Content:
1. Introduction
2. Functions of Specific Cortical Areas
3. Language Input and Output
4. Memory
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Introduction
Age-old questions which have drawn the attention of philosophers and scientists to neurosciences – such as: „What makes us who we are? What is behind human consciousness? How the human brain creates consciousness? – are the most difficult to answer and paradoxically, we still know very little about them. Cerebral cortex is one of the least explored parts of the human brain. Most of our knowledge comes from the episodic case-studies of patients, whose cerebral cortex was damaged in accidents, during surgical procedures or as a result of experiments with electrical stimulation of cortical areas.
Functional Morphology of Cerebral Cortex
The functional part of the cerebral cortex contains approximately 100 milliards neurons, which are comprised in a thin layer 2 to 5 millimeters in thickness, having a total area of one quarter square meter. These neurons are arranged in six cortical layers:
1) Lamina zonalis (molecular layer)
2) Lamina granularis externa (external granular layer)
3) Lamina pyramidalis externa (layer of pyramidal cells)
4) Lamina granularis interna (internal granular layer)
5) Lamina pyramidalis interna (large pyramidal cell layer)
6) Lamina multiformis (layer of fusiform or polymorphic cells)
Lamina zonalis
It is a layer located on the surface of the cerebral cortex. Lamina zonalis contains mainly the dendrites of the pyramidal cells out of layers III and V and the projections from intralaminar thalamic nuclei. There is also a small number of the Cajal-Retzius neurons, having an excitatory effect on the pyramidal cells.
Lamina granularis externa
In this layer we can find a large amount of basket cells with the inhibitory effect on the pyramidal cells in the third layer. Small excitatory pyramidal cells are freely dispersed in the external granular layer as well.
Lamina pyramidalis externa
The third layer contains medium-sized pyramidal neurons, which receive information especially from stellate interneurons of the IV. layer and from the thalamocortical projection. The commissural fibers heading towards to the contralateral hemisphere and the association fibers leading to the ipsilateral cerebral cortex arise in there.
Most of the commissural and cortical association pathways origin in lamina granularis externa (II.) and lamina pyramidalis externa (III.).
Lamina granularis interna
The internal granular layer is composed of interneurons of various shapes, mainly of excitatory stellate neurons. It is a very significant structure; most of the fibers of the thalamocortical projection terminate in there (it is its main destination). Furthermore, signals from the thalamus are distributed by the IV. layer into the others. It is notably enlarged in the sensory areas.
Lamina pyramidalis interna
Projection fibers continuing to the subcortical structures arise from giant neurons of the V. layer. Giant pyramidal neurons called the Betz cells, whose fibers form the pyramidal pathway, are located in lamina pyramidalis in the motor area.
Lamina multiformis
As the name suggests, in this layer neurons come in an astounding assortment of shapes. The interneurons, which influence the activity of the neurons from outer layers, may be found in there, as well as the cells whose axons create the corticothalamic pathway – the integral component of so-called thalamo-cortical oscillator. It is believed that the oscillator helps keeping consciousness.
The interaction between the thalamus and the cerebral cortex is crucial and mostly notable when the fibers from thalamocortical and corticothalamic pathway are damaged. Various thalamic nuclei or their functional groups are connected with a specific region of the cerebral cortex, to which it is functionally related. They intensively communicate with each other. In case of a disruption of this communication (mutual projections) the function of the corresponding cerebral cortex is lost completely.
Lamina pyramidalis interna (V.) and lamina multiformis (VI.) are the main sources of the projection fibers of the cortex. Projections to the striatum, tectum, reticular formation, mesencephalon, medulla oblongata and to spinal cord arise in lamina V. Fibers to the thalamus arise in lamina VI.
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Functions of Specific Cortical Areas
Since the time of Antic Greece, different parts of the cerebral cortex were associated with multiple functions. Korbinian Brodmann focused on these assumptions and conducted a highly accurate histological analysis, thanks to which he discovered 52 morphologically different areas. Based on this result, he assumed that among cytoarchitecturally variant areas, there would be functional differences.
Even though the Brodmann’s work is, due to the usage of modern technologies, nowadays partly obsolete, it led to a creation of the widely-used terminology, which is still being respected (even if there are many imperfections). The contemporary studies are much more complex; Brodmann’s work is quite deep-routed and understandable.
Interesting Fact:
The division of the cerebral cortex into functionally specific areas is, seeing from the evolutionary point of view, a pretty new phenomenon. Some reptiles – such as turtles – have a so-called generalized cortex, which has a uniform morphological structure and function.
