The Central Nervous System
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The electroencephalogram (EEG).

    The EEG is the measurement of electric fields on the surface of our skull, in fact of our scalp. It reflects the amount of nerve impulses, of electrical activity of the neurons located under the electrodes. Hence, the activity of the neurons located close to the surface of the skull will contribute more to the electric fields measured at the surface of the scalp. Thus, the EEG mostly reflects cortical activity. Conversely, electrical activity of the deep nuclei, midbrain, pons and medulla oblongata is virtually not recordable.

    To record an electroencephalogram, it is necessary to have at least a pair of electrodes on the surface of the head, and record the difference of electrical potential between these two electrodes. Over time the electrical activity will fluctuate giving the trace of a brain wave over the recorded area. Then, to record from more than single cortical area, multiple pairs of electrodes could be placed over the surface of the whole head. Now, with the advancement of technology and powerful computers one can easily record the electrical activity from more than 32, 64 or even 128 pairs of electrodes simultaneously.

    Our brain wave can show different patterns, different waveform. There will be differences in the frequency of waves (time between peaks) and differences in their amplitudes (height difference between the peaks and valleys of the waves). A wave of high frequency and low amplitude generally means that there is high neuronal activity bellow the pair of electrodes, and that this activity is rather random: meaning that the peak of activity of certain neurons oppose the valley of others and cancels out each others. This type of wave is seen when the brain is awake and active. In contrast, a wave of low frequency and high amplitude means that neurons have a slow and synchronous activity: the peaks and valleys tend to add to each others. This is the case of deep sleep waves.

    Depending on the frequency and amplitude of the brain waves, EEG is classified in four main categories:
- Alpha waves, with frequencies between 8-13 Hz and low amplitudes, represent a wake state with mental relaxation and closed eyes.
- Beta waves, with frequencies between 14 to 25 Hz and low amplitudes, represent an active wake state with sensory stimulation and active mental processing.
- Theta waves, with frequencies between 4 to 7 Hz and low or average amplitude, are more common in children.
- Delta waves, with frequencies lower than 4 Hz and high amplitude, occur primarily during deep sleep.

    And the absence of brain waves, a flat line, indicates cerebral death.

    Animals also, present similar brain activity. But, what about their level of consciousness. This notion of consciousness is difficult to define, especially in animals (they cannot be questionned). How are they perceiving feelings and actions? From this point of view, it is very difficult to know if other animals have consciousness of their being, self-consciouness. In this matter, few notions help distinguishing us, humans. These are notions such as memory, judgment and logic, where humans sometimes surpass the notion of instinct or basic reaction.

    Consciousness can also be defined according to our level of behavior. Vigilance is consider the highest level of consciousness. Then there would be stupor, lethargy and drowsiness. Finally, the coma would be the lowest level of consciousness.

Sleep.

    Sleep is a phase or a period of unconsciousness from which one can escape following a stimulus, an alarm. This contrasts with the state of coma which is a period of unconsciousness from which, even with an important stimulus, one could not escape. Thus, the sleeper remains in touch with reality. Also, unlike coma, control of cardiovascular and respiratory function remains intact during sleep.

    During our night, we go through several stages of sleep. In addition to the wake up state, we usually denotes five stages of sleep.
- The first stage is REM (Rapid Eye Movement) sleep. This is the stage when we dream. A stage where our brain is as active as if we were awake, but when all our skeletal muscles are inhibited, paralyzed. Only the diaphragm (the muscle of breathing) and the eye muscles remain active. The eye muscles are so active such that our eyes do not stop moving during the dream period, hence the term "REM sleep". In this stage, the brain seems even more active compared to the wake up state. Indeed, during this time, our brain consumes 30-40% more energy (oxygen and glucose) compared to the wake up state.
- Then comes the stage 1 of non-REM (NREM) sleep. This is the first phase of relaxation. The EEG presents alpha waves activity. During this phase, one can easily awaken.
- Then comes the stage 2 of NREM sleep. This is a deeper sleep, still irregular. The EEG is characterized by the appearance of some high amplitude peaks. Awakening becomes more difficult.
- In Stage 3 of NREM sleep, the EEG shows a mixture of theta and delta waves. Sleep deepens more, breathing and heart rates decrease.
- Finally, in stage 4 of NREM sleep, the deepest stage, the EEG presents slow delta waves. Wakening becomes very difficult. It is in this stage that involuntary voiding (urination), night terrors or sleepwalking may occur.

