CONSCIOUSNESS (AROUSAL)We can try and explain many brain functions in a mechanical way as with our

computer simile but as in all the major disciplines of science one eventually comes

upon a brick wall :- what is space, time, energy, what initiated the big bang, what was

there before it, and in the case of the biological sciences what is consciousness ?. This

is the only enigma that remains allowing philosophy to reign over neuroscience.

Nevertheless consciousness as we know it cannot exist without a brain and is lost

forever in brain disease or brain death. Even our deepest emotions such as love and

hate, happiness or deep depression can only exist in the conscious brain.

Consciousness is very difficult to define, Descartes dictum "I think therefore I am “

(Cogito Ergo Sum) falls short in defining consciousness since the converse is not true,

if I cant think I may be demented, deluded or hallucinated but I am not unconscious. If

unconscious for a prolonged time do I exist as a person with a mind, if for ever

unconscious and so brain stem dead do I exist. We all know when we are conscious

and aware of self existence and the passage of time and we can recognise

consciousness in others based upon their responses. We do not however know what is

going on in the conscious mind of another person if they do no communicate with us.

It is very difficulty to measure conscious awareness or level of arousal, we know

when someone is asleep or awake and absence of sleep wake cycles can be used to

define coma. Scales such as the Glasgow coma scale do not in fact measure

consciousness but behavioural responses to stimulation. If one gives a non

anaesthetised person curare they are fully conscious but how does an outsider

determine that there is a personal inner awareness. Is a newborn infant conscious ?

most people would agree that it is conscious in that it shows sleep wake cycles and

shows arousal to stimuli such as hunger. Is a baby conscious in utero before birth or

does consciousness appear at birth, they certainly show sleep wake cycles in utero,

when does that consciousness appear during development of the foetus when brain

stem develops, diencephalon or cortex, has it any content ?. Are we conscious in REM

sleep when dreaming and immediately aware but memory is switched off so there is

usually no recall. Clinical diffrentiation of different disorders with absent responses

may be impossible ie.

Coma

Persistent vegetative state

Sleep

Anaesthesia or drug overdose

Akinetic-mutism

Dystonia with non communication

An absence seizure or fugue state

Brain stem death

No one would doubt that their pet dog or horse was conscious shows recognition and

could remember people and places as well as understanding a limited vocabulary ( or

intonation pattern). Are all vertebrates conscious, are all animals with a rudimentary

cerebral cortex such as a shark or dogfish. Is consciousness, even a

microconsciousness a feature of all living cells and a huge protoplastmic conglomerate

such as the brain merely amplifies it into a macroconsciousness ?. If consciousness is

a feature of all living cells then an amoeba or any individual body cell has

microconsciousness and trees would be conscious The brain could amass a large

amount of consciousness by joining billions of cells in the form of what Graham

Cannon in Manchester used to call "organismal control " and death is simply the

permanent loss of this organismal control via the reticular formation and a return to a

mass cellular microconsciousness.

Do we simply need a nerve net such as the reticular formation linking millions of cells

as one unit to give us consciousness. Does the size of the cerebral cortex merely store

more information for the content of consciousness ( a human with gigabytes of

cerebral hard disc and a fish or bird megabytes, invertebrates with only a ganglion a

kilobyte ? !). Some experts in artificial intelligence have claimed that a computer if

made powerful enough would automatically become conscious. Apart from being a

frightening concept, the biggest argument against this is that loss of intelligence in

man in mental handicap or severe dementia does not mean a proportionate loss of

consciousness only diminution in its content.

The idea that consciousness, like self replication, is simply a property of some

macromolecules once they achieve a particular size and configuration is as equally

frightening as the computer model. It perpetuates the saga of ignoring the whole cell

as the unit of life. In neurology we have been obsessed by synapses, neurotransmitters

and nerve nets and have forgotten the actual living part of the brain ie the neuron. If

we believe that nerve networks achieve consciousness then there would appear to be

no sensible reason not to accept that a computer’s electronic networks could achieve

consciousness. We now know that the cell consists of organelles which are themselves

as complex as the organs of a whole body one can localise any cellular function to a

prescribed sub - cellular unit or organelle. Even accepting this we have completed the

circular argument to return to the idea of consciousness being a property that develops

in certain self replicating large molecules eg. DNA.