Sensory and motor areas are described in details in relevant chapters. In this part of the text we will discuss more the association areas of cerebral cortex.
Association Areas
Association areas gain and simultaneously process the information out of many sensory and motor areas as well as out of subcortical structures. Because these areas integrate and interpret individual information, they create a compact “picture of reality”. The most important association areas are:
1) The parieto-occipital association area
2) The prefrontal association area
3) The limbic association area
1) The Parieto-Occipital Association Area
This area lies between the somatosensory areas (rostrally), the visual cortex (caudally), and the auditory cortex (ventrally). It gains the information from the sensory areas, which surround it. These pieces of information are integrated and interpreted. In humans, it is even more divided into subareas, performing highly specialized functions.
Analysis of the Spatial Coordinates of the Body
Responsible subarea for analysis of the spatial coordinates of the body is located in the posterior parietal cortex and in the superior occipital cortex. It integrates the information from the visual cortex and from the somatosensory area. Out of these, it computes the inner representation of the position (spatial coordinates); the position of the body in the space, as well as the three-dimensional relationship among objects.
Wernicke’s Area
It is a subarea lying caudally from the primary auditory cortex, in the posterior part of the superior gyrus of the temporal lobe. It is developed mainly in the dominant hemisphere (in most of the people it is the left one). It has an essential meaning for language comprehension, which we will discuss closely later in this chapter.
Furthermore, many of the intellectual functions are localized there. Wernicke’s area is so important that it is sometimes called the main interpretation area. Information from most of the sensory and association areas is driven there, where it is integrated and processed.
In case of a lesion in this area – for example after the cerebrovascular accident in the left basin of the middle cerebral artery – severe language disorder occurs: sensory aphasia. Disabled person with this aphasia can distinguish different sounds of the words, yet he is unable to understand its meaning or to create a coherent sentence. Also, the person can recognize the process of noting down the words, but again is unable to understand them.
The loss of the whole area leads to a change of the person into a “shadow of the former human being” that is not capable of having any conversation, unable to perceive any command, totally dependent on someone else’s help. It is not expressed only by external manifestations – the loss of the ability to communicate or to understand any communication, most of the intellectual functions are lost.
Stimulation of the Wernicke’s area leads to many interesting phenomena; usually it is a very complex thought. Stimulated person is capable of recalling a whole speech he heard in the past, a distant memory with all the details such as smells or sounds or may start to hallucinate.
Generally, we can say that Wernicke’s area interprets motives in the inner representation of reality, which were gained based on the sensory inputs.
Wernicke’s area also interferes with the learning process. Most of the sensory inputs are converted into a language equivalent. Usually, we can remember a page with some text not as a photo, that we would recall, but as verbal information. This phenomenon is probably in a connection with fact that in the childhood, we perceive most of the information in the form of a spoken word. Later as we grow older, we learn how to read and we start to implement written words into the process of learning (therefore the gyrus angularis).
Angular Gyrus
It is located in the anterolateral part of the occipital lobe. Often, it is considered to be the “visual association area” thanks to its important connection with the visual cortex. This area is responsible for recognition of the written words, perceived by the visual cortex, and for sending information to the Wernicke’s area, where its meaning is decoded. Every moment, when you read this text, a massive communication in the axis: visual cortex → angular gyrus → Wernicke’s area occur.
When the gyrus angularis is damaged, the disabled person is unable to recognize written words, although all the other language skills are intact. Such retardation of the function of the gyrus angularis may have different levels of intensity and is called dyslexia.
Naming Objects
The subarea responsible for naming objects is located in the rostral part of the occipital lobe. It integrates the information about the name of the object, together with the inner representation of the given object, which origins from the visual cortex. However, at first the name of the given object must be acquired, using the inputs from the auditory cortex; its external appearance must be acquired by the visual cortex.
Simple explanation: If you learnt a name of some object (or for example someone told you the name) and you see it again, the name will be automatically assigned to it.
2) The Prefrontal Association Area
This area lies rostrally in front of the motor areas, with which it cooperates extensively on planning of the complex motor motives and sequences. To be able to effectively participate in the planning process of the motor activity, it is linked together by a massive subcortical bundle of association fibers with parieto-occipital area. Precise representation of the position of the body and surrounding objects is processed by the parieto-occipital area and handed over to the prefrontal association area. A plan of a movement from the prefrontal area then proceeds to a basal ganglia circuit.
The prefrontal association area is also essential for a process of thinking and for a creation of the representation of the “inner voice” – which is probably formed because of very close connections with the motor area including speech organs.
