ART OF BRAIN WHICH CONTROLS CONSCIOUSNESS, MEDICAL INTEREST.

Consciousness is defined as the state of awareness of self and the environment. Another way of describing
it is a condition for which a person is capable of perceiving stimuli from the environment and responding
appropriately.
The consciousness system has two principal functions:
1) Maintenance of waking state (arousal or level of consciousness)
2) Content of experience (awareness or content of consciousness)
The consciousness system is a diffuse yet organized neuronal system located in the brainstem,
diencephalon, and cerebral hemispheres with diffuse reciprocal connections. Although it is complex and
still much to be explored, it can be divided into few groups of structures for current understanding. This
includes:
1) Nuclei of the brainstem reticular formation, hypothalamus, basal forebrain, and thalamus;
2) The ascending projection pathways;
3) Widespread areas of the cerebral cortex
Reticular Formation
This is a complex aggregate of neurons with its cell bodies form clusters in the tegmentum of brainstem,
the basal forebrain, and the thalamus. It is known as reticular because of its diffuse multipolar synapses
and interconnection. This reticular formation can be further subdivided functionally into 3 columns: the
raphe (midline), the medial and lateral region. The function of each column is summarized in the diagram
below (Fig 1). The reticular formation has tremendous afferent and efferent connection ranging from
cerebral cortex, thalamus, hypothalamus, to the spinal cord. Generally, such tremendous pathway of the
reticular formation can be described into 2 parts, the rostral part and the caudal part. The rostral part
reticular formation, vaguely begin at the level of the upper pons and midbrain, contains neurochemically
classified groups of neurons that project to the cerebral cortex either directly or by relay in the thalamus.
This is the reticular ascending pathway (some named it activating reticular ascending pathway abbr. ARAS)
and it is important in the consciousness system. The caudal part (vaguely the lower pons and medulla) has
projection to the spinal cord and is involved in motor function, respiration and regulation of blood pressure.
This is the descending pathway. Although it is divided vertically as such, you should keep in mind that the
ascending pathway does arise from medulla as well. You may read in some textbooks that reticular
formation can be divided into cerebellar portion and non-cerebellar portion but it is not relevant here,
similarly to some of the more specifically named nuclei.

Fig 1. General organization of the brainstem reticular formation. Image obtained from [ref2]
In order to further comprehend the consciousness system, the ascending pathway can be categories into
different groups or nuclei by its neurochemical nature; cholinergic and monoaminergic systems.
Interestingly, both these system projects extensively to the cerebral cortex via the medial forebrain
bundle. This is a large tract that extends from the midbrain tegmentum through the lateral hypothalamus

and into its septum and preoptic area. Some of the neural tract from medial forebrain bundle enters into
cingulate gyrus.
The cholinergic system
These cholinergic nuclear groups, which utilize acetylcholine as neurotransmitter, are situated at :
1. Basal forebrain (divided into nucleus basalis of Meynert and the medial septum)
2. Mesopontine tegmentum (dorsal tegmentum of the upper pons and midbrain)

Fig 2. Cholinergic nuclear groups of the consciousness system. Shows in (A), the basal forebrain, including
the nucleus basalis of Meynert and medial septum, which project to the cerebral cortex. In (B), shows the
mesopontine cholinergic group, projects to the thalamus, basal forebrain, and brainstem. Image obtained
from [ref2].
The monoaminergic system
This group consists of 4 different subgroup of different neurotransmitter: dopamine, norepinephrine,
serotonin and histamine. Each has their specific location and pathway.
1. The dopamine-synthesizing neurons are located in the substantia nigra pars compacta and ventral
tegmental area of the midbrain.
2. The norepinephrine synthesizing neurons are located in the locus ceruleus, which is in the lateral part of
the upper pons.
3. The serotonin-synthesizing neurons are located in the raphe nuclei, which occupy the midline of the
brainstem as mentioned above. It is further divided into rostal and caudal parts.
4. The histamine-synthesizing neurons are located in the tuberomammillary nucleus in the posterior lateral
hypothalamus.

