COGNITIVE NEUROSCIENCE

KMK 1053

ASSIGNMENT 1

GENERAL ANESTHESIA DISTRUPTS BRAIN COMMUNICATION

GROUP 1

NAME MATRIC NO.

AISHAH BINTI AHMED 68979

JANAANIE A/P RAJENDRA KUMAR 69939
MOHD AMAR QAYU’UM BIN ROSLEN 70458
MOHD. ANUAR BIN ALI 70516
MOHD. QHAIRUL IZZUDDIN BIN MOHSIN 70523
REENA A/P SANDANASAMY 71383

Instructor’s Name : Dr. Philip Nuli Anding

Submission Date : 14 June 2020

Page of contents

content page
Abstract 3
Introduction 4-6
Discussion
1. What happens to the brain communication after general anesthesia is 7-13
given.
2. Who is the patient experienced disruptions in the brain and affects 14-15
the communication
3. How does general anesthesia distrupts the brain communication. 15-18
4. Which part of brain or neurons area the anesthesia disrupts the 18-19
communication in the brain.
5. When does General Anesthesia’s influences stop brain 20-21
communication.

Conclusion 22
References 23-26
 ABSTRACT

How does general anesthesia work? Anesthetics are pharmacological agents that target a
central nervous systems receptor. Once they bind to their brain receptors, anesthetics
modulate remote brain areas and end up interfering with global neuron networks, leading
to a controlled and reversible loss of consciousness, amnesia, hypnosis, analgesia and
areflexia which allows millions of people every year to undergo surgery safely most of
the time. How anesthetic agents suppress human consciousness has been investigated
with neuroimaging for two decades. Anesthetics reduces global cerebral metabolic rate
and blood flow with a degree of regional heterogeneity characteristics to the anesthetic
agent. Thalamus appears to be a common site of modulation by several anesthetic, but
this may be secondary to cortical effects. Stimulus-dependent brain activation is
preserved in primary sensory areas suggesting that unconsciousness cannot be explained
by cortical deafferentation or a diminution of cortical sensory reactivity. Anesthetics
depth often characterized by the subjects’ unresponsiveness, a partial but not complete
reduction in connectivity is observed. Anesthetic loss of consciousness is not a block of
corticofugal information transfer but a disruption of higher order cortical information
integration. The prime candidates for functional networks of the forebrain that play a
critical role in maintaining the state of consciousness are those based on the posterior
parietal-cingulate-precuneus region and the nonspecific thalamus.

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Introduction
For this assignment, our group have chosen the topic of general anesthesia. General
anesthesia is a combination of medicines that put a person in a sleep-like condition before
an operation or any other medical procedure. The main goal of this study is to show how
general anesthetics disrupts brain communication. Anesthesia is a critical part of surgery.
A patient does not feel pain under general anesthesia, because they are completely
unconscious. General anesthesia usually uses intravenous drugs combined with inhaled
gasses (anesthetics). It allows patients to undergo surgery safely without suffering or
distress. Therefore, this study focuses on how general anesthetics affect the brain.
The goal of this study is to prove that general anesthesia do disrupt the brain
communication. The part of brain that effect by anesthesia is thalamus. Thalamus could
be a small structure within the brain located just above the brain stem between the
cerebral cortex and therefore the midbrain. it's extensive nerve connections to both. the
most function of the thalamus is to relay motor and sensory signals to the cerebral cortex.
Thalamus also plays a big role in sensory perception and movement. When the
anaesthesia is given to a patient, the thalamus now not can function as normal. It cannot
relay motor and sensory signals to the cerebral cortex. Its function disrupts by the
anaesthesia. At a little dose, anaesthesia first suppress thinking, focused attention, and
dealing memory. because the dose increases, consciousness and voluntary responsiveness
begin to fade. When the patients now not respond to verbal stimulation, the doctors
presume that their consciousness is gone. For the nonce, loss of consciousness is
operationally defined as a loss of voluntary responsiveness excluding limiting factors like
the utilization of muscle relaxants, the presence of motor impairment or akinetism.
Therefore, all the evidences proved that general anaesthesia disrupts the brain
communication.
The relevance of this study is researchers want to analysis general anaesthesia
affects the human brain especially the communication part. Someone does not feel pain
under general anaesthesia, because they are fully unconscious. They are unconscious
because drugs make a patient unconscious and unresponsive. General anaesthesia is
generally very safe however older adults and those who have lengthy procedures are at

