The tremor of Parkinson's Disease is characterized by involuntary, rhythmic and alternating movements of one or more body parts. Typically, Parkinsonian tremor occurs at rest and is suppressed during voluntary movement, and is rhythmical, with a frequency of 4–10 Hz.
The basal ganglia are responsible for the planning, initiation, sequencing and smooth coordination of muscular activity. Normal movement involves changes in posture, maintenance of balance, and mechanisms that place the limbs and fingers precisely where they are needed. In some of the above disorders, postural elements may be present.
The basal ganglia project heavily to the pre-motor and supplementary motor areas of the cerebral cortex. Lesions of these cortical areas lead to a lack of motivation and difficulty in initiating movements. Some features of disorders of the basal ganglia may also be mediated by reticulo-spinal pathways.
Treatments include drugs such as dopamine agonists, as well as deep brain stimulation of the globus pallidus, subthalamic nucleus or thalamus.
The Basal Ganglia: Corpus Striatum, Globus Pallidus, Substantia Nigra, Subthalamic Nucleus
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Tremor in Parkinson's Disease, relieved by deep brain stimulation.
Origin of Tremor and Rigidity
One of the major roles of the basal ganglia is not only to initiate movements but to produce a smooth sequence of movements.
The reciprocal nigro-striatal and pallido-subthalamic connections have opposing effects on movement, and the balance between the two generates smooth movements. Lesions of either set of receiprocal connections leeds to a movement disorder.
Lesions of the substantia nigra give rise to Parkinsonian Tremor, while lesions of the subthalamic nucleus give rise to Hemiballismus.
In Parkinson's Disease, the tremor occurs at rest and is suppressed during voluntary movement; it is rhythmical, with a frequency of 4–10 Hz.
The tremor of Parkinson's disease is believed to be associated with excessive inhibitory output from the basal ganglia to the thalamus. In contrast, hemiballismus is associated the a reduction in this inhibitory output.
Patients with Parkinson's disease have abnormalities of movement, behaviour, learning, and emotions. Motor symptoms such as tremor, bradykinesia and rigidity, may involve different pathways from those involved in the emotional and cognitive consequences of the disease.
The basal ganglia appear to be important in organising the temporal and spatial pattern of movements generated by the motor cortex, and the deficiency of dopamine in the striatum in patients with Parkinson's Disease alters these patterns.
In addition to the mechanisms utilising the motor cortex, bradykinesia may also involve bulbo-spinal pathways. The changes in muscle tone in Parkinson's Disease - Parkinsonian rigidity - may be attributed to the reticulo-spinal pathways originating in the brainstem.
Psychiatric features in Parkinson's disease include apathy, anxiety, and depression and may be associated not only with deficiency of dopamine, but also other amines.
Effects of Dopamine Deficiency on Direct and Indirect Pathways
There are two pathways between the striatum and GPi : Direct and Indirect.
Both pathways exert their effects by converging on GPi neurones that release GABA in the thalamus.
Both are excited by the glutamatergic input from pre-motor and supplementary motor areas, but they respond differently to dopamine.
These two pathways have opposing effects on the thalamic nuclei,
because of the different ways they respond to dopamine release from nigro-striatal neurones, and
because GPi neurones in the direct pathway are disinhibited (i.e. less inhibitory GABA-ergic influence), whereas the GPi neurones in the indirect pathways have excitatory glutamergic inputs from the Subthalamic nucleus.
As a consequence the activity of GPi neurones in the direct pathway are facilitated and those in the indirect pathway are inhibited by dopamine.
Lack of dopamine within the striatum in Parkinson's disease reduced the normal disinhibition in the direct pathway, so the balance changes in favour of the inhibitory effects of the indirect pathway.
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The diagram shows the main pathways through the basal ganglia and changes in activity in Parkinson's Disease.
Parkinson's Disease and Neural Circuitry
The diagram shows dopaminergic neurones in the substantia nigra that degenerate in Parkinson's Disease. The deficiency of dopamine in the striatum (Caudate and Putamen) causes changes in the output of the striatum.
The indirect pathway through the globus pallidus to the subthalamic nucleus has increased activity, and the direct pathway from the striatum to the globus pallidus is diminished.
The increased GABAergic output of the globus pallidus interna causes increased inhibition of the thalamic nuclei, and consequently decreased excitatory input to the motor cortex.
Deep Brain Stimulation (DBS) is a technique that uses electrical stimuli to the globus Pallidus, subthalamic nucleus or thalamus of patients with Parkinson's Disease to help control Parkinsonian symptoms. DBS is preferable to lesions of the globus pallidus (pallidotomy), as it is more versatile, does not do permanent damage to the brain, and can be varied as the disease progresses. See http://emedicine.medscape.com/article/1965354-overview for a recent review.
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The diagram shows the main pathways through the basal ganglia and cerebellum and their connections to the executive pathways that control movement.
The bottom half of the diagram shows the spinal cord controlling muscles via alpha motoneurones. Sensory Receptors feedback information to higher levels of the brain as well as mediating spinal reflexes.
The thalamus is an integrating centre that receives information about the position of limbs and objects that might be touching the skin.
The thalamus is also an essential relay station for feedback of information from both the cerebellum and basal ganglia.
The basal ganglia intitiate movements that are organised and sequenced by the premotor cortex, and executed
by the motor cortex using its connection to motoneurones - the cortico-spinal (pyramidal) tract, and
the premotor cortex and its connections to bulbospinal pathways that control muscle tone and posture.
The cerebellum monitors any deviation from the command signal and relays it back to the cortex.
Extrapyramidal pathways (i.e. not the corticospinal - pyramidal - tract) originate in the brainstem and are involved in postural changes and balance.