    During the night, we go through 4-5 cycles, alternating between REM sleep and deep sleep, stage 4 of NREM sleep. At the beginning of the night, we spent more time in deep sleep and dream only for short period of time (5-10 min). Then, late in the night, it's the opposite; we spend a lot of time in REM sleep (20-50 min) and hardly reached the stage of deep sleep.

    The desire to sleep should come every 24 hours; this is the circadian rhythm. At the center of this biological clock lies the suprachiasmatic nucleus which drives the preoptic nucleus; both are localized in the hypothalamus. In turn, the preoptic nucleus inhibits the reticular system which is normally responsible for alertness/arousal of the cortex. The mechanisms that regulate cortical activity during REM sleep and synchronization of cortical neurons during the deep stages are complex, not always well known, and certainly beyond the scope of this discussion.

    Sleep is very important for our health and even essential to life. To my knowledge, all animals with a central nervous system need to sleep. Some sleep more, others sleep less, and others could sleep one cerebral hemisphere at a time. In humans, infants sleep for up to 16 hours per day, young adults usually sleep for 7.5 to 8.5 hours per day (except for some teenagers that can sleep for more than 12 hours straight ;-)), while the need for sleep decreases slightly with aging. Also, children spend almost half of their night in REM sleep, dreaming. Then, after the age of 10, REM sleep occupies little more than a quarter of the night. In the elderly, it is deep sleep, stage 4, that tends to disappear.

    Deep sleep is the stage of sleep when our body is said to repair itself. It is also during this deep sleep cycle that, in children, the growth hormone is secreted. About REM sleep, some people believe that our dreams can have certain meanings. Some say they are used to solve emotional problems we encountered during the day. Others believe they serve to forget unnecessary information that we have stored during the day and reinforce other memories. It is doubtful however that REM sleep is premonitory. At best, we know that lack of REM sleep causes emotional instability, personality disorders, and even hallucinations.

Language.

    The function of language occupies a large part of the left hemisphere. This is particularly true for right-handed people (95% of cases), because for several left-handed (30% of cases), the language centers are located on the right side of the brain. The other hemisphere of the brain, the right side for the majority of people would be involved more in the non-verbal language. It would deal with the emotional side of the communication, it would solve the tone, rhythm and gesture which, beyond words express our emotions.

    There are two areas particularly important for language: these are the Broca's and Wernicke's areas. People who have brain lesions involving the Broca's area can understand the language but have difficulties speaking or writing. Those with lesions in Wernicke's area have difficulties understanding language. They are usually able to speak, but their words do not make sense.

    The language is more than words placed one after the others to form a sentence. It has a grammatical structure, ideas and concepts more or less abstract with intermingled concepts. It is also a mean of communication with an interlocutor, a crowd or even with ourselves. The language is not always expressed aloud and is often accompanied by a whole body movement, including changes of rhythm and tone. It can be very formal or express a deep empathy. In fact, it involves much more than those two cortical areas. Indeed, it involves several neighboring cortical areas called associative areas.

Memory.

    Memory could be defined as the storage and recall of information. It is the ability to remember the past and is one of the basis for learning. We can classify or characterize the memory in different ways.

    There is the short-term memory and the long term memory. The short-term memory is often called the working memory, it is the first step in the process of memorization. This short-term memory retains only few elements, like the 7 or 8 digits of a phone number or the few steps of a mathematical equation. For example, if we want to subtract 7 from 100, and do that 5 times, we have to remember the starting point for each subtraction (100, 93, 86, 79, 72), remember the number to be subtracted (7) and the number of times it has been subtracted to know when to stop. This may sound simple, but it is complex enough that a person who begins to suffer from Alzheimer's disease, or some form of dementia, will be unable to perform such a task. His short term memory is affected.