Anatomy of Consciousness

Consciousness depends upon the reticular activating system and septal nuclei being

intact. One may have a gross lower brainstem, ie lower pons and medulla, lesion as

with a pontine glioma so that all body movement, speech and swallowing are

paralysed and yet the child may be fully conscious and can think normally. One may

equally remove a whole cerebral hemisphere thus limiting the content of

consciousness and yet the child is fully conscious. Extensive disease of both cerebral

hemispheres will cause severe mental defect or dementia and so limit or even abolish

all cognitive learning (as in post - traumatic persistent vegetative state) and thus

grossly restricting the content of consciousness (thought processes) and yet the child

is still conscious. That is to say there is a relatively small area of upper brain stem,

thalamus and septum which appears to be necessary to sustain consciousness and a

small lesion here as with tentorial herniation secondary to raised intracranial pressure,

primary midbrain injury in trauma, localised encephalitis or tumour may cause

prolonged coma. An irreversible lesion in the brainstem eg central ischaemic neuronal

necrosis, can result in permanent failure of cortical arousal and consciousness, hence

the concept of brain death depends upon brain stem function rather than cortex.

The mesencephalic reticular formation leads to continuous sleep and lesions in the

medullary reticular formation to constant wakefulness. The reticular formation is a

continuous network of small interconnected cells which have a basketwork of axons,

dendrites and side connections form ascending and descending pathways. The

dendrites are long and straight. The axons run upwards and downwards coveing many

levels from the same cell. The reticular formation starts caudally in the central grey

matter of the spinal cord and is then present in medulla as the medial and lateral

reticular nuclei which give rise to the reticulospinal pathways. There are some very

large cells in the medulla and pons ie the gigantocellular nucleus. The midbrain,

thalamic reticular nucleus and intralaminar thalamic nuclei all form part of the system

There are also the specific neurotransmitter pathways which influence the cerebral

cortex and basal ganglia eg.

Nor adrenaline from the locus coeruleus

Serotonin - from the median raphe nucleus ( plate of neurones in middle of

midbrain and pons)

Dopaminergic from the substantia nigra

Cholinergic from Meynherts nucleus.

Reticular Activating System.

Fibres to the cortex arise from the intralaminar thalamic nuclei, locus coeruleus and

Raphe nuclei. Possibly switch on specific areas via the cartridge on the apical

dendrite. Cuses arousal and wakefulness or vigilance, changes respiration and blood

pressure There is tonic activity of the arousal system.

The EEG desynchronises with reticular activating stimulation causes the synchronised

slow waves of sleep to disappear with lower amplitude asynchronous fast activity

appearing. It takes only 10 seconds of ischaemia to flatten the EEG and impair

consciousness but 4 minutes ro irreversibly damage the cortex. Even after reanimation

there is often consciousness with sleep wake cycles but little content or

communication. Consciousness depends upon energy from oxygenation but is not

permanently lost by periods of hypoxia,

Consciousness

Thought is the content of consciousnessShort term memory is the capacity of consciousnessAttention maintains the current content of consciousnessDistraction clears current content.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

No one would doubt that their pet dog or horse was conscious shows recognition and could remember people and places as well as understanding a limited vocabulary ( or intonation pattern). Are all vertebrates conscious, are all animals with a rudimentary cerebral cortex such as a shark or dogfish. Is consciousness, even a microconsciousness a feature of all living cells and a huge protoplastmic conglomerate such as the brain merely amplifies it into a macroconsciousness ?. If consciousness is a feature of all living cells then an amoeba or any individual body cell has microconsciousness and trees would be conscious The brain could amass a large amount of consciousness by joining billions of cells in the form of what Graham Cannon in Manchester used to call "organismal control " and death is simply the permanent loss of this organismal control via the

reticular formation and a return to a mass cellular microconsciousness.

Do we simply need a nerve net such as the reticular formation linking millions of cells as one unit to give us consciousness. Does the size of the cerebral cortex merely store more information for the content of consciousness ( a human with gigabytes of cerebral hard disc and a fish or bird megabytes, invertebrates with only a ganglion a kilobyte ? !). Some experts in artificial intelligence have claimed that a computer if made powerful enough would automatically become conscious. Apart from being a frightening concept, the biggest argument against this is that loss of intelligence in man in mental handicap or severe dementia does not mean a proportionate loss of consciousness only diminution in its content.

