(Transcribed from Dr. Glasser’s lecture, 31 May 2000 by Brian Buschman)
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The basal ganglia are responsible for extrapyramidal muscle control (i.e. not associated with the corticospinal tract). The function of the BG I to modify pyramidal output yet the BG are extrapyramidal. Hence a BG legion is an extrapyramidal legion.
As we already know the lentiform nucleus is made of the putamen and the globus pallidus (GP). The GP is broken into the GP intenus (GPI) and GP externus (GPE). Other functional BG include the subthalamus, caudate and the substancia nigra (SN). The SN is divided into the SN pars compacta (SNPC) and SN pars reticularis (SNPR). The SNPR functionally resembles a portion of displaced GP.
The BG function to suppress unwanted motor behavior. It is the site where fragments of learned movements are remembered and transmitted to the motor cortex for assembly and execution. Legions of the BG will result in hyperkinetic syndrome.
Legions of the straitum (caudate and putamen) will cause choreiform movements which are small involuntary jerky movements. They resemble isolated fragments of a whole movement. Choreiform movements cannot be controlled, decrease with sleep and increase with stress. (It’s amazing that all of us here don’t have an abundance of them.)
Hunington’s chorea is an autosomal dominant atrophy of the straitum, especially in the caudate nucleus that begins around mid-life. It results in choreiform movements and progressively degenerates. The only cure is death and many patients end up killing themselves.
Sydenham’s chorea is due to rheumatic fever from streptococci infection. The infection leads to microscopic hemorrhages in the straitum. It is usually acute with complete recovery.
Wilson’s disease is an autosomal recessive disease characterized by an inability to properly metabolize copper in the liver. It results in deposits in places including the brain. In particular it gives a Kaiser Fletcher ring which is a copper deposit in the sclera.
Dystonia is sustained muscle contractions that lead to abnormal posture or a twisting of the next, trunk or limbs.
Athetosis is a type of dystonia characterized by large writhing movements of the face, neck or trunk. Is is much worse then dystonia. It increases with stress and again decreases with sleep.
Damage to the BG, specifically the putamen, causes Tourette’s which presents with uncontrolled writhing movements and inappropriate verbal behavior.
Legions of the subthalamus cause hemi-ballismus which are large contralateral movements involving a limb or an entire side of the body. They disappear when the patient is asleep.
Legions of the substancia nigra cause Parkinson’s disease which is directly caused by a decreased dopamine level. The patient will present with a resting tremor (“pill role”). It only exists at rest as some surgeons have been able to continue practice with Parkinson’s. It also causes muscle rigidity which can be classified into two groups:
1) With a tremor. This is “cog-wheel rigidity” characterized by a small rigidity, a small amount of movement and then another point of rigidity.
2) Without a tremor. This is “led pipe rigidity” characterized by a large point rigidity. It is different from spactity because rigidity resists both flexion and extension while spactity only resists one or the other.
Patients will also demonstrate bradykinesia, a difficulty initiating movements, or akinesia, an inability to initiate movements. It is associated with paucity, a lack of movement. They also present with a mask like face (from lack of movement).
Parkinson’s is associated with a dopamine shortage, primarily in the substancia nigra (the primary source of dopamine in the body). Symptoms do not appear until about 80% of the domaminergic neurons have already been damaged and the disease is progressive.
You cannot treat with dopamine because it will first be degraded by plasma enzymes and second does not cross the blood brain barrier. Instead you can give a combination of L-DOPA and carbidopa. The L-DOPA will cross the blood brain barrier and be converted into dopamine. The carbidopa will be preferentially degraded by the plasma enzymes allowing L-DOPA to actually make it into the brain.
The prognosis is poor since the disease is progressive. You will constantly have to up the dosage of the drugs to treat the patient. There is a new alternative treatment that is being studied. If has been found that if you place a piece of fetal adrenal medulla into the substancia nigra of a Parkinson’s patient it will provide enough dopamine to effectively treat the disease.
The general rules of the BG is that all input is through the straitum and all output is from the GPI.
The thalamus is excitatory to the cortex and is held in check by the GP.
