P22 2020 PDF

P22: Neurobiološka podloga
promijenjenih stanja svijesti
Goran Šimić
Zavod za neuroznanost
Hrvatski institut za istraživanje mozga
Medicinski fakultet Sveučilišta u Zagrebu
16. XI. 2020.

Consciousness components
Christof Koch,
Sci Am 12
(2017)
Promjenjena stanja svijesti (ASC)
 The term altered state of consciousness refers to any state of
consciousness which is distinctively different in level of awareness and
experience from NWC (nomal waking conscioussnes), in terms of level of
awareness and experience, the quality and intensity of sensations,
perceptions, thoughts, feelings, and memories that are experienced.
 In an ASC mental processing shows distinct changes specific to that

particular state.
 Normalna / uobičajena: npr. spavanje, „daydreaming”,
poremećaji: nesanica (insomnija) – primarna vs. sekundarna
narkolepsija – pospanost po danu (odmah REM) 0.001% populacije
apnea za vrijeme spavanja
mjesečarenje (somnabulizam)
Neuobičajena: meditacija / hipnoza / droge – vidi. P23

Fig. 7.2 Sleep rhythms. Bars show periods of sleep during the fourth, fifth, and sixth weeks of an experiment
with a human subject. During unscheduled periods, the subject was allowed to select times of sleep and
lighting. In his case, the result was a 25-hour sleep rhythm. Notice how his free-running rhythm began to
advance around the clock. When periods of darkness were scheduled (colored area), the rhythm quickly
resynchronized with 24-hour days. (Adapted from Czeisler, 1981.)
Fig. 7.3 Development of sleep patterns. Short cycles of sleep and waking gradually become the night-day
cycle of an adult. While most adults don’t take naps, midafternoon sleepiness is a natural part of the sleep
cycles. (After Williams et al., 1964.)
Fig. 7.4 These Siamese twins share the same blood supply, yet one sleeps while the other is
awake. (Photo by Yale Joel, Life Magazine. © Time, Inc.)
States of Sleep
Rapid Eye Movements (REM): Associated
with dreaming; sleep is very light
 Body is very still during REM sleep
 Lack of muscle paralysis during REM sleep is
called REM Behavioral Disorder
Non-REM (NREM) Sleep: Occurs during
stages 1, 2, 3, and 4; no rapid eye movement
occurs
Seems to help us recover from daily fatigue
Table of Contents Exit
Fig. 7.6 (a) Average proportion of time adults spend daily in REM sleep and NREM sleep. REM periods
add up to about 20 percent of total sleep time. (b) Typical changes in stages of sleep during the night.
Notice that dreams mostly coincide with REM periods.
Table of Contents Exit

REM NREM
Cataplexy: muscles relax Individual can still move
to near paralysis
Eyes move rapidly Eyes don’t move
Most dreaming occurs Some dreams
Purpose: Purpose:
Consolidation of LTM Physical growth and body
repair
~20% of adult’s sleep ~80% of adult’s sleep

Negative correlation between age and hours of sleep.
Negative correlation between age and REM sleep.
Glavna obilježja ASC
- Distortions of perception (perceptions are often so
distorted in an ASC that people may lose their sense of identity /who
they are / or experience the feeling of being outside their body or
someone else entirely. This can occur with the use of the anesthetic
drug ketamine – danas se upotrebljava kao „klupska droga”)
& cognition (thinking is often illogical and lacking in sequence;

difficulties may be experienced in problem-solving; people may have
trouble remembering events that have occurred in an ASC as when
consuming alcohol people are often unable to recall the events that
occurred while intoxicated / marijuana use can also impair short
term memory and thinking)
- Disturbed sense of time
- Changes in emotional feeling, changes in
self control
 During adolescence there is a hormonally
induced shift of the body clock about 2h, making
the adolescent sleepier one or two hours later.
 This is known as the sleep-wake cycle shift

and this affects their ability to fall asleep at the
earlier time that they would of as a child.
 This also means that they have the biological

need to sleep a couple of hours longer in the
morning.
 For teenagers, this is virtually impossible given their
school and work schedules.
 As a results this nightly sleep loss can accumulate as a

sleep debt; that is, sleep that is owed and needs to be
made up.
 Eg. A nightly sleep debt of 90 minutes between Monday

and Friday would add up to a total sleep debt of seven
and a half hours.
 Often on the weekends teenagers would sleep for longer

to make up for this debt which can also be problematic.
Purpose of sleep - Restoration
 Restorative theories propose that sleep provides
‘time out’ to help us recover from depleting activities
during waking time that use up the body’s physical and
mental resources.
- Allows us to replenish the energy used up during the
day
- Allows damaged cells to be repaired
- Allows muscles to be detoxified and rid themselves of
waste products
 This is supported by our view that we feel tired before
we go to sleep and replenished when we wake up in
the morning.
Tko želi znati više pogledati: Russell Foster – TED talks