The idea that consciousness, like self replication, is simply a property of some macromolecules once they achieve a particular size and configuration is as equally frightening as the computer model. It perpetuates the saga of ignoring the whole cell as the unit of life. In neurology we have been obsessed by synapses, neurotransmitters and nerve nets and have forgotten the actual living part of the brain i.e. the neuron. If we believe that nerve networks achieve consciousness then there would appear to be no sensible

reason not to accept that a computer’s electronic networks could achieve consciousness. We now know that the cell consists of organelles which are themselves as complex as the organs of a whole body one can localise any cellular function to a prescribed sub - cellular unit or organelle. Even accepting this we have completed the circular argument to return to the idea of consciousness being a property that develops in certain self replicating large molecules eg. DNA.

The thalamus and neocortex maintain a continuous dialogue through a vast number of complex connections (Jones, 1985; Steriade et al., 1990; Guillery, 1995; Steriade et al., 1997). Depending on the interactions established in the network different states of vigilance will be generated, such as wakefulness and sleep (Steriade et al., 1990; McCormick and Bal, 1997). The neural mechanisms that give rise to changes from one conscious state to another operate in the thalamocortical network. During wakefulness, sensory inputs gain access to the cortex only after substantial processing in the thalamus (Steriade et al., 1990) and, when falling asleep, the thalamus functionally disconnects the cortex from ascending sensory inputs and generates slow rhythms characteristic of sleep (Steriade et al., 1990).

A key structure involved in all these mechanisms taking place in the thalamocortical network is the thalamic reticular (RE) nucleus. For long years regarded as a diffusely organized structure, having global rather than localized actions on thalamocortical pathways (Scheibel and Scheibel, 1966), the RE nucleus is known today to be divided into several distinct sectors, each related to a

particular functional group of thalamocortical pathways (Jones, 1985; Crabtree, 1989, 1992, 1996); and showing a crucial role in promoting sleep and waking activity (Steriade et al., 1990). There are, as yet, no morphological correlates of the two populations of RE nucleus described with different bursting properties (Contreras et al., 1992), one of which typically generates low-threshold spikes and is able to switch from tonic to burst firing, the other apparently lacking the low-threshold calcium conductance and firing only tonically (Contreras et al., 1992). Thus, bursting mode is exhibited during EEG-synchronized sleep, while tonic discharge is detected during waking and rapid eye movement sleep (Mukhametov et al., 1970; Steriade and Wyzinski, 1972; Steriade et al., 1986). The two firing modes depend on the membrane potential of the cell (Contreras et al., 1992; Bal and McCormick, 1993; Gentet and Ulrich, 2003). At depolarized membrane potentials (positive to -65 mV), intracellular injection of a positive current pulse results in the activation of a train of action potentials (Bal and McCormick, 1993). In contrast, intracellular injection of the same current pulse at hyperpolarized membrane potentials (negative to -65 mV) results in the generation of a high-frequency (300-500 Hz) burst of action potentials (Bal and McCormick, 1993). Barbiturate anesthesia depresses the cortical network activity and turns the membrane potential of RE neurons to hyperpolarized levels, favoring the generation of spike-bursts.

Neurons from the RE nucleus are all gabinergic exhibit a prominent tendency to generate rhythmic oscillations in the 10 Hz-band range, Spindles are the distinct EEG correlate of sleep

onset and the only rhythm, during the transition from wake to sleep, which involves the synchronous activity of a large number of thalamic neurons and of their cortical targets (Contreras and Steriade, 1996; Contreras et al., 1997), so that it can be recorded on the scalp. This means that electrical synapses might synchronize oscillations in the range of spindles, which are mediated by LTSs.Keeping awakeThese structures are the posterior hypothalamus, the basal telencephalon, and the intralaminar nuclei of the thalamus. Together they are often referred to as the “executive network”. Stimulating the posterior hypothalamus produces a state of wakefulness comparable to that induced by stimulating the reticular formation in the brainstem. The activity of the posterior hypothalamus diminishes naturally during sleep, when it releases less histamine, a molecule that it uses as a neurotransmitter. The antihistamines that people take for allergy symptoms are known to cause some sleepiness, by reducing the activity of histamine. he intralaminar nuclei of the thalamus contain thalamocortical neurons that send projections throughout the cortex. The activation of these thalamocortical neurons causes them to release excitatory amino acids such as aspartate and glutamate, thus contributing to excitation of the cortex and to wakefulness. During wakefulness, these neurons generate single action potentials at regular intervals, but as the individual falls asleep, these neurons begin firing in bursts