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greatest risk of negative results. Many people receive general anaesthesia during
operation using injection, or inhalation of anaesthetic gas. But not many people
understand the consequences of general anaesthesia on their brains. General anaesthetics
drive to a reversible loss of consciousness and analgesia to operate on a patient by the
surgeons. Their use is usual but it is still not fully understood how they achieve their
effect. While general anaesthetic helped make surgery a lot more convenient, these
function was a bit of a riddle. This study will provide information by researchers about
the effects of general anaesthetic on the communication of the human brain.
The usage of general anaesthesia may be derived throughout recorded history
within the writings of the traditional Sumerians, Babylonians, Assyrians, Egyptians,
Greek, Romans, Indians and Chinese. The Renaissance saw vital advances in anatomy
and surgical technique. Surgery remained as a final selection thanks to the post-surgery
pain and therefore the aspect effects caused by the surgery. Though there has been a good
deal of dialogue on UN agency deserves the foremost credit for the invention of general
anaesthesia, it is typically united that bound scientific discoveries within the late
eighteenth and early nineteenth centuries were important to the ultimate introduction and
development of recent anaesthetics techniques. Anaesthesia may be a comparatively new
field in fashionable medication. before its development, most surgical procedures were
either minor or emergency operations. it's clear that fashionable surgery and therefore the
sizable advantages it brings would be not possible while not the many tutorial,
pharmacological, and sensible advances in physiological condition throughout the
nineteenth and twentieth centuries.
First and foremost among these is that the development of safe and effective general
anaesthesia. Carbon dioxide was first explored as associate degree anaesthetic within the
1820’s by a people MD Henry H. Hickman. By inducement partial asphyxiation,
Hickman incontestable that animals can be rendered unconscious for a protracted amount,
sanctioning surgical procedures to be performed. This was a serious breakthrough,
widespread adoption of greenhouse emission as associate degree anaesthetics. Diethyl
ether, a solvent ordinarily noted merely as “ether”, was first utilized in clinically by yank
MD William E. Clarke for a tooth extraction in Jan 1824. when a number of months,
associate degree yank MD and health care provider, splendidly found and used ether as a

5
surgical anaesthetic to get rid of a growth on a young man’s neck and he discovered that
the patient felt nothing throughout the procedures. the invention of ether’s clinical utility
drawn a big advance in effective general anaesthesia, goad a flurry of interest in potential
anaesthetic agents. A former student of Wells, William T.G.Morton was instrumental
within the popularisation of ether as associate degree anaesthetic.
Morton performed a productive public demonstration of the anaesthetic capabilities
of ether in Gregorian calendar month 1846 at Massachusetts General Hospital. this will
be thought of because the birth of recent physiological condition wherever later day ether
was adopted by doctors and surgeons all round the world. Scottish medical specialist
James Y. Simpson was the primary to adopt the organs compound chloroform to alleviate
the pain of kid birth in 1847. Chloroform physiological condition grew in quality round
the world and was in use once Queen of England gave birth to aristocrat Leopold below
anaesthesia’s influence in 1853. The chloroform was administered by the celebrated MD
and epidemiologist, John Snow. within the early twentieth century, chloroform came to
succeed ether as a general anaesthesia in lightweight of its less offensive odour, and
speedy induction and emergence.
The introduction of muscle relaxants to clinical observe within the early Fifties
allowed for major advances in anaesthetics techniques and thereby surgery. A natural
organic compound traditionally used on poison darts and arrows by aboriginal folks
across Africa, Asia and America, was the primary non-depolarising relaxant used.
Through the late 1970’s to 1990’s, quaternary ammonium ion muscle relaxants were
developed. Considerable progress that has been created within the field of physiological
condition over the past 2 centuries. the event of safe, effective general permitting the
wide unfold growth of surgery and therefore the sizable advantages it brings. vital
advances on the far side the scope as well as the developments of local anaesthesia,
anaesthesia, acutely aware sedation and analgesia.

6
Discussion
What happens to the brain communication after general anesthesia is given.

A long term in neuroscience has been the identification of robust and neuronally
based measurement of consciousness. Anesthesia refers to loss of sensation for a certain
period of time and a medium that maintain the state of unconsciousness with minimal
pain sensation using pharmacological method. Local anesthesia provides analgesia only
in a localized area. General anesthesia provides generalized analgesia to generalized
hypnosis. Modern general anesthesia is based on the ability to provide adequate analgesia
and amnesia during surgical procedures. Neuromuscular blocking drugs maybe utilized to
facilitate surgical exposure by providing profound muscle relaxation. General anesthesia
is given in order to attempt both analgesia and amnesia, with or without muscle
relaxation, while maintaining the patient’s normal physiological functions. The challenge
in anesthesia is to maintain a balance between the stress of the surgical procedure and the
cardiorespiratory depressant effects of deepening levels of anesthesia. A state of general
anesthesia may be induced with the injection of anesthetic drugs, or by the inhalation of a
mixture of anesthetic vapours. With general anesthesia,muscle relaxant may be to
facilitate both tracheal intubation and muscle relaxation.

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ANESTHETICS OPTION
Local Anesthesia
Local Anesthesia with intravenous Propofol, midazolam, fentanyl, or music
conscious sedation for sendation
Neurolept-analgesia Used frequently, achieved with high
doses of droperidol with an opiod
(fentanyl) fro analgesic supplementation

Regional Anesthesia Spinal anesthesia, epidural anesthesia,

brachial plexus block, intravenous “Bier”
block, peripheral nerve blocks.