    In everyday life, it is not necessary to retain all the bits of information we are exposed to, so most of them will be forgotten very quickly. For practical purposes, almost all information of our lives will be forgotten relatively soon after acquisition because most of this information will become useless. Nobody remembers what they were wearing ten years ago, nor what the weather was on that day. But it is important enough, this bits of information will be transferred to a longer term memory. This long-term memory also has its peculiarities and limitations. The information can deform and eventually be forgotten, depending on the level of consolidation and remembrance. Unfortunately, the older we get, the harder it is to learn and remember new elements. With aging we tend to forget; our brain becomes less plastic, less malleable.

    Various factors can influence the consolidation of memory traces. The emotional charge is an important factor to strengthen the memory imprint. For example, we usually remember better our first love compared to others that follow. We remember dates which are important, significant for us, and we forget the others. Repetition also helps memorization and consolidation. That is why it is better to study more often compared to a one intense session. We also learn by association. We usually better retain the name of a person if we can associate it with something else. For example, if that person has the same name as my aunt, there is less chance that I will forget it. Finally, there are some automatic memories like the things we accept without even trying, like the tics of a person while he speak, the feelings of déjà vu or the yellow curtains in the last restaurant I visited. These are things that I do not want to remember, but they just pop-up in my mind, at least for some time.

    You can also categorize memory processes into declarative memory and non-declarative memory. Declarative memory is about the conscious facts and events. It is the memory that remembers what you learned in school, languages and faces you recognize. Non-declarative memory is poorly conscious or even unconscious. It is the memory of procedures (like playing music), motor functions (like bicycling which could not be forgotten) and emotions (such as acquired fear). It is through exercise and practice that we learn these things. We get them without even thinking about them.

    From an anatomical view, the memory traces could be stored in the cortex, in any region affected by the stimulus. Thus, the visual information would be stored in the occipital cortex while the auditory information would be stored in the temporal cortex. But there exist links between these traces of information, and several other structures, such as associative areas, the amygdaloid body and the hippocampus. We are just beginning to understand the chemical and electrophysiological basis of memory imprints, but there are still many more details remaining to be discovered. For example, is there grandmother neuron, a single neuron allowing us to recognize our grandmother in a crowd of elderly women? Or, is it the simultaneous activation of a selected set of neurons, each recognizing parts of my grandmother (the color of the hair, her eyes, her lips, the pattern of wrinkles, etc.) which allows us to recognize our grandmother? Also, how are we recognizing her smell or the sound of her voice over the phone; how those stimulus could trigger at the same time the remembrance of her figure, or the nice taste of her best cookies?

    There is an electrophysiological phenomenon allegedly involved in formation of memory traces and forgetfulness of these imprints. This phenomenon, or these phenomena are called long-term potentiation and long-term depression (LTP and LTD). They were first discovered in a structure now recognized for its paramount implication in memory processes, the hippocampus, but they could also be replicated in other structures. Long-term potentiation occurs when a neuron is highly stimulated at high frequency. Thereafter, that neuron will, to a standard stimulus, generate a response much more intense than it would normally do (or much less intense in the case of long-term depression). These phenomena are the result of many complex changes in the neuron: some genetic modifications, change of the form of dendrites, changes and movements of pre-synaptic terminals, and the release of more neurotransmitter.

The meninges.

    The meninges consist of three membrane layers of connective tissue that protect the central nervous system (CNS: the brain and the spinal cord) against shocks. A first thin membrane is apposed on the brain, it is the pia mater. The second membrane, also quite thin, is called the arachnoid. Finally, the outmost membrane is thicker and more resistant, it is the dura mater. In addition, when we look closer, we realized that the dura mater is in fact composed of two layers: a deep layer that penetrates between the two cerebral hemispheres, and a more superficial layer. Between these two sheets, on top of the brain, there is a venous sinus that drain blood from the brain toward the heart, it is the sagittal sinus.

The meninges: protecting the brain.