instead, thus causing the cortex to display the synchronized EEG pattern that is typical of sleep. http://thebrain.mcgill.ca/flas

midbrain reticular formation projects massively into the thalamic nuclei, which in turn influence the entire cortex. The role of this formation is to desynchronize the cortex in the broad sense, thus facilitating not only wakefulness but REM sleep as well. Formerly known as the ascending reticular formation, it is now regarded simply as part of the wakefulness network.

cholinergic mesopontine nuclei project to the thalamus. The acetylcholine produced by these nuclei has two effects: it reduces the activity of the thalamic reticular nucleus, which is part of the sleep system, and it activates the thalamocortical neurons involved in wakefulness. For example, the neurons of the mesopontine cholinergic nuclei of the ascending pathway, which are located in the rostral part of the pons, project their axons to the thalamus. There they make cholinergic connections not only in its sensory areas, but also in its reticular nucleus, a layer of neurons that surrounds the thalamus like a skin and exerts a general inhibiting effect on it by means of the neurotransmitter GABA. ( the thalamic reticular nucleus has nothing to do with the reticular formation.) The cholinergic neurons from the pons sensitize the sensory thalamus but inhibit the reticular nucleus. How can this be so? The answer is that these two structures have different kinds of receptors for acetylcholine and hence respond to it differently. The sensory thalamus is sensitized by the activation of its nicotinic receptors for acetylcholine, whereas the reticular thalamus is inhibited by the activation

of its muscarinic receptors for this same neurotransmitter.  Note that these pyramidal cells receive direct nicotinic cholinergic excitation directly from the basal nucleus of Meynert as well as from the thalamocortical neurons.

Central cholinergic pathways are ideally suited to regulate global functions that rely upon the cerebral cortex; such functions include attention, arousal, motivation, memory and consciousness (Woolf, 1991; Woolf, 1996). The basal forebrain contains two groups of cholinergic neurons: (1) the medial septal group (medial septal nucleus and vertical diagonal band: ms and vdb) that project cholinergic axons to the hippocampus and parahippocampal gyrus and (2) the nucleus basalis group (nucleus basalis, substantia innominata and horizontal diagonal band: bas, si, hdb) that project cholinergic axons to all parts of the neocortex, parts of limbic cortex and to the amygdala. The cholinergic pontomesencephalon neurons (laterodorsal tegmental and pedunculopontine tegmental nuclei: ldt and ppt) project onto hindbrain, thalamus, hypothalamus and  basal forebrain. 

magnocellular medullary reticular nuclei, whose neurons are cholinergic or aspartergic/glutamergic, are the origin of both the reticulo-thalamic-cortical pathway and the reticulo-hypothalamic-cortical pathway. Their projections therefore run to the midbrain reticular formation and the cholinergic mesopontine nuclei, as well as to the basal telencephalon and the posterior hypothalamus.

nuclei of the locus coeruleus are located in the dorsal part of the pons, and their noradrenergic projections influence brain structures such as the thalamus, the hippocampus, and the cortex. The locus coeruleus is at its most active when an individual is awake and active. It is less active during calm wakefulness, even less active during non-REM sleep, and completely quiescent during REM sleep.

serotonergic nuclei of the anterior raphe (also known as the superior raphe) send serotonin to the hypothalamus and the cortex. These nuclei are active during wakefulness. Their overall effect is to support wakefulness, and, unlike with other groups of aminergic neurons, lesions to these nuclei cause prolonged insomnia that lasts several days. The likely reason for this apparent contradiction is that this system, which innervates the anterior hypothalamus both in the preoptic area and in the circadian clock circuits of the suprachiasmatic nucleus, seems to measure the duration and intensity of wakefulness. This antiwaking system is set in

motion by serotonin one of the neurotransmitters secreted during waking periods:..