Evidence
 Study 1: When we are asleep our physiological
functions slow down and growth hormone which
promotes body repair is secreted at a much higher
level than when awake.
 Study 2: Athletes who competed in a 92km
marathon found that when allowed to sleep as long
as they wanted to they slept significantly longer and
deeper in the following two nights after the race.
 Study 3: Experiments with rats have found that
prolonged sleep deprivation results in the
breakdown of various bodily tissues and death
within three weeks.
Restoration
 NREM sleep is believed to be important for

repairing and restoring the body whereas
REM sleep is believed to restore the brain
and may have a role in higher mental
functions like memory and learning.
Restoration
 Psychologists generally believe that REM sleep
has some biological quality that we need.
 When lab patients are woken each time they
enter REM sleep they do not seem to show any
adverse signs, however, when left to rest
normally they will spend more time in REM sleep
than usual. This indicates that there is a need for
them to ‘catch up’ on lost REM sleep.
 This is called REM rebound which involves
catching up on REM sleep immediately following
a period of lost REM sleep when next asleep.
SURVIVAL
 The survival theory of sleep proposes that

sleep evolved to enhance survival by
protecting an organism through making it
inactive during the part of the day when it is
most risky or dangerous to move about.
 Sleep serves the function of protecting the
sleeper from harm or death, and therefore
enhances survival of the species.
Evidence
 Animals with few natural predators, such as lions,
tigers and gorillas, sleep as much as 15 hours a
day.
 Grazing animals like horses, zebras and cows have
many predators and would struggle to escape from
them. They cannot hide easily, climb trees or burrow
quickly to escape danger and therefore tend to only
sleep around 4 hours total in the day.
 Smaller animals like bats and possums eat less food
and take less time to digest it as well as usually
sleeping in safe places. This means they do not
need to spend much time awake.
Evidence
 Humans sleep at night because we are highly

visual creatures who need light to find food
and do other things necessary for survival.
 At night it may have been best for us during
our evolution to be asleep at night to avoid
any dangers.
Criticisms
 One criticism is that it does not explain why

sleep involves a loss of awareness since the
loss of consciousness during sleep may
place the organism at greater risk.
 There is only limited evidence to support
each of these theories.
Sleep deprivation
 Unethical to conduct research on humans so most
total deprivation research has been conducted on
animals (rats).
 The sleep deprived rats typically were unable to

maintain a constant body temperature, resulting in
excessive heat loss.
 They eventually died after 2-3 weeks.

Sleep deprivation
 Autopsies show that the rats immune systems had
collapsed, resulting in blood poisoning and untimely
death.
 It was then proposed that sleep is vital to the

regulation and stability of an animals internal
environment and this may also apply to humans.
 Research conducted on people that have voluntarily

become sleep deprived has found that although
there are some serious psychological and
physiological effects none of these are permanent.
Sleep Deprivation: partial
Tiredness
Lack of energy
Lapses in attention
Inability to concentrate for long periods
Low level of motivation
Impaired motor skills
Irritability
Occasional headaches
Decline in ability to perform cognitive tasks
Slower reaction times on motor tasks
Thinking in irrational and illogical ways
Difficulty making decisions
Partial sleep deprivation
 Generally over a short period of time, partial sleep
deprivation has temporary and relatively minor effects.
 A person can also quickly recover when the sleep debt
is repaid.
 People, however, underestimate the effects of partial
sleep deprivation over a prolonged period.
 William Dement (1999) believes that millions of people
throughout the world are ‘living less than an optimal
life and functioning at less than optimal level, impaired
by an amount of sleep debt that they are not even
aware they are carrying’.
 He believes that the high level of sleep
deprivation in adolescents could even be fatal
as they are in a high risk of accident
category.
 30% of road accidents occur when drivers fall
asleep on long boring stretches of road.
 After only 4 hours of sleep deprivation,
reaction time is as much as 45% lower than
usual.
 Memory processes may also be impaired.
Total sleep deprivation
 Studies on the effects of total sleep
deprivation in humans have tended to rely on
convenience samples.
 In one case of total sleep deprivation,
teenager Randy Gardener stayed awake for
264 consecutive hours (11 days) as part of a
high school science project.
 Although he experienced a range of
physiological and psychological effects
throughout the experience, he did not
experience any long lasting effects.
 Some people however, experience more debilitating
effects like depression, hallucinations, delusions and
paranoia.
 In 1959, American DJ Peter Tripp remained awake for
100 hours for charity and began to experience severe
psychological disturbances. He claimed to see a rabbit
run along the radio booth (hallucination) and cobwebs in
his shoes. He had difficulty thinking clearly and
remembering things. Eventually he became paranoid
believing people were trying to drug him to force him
asleep. He was escorted home after 201 hours without
sleep and slept continuously for 13 hours. When he
woke he had returned to normal.
Sleep Deprivation
Psychological Effects:
 Impaired cognition due to reduced concentration,
motivation and attention.
 Increased irritability
 Ability to perform simple tasks more affected than

performance on complex tasks
 Moodiness
 Increased anxiety
 Impairment of memory processes (STM)
 Depression
 Hallucinations, delusions & paranoia