General Anesthesia Maybe combined with regional

anesthesia, peripheral nerve blocks or
local anesthesia

Modern general anesthesia uses combination of medicines as an attempt to minimize the

side effect of drugs and maximize individual benefits. Rather than using halothane alone
to provide anesthesia for abdominal surgery an anesthetist often chooses a series of
medications to match the patient’s need. These medications may include opiods to blunt
the pain response to surgery, barbiturates to include the anesthetics state and volatile
anesthetics agents such as nitrous oxide and isoflurane to maintain anesthesia state. Other
common anesthetics drugs used during general anesthesia including anesthetics,
neuromuscular blocking agents and neuromuscular antagonists. Anesthetics agents
comprises a large sort of molecules functioning on varied receptors, channels, and
different macromolecule targets within the the body. (Alkire et al., 2008; Franks.,2006;
Hemmings et al.,2005; Rudolph and Antkowiak., 2004;). The anesthesia’s impact on
consciousness would not be mysterious if they suspend all brain functions by a
widespread, nonspecific suppression of somatic cell activity throughout the brain,
generally known as the wet-blanket theory. (Sukhotinsky et al.,2007). We still do have
tendency to all perceivance a number of subconscious and involuntary functions are still

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operational once aware. Anesthetics initialize impede thinking, centered attention and
dealing memory because the dose is exaggerated, consciousness, and voluntary
responsiveness begin to fade. The patient is now unable to verbally reply, and presume
their consciousness. At higher dosage of anesthesia, brain’s electrical activity becomes
intermitted. Loss of excluding limiting factors like the employment of muscle relaxants,
the presence of motor impairment or akinetism.

A longstanding challenge in neuroscience has been the identification of robust and

neuronally based measures consciousness. Though general anesthesia is widely used in
medical field to put patients into an unconscious state. Looking into the effects of
propofol, checking the neural correlates of consciousness. It is proven that anesthetics
effects human brain which is explained via functional imaging device. Functional
imaging methods, including positron emission tomography (PET) and functional
magnetic resonance imaging (fMRI). Recent imaging studies using fMRI and PET
techniques have demonstrated the regional effects of propofol on the brain. Unfortunately
the pharmalogical mechanism regarding the action of propofol is uncertain. Recent
research demonstrated regional effects of many anesthetics agents on the brain. The
propofil is measured and it shows slight changes in regional glucose metabolism rate and
regional cerebral blood flow. The focus on molecular and cellular targets of propofol was
mainly targeted. Propofol produces its hypnotic effects by a positive modulation of the
inhibitory function of the neurotransmitter through receptors and via presynaptic
mechanism. The study of anesthesia and it’s effects, the work of Jasper and Moruzzi, the
thalamus and the brainstem reticular formation have been known to play a critical role.
GABergic cells of the reticular thalamic nucleus seems to control bursting activity of the
thalamocortical neurons and modulate the cortical activity. PET measures rCBF
distribution across the brain state, glucose uptake and neurotransmission system
activities. Neuronal activation in the brainis assumed to be coupled by parallel changes in
rGMR and rCBF. As the patient undergoes into the unconscious state, propofol markedly
reduced GMR in all brain region. Cerebral glucose metabolism in the thalamus, cerebral
cortex, hippocampus and cerebrum was decreased, particularly in the thalamus. Which
indicates the thalamus is the targeted region for propofol to induce unconsciousness.

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However, cortical glucose metabolism, such as in the capital lobe, temporal lobe, and
frontal lobe was reduced at a sedative dosage of propofol but changes in subcortical
regions like the thalamus were not obvious. Most cortical evoked responses but not fully
blocked. Kersens and colleagues (2005), used sensory stimulation throughout and assesed
memory by sensory system recognition. Propofol is probably induced by direct inhibition
of the higher central cortical neurons that control consciousness and mental actions rather
than inhibition of the ascending reticular activating system. Under the propofol-induced
unconsciousness state, the reduced blood pressure and respiratory rate found that it is
related to neuronal actions in the hippocampus region and cingulated gyrus.

However it is possible that ketamine a hallucinogenic drug does not completely

suppress preserved subjective experience. Sanders and colleagues(2012), distinguishing
among consciousness, connectedness and responsiveness as three possible hallucinogenic
drug does not completely suppress preserved subjective experience. Sanders and
colleagues (2012), distinguish among consciousness, connectedness, and responsiveness
as three possible targets of general anaesthesia. Ketamine anaesthesia may be best
described as a state of disconnection, while with other agents may produce complete
unconsciousness that is, an absence of all subjective experience.
In addition to baseline changes in CMR and CBF, several investigations were
conducted to determine how anaesthetics agents altered the brain’s functional activation
patterns evoked by sensory stimuli. As it turned out, most cortical-evoked responses were
reduced, but not fully blocked under anaesthesia at sedative hypnotic depths. This
confirmed that the cause of unconsciousness could not be a block of thalamocortical
information transfer. Subsequently, Kersens and colleagues(2005) used auditory word
stimulation during 1% and 2% sevoflurane anaesthesia and found a dose-dependent
suppression of auditory blood oxygen level dependent activation, suggesting limited
processing and memory of the presented auditory material. Thalamic activation was
preserved at 1% sevoflurane. In the later two studies, Bonhomme and colleagues (2001)
evaluated the level of consciousness by the subjects response to a verbal command.
Kerssens and Colleagues (2005) assessed memory by auditory recognition after
emergence but they noted the general absence of motor responsiveness to scanner noise at