Fig 3. In (A), the dopamine-synthesizing neurons are located in the substantia nigra pars compacta. (B), the
norepinephrine-synthesizing neurons located at the locus ceruleus project extensively. Image obtained
from [ref2]

Fig 4. (A), The serotonin-synthesizing neurons are located in the raphe nuclei. The rostral raphe nuclei,
located in the upper pons and midbrain. (B), is the histamine-synthesizing neurons of the
tuberomammillary nucleus.
By now, you may have notice that all these nuclei are mostly situated at the midbrain and upper pontine
tegmentum. This shows how essential these parts of brainstem are in consciousness and interruption of
the ascending pathway would result in coma.
Thalamus in consciousness system
The thalamus can be divided functionally into 2 groups, the dorsal thalamus which has massive connection
with the cerebral cortex and brainstem, and reticular thalamus which interconnect among the thalamic
nucleus rather than externally.
In the interest of consciousness, among all nucleus of thalamus, the intralaminar nuclei and the midline
nuclei is significantly taking part in the consciousness role. They receive input from reticular formation,
basal forebrain, basal ganglia and the limbic system and widespread output to the cerebral cortex, basal
ganglia, and the hypothalamus. Another important structure in the consciousness system is the reticular
nucleus of the thalamus. This nucleus although do not has efferent pathway to cerebral cortex but does
receive afferent input from major portion of the brain.

Fig 5. Images show the nucleus of thalamus. Image obtained from [ref3].
Cerebral cortex
It is rather obvious that there is no single cortical area that is for maintenance of consciousness. Almost all
cortical interconnection has to be disrupted before someone can lose consciousness (provided the
thalamus and reticular formation is intact). Hence we can conclude that all cortical area is involved in
consciousness system as a whole.
Medical context
What damage will result in loss of consciousness?
From clinical and experimental evidence, we know that functional integrity of the upper pontine and
midbrain reticular formation, interlaminar nucleus, midline nucleus of thalamus, reticular thalamus, and
bilateral cerebral cortex is critical for the maintenance of consciousness. To summarize, there are 3
primary mechanisms that will affect the consciousness system. These are:
1. Lesion of the brainstem reticular activating system or bilateral posterior hypothalamus
2. Bilateral disruption of the ascending projections at the level of thalamus
3. Diffuse bilateral hemispheric cortical lesion.
Although the consciousness is affected, different level of interruption results in different consequences as
shown in the diagram below.

Fig 6. Image shows the effects toward consciousness resulting from different level of interruption. Image
obtained from [ref2]
Coma, however, can occur from the following entity:
1. focal lesion of the posterior fossa that involved the brainstem
2. focal supratentorial lesion, which if large enough, involved the midline diencephalic structure (e.g.
intralaminar and midline nucleus of thalamus) either directly or indirectly.
3. Diffuse lesion from any causes such as anoxia, toxin, metabolic factor and inflammation.
References.
1. Anthony H.V. Schapira, ed. Neurology and clinical neuroscience. Elsevier, Philadelphia, PA. 2007