Sleep Deprivation
Physical Effects
 Sleepiness and fatigue
 Droopy eye lids
 Difficulty focusing
 Slurred speech
 Increased sensitivity to pain
 Hand tremors
 Headaches
After 5 consecutive days:

 The heart and respiratory system become slower
 Body temperature drops
 The immune system is lowered making us more vulnerable

to illness
Sleep deprivation
 After 3-4 sleep-free days we involuntarily drift into microsleeps
 A microsleep is a very short period of drowsiness or sleeping that

occurs while the person is apparently awake.
 During a microsleep the EEG pattern resembles the early stages of

NREM sleep.
 During this time the person will have no recollection of the events
unfolding.
 We do not seem to have to fully compensate for all sleep lost, but
we will make up for lost sleep by gaining a few extra hours over the
next few nights.
Sleep deprivation vs alcohol
 Does fatigue really kill?

 Yes!
 20 hours sleep-free = perform at same level
as with BAC 0.05%
 24 hours sleep-free = perform at same level
as with BAC 0.10%
Fig. 7.10 A sensory isolation chamber. Small floatation tanks like the one pictured have been used by psychologists
to study the effects of mild sensory deprivation. Subjects float in darkness and silence. The shallow body-
temperature water contains hundreds of pounds of salt so that the subjects float near the surface. Mild sensory
deprivation produces deep relaxation.
Pitanje razina svjesnosti
• Priming (implicit memory effect)
• Blindsight fenomen
• Fear blindsight
• Više u: Antonio Damasio „The feeling of

what happens” (Algoritam, preveo prof.
Judaš)
HIPNOZA i TRANS
Medicinska hipnoza – uvesti pacijenta u trans otvara
mogućnost lakše komunikacije s nesvjesnim (pronalaženje
psihosoc. „zastrtog” uzroka bolesti i poticanje mentalnog
sudjelovanje bolesnika u liječenju)
Direktna hipnoza (<30% Freud)

Indirektna hipnoza (po Milton-Ericksonu >50%)
- Započinje uvođenjem u ALFA stanje (događaji iz okoline
postaju nevažni); osobe s višim IQ i EQ lakše stupaju u
hipnotički trans
Za vrijeme hipnoze javlja se:

- promjena percepcije vremena
- pojačano osvješćivanje emocija
- pojačana sugestibilnost (terapeut daje direktne/indirektne
sugestije)
2002. HDMH
© Dan Francis/Mardan Photography
Fig. 7.9 Arrange three chairs as shown. Have someone recline as shown. Ask him to lift slightly while you
remove the middle chair. Accept the applause gracefully! (Concerning hypnosis and similar phenomena,
the moral, of course, is “Suspend judgment until you have something solid to stand on.”)
INDIKACIJE
- Depresija
- Strahovi i fobije
- Priprema za porođaj (i sam porođaj!?)
- Stomatologija bez anestezije
- Astma
- Iritabilni kolon i druge psihosomatske bolesti
- PMS, amenoreja, neplodnost
- Kronična bol
- Onkološki bolesnici
- Mentalni trening za sportaše
Introduction
• Attention: ability to focus on one aspect of sensory input
• Preferentially process some information and ignore the
rest
• Attention has significant effects on perception.
• Corresponding changes in sensitivity of neurons at many
brain locations
• Consciousness: awareness of something
• Neural basis of the conscious brain?
Copyright © 2016 Wolters Kluwer • All Rights Reserved

Resting State Brain Activity
• Generally, neurons become more active in cortical areas
processing ongoing perceptual or motor information.
• Resting state activity
– Some regions are fairly quiet.
– Others surprisingly active
– Revealed by PET and fMRI imaging of whole brain

The Brain’s Default Mode Network
• Engaging in task  decreases in activity of some brain
areas, whereas task-relevant areas become more active.
• Resting brain activity: fundamental and significant
• Patterns in brain activity changes consistent across
human subjects
• Brain areas active in resting state
– Medial prefrontal cortex, posterior cingulate cortex,
posterior parietal cortex, hippocampus, lateral
temporal
– Together, the default mode network

The Default Mode Network

Functions of the Default Mode Network
• Two hypotheses
– The sentinel hypothesis
• Broadly monitoring the environment
• Rare disorder: simultagnosia
– The internal mentation hypothesis
• Supports thinking and remembering, like
daydreaming
• Imaging: state like remembering

Attention
• Selective attention—directed, filers out input
• Limited capacity of attention
– Attention-deficit hyperactivity disorder
• Exogenous attention—bottom–up attention
– Like animal detecting predator
• Endogenous attention—top–down attention
– Deliberately directed by the brain

Behavioral Consequences of Attention
• Attention enhances
visual sensitivity.