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1% sevoflurane. Even at the deepest sedative level, propofol did not totally eliminate
primary cortical responses to acoustic stimulation, suggesting that auditory information
was still processed at some level. Plourde and coworkers (2006) also investigated the
dose-dependent effect of propofol anaesthesia on auditory processing with stimuli
increasing complexity. They found that propofol anaesthesia 4.6ml plasma concentration
reduced BOLD activations by 40%-50%, although voice-specific and word specific
activations were abolished. Paradoxically, in some brain regions, scrambled works
elicited greater activation than regular words during anaesthesia, perhaps reflecting a
greater effort to analyse word meaning. Both primary and association auditory cortices
remained responsive to auditory stimuli, but the response become nonspeci
loss of higher-level analysis. In the study by Ramani and coworkers (Ramani et.,al;2007),
light sedation with 0.25 MAC sevoflurane attenuated CBF responses predominantly in
the visual and other higher-order association cortices. Boveroux amd coworkers (2010),
found the cross-modal interactions between visual and auditory cortices disappeared
during deep sedation with propofol, memory task-related responses to auditory word
presentation persisted in the primary auditory cortex (PAC), but they vanished in higher
areas associated with memorized processes such as the inferior frontal gyrus (IFG).
Taken together, with the exception of somatosensory responses (Antognini
et.,al;1997; Bonhomme et al., 2001), functional imaging studies have shown that general
anaesthetics at a hypnotic dose preferentially reduced brain activation but not in the
primary sensory areas. We speculate that the stronger suppressive effect of anaesthetics
on tactile or nociceptive activation maybe due to peripheral and spinal suppression of the
ascending stimuli an effect that is absent in other sensory modalities. In the follows that
the loss of consciousness is not due to a simple block of corticofugal information transfer
but presumely to a lack of higher-order integration in the cortex. It should be noted that
the latter may not be due to selective anaesthetics sensitivity of higher-order cortex.
Anaesthetics drugs may target brain regions fairly and evenly as the wet-blanket theory
suggested. However, the attenuation of neuronal activations may result in a cumulative
effect upward in the cortical hierarchy, in the direction of primary information flow, thus
making the higher-order regions fail first. The anaesthetics cascade may appear as a top-
down failure, but really driven by bottom-up effects. The more extensive and complex the

11
neuronal system is, the more sensitive it may be to the accumulation of locally disruptive
effects. Polysynaptic pathways have been known to be vulnerable to anaesthetics because
of their cumulative effects along the signalling chain.( Banoub et al., 2003). In the same
year, Martuzzi and colleagues (2010), compared several RSNs between wakefulness and
1% (0.5 MAC) sevoflurane anaesthesia using seed-based connectivity analysis. They
showed that during sevoflurane administration, functional connectivity in the primary
somatosensory, visual, and auditory cortices, and the DMN was preserved or even
increased. At the same time, functional connectivity of higher-order networks for memory
and pain, centered on the hippocampus and insula, was reduced. This observation
appeared consistent with the amnesic and analgesic effects of light sevoflurance
anaesthesia, and the relative robustness of the early sensory systems and at least a
significant part of the DMN. The significance of connectivity changes in the prefrontal
regions for loss of consciousness remains to be confirmed.
The importance of thalamocortical interactions for consciousness has already been
indicated. So far, few studies have examined the anaesthetics modulation of
thalamocortical connectivity. In an early study, White and Alkire (2003) used PET to
determine the changes in effective connectivity in volunteers anesthesized by halothane
or isoflurane to loss of responsiveness. Using structural equation modelling, the found
impaired thalamocortical and corticocortical connectivity. Obviously, due to the temporal
limitations of PET, these results were not yet based on temporal correlation of signals.
More recently, in the just-mentioned functional magnetic resonance imaging study by
Stamatakis and colleagues (2010), resting-state connectivity of the PCC with the anterior
thalamus was increased in a linear relationship with propofol plasma concentration.
Mhuircheartaigh and colleagues (2010), also used fMRI and found that
thalamocortical connectivity was preserved with propofol titrated to loss of verbal
responsiveness. An interesting exception was the putamen, which showed reduced
functional connectivity with the thalamus, as well as with several other brain regions. Of
note is that whole-brain connectivity of the thalamus and putamen was assessed during
auditory and somatosensory stimulation, so the results may not parallel those obtained
during resting conditions. Moreover, the effect of anaesthetics on the thalamus may be
indirect, driven by actions on the cortex or subcortical areas that project to the thalamus