GABAergic neurons, sometimes described as non-REM (or NREM) sleep-on neurons, are at their most active during deep (non-REM) sleep and are inactive during wakefulness and REM sleep. Electrical stimulation of these neurons quickly causes sleep, and their destruction causes insomnia. This insomnia can be interrupted, however, by the injection of muscimol (a GABA analogue) into the posterior hypothalamus, where several components of the wakefulness system converge

suprachiasmatic nucleus, which is the main component of this biological clock, is thus also involved in triggering sleep. When its neurons are damaged, the normally long periods of wakefulness shorten and become randomly distributed across the day. These neurons influence wakefulness through one of their neuropeptides: vasopressin. (Note that the effects that the vasopressin synthesized by the suprachiasmatic nucleus has on the brain are completely different from those of the vasopressin produced by the posterior pituitary gland, which acts mainly on kidney function and blood pressure.) Back to serotonin, however. This neurotransmitter plays a specific dual role. On the one hand, it is produced in large amounts during wakefulness and contributes importantly to this state. But on the other hand, serotonin also plays a fundamental role in the process of falling from wakefulness into non-REM sleep.The explanation for this contradiction took scientists a while to find. They had even long regarded serotonin as the “sleep hormone”, because in animal experiments, destroying the neurons that synthesized it, or inhibiting its synthesis in other ways,

caused periods of sleeplessness that lasted several days, but the same animals could sleep again if the immediate precursor of serotonin was then injected into the preoptic area of their anterior hypothalamus. The expression of robust circadian rhythms depends on the integrity of the biological clock and on the integration of thousands of individual cellular clocks found in the clock. Neurotransmitters are required at all levels, at the input, in the clock itself, and in its efferent output for the normal function of the clockSince, then, scientists have obtained a far better understanding of why a lack of serotonin in the anterior hypothalamus prevents the onset of sleep. This improved understanding led to the hypothesis that the preoptic area of the anterior hypothalamus did not operate as a “sleep centre”, but rather as an area that imposed an inhibition on wakefulness. This hypothesis was subsequently confirmed electrophysiologically. It was found that the measured unit activity of the serotonergic raphe neurons is at its greatest during wakefulness, declines at the onset of non-REM sleep, and ceases during REM sleep. This gradual onset of electrical silence as someone moves from non-REM sleep into REM sleep thus indicates that the raphe neurons stop releasing serotonin into the synapses because it has done its work of inhibiting wakefulness, and its levels can therefore be allowed to decline.

When the brain is awake, its cholinergic, histaminergic, and noradrenergic networks thus activate the thalamus in two

ways: directly, by facilitating the sensory thalamus, and indirectly, by inhibiting the reticular nucleus and thus suppressing its general inhibiting effects on the thalamus. Note that these pyramidal cells receive direct nicotinic cholinergic excitation directly from the basal nucleus of Meynert as well as from the thalamocortical neurons. During the minutes when an individual is falling asleep (Stage 1 non-REM sleep), the firing frequency of the noradrenergic, cholinergic, and serotonergic neurons of the activating system in the brainstem decreases, so that the thalamus is less activated.

Stage 2 of non-REM sleep, the cortex goes into an automatic activity pattern of thalamic origin, characterized by sleep spindles on the EEG. These spindles are caused by the process just described: the rhythmic firing of the reticular neurons produces cyclical hyperpolarizations in the thalamocortical neurons, followed by bursts of action potentials. These potentials are received by the cortical cells, where they generate the sleep spindles. The slow, high-amplitude waves produced in stages 3 and 4 of non-REM sleep result from the hyperpolarization of the pyramidal cells of the neocortex, which is triggered by local GABAergic interneurons, most likely under the influence of the preoptic neurons of the anterior hypothalamus. The thalamic neurons, whose membrane potential is then even more negative than during sleep spindles (seen mainly in Stage 2) probably also contribute to these slow cortical waves.Anatomy of ConsciousnessConsciousness depends upon the reticular activating system and septal nuclei being intact. One may have a gross lower

