ISBN
978-3-00-037458-6
ISBN 978-3-00-042153-2
Although still relatively poorly understood, deep brain stimulation is sometimes used successfully in basal ganglion disease. This section attempts to analyze the various circuit-related causes of basal ganglion disease. It is not possible to assess here what caused these circuit changes. But it can be shown which circuit changes lead to which problems and how these can be influenced by deep brain stimulation. In particular, it will be shown that deep brain stimulation can cause undesirable side effects in certain cases over the long term.
In the course of this section, it will also be clarified which tasks the projection paths in the basal ganglia model in sketches 2.1 and 2.2 have which have not been discussed so far.
First of all, the faultless functioning of the basal ganglia depends on an inconspicuous neuron nucleus, whose activity makes all subsequent activities possible. This key nucleus is the nucleus subthalamicus. According to theorem 1.5, the nucleus sub-thalamicus is a positive single-signal nucleus.
Let's recap: All signal neurons of a cortex cluster excitably project onto a mean neuron of layer V of the cortex cortex of the cluster. The mean value neurons of larger contiguous cortex areas project excitatory into the nucleus subtha-lamicus on a second stage mean value neuron, which generates a continuous signal from this input. This permanently active signal is our single signal. It represents the (usually always present) mean excitation of a larger cortex area out of many small cortex clusters.
This single signal is needed for the negation of the signals of the signal neurons of the cortex, but the mean signals are also negated with the help of the single signals of the nucleus subthalamicus.
As a reminder, we list here the individual negation nuclei that require an exciting input from the nucleus subthalamicus:
- Globus pallidus interna in the striosome system, generates the climbing fibre signals of the magnocellular system
- Nucleus pedunculopontinus in the striosome system, generates the input for the Ramacher resolution pyramid
- Globus pallidus externa in the matrix system, necessary for the second negation of the elementary signals of the cortex cluster
- Substantia nigra pars reticulata in the matrix system, necessary for the third negation of the elementary signals of the cortex cluster
- Nucleus pedunculopontinus in the matrix system, required for the fourth negation of the elementary signals of the cortex cluster on their way to the thalamus VA/VL
Thus, a failure of the averaging and thus of the single signal generation in the nucleus sub-thalamicus has devastating consequences in the basal ganglion system. There is no need to generate climbing fiber signals for relearning complex signals and also no ability to bind different but related objects to one unit.
The cognitive ability of object recognition based on reduced images within the resolution pyramid is also no longer required.
Likewise, the elementary signals from the primary cortex cannot reach the secondary clusters in the cortex or the primary clusters in the cerebellum assigned to them, since they are no longer formed at all due to the omission of the necessary fourfold negation. However, the system of associative matrices in the cerebellum is thus no longer available, nor is the ability to detect time in the secondary cortex cortex. The latter, i.e. the recognition of temporally coherent signal sequences, is greatly reduced and initially has very clear effects with regard to the execution of coherent movements. Therefore, motor disturbances - a freezing of the system - are the first serious signs of the failure of the function of the subthalamic nucleus.
It's like a computer. The failure of the single signal formation in the subthalamic nucleus is comparable to the failure of the clock frequency of a computer. The computer is freezing!
However, the loss of the time-delayed signals also leads to cognitive deficits, since now-more time-related sequences or signals cannot be learned anew. Likewise, already learned time sequence signals cannot be properly recapitulated. The memory suffers as well as the ability to relearn. And all because of the failure of the permanent excitation - the neuronal input signal - in the subthalamic nucleus.
Therefore, a quite understandable treatment approach in this specific case is the artificial delivery of an excitatory continuous signal to the subthalamic nucleus. For this purpose, an electrode is implanted into the patient's brain, which stimulates the subthalamic nucleus with a suitable electronic frequency. This procedure is called deep brain stimulation and is not limited to the core area of the subthalamic nucleus. It is noticeable that mainly the core areas of the basal ganglia system are selected for deep brain stimulation.
Thus, if the author's basal ganglia theory is correct, deep brain stimulation of the subthalamic nucleus will be particularly useful if the single signal formation in the subthalamic nucleus is too weak or has failed partially or completely.
A possible cause in this case is the absence of signals from the mean neuroma in layer V of the cortex cortex. Whether these neurons have lost their output capacity or whether the range of action potentials of these neurons has been greatly reduced by possible demyelination can only be determined on site in the patient himself. This monograph provides only the theoretical analyses of the effect of circuit disturbances within the basal ganglia system. So let us summarize the first findings in a new theorem:
If the single signal formation in the subthalamic nucleus is disturbed or failed, the resulting disturbances in the work of the basal ganglia can be reduced by deep brain stimulation of the subthalamic nucleus.
The average frequency of the different single signals of the subthalamic nucleus depends on the average activity of the assigned cerebral cortex regions. This cannot (currently) be taken into account when external signals are applied.
In sketch 2.1 of the striosome system there is a hitherto unexplained exciting projection of the nucleus centromedianus (3) to the striosomes (2). What task has nature assigned to this projection?