Effect of Cueing on Target Detection

Attention Speeds Reaction Times

Shifting Attention
• What happens to neural activity?
• What brain areas are involved?
– Effects of attention observed in high-level cognitive
and numerous sensory areas
• Consequences of allocating attention revealed
– Imaging studies in humans
– Individual neuron changes in animal studies

Functional MRI Imaging of Attention to
Location
• Subjects view stimulus
• Location of cued sector
changes
• Brain activity shifts
retinotopically.

PET Imaging of Attention to Visual
Features
• Same–different discrimination task:
color, shape, speed
• (A) Selective attention experiment
• (B) Divided attention experiment
• Subtract B from A shows brain
activity associated with attention to
one feature.
• V4, IT, and other visual areas in
temporal lobe color and shape
• Area MT speed of motion

Feature-Specific Effects of Visual
Attention

Enhanced Neuronal Responses in Parietal
Cortex
• Attention: experimental versus normal conditions
• What happens to attention under normal conditions?
• Assumption: Attention changes location prior to eye
movement.
• Experiments of Wurtz, Goldberg, and Robinson
– Recorded neural activity from several brain regions
– Response enhancement in posterior parietal cortex
• May speed visual processing and reaction times

Enhanced Neuronal Responses in Parietal
Cortex
• Effect of attention
on the response
of a neuron in
posterior parietal
cortex

Effect of Attention in Visual Cortical Area V4

Brain Circuits for the Control of Attention
• Cortical, subcortical areas
– Guide attention
– Saccadic eye movements
• The pulvinar nucleus
– Projects to many areas of
cortex
– Regulates visual
information flow

Attention and Eye Movements
• Frontal eye fields (FEF)
– Cortical area in
frontal lobe
– FEF neurons—
motor fields

Attention and Eye Movements—(cont.)
• Experiment of Moore and colleagues
– Train monkeys to look at display of small light spots
– Place electrode in FEF and determine motor field of
neurons at its tip
– Small electrical stimulation  enhancement?
• Results
– FEF is involved in directing attention, enhances visual
performance.
– FEF stimulation mimics physiological and behavioral
effects of attention.

Effect of FEF Stimulation on Neuron
Activity in Area V4 in Monkey Brain

Directing Attention with Salience and
Priority Maps
• Hypothesis of how certain visual features grab attention
– Bottom–up attention
– Salience map shows locations of conspicuous
features.
• Top–down attentional modulation from cognitive input
– Priority map shows locations where attention should
be directed.
• Based on stimulus salience and cognitive input

A Priority Map in the Parietal Lobe
• Lateral intraparietal cortex
(area LIP)—priority map
based on bottom–up and
top–down inputs
– Guides eye
movements and
attention
• Lesions in parietal cortex
associated with neglect
syndrome

Hemispatial Neglect Syndrome as
Attentional Disorder
• Person ignores objects, people, and their own body to
one side of the center of the gaze.
• Associated with right-sided lesions in posterior parietal
cortex
• Neglect syndrome might be a disruption of ability to
shift attention.
• Hypothesis: Left hemisphere attends to right hemifield,
whereas right hemisphere attends to both right and
left hemifields.

Frontoparietal Attention Network
• Bottom–up attention
– Input from visual areas in the occipital lobe reaches
area LIP.
– Construction of salience map
– Visual processing is enhanced; eyes may move.
• Top–down attention
– Attention effects occur first in frontal and parietal
areas.
– Priority map in LIP and FEF
– Visual processing is enhanced; eyes may move.

Frontoparietal Attention Network in
Macaque Brain

Consciousness
• Materialist perspective
– Consciousness arises from physical processes
– Based on structure and function of nervous system
• Alternative: dualism
– Mind and body are different things.
– One cannot be fully explained by the other.

What Is Consciousness?
• Nature of human consciousness problematic
– Even defining consciousness is controversial.
• The easy problems of consciousness
– Phenomena answerable by scientific methodology
– Example: sleep–awake difference
• The hard problem of consciousness
– The experience itself
– Why the experience is the way it is

Neural Correlates of Consciousness
• The minimal neuronal
events sufficient for a
specific conscious percept
• Experimental approach
with bistable visual
images—changes in
neural activity?

Neuronal Correlates of Alternating
Perception in Binocular Rivalry
• Different images seen by the two eyes.

– Perceptual awareness alternates
• Experimentally demonstrated
– Neural recordings in monkey area IT show changes
correlated with perceptions.
– Neural activity in IT may be neural correlate of this
awareness.

Visual Awareness and Human Brain
Activity
• Rivalry experiments in humans using fMRI to record brain
activity
– Using rival images of a face and a house
– Recording in FFA (faces) and PPA (places)
– Produced alternating patterns of brain activity in FFA
and PPA
• Imagining imagery activates same visual processes
– Similar results with neuronal probe recording in
human subject

Challenges in the Study of Consciousness
• Small steps succeeding in studying neural correlates of
consciousness (NCC)
• Challenges of interpreting NCC study data
– What is “minimal” brain activity sufficient for
conscious experience?
– Is the neural activity a prerequisite for conscious
experience or consequence of the experience but not
NCC?
– Can attention be confounded with awareness?
• The “hard problem” of consciousness remains.

