THALAMUS

The thalamus is a midline paired symmetrical structure within the

brains of vertebrates, including humans. It is situated between the
cerebral cortex and midbrain, both in terms of location and
neurological connections. Its function includes relaying sensation,
spatial sense and motor signals to the cerebral cortex, along with
the regulation of consciousness, sleep and alertness. The thalamus
surrounds the third ventricle. It is the main product of the
embryonic diencephalons.

STRUCTURE

The thalamus is the largest structure in the diencephalon, the part

of the brain situated between the midbrain (mesencephalon) and
forebrain (telencephalon). Anatomically, the thalamus is perched
on top of the brainstem, near the center of the brain, in a position to
send nerve fibers out to the cerebral cortex in all directions. The
diencephalon includes also the dorsally located epithalamus
(essentially the habenula and annexes) and the perithalamus
(prethalamus formerly described as ventral thalamus) containing
the zona incerta and the "reticulate nucleus" (not the reticular, term
of confusion). Due to their different ontogenetic origins, the
epithalamus and the perithalamus are formally distinguished from
the thalamus proper.

In humans, the two halves of the thalamus are prominent bulb-

shaped masses, about 5.7 cm in length, located obliquely (about
30°) and symmetrically on each side of the third ventricle.

ANATOMY

The thalamus comprises a system of lamellae (made up of

myelinated fibers) separating different thalamic subparts. Other
areas are defined by distinct clusters of neurons, such as the
periventricular gray, the intralaminar elements, the "nucleus
limitans", and others. These latter structures, different in structure
from the major part of the thalamus, have been grouped together
into the allothalamus as opposed to the isothalamus. This
distinction simplifies the global description of the thalamus.

The thalamus is a paired structure joined at the midline and sitting

very near the center of the brain. In the human, each half is roughly
the size and shape of a walnut. There are two major components.
First is thedorsal thalamus, which is comprised of roughly 15
nuclei with relay cells that project to the cerebral cortex. (By
"cortex" in this account, we mean "neocortex.") Second is
the ventral thalamus, the major portion of which is the
thalamic reticular nucleus, which sits like a shield flush against
the lateral surface of the dorsal thalamus; reticular cells
are GABAergic and project into the dorsal thalamus to inhibit relay
cells. The figure schematically shows the major thalamic nuclei.
The other cellular component of thalamus, in addition to relay and
reticular cells, is interneurons, which are also GABAergic, sit
amongst the relay cells, and inhibit them. Generally, the relay cell
to interneuron ratio is between 3 and 4 to one. An exception is
found the mouse and rat, in which interneurons are essentially
missing from all thalamic nuclei except the lateral geniculate
nucleus (Arcelli et al, 1997).
Most of the relay nuclei topographically innervate the middle
layers of cortex, but a few along the midline and extended between
other nuclei project rather diffusely to upper cortical layers,
including layer 1; rather little is known of these latter, diffusely-
projecting nuclei, and they are not further considered in this
account. The remaining thalamic relay nuclei each innervate one or
a small number of cortical areas. Indeed, all information reaching
cortex passes through thalamus, and thus thalamus sits in a
strategic position for brain processing.
The major role of thalamus is to gate and otherwise modulate the
flow of information to cortex. For example, visual information
from the retina is not sent directly to visual cortex but instead is
relayed through the lateral geniculate nucleus of the thalamus.
Thus thalamus represents the final bottleneck of information flow
before it gets into cortex. In other words, to modify information
flow for processes of attention and other behavioral requirements,
it is more efficient to do this at the level of thalamus before it
reaches cortex. While there is still much to learn about the cell and
circuit properties of thalamus in this role, what we do know
supports this general view of thalamic function.

ARTERIAL SUPPLY

The thalamus derives its blood supply from four arteries including
the polar artery(posterior communicating artery), paramedian
thalamic-subthalamic arteries, inferolateral (thalamogeniculate)
arteries, and posterior (medial and lateral) choroidal arteries. These
are all derived from the vertebrobasilar arterial system except the
polar artery.