brainstem, ie lower pons and medulla, lesion as with a pontine glioma so that all body movement, speech and swallowing are paralysed and yet the child may be fully conscious and can think normally. One may equally remove a whole cerebral hemisphere thus limiting the content of consciousness and yet the child is fully conscious. Extensive disease of both cerebral hemispheres will cause severe mental defect or dementia and so limit or even abolish all cognitive learning (as in post - traumatic persistent vegetative state) and thus grossly restricting the content of consciousness (thought processes) and yet the child is still conscious. That is to say there is a relatively small area of upper brain stem, thalamus and septum which appears to be necessary to sustain consciousness and a small lesion here as with tentorial herniation secondary to raised intracranial pressure, primary midbrain injury in trauma, localised encephalitis or tumour may cause prolonged coma. An irreversible lesion in the brainstem eg central ischaemic neuronal necrosis, can result in permanent failure of cortical arousal and consciousness, hence the concept of brain death depends upon brain stem function rather than cortex. The mesencephalic reticular formation leads to continuous sleep and lesions in the medullary reticular formation to constant wakefulness. The reticular formation is a continuous network of small interconnected cells which have a basketwork of axons, dendrites and side connections form

ascending and descending pathways. The dendrites are long and straight. The axons run upwards and downwards coveing many levels from the same cell. The reticular formation starts caudally in the central grey matter of the spinal cord and is then present in medulla as the medial and lateral reticular nuclei which give rise to the reticulospinal pathways. There are some very large cells in the medulla and pons ie the gigantocellular nucleus. The midbrain, thalamic reticular nucleus and intralaminar thalamic nuclei all form part of the systemThere are also the specific neurotransmitter pathways which influence the cerebral cortex and basal ganglia eg.

The EEG desynchronises with reticular activating stimulation causes the synchronised slow waves of sleep to disappear with lower amplitude asynchronous fast activity appearing. It takes only 10 seconds of ischaemia to flatten the EEG and impair consciousness but 4 minutes ro irreversibly damage the cortex. Even after reanimation there is often consciousness with sleep wake cycles but little content or communication. Consciousness depends upon energy from oxygenation but is not permanently lost by periods of hypoxia,

This study sought to determine whether electrical stimulation of the amygdaloid central nucleus (ACe) produces cholinergically mediated neocortical arousal manifested in the suppression of frontal cortex delta wave (1-4 Hz) activity.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

The components of these ascending systems can be divided into two major pathways, one ventral, the other dorsal, both of which arise from the reticular nucleus in the medulla oblongata. In addition to maintaining wakefulness, several of the nuclei of these two pathways use acetylcholine and glutamate as neurotransmitters and are partly responsible for the cortical activation that occurs during

The ventral pathway is called the reticulo-hypothalamic-cortical pathway. It projects to the posterior hypothalamus and to the nucleus of Meynert, which consists of cholinergic neurons and is located in the basal telencephalon.The dorsal pathway is called the reticulo-thalamic-cortical pathway. It activates the cholinergic mesopontine nuclei, the aspartergic and glutamergic neurons of the

midbrain reticular formation, and the thalamus.

1 Ventrolateral nucleus – motor from Cerebellum (motor cortex) and basal ganglia (supplementary motor area)

2 VPL and VPM – sensory information from spinothalamic and posterior column / medial lemniscus

3 Vision – lateral geniculate- Visual Cortex area 17

4 Hearing – medial geniculate – Heschl’s gyrus

5 Intralaminar thalamic N - Reticular formation – arousal & attention.

6 Nucleus reticularis – surface rim Gabinergic cells and controls all thalamic nuclei – attention

7 Dorso medial N major input to prefrontal lobe from Amygdala reticular formation and hypothalamus and reciprocal frontal.

8 Anterior Nucleus project to Cingulate Gyrus. (Papez) from Mamillary body

Reticular Inhibiting system.

Links limbic, hypothalamic, amygdala and cortex.

Causes of Unconsciousness.

Most cases of coma are due to

a) Tentorial herniation with midbrain compression from raised

intracranial pressure, Duret haemorrhages

b) Trauma with primary midbrain injury

b) Hypoxia

c) Drugs affecting the reticular formation including general

anaesthetics.

Primary upper brain stem tumours and infarcts are uncommon, upper brain stem

infarcts and haemorrhages are most commonly secondary to raised intracranial

pressure. Trauma can cause primary brainstem injury without any raised pressure.

Loss of cerebral perfusion as in syncope or any other transient ischaemic attack will

cause rapid loss of consciosness.