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(Alkire et al., 2000,2008; Vahle-Hinz et al., 2007). Detailed analyses of both
corticocortical and thalamocortical RSN’s during wakefulness and two levels of propofol
sedation were performed by Boveroux and coworkers(2010). The level of consciousness
was evaluated at each sedation level using the Ramsay scale (Ramsay et al., 1974).
Propofol also suppressed thalamic connectivity with the frontal-parietal association
regions, and disrupted the anticorrelation between the default amd executive-control
systems normally observed during wakefulness. Consistent with previous findings,
corticocortical and thalamocortical connectivities of the primary sensory regions were
relatively preserved during deep sedation. However, functional connectivity representing
the auditory-visual cross-modal interactions was conspicuously absent, again suggesting
the loss of higher-order integration.
The latter was interesting from the point of recent findings, suggesting that induction
and recovery may be mediated in part by different neuronal mechanisms(Friedman et al.,
2010). As in former studies, cortical activation to auditory stimuli persisted, confirming
that anaesthetic unconsciousness cannot be explained by cortical deafferentation or a
diminution of cortical sensory reactivity. Thus, these findings support the theory that the
cause of anaesthetics unconsciousness is a failure of information integration (Alkire et al.,
2008; Hudetz., 2006) that appears to correlate with a dysfunction of the nonspecific
thalamocortical system. This finding has been supported by work in human
electocorticography, showing disruptions of cortical coherence across similar
sensorimotor regions during propofol anaesthesia. Thus, anaesthetics with distinct
mechanisms do, indeed, suppress coherence and information transfer across structurally
connected frontal-parietal networks. Taken in context, frontal-parietal connectivity
patterns depends on the specific circuit, even if there is a clear structural connections.
Excessively high functional connectivity could also be associated with a reduction of
information transfer by isolating the circuit or reducing its repertoire of responses. Recent
work in general anaesthesia and disorders of consciousness suggests that there is a “sweet
spot” that balances cortical dynamics and functional connectivity to maintain normal
levels of consciousness.

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Who is the patient experienced disruptions in the brain and affects the
communication.

Generally, any person that experience the effects of general anesthetics are the ones
that undergoes a surgery. General anesthetics are widely used in major surgery. To reach
the scope of anesthesia for surgery, patients are being exposed to a number of general
anesthetics, alone or in combination. (Wu et al., 2019) Effects vary on patients that render
the patient unconscious or numb on some region of their body once given specific type of
anesthetics, which may also cause amnesia.

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 Figure 1 : Patient undergoes surgery using General Anesthesia

Patients can also have choice of anesthetics to be administered on them. Some

15
notable example of anesthetics used in surgery is during childbirth; although general
anesthesia is rare during childbirth since childbirth requires participation; it is
administered to mothers during emergencies; if the mother decides to be unconscious for
cesarean section (c-section). Mainly, mothers will be given regional anesthetics
specifically spinal anesthesia and epidural anesthesia to nullify the pain from the waist
down. Another notable example is for patients that undergoes limb amputation due to
severe injury, cancerous tumor, serious infection and etc. (DerSarkissian, 2020) The
patient will be administered two types of anesthesia; general anesthesia, to render
unconsciousness and regional anesthesia; to numb down a specific limb. The patient that
received epidural and spinal (regional) anesthesia recalled less pain than when received
general anesthesia. (Ong et al., 2006). Usage of general anesthesia on patients are not
limited to these examples however, it used in other major surgical procedure that require
the patient to fall unconscious to numb down pain.

How does general anesthesia distrupts the brain communication.

Little is known about general anesthetics, the drugs that put patients in a coma-like
state, feeling no pain or discomfort while being operated on. Most anesthesia drugs work
by dampening down the neurons in the brain in a straightforward way. Nevertheless, one
anesthetic method has proven it is ketamine. Ketamine is a medication mainly used for
starting and maintaining anaesthesia. Many ketamine doses cause general anesthesia,
while brain activity may still be robust and the ketamine usually uses on the patient and
in the laboratory room.

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 Figure 2 : Ketamine anesthesia

You may be given a' pre-med' a few hours before the surgery, which can be an
injection or tablets that will make you tired and comfortable. These medications also
allow the excess saliva to dry up. Then you are wheeling into the operating theatre. A
trained anesthetist, who is a doctor with specialized anesthetic training, administers the
general anesthetic. The anesthetist may administer the anesthetic intravenously or by a
gas mask, or both. After a few seconds, you feel sleepy and then lose consciousness.
Next, the anesthetic inserts a small tube to connect to a ventilator into your airway. The
anesthetist controls the length of time you are sleep and constantly monitors your pulse,
breathing and blood pressure. Once the surgery is over you may have other drugs injected
that will reverse the effect of the anaesthetic and any other drugs used during the

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operation.
As soon as patient injected ketamine, the sensory information disappeared from the
motor cortex. Normally these areas are tightly connected. General anesthesia reflects a
communication breakdown in the cortex, even though sensory information is getting
processed. Generally, when the patient is under the general anesthesia the two different
areas of the brain that work together will stop talking each other. When the patient awake
the communication between the somatosensory cortex and the primary motor cortex is
critical to normal function. Somatosensory cortex that known as sensory area is a part of
your brain that receives and processes sensory information from the entire body.
The anesthesia cause the unconsciousness that interrupt communication between
brain areas and stopping the processing of higher-level information. The loss of
consciousness coincided with the rapid onset of brain waves known as slow oscillations.
The onset was precisely measured when the patients lost consciousness and started in
various area of the cerebral cortex at different times. Individual neurons became less
active, with their activity spiking at the same time as the slow oscillations in that region.
The researchers believe that these slow oscillations are making the processing of
information within specialized brain regions less efficient, and prevent contact between
the different parts of the brain from communicating. The researcher says that it’s still not
clear whether the slow oscillations actually cause the loss of consciousness or are a
consequence of it. It’s also possible that the patients had different brain activity from
healthy people, because of the seizures and medication involved with epilepsy. However,
the electrodes were placed 2 cm away from abnormal tissue areas, and the behavioral
effects were the same as those in healthy people.