This area also most likely ensures the right function of a working memory, which temporarily stores new conscious information from other sensory areas. Thanks to the working memory, we can plan our future, solve complex mathematical and philosophical problems, and control our behavior (by comparing the planned scheme of behavior with our moral principles), etc. All of these abilities are lost if the prefrontal cortex is damaged. In the past, it was a pretty common brain damage due to a prefrontal lobotomy, an excessive intervention used on psychotic patients. The principle of the prefrontal lobotomy was to discontinue the connection between the prefrontal cortex and other parts of the brain.
Broca’s Area
Part of Broca’s area (or Broca’s center) can be found in the prefrontal association cortex and other part in the premotor area. It is responsible for a word formation, by synchronizing the movements of muscles of respiration together with the muscles of larynx and mouth. It is also the place of origin of any plan; place where the articulation of words and short phrases is initiated.
Area for Recognition of Faces
It is an autonomous association area. Most probably this part of the cerebral cortex was created in the process of evolution, when the human ancestors started to socialize more intensively. It is located on the medial surface of the occipital and temporal lobes. It is associated with the visual cortex and the limbic system. This area was discovered in a connection with prosopagnosia, brain damage which results in a disability of the patient to recognize faces. Prosopagnosia is the only pathology which appears, after a damage of such a large area of the cortex.
Lateralization
The term lateralization means that one of the hemispheres is dominant. Specifically, it is the one in which the Wernicke’s interpretation area, gyrus angularis, motor areas and other language centers are more developed. In about 95 per cent of all the people, the left hemisphere is the dominant one – it is valid for both left-handed and right-handed individuals. We can see this, even when a child is born, when most of the newborns have more than 50 per cent larger Wernicke’s area in the left side. Interestingly, if the left hemisphere is damaged in a newborn, the right one adapts and becomes dominant.
Lateralization is present among most of the mammals. The theory of how it is being established says that it starts during the process of learning in the early childhood. The hemisphere which is naturally more used, is the one, whose temporal lobe (respectively the Wernicke’s area) developed more during the perinatal period. In the process of learning, it is then used more; in the interpretation of the information as well as in the execution of the movements. From the point of the neuronal plasticity, it undergoes more changes.
Among the 5 per cent of the population, both hemispheres usually develop without lateralization. In extremely rare cases, the right hemisphere is the dominant one.
Broca’s area is also more developed in the dominant hemisphere. With regards to the fact that it is responsible for the word formation by synchronizing the movements between breathing muscles and muscles of larynx and mouth, any intervention into the natural development of the lateralization may lead to a language disorder. For example, if the child is left-handed and is being forced to write with its right hand, it may lead to a stammering, despite the fact that most likely its dominant hemisphere is the left one. It is an inappropriate interference into a very complex process.
In spite of the existence of the dominant hemisphere, both hemispheres are capable of having control over the movements and over recording of the sensory functions. To be sure that both hemispheres are synchronized and there is no meaningless interference, a massive bundle of commissural fibers – corpus callosum exists.
If the corpus callosum is damaged, affected person loses control over half of his body; two autonomous conscious hemispheres appear. Case-studies were reported, in which patient shaved only half of his face, combed hair only on one side or, in extreme case, was attacked by the limb ho could not control.
Persons with affected non-dominant hemispheres suffer from miss-interpretation of music, body language and intonation of other people, etc. It is most likely, that the non-dominant hemisphere is being used for different activities.
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Language Input and Output
The ability to communicate is one of the most intensively studied functions out of the higher functions of the central nervous system. There are two aspects to communication: the sensory aspect (language input), which deals with the inputs from the auditory and visual cortex and the motor aspect (language output); responsible for the integration of the motor areas with the synchronization of the breathing muscles and speech organs (process of vocalization).
Sensory Aspects of Communication
If we communicate with another person, sounds which form words are being perceived in the primary auditory cortex and in the secondary one, they are being recognized as the sound patterns of the words. These patterns are conducted to Wernicke’s area, where their meaning is being assessed. Wernicke’s area also prepares the thought, we want to express, and assigns proper words to it. The prefrontal cortex is most likely slightly involved in this step as well, because its damage limits proper expression. Lexically and stylistically prepared right content is then transferred into the Broca’s area, using fasciculus arcuatus (arcuate fasciculus).
The sensory aspect works the same way in the process of understanding the written word, just between the visual cortex and the Wernicke’s area, the angular gyrus is inserted (see above).
Motor Aspects of Communication
Based on the input from the Wernicke’s area, the motor plan of vocalization is being prepared in the Broca’s center. This plan is then transferred, thanks to the association fibers, into the motor area responsible for the appropriate muscles. The cerebellum participates in this step as well, while it determines and controls exact timing of the movements. Also basal ganglia are included.
