UofR: Neural Basis of Cognition
Lecture 4
Motor Control, Part II
Motor Disorders
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
Synaptic Transmission
Synaptic Transmission
Parkinson’s Disease
• Damage to dopaminergic neurons of the substantia
• 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
Parkinson’s Disease
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 60-70 years of age,
compensation mechanisms fail and behavioral
effects are observed
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
• Term refers to mechanical nature of movements
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
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
Parkinson’s Disease
• Overactivation of the cholinergic system is
• How would one treat Parkinson’s?
• First, dopamine synthesis
Dopamine Synthesis
Dopamine Synthesis
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
• L-DOPA is therefore used
• Anticholinergic compounds help alleviate
overactivity of the cholinergic system
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)
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 30-45 years of age, followed
by slow decline of 10-15 years and ending in death
• No cure or established treatment of symptoms
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): 1259-63.
Tourette’s Syndrome
• 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
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
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 habitforming systems form habits of their own?" Neuron 28(2): 349-54.
Tourette’s Syndrome
Tourette’s Syndome
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)
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
• New antipsychotic treatments that do not block
D2 receptors like traditional antipsychotics
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
Alien Limb Syndrome
• Symptoms:
– 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): 349-54.
• In almost all cases, only one limb, contralateral to a site of
lesion, is affected
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
• Damaged areas of the frontal cortex tend to
invlude the SMA
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
• 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
• Oral 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
• 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
• Complex sequences of moves can still be performed
• There is debate on how, exactly to differentiate between
these two classifications
• Underlying cause is unclear
– Sequencing of motor acts?
– Understanding of abstract meanings of motor
– Linkage between visual/kinesthetic cues with
motor plan?
• Other varieties of apraxia, related to spatial
– 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
– 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
• Other apraxias can occur from disconnection
• 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
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.

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