For Sedation, Ketamine is incredibly used to treat analgesia and sedation in

prehospital and emergency medicine. It is best suited to handling traumatic events such as
fracture reduction and burn treatment. It is possible to induce the typical dissociative state
seen with ketamine with a dosage range between 0.25 and 1.5 mg / kg1 IV. A charge dose
administered over 30-60 seconds is recommended for procedural sedation in the
emergency department. This causes sedation within 1 minute, which lasts 5-10 minutes.
There is a broad range in recommended loading doses for adults from 0.25 to 1.0 mg /

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kg1 IV and for children from 0.25 to 2.0 mg / kg1 IV. Ketamine can also be used safely in
combination with the other induction as well as sedation medications such as propofol.
The use of intramuscular, oral, or intranasal ketamine was described with good effect for
cases where IV access is difficult. The time of onset of effect for these routes is usually
longer when compared with IV administration and required doses show greater variability
due to vascularity and gastrointestinal absorption variations as shown below.

Table 1 : Routes of ketamine administration and dose range in children and adults.
The previously stated doses produce a continuum of effects from mild sedation to full
anesthetic induction. As with any sedative medication, appropriate expertise and proper
monitoring are required. Variable dosing has been suggested for intranasal, intraosseous
and intramuscular routes in children and there is a lack of consensus in the literature on
specific doses

Which part of brain or neurons area the anesthesia influences and disrupts the
communication in the brain

Thalamus appears to be a typical site of modulation by anesthesia. Thalamus is a

small structure within the brain located just above the brain stem between the cerebral
cortex and the midbrain and has extensive nerve connections to both.( Mandal, Ananya,
2019). The important function of the thalamus is to relay motor and sensory signals to
the cortex. It also regulates sleep, alertness and wakefulness. The thalamus lies at the
highest of the brain steam near the centre of the brain from where fiber project out

19
towards the cortex. The thalamus is split into two prominent bulb shaped masses of
around 5-7cm long and positioned symmetrically on both sides of the third ventride. The
thalamus is furnished blood by four branches of the posterior artery, namely the polar
artery, paramedian thalamic-subthalamic arteries, thalamogeniculate arteries and
therefore the posterior choroidal arteries. The effect of general anaesthesia in functional
and effective connectivity is varied looking on the agent and dose. When the
consequences of halothane and isoflurane were first compared, a standard site of regional
suppression clad to be thalamus. This observation led to the speculation of a thalamic
switch of consciousness suggesting that a hyperpolarization block of thalamocortical
neurons would disrupts the functioning of thalamocortical circuits necessary for
consciousness. The thalamus as a common site of anesthetic modulation has been
subsequently confirmed for several other anesthetic agents, as well as other states of
unconsciousness such as non-REM(dreamless) sleep and persistent vegetative
state( Alkire&Miller, 2005). Whether the thalamus itself is that the primary target of
anesthetic modulation or its changes reflect indirect effects on other parts of the brain is
currently unclear. Some investigations suggest that the thalamus is more of a read-out of
cortical information, integrating the results of cortical computations ( Mumford, 1991;
Ward, 2011 ). Thalamic suppression by anesthetic may of course follow in time the
anesthetic suppression of cortical activity, suggesting an indirect role. Therefore, the
thalamic effects of anesthetic are more likely to be consequential, secondary to the
cortical effect of anesthetic.Yet, the thalamus could also too intimately interacting with
the cortex to separate their roles from each other entirely. Hence, thalamus is
extremely effected when anesthesia is given.

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 Figure 3 : The thalamus has two ends and four surfaces, the anterior and posterior
poles: medial, lateral, superior, and inferior. Nuclei in a given pole or surface regulate
specific functions or sensory information, processing and maintain specific connections
to parts of the nervous and limbic system.
When does General Anesthesia’s influences stop brain communication.
Carol DerSarkissian (2018) describe that in a certain type of surgery, a specially
trained doctor or nurse called anesthesiologist will give the patient general anesthesia
before the surgery begin. The general anesthesia given by the anesthesiologist will
interrupt the nerve signal in brain and body, in other word it limits the patient's brain from
processing pain and remembering the event throughout the surgery. The anesthesia given
will goes into the vein in patient's arm, and within a couple of minutes, the patient will
fall asleep.
Once patient inhaled the anesthesia drug given by the anesthesiologist, the ether

21
derivatives and intravenous propofol, the most widely used anesthetic drug, bind the
inhibitory GABAA receptor, as Emery N. Brown and Francisco J. Flores (2019) said. If
the condition is normal, the receptor will be activated by gamma-aminobutyric acid
released from inhibitory neurons, which allows the chloride ions to flow into the cell,
then decreasing the probability of firing neuron because it decrease the relative voltage of
the neuron’s interior. This kind of drug that target the inhibitory GABA A receptor act as
agonists to promote the inflow of chloride ions, further resist the neuron’s ability to fire
If the patient given other kind of anesthetic drug such as ketamine and nitrous oxide,
it will block the channel of the N-methyl D-aspartate (NMDA) glutamate receptor.