2. Eduardo E. Benarroch et al., ed. Mayo Clinic Medical Neurosciences: organized by neurological systems
and levels. Fifth edition. Mayo Clinic Scientific Press. Rochester, MN. 2008
3. Stanley Jacobson and Elliott M. Marcus, ed. Neuroanatomy for neuroscience. Springer, Boston. MA. 2008
lateral ventricles--> foramen of Monro third ventricle --> aqueduct of Sylvius --> fourth ventricle -->
foramina of Magendie and Luschka --> subarachnoid space over brain and spinal cord --> reabsorption into
venous sinus blood via arachnoid granulations.
Pathological and clinical consequences of infection The macroscopic consequences of infection have been
researched post mortem and, more recently, through CT and MRI (figure 2) of the brain. Neurological
abnormalities occur with the development of an inflammatory exudate that affects mostly the sylvian
fissures, basal cisterns, brainstem, and cerebellum.10 Three processes cause most of the common
neurological deficits: the adhesive exudate can obstruct CSF causing hydrocephalus and compromise
efferent cranial nerves; granulomas can coalesce to form tuberculomas (or an abscess in patients with
uncharacteristic disease) which, depending on their location, cause diverse clinical consequences; and an
obliterative vasculitis can cause infarction and stroke syndromes.10 T
Pathogenesis and immune response of cerebral tuberculosis: The lung is initially infected by the aereal
route (1); bacilli grow in the lungs and disseminate after blood vessels invasion (2) producing systemic
infection (3) affecting the brain (4). Small groups of inflammatory cells are located in the subpial or
subependymal areas (Rich nodules) after early bacteremia (5), where bacilli are content and may remain
dormant for long time. Later, growth and rupture of these lesions produces meningeal tuberculosis (6).
Mycobacterial infection induces the production of proinflammatory cytokines that are important for bacilli
killing but they can also produce immunopathology (7). Antinflammatory cytokines are also highly
produced; they protect tissue damage by excessive inflammation and induce nervous tissue regeneration
(7).
At the early stage of brain infection, cytokines such as TNF, IL-1, and IL-6 are released by migrated
activated macrophages, microglial cells, astrocytes, and endothelial cells. These cytokines can contribute
to the entry of diverse compounds into the brain by breaching the BBB (16). It has been demonstrated an
increase in the permeability of endothelial cells in vitro after the administration of these proinflammatory
cytokines (17). Moreover, IL-1 is produced by damaged BBB and its permeability is increased by this
cytokine (18). Astrocytes and microglial cells can also produce IL-1 affecting the BBB permeability (19).
Thus, it seems that the function and integrity of BBB is affected by the production of proinflammatory
cytokines produced by astrocytes, microglial, and endothelial cells (16), which perhaps are not specific for
mycobacterial infection and other organisms may trigger this inflammatory process in the nervous system
with similar consequences.

PATHOGENESIS
The large-scale inflammation that during meningitis is largely be attributed to response of immune
system Immune cells of brain (astrocytes and microglia),respond by releasing large amounts of
cytokines, hormone-like mediators that recruit other cells &stimulate other tissues to participate in an
immuneresponse.
The blood-brain barrier becomes more permeable,leading to "vasogenic" cerebral edema (swelling ofbrain
due to fluid leakage from blood vessels) Large numbers of WBC enter CSF, causinginflammation of
meninges, & leading to "interstitial"edema (swelling due to fluid between cells). In addition, walls of
blood vessels become inflamed(cerebral vasculitis), which leads to a decreasedblood flow and a third type
of edema, "cytotoxic"edema
18. The three forms of cerebral edema all lead to an increased ICP together with low BP often encountered
in acute infection, Brain cells are deprived of oxygen & undergo apoptosis (automated cell death)

Normal values (CSF):

CSF opening pressure: 50180 mmH2O
Glucose: 4085 mg/dL.
Protein (total): 1545 mg/dL.
Lactate dehyrogenase: 1/10 of serum level.
Lactate: less than 35 mg/dL.
Leukocytes (WBC): 05/L (adults / children); up to 30/L (newborns).
Gram stain: negative.
Culture: sterile.
Specific gravity: 1.0061.009.
Syphilis serology: negative.
Gross appearance: Normal CSF is clear and colorless.
Differential: 6070% lymphocytes; up to 30% monocytes
and macrophages; other cells 2% or less.

Tubercular Meningitis
Glucose (mg/dL):

<40 mg/dL (Low)

Protein (mg/dL)

(moderate to marked increase) 50 -500 mg/dL

WBCs (cells/L)

Variable (10 -1000 cells/L) <500cells/L.

Cell differential:

Predominance of Lymphocytes

Culture:

Positive for AFB

Opening Pressure

Variable