Hypnotic drugs have specific actions on the reticular activating system there may be

natural endogenous hypnotics such as natural benzodiazipines in the same way that

there are natural endogenous opoids. Toxic substances accumulate in renal and hepatic

failure or inborn errors in metabolism appear to work in the same way on the high

metabolic activity of this multisynapse system, it is for the same reason that hypoxia

or hypoglycaemia can also rapidly produce coma.. Another way to very rapidly make

a person unconscious is to give them a general anaesthetic. These substances are

usually alcohols or ethers of fatty acids such as chloroform, ether and Halothane.

They are postulated to work through GABA receptors causing inhibition of the cell.

The brain forms 2% body weight (1.5 / 70 Kg) but takes 20% oxygen consumption.

The most sensitive way to reduce consciousness and flatten the EEG is to reduce the

cells metabolism by hypoxia. This suggests that consciousness requires a constant

energy supply and is an active process in the cell. The reticular formation,

hippocampus and basal ganglia have the highest oxygen uptake.

Inhaled anaesthetic agents act in different ways at the level of the central nervous system. They may disrupt normal synaptic transmission by interfering with the release of neurotransmitters from pre-synaptic nerve terminal (enhance or depress excitatory or inhibitory transmission), by altering the re-uptake of neurotransmitters, by changing the binding of neurotransmitters to the post-synaptic receptor sites or by influencing the ionic conductance change that follows activation of the post-synaptic receptor by neurotransmitters. Both pre- and post-synaptic effects have been found.Direct interaction with the neuronal plasma membrane is very likely, but indirect action via production of a second messenger also remains possible. The high correlation between lipid solubility and anaesthetic potency suggests that inhalational anaesthetic agents have a hydrophobic site of action. Inhalational agents may bind to both membrane lipids and proteins. It is not clear which of the different theories are most likely to be the main mechanism of action of inhalational anaesthetic agents.The Meyer-Overton theory describes the correlation between lipid solubility of inhaled anaesthetics and MAC and suggests that anaesthesia occurs when a sufficient number of inhalational anaesthetic molecules dissolve in the lipid cell membrane. The Meyer-Overton theory postulates that it is the number of molecules dissolved in the lipid cell membrane, and not the type of inhalational agent, that causes anaesthesia. Combinations of different inhaled anesthetics may have additive effects at the level of the cell membrane.

The protein receptor hypothesis postulates that protein receptors in the central nervous system are responsible for the mechanism of action of inhaled anaesthetics. This theory is supported by the steep dose-response curve for inhaled anaesthetics. However, it remains unclear if inhaled agents disrupt ion flow through membrane channels by an indirect action on the lipid membrane, via a second messenger or by direct and specific binding to channel proteins.Another theory describes the activation of gamma-aminobutyric acid (GABA) receptors by the inhalational anaesthetics. Volatile agents may activate GABA channels and hyperpolarise cell membranes. In addition, they may inhibit certain calcium channels and therefore prevent the release of neurotransmitters and inhibit glutamate channels. Volatile

anaesthetics therefore may share common cellular actions with other sedative, hypnotic and analgesic drugs.

We have already discussed the hypothesis that the current content of consiousness is

the equivalent of that part of short term memory which would appear on the video

display unit in computer terms. All material must be brought into consciousness to be

processd, ie. thought about. There are varying degrees of consciousness ranging from

wide awake and alert to coma.

Thought is the content of consciousness

Short term memory is the capacity of consciousness

Attention maintains the current content of consciousness

Distraction clears current content.

It is lesser degrees of loss of cortical arousal which are important to the teacher and

learning. The teacher may know if a child is sleepy and lethargic but there are

obviously different degrees of arousal which are not always easy to define.

If a child is on certain anticonvulsant medication , is bored, was watching television

till late at night then he may be drowsy with impaired speed and accuracy of thought

processes. The same applies to the taking of drugs, alcohol or solvent sniffing.

Sleep

Anaesthesia

Coma Scores

ATTENTION.

Attention is the willed or voluntary selection of a topic to hold within consciousness

utilising short term memory in order to allow mental processing (thinking). Attention

is the focusing of conscious awareness upon

i) a particular motor activity - especially whilst it is being learned.

ii) a specific sensory input or perception.

iii) memories and concepts retrieved from long term memory stores into

short term memory.