The NMDA
receptor allow the
flow of potassium
ions out of the cell
and calcium and
sodium ion, which
activated by
neurotransmitter
glutamate released
from excitatory
neurons. With the
oblige of the potassium ions, the relative voltage of the neuron’s interior increased which
then the probability of firing an action potential increased. This anesthetic drug that target
NMDA receptor act as antagonist to block these ions fluxes, decreasing the ability of the
cell to fire.

22
Conclusion

All the experiment related to anaesthesia and human consciousness revealed that
thalamus reticular formation to be at the intersection of the anaesthetic effect on human
consciousness. As thalamus plays an important role in sensory perception and movement,
it could not function as normal when anaesthesia is given. The anaesthesia disrupts the
function of the thalamus by not let it to relay motor and sensory signals to the cerebral
cortex. Each anesthesia drug’s effect on the thalamus has different time reaction based on
the type of anesthesia that exposed to the patient. It also affects different type of receptor
inside the body, like the intravenous propofol that affect the GABA A receptor which allow
the chloride ions to flow into the cell, which decrease the voltage of the neuron’s interior,

23
resulting in inability for neuron to fire. In order reveal neural basis, the anesthetic
unconsciousness neuroimaging techniques measure the neural activities relevant to those
that are minimally necessary to support consciousness. EEG, magnetoencephalography
(MEG), and intracortical electrophysiology can be used to provide more information in
detail but this should be done with lower spatial coverage. Till date, most of the clinical
test has been conducted, the scientists reveal that anesthetized patients are able to
communicate verbally and respond towards the anaesthetician. The modulation of
anesthesia and brain is an active area of research. The brain function changes when
general anesthesia is given. The effect of anesthetics on corticocortical connectivity is
varied, it depends on the anesthetics agent and the specific network examined. The
observed changes in functional connectivity during anesthesia induction and emergence
do not mirror each other and the recovery from anesthesia may involve increases in
functional connectivity above the normal wakeful baseline. Future efforts should also
focus on the determination of anesthetic-induced changes in directional or effective
connectivity in local and large-scale networks as a means to better understand their
necessary and sufficient role for modulating the state of consciousness. Using the latest
technologies like MRI, EEG and MEG, as well as animal models in which specific
neuronal pathways may be experimentally manipulated, should aid the understanding of
the basis of anesthetic modulation of consciousness.

References

1. Anthony G. Hudetz. (2012). General Anesthesia and Human Brain Connectivity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621592/
2. Antognini JF. Buonocore MH. Disbrow EA. Carstens E. Isoflurane anesthesia blunts
cerebral responses to noxious and innocuous stimuli: a fMRI study. Life
Sci. 1997;61:PL349–PL354.

3. Alkire MT. Haier RJ. Fallon JH. Toward a unified theory of narcosis: brain imaging
evidence for a thalamocortical switch as the neurophysiologic basis of
anesthetic- induced unconsciousness. Conscious Cogn. 2000;9:370–386
4. Alkire MT. Miller J. General anesthesia and the neural correlates of consciousness.

24
 Prog Brain Res. 2005
5. Alkire MT. Probing the mind: anesthesia and neuroimaging. Clin Pharmacol
Ther. 2008;84:149–152. 
6. Banoub M. Tetzlaff JE. Schubert A. Pharmacologic and physiologic influences
affecting sensory evoked potentials: implications for perioperative
monitoring. Anesthesiology. 2003;99:716–737. 

7. Bonhomme V. Fiset P. Meuret P. Backman S. Plourde G. Paus T, et al. Propofol

anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a
positron emission tomography study. J Neurophysiol. 2001;85:1299–1308.

8. Brown, E., & Flores, F. (2019). General Anesthesia Causes Telltale Brain Activity
Patterns. Retrieved from https://www.the-scientist.com/features/general-
anesthesia-causes-telltale-brain-a ctivity-patterns-65501

9. Boveroux P. Vanhaudenhuyse A. Bruno MA. Noirhomme Q. Lauwick S. Luxen A, et

al. Breakdown of within- and between-network resting state functional magnetic
resonance imaging connectivity during propofol-induced loss of
consciousness. Anesthesiology. 2010;113:1038–1053. 

10. DerSarkissian, C. (2020, February 5). Limb Amputation: Reasons, Procedure,

Recovery. Retrieved from https://www.webmd.com/a-to-z-guides/definition-
amputation

11. DerSarkissian, C. (2018). What Is General Anesthesia?. Retrieved from

https://www.webmd.com/a-to-z-guides/what-is-general-anesthesia#2
12. Franks NP. Molecular targets underlying general anaesthesia. Br J
Pharmacol. 2006;147(Suppl 1):S72–S81. 
13. Friedman EB. Sun Y. Moore JT. Hung HT. Meng QC. Perera P, et al. A conserved
behavioral state barrier impedes transitions between anesthetic-induced

25
 unconsciousness and wakefulness: evidence for neural inertia. PLoS
One. 2010;5:e11903.