The cortex is not always active. There are phases of less activity, e.g. during physical rest or sleep. But also a serious illness - e.g. a coma - reduces the activity of the cortex considerably. There are failures in the activity of the cerebral cortex due to accidents or illness, and chemical substances can also paralyse the cerebral cortex.
In all these cases, the nucleus subthalamicus receives hardly any excitatory mean value signals from the cortex. Therefore, its single signal fails or becomes too weak in some areas. Then the vital system clock of the brain would come to a standstill.
Nature has provided for these cases: An exciting influx of signals from the nucleus centromedianus to the striosomal neurons and also to the substantia nigra pars compacta restores the system to normal. Therefore, deep brain stimulation of the nucleus centromedianus in coma patients can have positive results.
In this case, however, no continuous electronic signal (single signal) may be fed into this nucleus, but only the neuronal system clock as it is generated in the oscillating circuit system of the striosomes. This is because a continuous signal would lead to the uninterrupted generation of action potentials in the neurons of the striosomes. Their uninterrupted firing would permanently inhibit the substantia nigra pars compacta. This would cause the neuronal system clock of the striosome system to collapse completely. Therefore, only a neural system clock as shown in sketch 1.19 may be used here via deep brain stimulation.
Nature has recognized this problem and as a precautionary measure has switched an inhibitory connection from Globus pallidus interna (5) to Thalamus centromedianus (3). This means that an uninterrupted flow of centromedian input to the striosomes is always interrupted exactly when it is undesirable and would disturb the striosomal system clock. The loss of these inhibitory connections could be a circuit error that leads to a continuous inhibitory signal from the striosomes to the substantia nigra pars compacta and causes the striosomal system clock to break down. If the nucleus centromedianus is artificially inhibited, it should be noted that this inhibition must be periodic and time-delayed in relation to the activity of the substantia nigra. An external excitation of the centromedianus must also be periodic and precise, whereby the basic rhythm is determined by the substantia nigra pars compacta. The substantia nigra pars compacta is partially autoexcited due to the dendrodendritic coupling of the dopaminergic neurons and is subject to the striosomal system clock in its activity.
There is an analogy in the matrix system (sketch 2.2). If the cortex (1) does not provide enough excitation for the main neurons of the matrix (2), an attempt is made to compensate for this. In this case the thalamus VA/VL (3) then provides the excitation input so that the main neurons of the matrix can form their necessary single-signal excitation. To keep the system stable, the substantia nigra pars reticulata inhibits the thalamus VA/VL.
The additional supply of exciting signals from the thalamus and an additional recurrent inhibition of this thalamus causes additional feedback in the system, which can lead to the formation of resonances. This causes additional natural oscillations of the system - usually in the case of circuit disorders - which are referred to in neurology as tremors. A natural oscillation which is wanted and specially invented by nature is the striosomal system clock, which is the basis for the generation of the magnocellular climbing fibre signal.
Any return of a signal to one of its origins can thus generate natural resonances, which are also reflected in real oscillations that are impressed on the system in addition to the normal signals.
As different signals within the nervous system are fed back to their places of origin via different feedback paths, with different time delays of the action potentials concerned, different types of tremor occur. Usually the feedback is caused by recurrent inhibition of the original excitatory signals.
Of course, with regard to deep brain stimulation, an external input signal can be injected into any nucleus that normally receives its input signal excitation from the subthalamic nucleus. However, in addition to the positive effects of deep brain stimulation, there are certain side effects to be expected from a systems theory perspective.
The external supply of an electronic input signal via an electrode (or via very few electrodes) causes the activity of the subthalamic nucleus to be synchronized. There are usually always areas that are more active and whose input signal fires strongly, while other areas are more inactive and fire less. There may even be areas in the subthalamic nucleus that hardly fire at all. E.g. the gustatory areas, which receive their mean input from the cerebral area, which evaluates the taste information. These are known to be only really active when we eat or drink something.
The externally applied signal during deep brain stimulation makes the subthala-micus nucleus believe that all or many areas are neurally active. This is particularly unfavorable in areas that are currently inactive or only weakly active. This is because the basic climbing fibre frequency is derived from the single signal. The climbing fibre signal is generated by temporary blanking (temporary total suppression) of exactly the neuronal continuous oscillation of the subthalamic nucleus.
In the long run, deep brain stimulation creates strong climbing fibre signals where none would otherwise be created. Suddenly weak signals are treated in the same way as strong signals. New complex signals are stored in the Purkinje cells, which would otherwise never have been stored there. For example, the quiet ticking of a clock could be linked to the music that is currently being played by a climbing fibre signal and burned into the Purkinje cells. Later, it is precisely this stored ticking that disturbs the enjoyment of the music. But other "forced couplings" of otherwise completely independent signals could also occur. Cognition then suffers from this. For example, reading difficulties could occur, or any other deficits (movement disorders in space, orientation problems, ...). Research into the actual side effects of deep brain stimulation is only just beginning. The theory of the basal ganglia developed by the author and presented in this monograph can certainly provide theoretical support here. Should this be true, it would be further proof of the applicability of mathematical theories in everyday practice.
ISBN
978-3-00-037458-6
ISBN 978-3-00-042153-2
Monografie von Dr. rer. nat. Andreas Heinrich Malczan