Final Flashcards
Ways to think about sleep
Phylogeny – all animals studied have some sort of quiescence or rest
Ontogeny – how does sleep change across the lifespan? Babies get disproportionately large amount of sleep especially REM which tapers off into adulthood
Mechanisms – what is generating REM sleep and how is sleep occurring
Function(s) – memory consolidation, glymphatic system
Our working hypothesis: “Sleep is of the brain, by the brain, and for the brain.”
Sleep deprivation aka total sleep deprivation (TSD)
absence of sleep entirely from your day
Related to a large amount of car crashes and all sorts of other cognitive impairments
Most organisms do not do this in any natural way
Sleep restriction
reduced total amount of sleep -> valuable because they accurately model how many of us sleep
Delta rebound
TSD and even sleep restriction leads to delta “rebound” (except after extended TSD)
Delta rebound: subsequent sleep will have either one more delta or 2 deeper delta (higher amplitude of delta)
Delta waves may be linked to removal of metabolic waste - pulsing nature of BOLD and arteries dilating and contracting
After extended TSD, delta goes in the opposite direction; decrease in delta overall (peoples brains look weird and we don’t know why)
REM rebound
If you remove REM sleep by waking people or animals up whenever they are in REM sleep
Loss of only REM leads to REM rebound
In general, loss of sleep leads to SWS rebound
But also some REM rebound too
Adolescents circadian rhythm
Adolescents have delayed circadian rhythm, reduced SWS, reduced delta (less and more shallow amplitude delta)
They do not get into late stages of NREM or REM as deeply
Delayed circadian rhythm leads to impaired sleep and impaired cognitive function the next day
Loss of sleep: effects
Attention and cognition:
TSD and restriction both lead to increase in “microsleeps” or “local sleep”, and substantial lapses in attention, vigilance, driving ability; also leads to diminished executive function
Local sleeps and microsleeps are cognitively relevant as they lead to major lapses in cognitive performance and attention
After around a week of sleep restriction (<6hr a night), you start to see the number of lapses which is roughly equivalent to TSD in 24 hrs
Diminished executive function may be due to stress from staying awake so long
microsleeps
When people do not sleep TSD, they still end up sleep
microsleeps: losing consciousness for msecs, little fragments at a time
Local sleeps
local individual neurons or small populations of neurons will switch between on and off states, suggesting that down to the cellular level, there are is something happening in relation to sleep
Mood
Loss of sleep: effects
decreased mood and increased irritability
Depression associated with changes in sleep (in either direction: in too little and too much sleep)
Changes in sleeping pattern are often associated with higher occurrences of depression
Immune system
Loss of sleep: effects
increased likelihood of infection, increased inflammation
SWS in “formation of immunological memory” (Besedovsky et al. 2012)
Building antibodies to particular pathogens is especially reliant on SWS
With less SWS or NREM -> less immunological memory
Chronic stress can lead to compromised immune system
Loss of sleep: effects
CVD
restriction (<6 hr/day) associated with greater heart attacks, stroke, etc
Loss of sleep: effects
Cancer
Increased risk for some but not all, esp. <5 hours sleep per night
When looked overall at all cancers, there is no association but in certain cancers there are some correllations
Loss of sleep: effects
Dementia
sleep disturbances (TSD and sleep restriction) associated with Alzheimer’s disease and dementia in general
TSD leads to increased A-beta and tau accumulation in brain
Suggests what sleep is doing is removing A-beta plaques
Impaired SWS associated and predicts with A-beta levels in brain 10 years later
A-beta accumulation is correlation is most for frequencies under 5Hz (delta waves)
___________seems to be the one important in cognition and attention but ___ is also important in that it rebounds suggesting there is an important function
SWS (NREM) ; REM
Mortality and sleep restriction
7 hours asleep seems to be the sweet spot - mortality rate is lowest for the group that sleeps 7-8 hours
Mortality increases with more or less sleep
especially above 7.5 hours -> people who sleep for a really long time may be dealing with some other chronic illness
< 7 hrs -> some of these individuals may be dealing with insomnia, etc.
All this said: Some of us need more, some less If you’re tired, sleep more; if not, don’t
Studying sleep deprivation and restriction
Humans
Case studies: Roy Gardner stayed awake over 200hrs (11days)
Day 2: trouble focusing his eyes and astereognosis (inability to identify objects by touch)
Day 3: moody, having trouble with some motor coordination tasks (e.g. tongue twisters)
Day 4: irritable, uncooperative, memory lapses, 1st hallucination
Day 5: more intense hallucinations continue
Day 6: speech starts slowing down, and having trouble identifying the name of common objects
Day 7+ 8: more irritable, more speech slurring, more memory lapses
Day 9: starts sentences and never finishes them
Day 10: paranoia
Day 11: completely expressionless, must be encouraged to talk, short attention span
TSD leads to impairments in cognition and disconnection from reality
Studying sleep deprivation and restriction
Humans
Familial Fatal Insomnia (FFI)
genetic version - lots of damage occurs due to single gene
No symptoms for a while then -> When onset, not long to live
Become catatonic, lose touch with reality, and eventually die
Neurodegenerative disorder - causing death of a variety of disorders
Holes in brain
Great dysfunction in immune system and heart troubles
Studying sleep deprivation and restriction
Animal models
3 models
Intracranial EEG to measure when they are sleeping to wake them up accordingly
- Disk-over-water
- “Flowerpot”
- slowly spinning wheel
slowly spinning wheel
only used for 24 hours otherwise, the rats will just sleep on the turning wheel
Flowerpot
(to restrict REM) -> upside-down flower pot -> put water underneath which can rise or shrink
When certain animals sleep, they still maintain their posture
As soon as the animal enters REM sleep, they have muscle atonia and they will slide off and fall into the water
Disk-over-water
(aka carousel method) -> when animals starts to fall into a certain type of sleep, the carousel starts turning, if animal does not wake up, they will slide into the water
Can sleep loss kill you?