14. Health. (2017, Dec 21). This Is What Happens To Your Brain During Anesthesia.
Retrieved from https://www.vice.com/en_us/article/d3489z/this-is-what-
happens-to-your-brain-d uring-anesthesia
15. Hemmings HC., Jr. Akabas MH. Goldstein PA. Trudell JR. Orser BA. Harrison NL.
Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol
Sci. 2005;26:503–510. 
16. Hudetz AG. Suppressing Consciousness: mechanisms of general anesthesia. Semin
Anesth Perioper Med Pain. 2006;25:196–204.

17. InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and

Efficiency in Health Care (IQWiG); 2006-. Pregnancy and birth: Cesarean
sections: What are the pros and cons of regional and general anesthetics? 2008
Mar 19 [Updated 2018 Mar 22]. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK279566/

18. Kerssens C. Hamann S. Peltier S. Hu XP. Byas-Smith MG. Sebel PS. Attenuated
brain response to auditory word stimulation with sevoflurane: a functional
magnetic resonance imaging study in humans. Anesthesiology. 2005;103:11–19. 

19. Mandal, Ananya. (2019, February 27). What is the Thalamus?. News-Medical.
Retrieved on April 10, 2020 from https://www.news-
medical.net/health/What-is-the-Thalamus.aspx

20. Martuzzi R. Ramani R. Qiu M. Rajeevan N. Constable RT. Functional connectivity

and alterations in baseline brain state in humans. Neuroimage. 2010;49:823–834.

21. Mhuircheartaigh RN. Rosenorn-Lanng D. Wise R. Jbabdi S. Rogers R. Tracey I.

Cortical and subcortical connectivity changes during decreasing levels of
consciousness in humans: a functional magnetic resonance imaging study using
propofol. J Neurosci. 2010;30:9095–9102.

22. Mumford D. On the computational architecture of the neocortex. I. The role of the
thalamo-cortical loop. Biol Cybern. 1991

26
23. Ong, B. Y., Arneja, A., & Ong, E. W. (2006, December 15). Effects of anesthesia on
pain after lower-limb amputation. Retrieved from
https://www.sciencedirect.com/science/article/abs/pii/S0952818006002236

24. Plourde G. Belin P. Chartrand D. Fiset P. Backman SB. Xie G, et al. Cortical
processing of complex auditory stimuli during alterations of consciousness with
the general anesthetic propofol. Anesthesiology. 2006;104:448–457.

25. Ramani R. Qiu M. Constable RT. Sevoflurane 0.25 MAC preferentially affects
higher order association areas: a functional magnetic resonance imaging study in
volunteers. Anesth Analg. 2007;105:648–655.

26. Ramsay MA. Savege TM. Simpson BR. Goodwin R. Controlled sedation with
alphaxalone-alphadolone. Br Med J. 1974;2:656–659. 

27. Rudolph U. Antkowiak B. Molecular and neuronal substrates for general

anaesthetics. Nat Rev Neurosci. 2004;5:709–720.
28. Shin, Y. D., Park, S. H., Kim, H. T., Park, C. J., Lee, J. H., & Choi, Y. J. (2016). The
effect of anaesthesia technique on caesarean section. Pakistan journal of
medical sciences, 32(1), 147–150. https://doi.org/10.12669/pjms.321.9028
29. Stamatakis EA. Adapa RM. Absalom AR. Menon DK. Changes in resting neural
connectivity during propofol sedation. PLoS One. 2010;5:e14224.

30. Sukhotinsky I,   (2007) Neural pathways associated with loss of consciousness

caused by intracerebral microinjection of GABA A-active anesthetics. Eur J
Neurosci 25:1417–1436.

31. Vahle-Hinz C. Detsch O. Siemers M. Kochs E. Contributions of GABAergic and

glutamatergic mechanisms to isoflurane-induced suppression of thalamic
somatosensory information transfer. Exp Brain Res. 2007;176:159–172.

32. Velly LJ. Rey MF. Bruder NJ. Gouvitsos FA. Witjas T. Regis JM, et al. Differential
dynamic of action on cortical and subcortical structures of anesthetic agents
during induction of anesthesia. Anesthesiology. 2007.
33. Ward LM. The thalamic dynamic core theory of conscious experience. Conscious
Cogn. 2011.

27
34. Wu, L., Zhao, H., Weng, H., & Ma, D. (2019). Lasting effects of general anesthetics
on the brain in the young and elderly: "mixed picture" of neurotoxicity,
neuroprotection and cognitive impairment. Journal of anesthesia, 33(2),
321–335. https://doi.org/10.1007/s00540-019-02623-7
35. University of Michigan Health System. (2016, May 11). 'Communication breakdown'
during general anesthesia. ScienceDaily. Retrieved June 9, 2020 from
www.sciencedaily.com/releases/2016/05/160511131725.htm

28