Concluding Remarks
• Resting state activities likely include monitoring
environment and daydreaming.
• Attention confers behavioral flexibility.
– We use attention to focus mental resources.
– Network of brain areas, priority maps
– Allocation of attention followed by selective enhanced
processing in sensory cortex
• Many mysteries remain about consciousness of
information we attend to.

fMRI
• Ne-invazivna metoda mjerenja aktivnosti mozga

• Aktivnost živčanih stanica se promatra indirektno putem mjerenja
vaskularnih i hemodinamskih signala
• Najvažniji oblik fMRI snimanja je ono koje koristi BOLD signal
• Seiji Ogawa 1990, AT&T Bell labs, Murray Hill, NJ, USA
Blood Oxygen Level Dependent signal
Mxy
Signal
Mo
sin T2* aktivacija
T2* kontrola
Saktivacija
Skontrola S
TEoptimum vrijeme
Task-related fMRI
• An experimental task of interest is presented alternately
with a control task and the BOLD signal during the
experimental task is compared to the BOLD signal during
the control task
• The difference between baseline and task-related activation

accounts for about 1–5% of the total BOLD signal
• Thus, compared to ongoing ‘baseline’ brain activity, only a

small percentage is needed to respond to an external
stimulus
• However, the functions of this vast amount of baseline

activity remained unclear
fMRI
projekcijsko
platno
LCD ogledalo
projektor
fMRI protokol
paradigma imenovanja predmeta
+ + +
30 s 30 s 30 s 30 s 30 s 30 s
Korelacija podražaja i signala
slika slika slika
+ + +
Ima
korelacije
podražaja
i signala
slika slika slika
+ +
Nema
korelacije
podražaja
i signala
Promjena intenziteta signala u fMRI
1020
2,5%
995
Relativno male primjene u intenzitetu signala (1 – 5%)

Elokventni korteks
Područja povećane aktivnosti
ežanj
zatiljni režanj
čeoni režanj
sljepoočni režanj
Functional reorganization of the primary motor
cortex in a patient with a large arteriovenous
malformation involving the precentral gyrus
Radoš et al., Transl. Neurosci. 2013

Functional MRI (fMRI)
• Non-invasively measure brain activity
• Most popular method observes neuron activity indirectly
by measuring vascular and hemodynamic signals:
- change in blod flow and oxygenation
(oxygenated vs. deoxygenated blood) in
active brain areas is measured using MRI
- the primary form of fMRI uses the BOLD
(blood oxygenation level dependent) contrast
first used by Seiji Ogawa in 1990 at AT&T Bell labs,
Murray Hill, NJ, USA
Ogawa S. et al., Brain magnetic resonance imaging with contrast dependent on
blood oxygenation. PNAS, 1990, 87, 9868-9872
Task-related fMRI
• An experimental task of interest is presented alternately
with a control task and the BOLD signal during the
experimental task is compared to the BOLD signal during
the control task
• The difference between baseline and task-related activation

accounts for about 1–5% of the total BOLD signal
• Thus, compared to ongoing ‘baseline’ brain activity, only a

small percentage is needed to respond to an external
stimulus
• However, the functions of this vast amount of baseline

activity remained unclear
Resting-state fMRI
• Focuses on spontaneous, rather than task-induced, fluctuations
in the blood oxygenation level-dependent (BOLD) signal
• In the first resting-state fMRI study (Biswal, Magn. Reson.

Med., 1995), the time course of a seed region-of-interest (ROI)
in the left motor cortex was correlated with the time course of
all other brain voxels
• The resulting map demonstrated functional connectivity

between the left and right motor cortex even in the absence of
a task
• fMRI has since been used to demonstrate that the brain is

segregated into a wide array of 15 or more functional networks
mediating a host of sensory, motor, cognitive, and affective
functions (Smith et al., PNAS, 2009)
Resting-state fMRI (2)
Limitations: the seed ROI must be selected by ICA separates linearly mixed sources:
the investigator; a preprocessing step of
regressing the global signal can induce false
Task related
negative correlations between brain regions
(Murphy et al., NeuroImage, 2009)
Heart-beat related
To avoid these issues independent component

analysis (ICA) decomposes (separates) the 4-
dim. (brain volume over time) BOLD signal into
a set of spatially distinct maps and their Breathing related
associated time courses (Beckmann et al.,

Philos. Trans. R Soc. Lond. B, 2005).
Vasomotor oscillation
A general limitation to resting-state fMRI is that

it is very difficult to separate physiological Motion related
noise, induced by the cardiac pulse and „white noise”
respiration, from the BOLD signal (Birn et al.,