Familial fatal insomnia (FFI) is fatal
But FFI causes many problems beyond insomnia including heart and immune dysfunction
More relevant for most of us: sleep restriction has lasting effects (usually less than 6 hrs)
Can sleep loss kill you?
Rats
Rats die on disk-over-water sleep deprivation after ~18 days (16-20 days depending on the study)
Rechtschaffen studies
But animals have many signs of stress
Lesions on their paws from excessive grooming
There is a control condition, though - the animals that are in the condition but are allowed to sleep do not die
Only REM or only NREM will eventually kill them
Studies suggesting sleep loss is also fatal in dogs, cockroaches, flies
mechanisms of sleep
Waking and sleeping states are generated by the brain!
Many brain regions and neurotransmitter systems involved in these states
Such as the reticular formation/activating system, structures in basal forebrain, hypothalamus
The hindbrain is required for generating wakefulness and REM
generating wakefulness and REM
Spinal animal
animal will generate all three states waking, SWS, and REM in cortex
Sleep is generated by the brain for the brain
generating wakefulness and REM
Low decerebrate animals (
(disconnect between midbrain and pons) -> only SWS, animals in permanent sleepy state (only delta waves)
Something in midbrain and up that is generating SWS
No signs of consciousness
generating wakefulness and REM
Disconnect between pons & medulla
SWS and REM
There’s probably someone in the medulla that is generating wakefulness
There’s something in the pons that is generating REM
The reticular formation
bunch of nuclei that look like a net or a mesh though mesencephalon to metencephalon to myelencephalon (midbrain -> pons + cerebellum -> medulla)
Reticular formation / Reticular activating system: waking!
There are many clusters of brain matter: VTA (DA), SNc (DA), locus coeruleus (norepinephrine), subcoeruleus (release ACh), raphe nuclei (serotonin), hypothalamus (His)
Lots of input/output to the basal forebrain (incl. NAcc, and globus pallidus)
Basic biological mechanisms, too (e.g. breathing, heart rate) -> we can breathe when we are unconscious which is driven by RAS, especially near the medulla
The reticular formation lesions
persistent sleep, never in waking state, can easily lead to fatal consciousness
RAS crucial for wakefulness and arousal
The reticular formation stimulation
rapid awakening
RAS
Lots of output to thalamus (gating):
when you have input from RAS to the thalamus, it opens the gate -> allows sensory signals to go up to cortex, allowing for conscious perception
When asleep, the thalamus gate is shut and we are unconscious
Cortex has not changed in terms of baseline level of activity but when thalamus gate opens, we can activate the thalamocortical loops to allow for conscious perception
Dreaming is thought but not conscious experience; dreaming does not include meta-cognition (thinking about thinking)
RAS neuromodulators
Lots of neuromodulators (DA, ACh, 5-HT) -> Primary releasing amine NT
Activating many neurons at once or repressing many neurons at once (watering the lawn)
Modulating state of the brain
Constant steady tonic release of dopamine from dopamine producing regions
The subcoeruleus, aka peribrachial nuclei
overview
lesion
stimulation
Often thought of as part of reticular formation
Subcoeruleus/peribrachial of pons: REM!