    The space between the dura mater and the arachnoid, the subdural space is filled with a thin layer of serous fluid. Then, the space between the arachnoid and the pia mater is called the subarachnoid space. This more important space is maintained by multiple filamentous extensions. It is in the subarachnoid space that cerebrospinal fluid circulates. Altogether, this succession of membranes and liquid absorbs the vibrations and protects the CNS against shock. Then, as we will see in the following section, the cerebrospinal fluid is evacuated by the arachnoid villi into the sagittal sinus.

Cerebrospinal fluid.

    The cerebrospinal fluid (CSF) is the liquid that is produced in the cerebral ventricles and is expelled via the subarachnoid space. As mentioned in the previous section, it serves, among other things, to absorb shocks. Also, given that the brain has a rather gelatinous composition, the CSF helps the brain to 'float' in the liquid thus preventing it crashing under its own weight. In addition, the flow of CSF enables the transport, throughout the brain, of nutrients as well as certain hormones and neurotransmitters.

    The composition of the CSF resembles, to some extent, to the composition of the plasma, except that it contains much less protein and sugars, a little more Na+, Cl- and H+, and a little less of Ca 2+ and K+. The CSF is formed from the plasma that has been filtered by the choroid plexus. These plexus are composed of semi-permeable capillaries leaking some of the plasma into the cavities of the brain, the ventricles. The capillaries of the choroid plexus are surrounded by a layer of cells, the ependymocytes, that filter the leaking plasma and prevent the passage of proteins and glucose, and control the levels of certain ions.

    The choroid plexus are concentrated in two locations: at the junction between the lateral ventricles and the third ventricle and at the roof of the fourth ventricle, just under the cerebellum. The volume of CSF in the ventricles and subarachnoid space is about 150 mL, and it is estimated that this amount of liquid is replaced approximately every eight hours. Thus, the choroid plexus produce approximately 450 to 500 mL of CSF every day. The CSF flows from the choroid plexus to the fourth ventricle, then some passes through special channels around the medulla oblongata and some passes in the central canal of the spinal cord. Then, the CSF reach the subarachnoid space and flows toward the sagittal sinus where it is discharged by, or through, the arachnoid villi.

The blood-brain barrier (BBB).

    Most capillaries in our body are fenestrated. They have small holes allowing small molecules such as minerals, glucose and nutrients to diffuse out of the vessel and support surrounding cells. In the brain, the capillaries are not fenestrated and they are surrounded by a barrier which prevents the diffusion of these molecules to the neurons. Indeed, the homeostasis of the brain is so important that it is necessary that the supply of minerals, nutrients and glucose needs to be controlled, or regulated, in order to match the metabolic needs of neurons, no more and no less.

    Certain hormones, amino acids or ions in the blood stream could have an impact on neuronal activity if they were diffusing freely. To retain these molecules in the blood stream and control their entry into the brain, our brains capillaries have developed a particular architecture. Instead of a discontinuous endothelium, leaving fenestration, the endothelium of the brain capillaries is continuous and have tight junctions between cells. In addition, there is a thick basal lamina (a protein layer of 40 to 50 nm) that surrounds the brain capillaries. Finally, these capillaries are surrounded by perivascular legs which are extensions of astrocytes and are involved in the regulation of nutrient intake and their distribution in the neuronal extracellular milieu.

    This barrier, however, can not control everything. Soluble substances such as fatty acids, alcohol, nicotine, drugs and anesthetics can diffuse relatively freely through these membrane layers. Similarly, oxygen and carbon dioxide can also diffuse freely.

    Moreover, this barrier is not present, or as thight, throughout the CNS. Indeed, there are few places lacking this blood-brain barrier. These places are called the circumventricular organs. There are six of these regions which are located mainly around the third and fourth ventricles. They are the subfornical organ, the vascular organ of lamina terminalis, the neurohypophysis, the epiphysis or pineal gland, the subcommissural organ, and the area postrema. Because these areas are devoid of BBB, they could detect toxic substances as well as the composition, the osmolarity and the temperature of the blood. These regions participate in the control of vomiting, hunger, thirst, secretion of hormones and regulation of body temperature.