FUNCTION

The thalamus has multiple functions. It is generally believed to act

as a relay between a variety of subcortical areas and the cerebral
cortex. In particular, every sensory system (with the exception of
the olfactory system) includes a thalamic nucleus that receives
sensory signals and sends them to the associated primary cortical
area. For the visual system, for example, inputs from the retina are
sent to the lateral geniculate nucleus of the thalamus, which in turn
projects to the primary visual cortex (area V1) in the occipital lobe.
The thalamus is believed to both process sensory information as
well as relaying it—each of the primary sensory relay areas
receives strong "back projections" from the cerebral cortex.
Similarly the medial geniculate nucleus acts as a key auditory relay
between the inferior colliculus of the midbrain and the primary
auditory cortex, and the ventral posterior nucleus is a key
somatosensory relay, which sends touch and proprioceptive
information to the primary somatosensory cortex.

The thalamus also plays an important role in regulating states of

sleep and wakefulness. Thalamic nuclei have strong reciprocal
connections with the cerebral cortex, forming thalamo-cortico-
thalamic circuits that are believed to be involved with
consciousness. The thalamus plays a major role in regulating
arousal, the level of awareness, and activity. Damage to the
thalamus can lead to permanent coma.

Many different functions are linked to various regions of the

thalamus. This is the case for many of the sensory systems (except
for the olfactory system), such as the auditory, somatic, visceral,
gustatory and visual systems where localized lesions provoke
specific sensory deficits. A major role of the thalamus is devoted to
"motor" systems. This has been and continues to be a subject of
interest for investigators. VIm, the relay of cerebellar afferences, is
the target of stereotactians particularly for the improvement of
tremor. The role of the thalamus in the more anterior pallidal and
nigral territories in the basal ganglia system disturbances is
recognized but still poorly understood. The contribution of the
thalamus to vestibular or to tectal functions is almost ignored. The
thalamus has been thought of as a "relay" that simply forwards
signals to the cerebral cortex. Newer research suggests that
thalamic function is more selective.

PATHOLOGY

Cerebrovascular events (strokes) can cause thalamic syndrome,

which results in a contralateral hemianaesthesia, burning or aching
sensation on one half of a body (painful anaesthesia) often
accompanied by mood swings. Ischemia of the territory of the
paramedian artery, if bilateral, causes serious troubles including
akinetic mutism accompanied or not by oculomotor troubles. It is
also related to Thalamocortical Dysrhythmia.

Korsakoff's Syndrome stems from mammillary bodies,

mammilothalamic, or thalamic lesions.

Fatal familial insomnia is a hereditary prion disease in which

degeneration of the thalamus occurs, causing the patient to
gradually lose his ability to sleep, progressing to a state of total
insomnia, which invariably leads to death.

DEVELOPMENT

The thalamic complex is composed of the perithalamus (or

prethalamus, previously also known as ventral thalamus), the mid-
diencephalic organiser (which forms later the zona limitans
intrathalamica (ZLI) ) and the thalamus (dorsal thalamus) The
development of the thalamus can be subdivide into three steps

EARLY BRAIN DEVELOPMENT

After neurulation the anlage of the prethalamus and the thalamus is

induced within the neural tube. Data from different vertebrate
model organisms support a model, in which the interaction
between two transcription factors, Fez and Otx, is from decisive
importance. Fez is expressed in the prethalamus, and functional
experiments show that Fez is required for prethalamus formation
Posteriorly, Otx1 and Otx2 abut the expression domain of Fez and
are required for proper development of the thalamus.

The formation of the mid-diencephalic organiser (MDO)

At the interface between the expression domains of Fez and Otx,

the mid-diencephalic organizer (MDO, also called the ZLI
organiser) is induced within the thalamic anlage. The MDO is the
central signalling organizer in the thalamus. A lack of the
organizer leads to the absence of the thalamus. The MDO matures
from ventral to dorsal during development..

Besides its importance as signalling center, the organizer matures

into the morphological structure of the zona limitans intrathalamica
(ZLI).
RETICULAR FORMATION

The reticular formation is a part of the brain that is involved in

actions such as awaking/sleeping cycle, and filtering incoming
stimuli to discriminate irrelevant background stimuli.It is essential
for governing some of the basic functions of higher organisms, and
is one of the phylogenetically oldest portions of the brain.