Using synchronized movements of the mouth, tongue, larynx, vocal cords and breathing muscles, we are able to accurately vocalize our thought which was established in the Wernicke’s center.
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Memory
Memories are caused and being kept in the brain by changes in the synaptic transmission from one neuron to the next as a result of previous repeated and frequent activation of a specific sequence of neurons. These changes may turn into a variety of forms, from a modification of preexisting connections (for example: due to a mechanism when the response of the postsynaptic neuron or stimulus is enhanced or suppressed, or when the postsynaptic density is modified), to a creation of new synapses. Such modified synapses are called memory traces.
The memory traces may be established in the whole central nervous system; for example, in the spinal cord, reflexes may be modulated this way. However, long-term memories which we connect with the intellectual functions of the brain are stored in the cortex.
It is assumed that the position of a certain memory trace in the cortex is dependent on its character and on the incoming sensory stimulus. Based on this, information about the shapes of objects is stored in the visual cortex and their names in the auditory cortex.
Although we usually connect the process of learning (and therefore the creation of new memory traces) with gaining of information, the opposite is true. Most of the sensory impulses are labelled as useless and the sensory pathways are modified in a way that they would such stimulus ignore. This is the fate for more than 88 per cent of the incoming sensory information. The limbic system plays a major role in deciding if the information will be ignored. It assigns a so-called affective quality to the sensory inputs, which activates punishment or pleasure center.
In case that the sensory input has no effect on the activity of the punishment or pleasure center, and therefore the affective quality is not assigned to it, progressive response loss occurs and the cortical areas are no longer activated by it. This resulting effect is called habituation, and it is an example of a type of negative memory. If the limbic system assigns the affective quality to some sensory input, and the cortex encounters the stimulus repeatedly, we may observe rising intensity of the response, because the facilitation of the synaptic pathways occurs. We say that the response was enhanced. This type of the positive memory is called sensitization.
E. Kandel and his colleagues discovered a mechanism which causes changes in the synaptic pathways, in the sea hare Aplysia. They found out that the presynaptic terminal of the sensory neuron (sometimes also known as sensory terminal) is attached to another axon termination. This is called the facilitator terminal, and it origins in a serotonergic neuron. In the sea hare Aplysia, it is activated by a pain stimulus. In a human body, the neurons that establish the facilitator terminals are probably closely linked with the limbic system. This terminal also plays a major functional role in the mechanisms of habituation and facilitation.
Habituation
Habituation occurs when the presynaptic terminal of the sensory neuron is being activated repeatedly, without simultaneous activation of the facilitator terminal. In the beginning, the excitatory postsynaptic potential is normal, but with the repetitive stimulation, it becomes progressively lower till its extinction. We can say that the facilitator terminal is activated, after the affective quality is assigned to it. In case that the stimulus is not provided with this quality in the limbic system, the facilitator terminal is not activated and the sensory terminal is habituated.
On a molecular level, the mechanism of the habituation depends on the progressive closure of the calcium channels of the presynaptic terminal. The reason why the channels are closing is so far unknown. Because the quantal release of the neurotransmitter is proportional to the intracellular concentration of the calcium ions, progressive closure of the channels is followed by noticeable decrease in the excitatory postsynaptic potential.
Facilitation
If the sensory input activates the limbic system, the facilitator terminal is stimulated together with the sensory terminal. Then, the facilitator terminal releases serotonin on the surface of the sensory terminal, where it activates adenylate cyclase using its receptors. Further in this signaling pathway, cAMP dependent protein kinases are activated, which leads to the phosphorylation of the potassium channels and their closure. The loss of the membrane permeability prolongs the duration of the action potential; it ends up in the longer interval of the opening of the calcium channels, in a higher concentration of intracellular calcium, in the large-scale release of quanta of the neurotransmitter and finally, in the enhancement of the excitatory postsynaptic potential.
Such facilitated response may last for three weeks, even without further stimulation of the facilitator terminal.
Classification of Memories
Memories can be classified based on the kind of the stored information or based on the duration, during which memory traces persist.
Based on the kind of the stored information:
1) Declarative memory (or explicit)
2) Procedural memory (or implicit)
Declarative Memory
Explicit memory requires working with the memory trace on a conscious level. It can be further divided into semantic and episodic memory.
Semantic memory includes impersonal information independent on its context. Mostly, it is connected with abstract knowledge, for example: Prague is the capital city of the Czech Republic. It is a typical abstract knowledge independent on the context, which followed its acquiring.