Hum. Brain Mapp., 2008)
ICA principle
A
2 independent sources
B
Linear mix: A-2B Linear mix: 1.73*A+3.41*B

ICA algorithm
ICA applied to resting-state data identifies 8 main cortical networks
Primary Higher order

vision visual
processing
Hearing Touch and

movement
DMN Salience
(memory) processing
Executive Executive
control control
Beckman et al., 2005, Philos. Trans. R Soc. Lond. B, 2005, 360, 1001–1013
Greicius M, Curr. Opin. Neurol., 2008, 21, 424-430
DMN activity at individual and group level
Individual best fit to standard DMN Computed from 13 mean images

template among 26 components
Greicius and Menon, J. Cogn. Neurosci., 2004, 16, 1484-1492

fMRI - default mode network (DMN)
The DMN
includes:
mPFC,
PCC,
precuneus,
ACC,
parietal cortex
and in a minority
of studies also the
hippocampus
Hafkemeijer et al., Biochim. Biophys. Acta, 2012, 1822, 431-441
• It seems that DMN connectivity reflects the level of consciousness (Greicius et al., Hum.
Brain Mapp., 2008; Vanhaudenhuyse et al., Brain, 2010), generates spontaneous thoughts,
and preferentially activates when individuals engage in internal tasks such as daydreaming,
envisioning the future, and retrieving memories, while it is negatively correlated with brain
systems that focus on external visual signals
• In a subject resting quietly for 8 min during an fMRI scan, BOLD signal will fluctuate up and
down at a very low frequency (<0.1 Hz) - these low-frequency BOLD signal fluctuations are
strongly correlated in time across regions that are known to be functionally connected
• DMN undergoes developmental changes and coherent neuronal oscillations at a rate lower
than 0.1 Hz become more consistent in children aged 9-12 years and in older subjects
F-nal vs. structural connectivity
• It is commonly assumed that functional brain connectivity
reflects structural (anatomical) brain connectivity
• The exact relationship between structure and function,
however, might not be straightforward
• If two regions were found to be functionally connected and it is
impossible to detect any white matter tracts connecting these
two regions structurally, this suggests either that:
(a) these two regions do not share a direct structural connection

and so functional connectivity must be mediated through a third
region (usually a ‘hub’ region) or
(b) the absent structural connectivity reflects a false negative

result in the tractography analysis
Default mode network (DMN)
• Most of baseline
activity is mediated by
fMRI neurons that are
constantly active and
participate in the
default mode network
(DMN, also known as
„the resting state” or
„task-negative”
network) (Deco et al.,
DTI TINS, 2013).
• 8 studies published so
far that used both
resting-state fMRI and
DTI to study DMN
DMN FC correlates with the level of
consciousness
Vanhaudenhuyse et al., Brain, 2010, 133, 161-171

DMN in vegetative state/unresponsive wakefulness syndrome, minimally conscious state, healthy
controls-sagittal view. In vegetative state/unresponsive wakefulness syndrome (VS/UWS), the
anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) are hypoconnected to the
default mode network (in blue) and hyperconnected to the fronto-insular cortex (in red), axial
view. Correlation from random effect (P < 0.01) and clustered corrected (P < 0.05) results based
on general linear model maps with seed region of interest comparing VS/UWS to healthy
controls. MCS: Minimally conscious state.
DMN activity is weaker in children (in mPFC)
Supekar et al., NeuroImage, 2010, 52, 290-301

Why is DMN particularly relevant for
studying aging and dementia?
• DMN structures are vulnerable to atrophy (Good et al.,
NeuroImage, 2001)
• DMN structures are vulnerable to deposition of β–amyloid

(Buckner et al., J. Neurosci., 2009)
• DMN structures show a reduced glucose metabolism (Minoshima

et al., Ann. Neurol. 1997)
• Abnormalities in resting-state BOLD fMRI of DMN may represent

early functional impairment associated with risk for AD, so it is a
candidate for a biomarker of preclinical dementia, and potentially
a valuable tool in dementia prediction, prognosis, and preventive
treatment development
Diminished DMN activity in normal aging
needs to be reliably differentiated from that observed in

neurodegenerative dementia
Koch et al., NeuroImage, 2010,
DMN in normal aging
Resting-state fMRI
Decreased f-nal conn. was demonstrated in PCC,
sup. & mid. frontal gyrus and sup. parietal region
(4 studies done so far: PNAS, 2007; Cereb.
Cortex, 2008; NeuroImage, 2010; Neuron, 2010)
In none of these studies increased DMN conn. Seed

with advancing age was observed (although
increases in conn. were noticed in regions in
outside the DMN) (Biswal et al., PNAS, 2010)
PFC
One study (Damoiseaux et al., Cereb. Cortex,
2008) corrected signal for grey-matter atrophy,
and observed decreases in f-nal conn. remained
significant, indicating that aging-related changes
in connectivity are not solely associated with
reductions in grey matter volume
Task-induced fMRI Seed