Functions

Functions of the Reticular Formation

• The reticular formation is involved in 4 general types of

function:

1. Motor control;
2. Sensory control;
3. Visceral control;
4. Control of consciousness.

Motor Control

• Motor control has several different aspects.

1. Certain reticular regions are closely related to

the cerebellum and its motor control functions.
o A fairly discrete collection of cells in the medullary
reticular formation, the lateral reticular nucleus is
resolved adjacent to the spinothalamic tract.
o It receives direct spinoreticular
fibres, collaterals of spinothalamic fibres, and projects
them to the cerebellum.
o It also receives input from the red nucleus, so it
is more than a straightforward somatosensory
relay to the cerebellum.
 o Collections of reticular neurons near the medullary
midline, the paramedian reticular nucleus, also
project to the cerebellum.
o Afferents to the paramedian nucleus arise in
the cerebellum and in other locations, including
the cerebral cortex.
o The reticular tegmental nucleus, located between
the medial lemnisci in the rostral pons, receives inputs
from the cerebral cortex and other sites.
o It also projects to the cerebellum.

2. There are 2 reticulospinal tracts arising from the medial

zone of the pontine and the rostral medullary reticular
formation.
o Fibres from the pons descend with the ipsilateral
MLF and travel through the ventral funiculus in
the spinal cord, as themedial reticulospinal tract.
o Fibres from the medulla descend bilaterally in
the ventral part of the lateral funiculus, as the lateral
reticulospinal tract.
o These tracts are a major alternate route to
the corticospinal tract.
o These reticular neurons receive
projections from many areas, including the basal
ganglia, red nucleus, and substantia nigra.
o Input from widespread areas of the cerebral cortex,
particularly the somatosensory and motor cortex,
seems to be especially important.
o Most of these descending fibres travel to
their reticular terminations in the central tegmental
tract.

3. The reticulospinal tracts also carry descending motor

commands generated within the reticular formation itself.
 o The reticular formation contains the neural machinery
for considerably complex patterns of movement.
o A cat whose brainstem has been surgically
separated from its diencephalon can, after a recovery
period, assume a variety of complex tasks such as
walking and running, and righting itself if tipped over.

Sensory Control

• Reticular neurons exert some control over activity in spinal

reflex arcs.
• They can control over the access of sensory
information to ascending pathways.

• Tonic inhibition of flexor reflexes originates in

the reticular formation.
• The result that only noxious stimuli can normally evoke
such a reflex.

• In addition, stimulation of certain regions of the medullary

reticular formation causes inhibition of some sensory
interneurons andtract cells in the spinal cord.
• This seems to be important in the regulation of pain
perception.

Visceral Control

• Centres controlling inspiration, expiration, and

the normal rhythm of breathing have been identified
physiologically in the medullaand pons.
• Other centres controlling heart rate and blood
pressure have been identified in the medullary reticular
formation.
Control of Consciousness

• Ascending projections from the reticular

formation terminate in
the thalamus, subthalamus, hypothalamus, and basal
ganglia.
• The functions of most of these are poorly understood, but
those to the thalamus seem to be particularly important.
• They terminate in the intralaminar nuclei, which in
turn project to widespread areas of the cortex.

• Activity in this pathway is essential for the maintenance of

a normal state of consciousness.
• Bilateral damage to these fibres as
they traverse or originate in the midbrain reticular
formation results in prolonged coma.

STRUCTURE
The reticular formation has been functionally cleaved
both sagittally and coronally.

 The original functional differentiation was a division

of caudal and rostral, this was based upon the observation that
the lesioning of the rostral reticular formation induces
a hypersomnia in the cat brain. In contrast, lesioning of the more
caudal portion of the reticular formation produces insomnia in
cats. This study has led to the idea that the caudal portion
inhibits the rostral portion of the reticular formation.
  Sagittal division reveals more morphological distinctions.
The raphe nuclei form a ridge in the middle of the reticular
formation, and, directly to its periphery, there is a division
called the medial reticular formation. The medial RF is large
and has long ascending and descending fibers, and is
surrounded by the lateral reticular formation. The lateral RF is
close to the motor nuclei of the cranial nerves, and mostly
mediates their function.