Episodic memory deals with information specific to a particular context – we can remember place and time, where the event happened, etc. Often, this type of memory includes very personal experiences followed by emotions. Significant part of the episodic memory consists of autobiographical memories.
Procedural Memory
It does not require conscious recall of the memory trace; for example motor skills belong there. In the procedural memory, there are stored skills such as how to play guitar, golf swing, etc. Procedural memory traces are acquired during a process of motor learning, which uses basal ganglia and cerebellum.
Based on the duration, during which memory traces persist, we distinguish:
1) Short-Term memory (seconds to minutes)
2) Intermediate long-term memory (days to weeks)
3) Long-term memory (months to years)
Short-Term Memory
Short-term memory has the ability to store maximally 7 to 10 discrete information at once – for example a phone number. The principle how it works is probably connected with a repetitive circuit of reverberating neurons, in which we keep activity on a conscious level. Coded information circles in this circuit and its activity is lost when we lose concentration.
We must not confuse short-term memory with operational memory, a special function of the prefrontal cortex. The information stored is different: discrete facts (for example digits) in short-term memory; complex abstract constructs, problems and plans in operational memory. Another difference is that a problem stored in operational memory is taken away after it is solved.
Example of the difference:
Operational memory: If we think about eating breakfast, brushing teeth and leaving to work, the plan “to brush my teeth” will be immediately removed from the operational memory after its completion.
Short-term memory: If we remember a sequence 7-5-3-2-4-5, it will stay stored as long as we fully concentrate on it.
Intermediate Long-Term Memory
Long-term memory traces persist for weeks and they are lost, if they are not reactivated. After a frequent repetitive recalling they become long-term memory traces. It is very likely that storing memories into intermediate long-term memory is essential for the establishment of long-term memory traces. Habituation and facilitation (described above) represent the mechanisms of the intermediate long-term memory.
Long-Term Memory
There is no sharp boundary between a maintained intermediated long-term memory trace and a long-term memory trace. It is believed that the long-term memory is preserved by morphological changes of synapses instead of physical and chemical changes, as it is the case of habituation and facilitation.
It results from the experiments that memory trace cannot be stored in long-term memory, if the person takes substances which block replication of proteins. Therefore, it is supposed that the memory trace is stored for a long time in a form of a change in morphology of the presynaptic terminal, among which belong:
1) Increase in the area of the active zone
2) Increase in the number of vesicles releasing the neurotransmitter, which undergo the process of exocytosis
3) Increase in the number of presynaptic terminals of a given neuron
4) Inducement of changes in postsynaptic density, which modifies morphology of the postsynaptic neuron (for example the establishment of dendritic spines)
Changes in the synaptic strength are summarized into the term synaptic plasticity.
Part of these changes is caused by an excessive influx of calcium ions into the cytoplasm of the neuron, which activates calcium-calmodulin dependent kinases and the corresponding signaling pathways.
It is quite interesting, how the changes in the presynaptic terminal influence the postsynaptic terminal. The most excessively studied relation in this type of the synaptic plasticity is the long-term potentiation (LTP) of hippocampal neurons. The principle is a long-term amplification of the synaptic transmission among two neurons as a result of their simultaneous stimulation.
Presynaptic neuron releases glutamate into the synaptic cleft, where it binds to AMPA receptors (AMPARs); the non-specific cation channels with the highest permeability for sodium ions. Glutamate binds not only to AMPARs receptors, but also to NMDA receptors (NMDARs). During their resting state, their pore is blocked with a magnesium ion. When the excitatory postsynaptic potential from AMPARs reaches sufficient value, magnesium cation is removed from the NMDARs pore with Coulombic forces. After this, the NMDARs start to manifest as cation channel and increases the permeability of the membrane for calcium ions (it is a non-specific channel). Excessive intracellular calcium level activates calcium-calmodulin dependent kinases and the reconstruction of the postsynaptic density occurs. At first, the number of exhibited AMPARs and NMDARs is increased. Later, even the structural components of postsynaptic density are increased; a small eminence on the postsynaptic terminal appears (and may form a dendritic spine, if the activity is being repeated).
Consolidation of Memory
Consolidation of memory is a process, which activates chemical, physical and morphological changes in the synapses in a way that the input would be stored in a long-term memory. The minimal amount of time needed for consolidation of the memory traces is 10 minutes; the more we consciously recall the memory, the stronger the consolidation is.
The important thing is that new memory traces are codified; meaning they are compared with old memories, and based on the differences they are categorized into groups and attached to pre-existing memories. This helps the learning process significantly.
Subchapter Author: Patrik Maďa