Elderly subject showed a decreased task-
induced deactivation in the DMN (part. in PCC
in
and medial parietal regions) compared to PCC/
younger adults, meaning that there is age- retrosplen.
cx
related reduction in the ability to suspend DMN
activity when the experimental condition
requires focused attention (Lustig et al., PNAS,
2003; Grady et al., J. Cogn. Neurosci., 2006)
DMN in healthy elderly and AD subjects
(Washington Univ. data)
Healthy elderly Alzheimer’s disease

subjects subjects
Greicius et al., PNAS, 2004, 101,

4637-4642
AD subjects showed highly significant decreased resting-state activity in
PCC (blue arrow), hippocampus and entorhinal cortex (green arrow).
DMN in healthy elderly and AD subjects (2)
Age-matched normal controls AD group 2 sample t-test
Wu et al., Hum. Brain

• Mapp.,
Decreased DMN connectivity even in patients with mild 2011 AD (Zhou et al.,
or preclinical
Brain, 2010), particularly in PCC and precuneus (He et al., NeuroImage 2007; Liu et al.,
Neuropsychologia, 2008) even when correcting for grey matter atrophy
• Decreased DMN connectivity was associated with AD progression and severity (Allen et
al., Arch. Neurol., 2007; Zhang et al., Radiology, 2010; Wu et al., Hum. Brain Mapp.,
2011)
Resting state DMN distinguish AD risk groups
• 17 cognitively normal individuals with a family history of AD

and at least one copy of the apolipoprotein ε4 allele were
compared to 12 individuals who were not carriers of the
APOE4 gene and did not have a family history of AD
Fleisher et al., NeuroImage, 2009, 47, 1678-1690
Cortical hubs and β-amyloid deposition
PIB PET
Buckner et al., J. Neurosci., 2009, 29, 1860-1873

Cortical hubs and β-amyloid deposition overlap (cont.)
PCC
PCC
Buckner et al., J. Neurosci., 2009, 29, 1860-1873

DMN FC and global PIB uptake overlap
Congruence (red) is highest in PCC, precuneus and

mPFC.
Mormino et al., Cereb. Cortex, 2011
Correlation of β-amyloid deposition (PIB PET)
and DMN f-nal connectivity
Clinically normal
participants with high
Seed in PCC amyloid
burden displayed
(blue box) significantly reduced f-nal
correlations within DMN,
including f-nal disconnection
of the hippocampal
formation relative to
participants with low
amyloid burden. These
reductions were also
observed when controlling for
age and structural atrophy
Hedden et al., J. Neurosci., 2009, 29, 12686-12694;

findings confirmed in Sheline et al., Biol. Psychiatry, 2010, 67, 584-
Latest findings
CSF Aβ<500 pg/mL CSF p-tau181>80 pg/mL
vs. CSF Aβ >500 pg/mL vs. CSF p-tau181<80 pg/mL
The main opposing
network to DMN is the
Dorsal Attention
Network (DAN): DAN
turns off when DMN
activates and vice-versa
In participants with low

CSF Aβ42 and high p-
tau181 (207 cognitively
normal participants
with preclinical AD), this
switching between
networks becomes increase decrease in f-nal conn. increase decrease
sloppy: in these people, PCC & MTL MTL & mPFC
some nodes of the DAN
did not turn off when
DMN was active Wang et al., JAMA Neurol., 2013, Aug 29, Epub ahead of print
Najvažnija neurološki važna
promijenjena stanja svijesti
• Sindrom „zaključanosti”
• Akinetski mutizam
• Trajno vegetativno stanje
Locked-in syndrome - lesion of
corticobulbar fibers (A) due to infarction in
the ventral midbrain (basilar artery). MRI
shows that area in front of aqueduct is
preserved (B)
Locked-in syndrome – 38-year-old
Locked-in syndrome – 53-year-old

If the cortex is destroyed (C) or if the link of reticular formation with the cortex is severed
(B) (usually by a midline lesion near the third ventricle or the upper part of brainstem)
there is a loss of arousal and the patient will remain permanently in a state of coma.
These situations have been labelled PERSISTENT

VEGETATIVE STATE (for lesions in C) or AKINETIC
MUTISM (for lesions in B), although the terms do not seem
to be used consistently throughout the literature.
In both the patient is unaware of his surroundings, although

the eyes may open and make random movements, and
respiration and the sleep/wake cycle are normal because
the brainstem is intact.
Akinetic mutism and the persistent vegetative state MUST NOT be confused
with the locked-in syndrome in which the cortex, the reticular formation and
their connections are intact. So too are the direct links between the cortex
and the III nerve nuclei: the patient is therefore fully conscious and can open
his/her eyes and look upward and downward to order.
GLASGOW COMA SCALE
UZROCI ENCEFALOPATIJA UZ KOJE MOŽE NASTUPITI GUBITAK SVIJESTI
- Strukturni
- Metabolički:
Hipoksija
Hipoglikemija ili hiperglikemija (hiperosmolarnost)
Globalna ishemija – moždani udar
Hipo- ili hipernatrijemija
Hiperkalcemija
Epilepsija
Hipotireoza
Hipokortizolemija
Toksini
Droge – vidi P23
Hepatička
Uremička
Meningitis/encefalitis/meninogoencefalitis
Sepsa
Subarahnoidalno krvarenje
itd.
Respiratory signs in coma
Rohkamm R, Color atlas of Neurology, Thieme, 2004