The cerebral cortex stimulates the straitum. The straitum functions to inhibit the GPI. The GPI normally functions to inhibit the thalamus but the straitum disinhibits the thalamus by inhibiting the GPI. When the thalamus is disinhibited it will then stimulate the cerebral cortex to cause the movement. This is the central circuit that you must understand to grasp the variations in BG function. There are three sub-loops off of this central pathway of the BG.
The substancia nigra plays a role in the first sub-loop of the BG system. It is primarily composed of two opposing tracts:
1) Straitonigral tract – The straitonigral tract is a two neuron system where the first neuron is excitatory via ACh and the second inhibitatory via GABA. The straitonigral tract runs from the straitum to the SNPR. From the SNPR the signal is primarily carried to the SNPC but some fibers run to the reticular formation of the brain stem or are inhibitatory to the thalamus (via GABA).
2) Nigrostraital tract – The second tract is the nigrostraital tract running from the SNPC to the straitum. It is a single neuron tract that is inhibitory via dopamine.
This system must have a proper balance. If the straitonigral tract dominates, there is too much GABA relative to dopamine, it will cause Parkinson’s. If the nigrostraital tract dominates and there is excessive dopamine relative to GABA the patient will have chorea.
The organic theory of emotional health teaches that mental health is a result of NT balances or imbalances. Different parts of the brain release different NTs and that if the ratios get out of wack you get a “nut case” (to use a technical term). It is shown that the:
- Locus cerulius uses NE as it’s NT.
- Raphe uses 5-HT.
- Midbrain tegmentum uses dopamine.
The current theory believes that if you have:
1) Excess dopamine will cause schizophrenia. Schizophrenia is treated with halidol, a D2 antagonist. It does have a side effect in that it causes tardine dyskenesia which is a set of choreiform movements specifically around the mouth and lower face because of interference with D2 receptors in the straitum. After a few months damage is irreversible and the PT will always have the tardine dyskenesia. Newer antipsychotic drugs function as D4 receptor antagonists. This does not cause tardine dyskenesia because there are no known D4 receptors in the straitum.
2) Shortage of 5-HT causes depression. It is treated with Prozac which is a SSRI (selective seretonin reuptake inhibitor).
The next sub-loop is a simple one, as it provides feedback from the centromedial nucleus of the thalamus to the straitum.
The basic circuit is called the direct circuit and functions in fine low-speed movements. One of the sub-loops is the indirect circuit that functions in large amplitude high-speed movements. This pathway diverges from the direct circuit at the straitum. Rather then go to the GPI it goes to the GPE where it is inhibitatory via GABA. The GPE is inhibitatory to the subthalamus via GABA which stimulates GPI via Glu. At this point it is back along the main circuit.
This is the overall organization of the BG. You will need to add to this diagram which synapses are excitatory and which are inhibitatory.
When we look at the basic circuitry of the BG we see it pass through the thalamus but there are four nucli of the thalamus functionally associated with that circuit.
1) VA – ventral anterior
2) VLA – ventrolateral anterior
3) VLP – ventrolateral posterior
4) MD – mediodorsal
Motor function is initiated in the cortex in area 4;6; 3,1,2 and the signals are passed to the straitum and GPI as usual. From the GPI the signals pass to the VLA and VLP. Signals bound for area 6 (pre and suplamentary motor) will pass from the GPI to the VLA of the thalamus and then on to area 6. Signals that go from the GPI to the VLA are bound for area 4 (primary motor). The anterior nucleus goes to the anterior of the two areas and so forth.
The pathway for cognitive motor behavior is lightly different. It begins in the prefrontal cortex and parietal lobes which send the signals to the caudate on the way to the GPI. From the GPI they go to the VA nucleus of the thalamus and on to areas 6 and 8. Area 8 is the frontal eye fields located immediately anterior to area 6.
In emotional behavior the signals begin in the temporal lobe, amigdilla, or substancia innominata (substance without a name). From there it goes on to the nucleus accumbens (of the ventral straitum) and passes to the ventral pallidum. It will them find it’s way to the MD nucleus of the thalamus and to the prefrontal lobe.
Because of it’s diverse functions in motor behavior the BG are important for:
1) Emotional behavior
2) Learning of movements
3) Memory of movements
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