manipulated in regard to their spatial relations, e.g. wooden blocks cannot be manipulated to copy an arrangement created by someone else
Dressing apraxia: difficulty manipulating and orienting both clothes and limbs so that clothes cannot be put on correctly
Generally observed after right hemisphere lesions and often associated with spatial-processing difficulties and hemineglect; thus, often considered to be motor manifestations of visuoconstructive disorders

34. Apraxia Other apraxias can occur from disconnection syndrome
Callosal apraxia: inability to perform movements or manipulate objects with the left hand in response to verbal commands due to damage to the corpus callosum
Verbal instructions are understood via Wernicke’s area and translated into a motor plan in the left hemisphere, but the motor plan cannot be relayed to the right hemisphere to control the left hand

35. Motor control
Neural control of motor actions is a very complex system that is highly regulated and integrates many different areas of the brain
There are many ways in which normal motor control can be disrupted, sometimes in very strange and unusual ways
As our understanding of motor control increases, treatments improve
Motor control also involves a huge amount of work done by other portions of the brain, especially relating to the various sensory modalities and our understanding of the world; these will be subjects for further discussion.