Cheyne-Stokes
hiperventilacija
apneusis: breathing holds

briefly at full inspiration
ataxic breathing
respiratorni arest
„pupilarna atetoza”
Anisocoria (nejednake zjenice)
- Fiziološka (svaka 5. osoba, asimetrička inervacija sfinktera zjenice parasimpatičkim vlaknima)

- Hornerov sy (ipsilateralna mioza, ptoza, anhidroza, crvenilo, bolje se uočava u mraku)
- Holmes-Adie sy (upala g. ciliare ili oštećenje njegovih postganglionarnih parasimp. vlakana)
- Paraliza n. III zbog intrakranijskih aneurizmi, tm ili npr. edema mozga i gornje hernijacije
(unkusa) s pritiskom na n. W-E (n. accessorius n. III)
- Paraliza n. III rijetko se javlja kao izolirana (ipsilateralna) midrijaza (+ptoza, -akomodacija, +
„pogled nadolje i prema van”):
Argyll Robertsonova zjenica („zjenica
prostitutki”) – ne reagira na svjetlo, ali
akomodira (najčešči uzrok je sifilis, ali
može biti i dijabetička neuropatija)
- Zjenice su češće bilateralno smanjene, nepravilne,

ali moguća je i jednostrana prezentacija
- Misli se da je uzrok AR zjenica oštećenje eferentnih
parasimpatičkih vlakana iz dorzalnog dijela WE jezgre
koja su odgovorna za inervaciju m. sphincter pupillae
(nakon prekapčanja u g. ciliare dolaze kao na mišić kao Douglas Argyll Robertson
n. ciliares breves), ali ne i ona ventralnija koja su

odgovorna za inervaciju cilijarnog mišića)
Holmes-Adie sy (midrijaza, sporija akomodacija)
A. normal
B. cupping of the optic
disk due to glaucoma
C. papilledema (papilla
stagnans) due to
increased ICP
CT / haemorrhage
EDH / SDH / SAH
Glasgow coma scale

2 i 7 tonički pojačani
oštećenje u diencefalonu,
mezencefalonu ili ponsu (katkad
teška hipoksija ili hipoglikemija
hiperekstenzija i nogu i ruku
opistotonus
hiperekstenzija nogu uz hiperfleksiju ruku

Single GNW state
General anaesthesia
Hvala na pozornosti!

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P22: Neurobiološka podloga

promijenjenih stanja svijesti

16. XI. 2020.

 In an ASC mental processing shows distinct changes specific to that

Neuobičajena: meditacija / hipnoza / droge – vidi. P23

Table of Contents Exit

~20% of adult’s sleep ~80% of adult’s sleep

& cognition (thinking is often illogical and lacking in sequence;

 This is known as the sleep-wake cycle shift

 This also means that they have the biological

 As a results this nightly sleep loss can accumulate as a

 Eg. A nightly sleep debt of 90 minutes between Monday

 Often on the weekends teenagers would sleep for longer

Tko želi znati više pogledati: Russell Foster – TED talks

 NREM sleep is believed to be important for

 The survival theory of sleep proposes that

 Humans sleep at night because we are highly

 One criticism is that it does not explain why

 The sleep deprived rats typically were unable to

 They eventually died after 2-3 weeks.

 It was then proposed that sleep is vital to the

 Research conducted on people that have voluntarily

 Ability to perform simple tasks more affected than

 Impairment of memory processes (STM)

 Hallucinations, delusions & paranoia

 Droopy eye lids

 Increased sensitivity to pain

After 5 consecutive days:

 Body temperature drops

 The immune system is lowered making us more vulnerable

 A microsleep is a very short period of drowsiness or sleeping that

 During a microsleep the EEG pattern resembles the early stages of

 Does fatigue really kill?

• Više u: Antonio Damasio „The feeling of

Direktna hipnoza (<30% Freud)

Za vrijeme hipnoze javlja se:

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Copyright © 2016 Wolters Kluwer • All Rights Reserved

Copyright © 2016 Wolters Kluwer • All Rights Reserved

Copyright © 2016 Wolters Kluwer • All Rights Reserved

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Copyright © 2016 Wolters Kluwer • All Rights Reserved

Copyright © 2016 Wolters Kluwer • All Rights Reserved

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Linear mix: A-2B Linear mix: 1.73A+3.41B