MEDIAL AND LATERAL RETICULAR FORMATION

The medial reticular formation and lateral reticular formation are
two columns of neuronal nuclei with ill-defined boundaries, which
go up through the medulla and into the mesencephalon (midbrain).
The nuclei can only be teased out by function, cell type, and
projections ofefferent or afferent nature.

DAMAGE TO THE RETICULAR FORMATION

The reticular formation is a part of the brain which is involved in

procedural actions, such as walking, sleeping and lying down. It is
located in the brain stem, centered in the pons. It plays a major role
in controlling physical behaviors such as sleep and mental
activities such as motivation and attention. It is the base of
consciousness that is responsible for mental alertness.

Damage to this particular structure can result in impairment in

motor skills, visual discrimination, concentration and attention .
An individual will display poor memory, difficulty with learning, a
lack of consciousness, and in some cases fall into a coma in which
the individual is not in a state of awareness and is totally
unresponsive.
Thalamic Disorders

After a stroke, a person may experience thalamic pain or “central

pain syndrome” due to damage to the spinal tracts that carry pain
and temperature sensation from the periphery to the thalamus.
Damage to the spinothalamic or trigeminothalamic tract result in
severe, spontaneous pain in the parts of the body connected to the
damaged tracts. Thalamic pain starts several weeks after the stroke
and presents as an intense burning pain on the side of the body
affected by the stroke and is often worsened by cutaneous
stimulation. Blood supply to the thalamus is via the anterior or
carotid arterial system.

It is important to know the different types of deficits resulting from

damage to the thalamus and to remember that the thalamus can be
selectively damaged with little or no damage to the internal capsule
or deep motor nuclei by blockage of the thalamoperforating
branches of the posterior cerebral artery. Damage to the
thalamoperforating branches can cause a thalamic syndrome.

Symptoms Following Lesions of the Thalamus

There are two considerations that must be taken into account when
attempting to diagnose lesions of the thalamus:

1) thalamic nuclei are small so that lesions producing highly

specific effects are uncommon (although they do occur), and

2) the thalamus is immediately bounded by the internal capsule and

is in close proximity to the deep motor nuclei of the cerebral
hemisphere (putamen, caudate and globus pallidus) so that
thalamic lesions frequently are accompanied by symptoms from
damage to these other structures. However, since small branches of
the posterior cerebral artery supply much of the thalamus but not
adjacent structures, selective thalamic lesions do occur.
 Occlusion of these small branches results in a number of
symptoms characteristic of the thalamic syndrome.

1) If the damage includes VPL and VPM a contralateral

hemianesthesia usually results. Typically, all somatic sensory
modalities are affected: light touch, conscious proprioception, 2-
point discrimination & vibration, and pain & temperature. This
loss of all somatic sensory modalities is an important diagnostic
sign for thalamic damage (lesions of the internal capsule or cortex
that impair somatic sensory function typically affect different
modalities to different extents, often leaving pain

sensation unchanged).

2.) Sometimes seen after a period of recovery from damage to

VPL and VPM (days to months) is hyperalgesia (an exaggerated
unpleasant or painful sensation resulting from mild cutaneous
stimulation) or in some cases spontaneous pain with no apparent
stimulation (causalgia). Such pain can be severe and intractable.
Hyperalgesia and spontaneous pain do not occur with lesions
confined to the cerebral hemispheres (cortex, internal capsule, or
deep nuclei). Obviously, damage to the postero-lateral part of

the thalamus also will involve other nuclei such as the pulvinar and
lateral posterior, but unilateral infarcts in these higher order
“association” nuclei typically result in no obvious deficits.

3.) If the LGB is affected there is a contralateral homonymous

hemianopsia.
4) If the damage extends into the VA/VL nuclei complex
movement disorders can result. The movement disorders can be
reminiscent of cerebellar damage (ataxia and intention tremor)
and/or basal ganglia damage (choreoathetoid movements). This
reflects, in part, the fact that both the cerebellum and basal ganglia
project to VA and VL. All such problems occur contralateral to
the side of the lesion