Sustained attention requires a high level of arousal and the drowsy child or bored

child will have a short attention span. Distractability is the opposite to “paying

attention” the child loses attention, short term memory is cleared and one loses the

train of thought. Attention is accompanied by the rejection of simultaneous unwanted

sensory stimuli which are said to be "gated" out eg. enviornmental noise as distinct

from speech sounds, sensation from muscles, skin eg seating and clothing and other

visual stimuli other than those relevant to the task in hand. If these irrelevant stimuli

are not gated out they enter conscious awareness and interfere with thought processes

so that one may " lose the stream of thought " ie one is distracted and this clears short

term memory so one has to start again. Attention is also lost, a secondary attention

deficit, when the material is boring, irrelevant, or provokes anxiety and equally is

sustained when it is interesting and excites curiosity.

It is though that the intralaminar thalamic nuclei and the pre-frontal lobes are

important anatomically in the maintenance of attention. It is a well documented

clinical observation that certain drugs such as phenobarbitone and benzodiazipines

will disrupt attention causing the child to be more distractible. Frontal lobe damage

following head injury can often be demonstarted by SPECT scans and is associated

with a major attention deficit. True Lead poisoning with clinical signs can cause

severe overactive behaviour but the evidence that normal low levels are responsible

for any behavioural abnormality is not proven. The evidence that colouring agents,

salicylates and E numbers in foods cause a true toxic encephalopathy with selective

damage to the prefrontal lobes and intralaminar thalamic nuclei is not convincing.

Children with Coeliac disease certainly are overactive in the true sense with a

measurable increase in motor activity and restlessness are also very irritable children

possibly due to a true toxic encephalopathy from absorbtion of larger peptides which

improves with institution of gluten free diet.

If Attention loss is situational eg when trying to read, and yet the child will perform

the most boring tasks when succeeding, such as watch T.V. for long periods, sustain

play or games and may sit patiently for several hours during assessment or computer

psychometrics then a primary attention deficit is unlikely. Anxiety is certainly a cause

of disrupted attention, the child will concentrate if succeeding but as soon as his area

of difficulty arises and failure is iminent then concentration goes and the child figits

and becomes restless. In very many children with learning disorder the attention

defect is a secondary situational disorder from induced anxiety and not a primary

biological defect.

A primary disorder of attention has been postulated for many years as a major cause of

learning disorder. A.D.D. or attention deficit disorder, this is considered in more detail

in another chapter of this book ( see page - ). This is in some cases a more acceptable

excuse for P.D.D. - parent discipline disorder. This is not to deny the existence of a

hyperkinetic syndrome with learning disorder, poor concentration and distractibility

which shows concordance in twin studies and suggests a true genetic basis. For a

sustainable diagnosis the condition must be diagnosed before 7 years with at least 6

symptoms attributable to attention deficit and 6 to hyperactivity or poor impulse

control ie “rages”. The condition must also not be situational and so occur at school

and at home. Anxiety with parental marriage breakdown and inconsistent discipline

particularly during the “terrible twos” stage may cause hyperactivity at home and

anxiety from an undiagnosed learning disorder mainly at school. True cases may show

impaired frontal lobe perfusion which is reversed with sympathomimetic amine

therapy such as Methylphenidate. This is thought to be a dopamine reuptake inhibitor.

Search for an abnormality of Dopamine receptors particularly DRD4 have bees

suggestive but not conclusive. Poor impulse control with bias of the fight and flight

reaction in favour of fight shows as a low frustration tolerance and rage reactions.

Sleep disturbance is also a major component and often an early sign present from

infancy. The place for ADD as the causation of the vast majority of children with

learning disorder is questioned by the authors. The attention disorder is in most cases

due to anxiety from chronic failure and the answer is a good remedial teacher who

makes the child feel secure and not a failure and motivates him rather than prescribing

large doses of sympathomimetic amines.

Children with epilepsy especially complex partial seizure arising in the temporal lobe

or children brain damaged from asphyxia at birth, encephalopathy of low birth weight,

hydrocephalus and after head injury may certainly show attention deficit and learning

disorder. Most children with learning disorders are not brain damaged.

In the case of the mentally handicapped child his deficit in cognitive learning means

that he cannot sustain thought on a particular subject as for example how to sustain

play through imagination and "saying to himself" in order to know what to do with a

toy car or aeroplane. The child cannnot sustain play and flits from toy to toy or

activity to activity this makes him appear to have attention defect which is again a

secondary phenomn due to his cognitive difficulty.