Lesions: no REM
Stimulation: activates REM sleep
Subcoerulus generates REM
Subcoeruleus -> medulla -> spinal cord: muscle atonia, preventing motor output through descending signals
Glutamate releasing neurons from subcoeruleus to the medulla
Reason why we do not act out during our dreams
REM looks a lot similar to waking -> busy or active brain but RAS is still very low activity
Cortex is active but the RAS is inactive so the gate is closed to consciousness
REM Behaviour Disorder (RBD)
The subcoeruleus, aka peribrachial nuclei
Lots of ascending projections - to the forebrain (pockets of brain activity during REM)
Abnormalities may be related to REM Behaviour Disorder (RBD) -> act out REM dreams because they do not have muscle atonia during REM
RBD in 98/100 cases predicts bad things on the way -> they often develop neurodegenerative disorders (PD, dementia, etc) associated with protein aggregation
Often occurs in 60s
Not sleepwalking - sleepwalking is during SWS - a lot of reactivating occurs during SWS
The locus coeruleus (blue region)
a part of reticular formation
Main nuclei of norepinephrine -> widespread release across the neocortex
Ascending pathway -> heightened levels of arousal; increase in activity
Emotional learning driven in part by norepinephrine
If you block norepinephrine signalling when remembering a traumatic event, can lessen the trauma - the details of the event hurt less as it is reconsolidated into a less emotional form
Locus coeruleus -> subcoeruleus
Some loud or spontaneous stimulus is going to activate the locus coeruleus -> inhibits the subcoeruleus and inhibit the formation of REM and switch into wakened state
inhibits REM
Locus coeruleus -> telencephalon: heightened arousal
The raphe nuclei
don’t forget to mention about lesion bro
a part of reticular formation
Main nuclei of serotonin
Raphe -> projects to other parts of the RAS: decreased wakefulness
Serotonin acting as an inhibitory neuromodulator -> inhibition leads to decrease in likelihood of wakefulness
Raphe lesions: insomnia - difficulty falling asleep
Raphe -> peribrachial: decreased/inhibiting REM
Increase likelihood of slow wave sleep
The basal forebrain (telencephalon- anterior to Hypothalamus)
A nebulous anatomical region
Includes ventral striatum (NAcc) and ventral parts of globus pallidus, nucleus basalis, septum
GABA and acetylcholine (ACh) neurons
If selectively lesioned basal forebrain => no SWS
Stimulation of basal forebrain GABA neurons
induce SWS -> driving delta waves
related: drugs - most sleep aid drugs are hypnagogic (GABA agonists or GABA positive allosteric modulators), facilitating the function of the GABA NT system
Sleepiness effect is specifically within GABA releasing neurons of the basal forebrain
E.g. alcohol, benzodiazepine, anaesthetics
Stimulation of basal forebrain ACh neurons: induce wakefulness or likelihood of REM
Difference between REM and wakefulness is governed by the thalamic gating
Effects of caffeine prominent here
The basal forebrain (telencephalon- anterior to Hypothalamus)
Most of the body as adenosine receptors (ATP -> ADP -> AMP -> A)
Adenosine = by product of activity in the day
Adenosine receptors normally make you sleepy, especially on ACh releasing neurons of the basal forebrain
Caffeine is blocking adenosine receptors in brain -> keeps you awake
Tuberomammillary nucleus
Part of the hypothalamus, sometimes considered part of RAS
Cells release histamine
Promotes wakefulness/arousal
Inhibited by basal forebrain GABA neurons -> inhibited during SWS
Releasing Histamine when not inhibited by the basal forebrain GABA
some allergy drugs (Antihistamines) -> negative effects on wakefulness
Histamine is also used as an amine neuromodulator
Lateral hypothalamus
Some neurons release orexin/hypocretin (same thing)
Orexin is related to eating
Project to most other sleep-related regions
Act like “the finger on the light switch” -> orexin producing neurons projecting to basal forebrain, RAS including some of the subareas
Maintaining or Stabilising the states (awakening, SWS, REM)
narcolepsy
Loss of orexin neurons in narcolepsy
Without orexin, the system is quite volatile - will flip in and of REM, SWS or waking states
Noisy unstable signal
Leads people to fall asleep spontaneously, and persistently sleepy, probably not allowed to drive, and may have to use psychostimulants to stay awake throughout the day
Cataplexy
These people may faint after a sudden or salient stimulus, or emotionally intense situations
attention in psychology is often referred to as _____ attention
selective
Attention vs. arousal/vigilance
Arousal is fundamentally different than focusing yourself onto certain aspects of the environment and not on other ones
Vigilance is often seen as a global level of alertness - not specific mechanism
Attention vs. consciousness
Attention is an important part of consciousness
The contents of conscious experience are related to what you are attending to
Consciousness is not simply attention
The awareness that you are an individual are separate; meta-cognition; body awareness
Attention vs. effort
intimate relationship between the two
If you exert a certain amount of effort, with effort invariably comes a shift in attention
It is impossible to be effortful at something you are not attending to
Attention is limited
We are good at organising and perceiving information but the quality of info and the amount that we can perceive in the moment is substantially limited
Attention is limited because we want to focus our attention onto the important things in the world and ignore things that are less important => filtering
There is so much sensory information coming in that will never reach the contents of my consciousness
Attention
Early model
bottleneck sensory information coming in at an early level before processing has occurred
Information may reach your primary visual cortex but with each successive step, far less info is going from primary to secondary visual cortex - filtered out at early stage
Not reaching conscious knowledge of what the state of the world is
Same regions involved in perception are probably related to conscious experiences
E.g. fusiform face area and the parahippocampal place area - high level visual processing - areas that are activated during consciousness
In reality bottleneck is probably earlier in processing
Attention
Late model
bottleneck sensory information coming in at an later level after processing has occurred
Probably some late stage bottlenecking that is occurring
Perceptual load
the idea that there is a total pool of sensory info and resources; this pool can be divided in a variety of ways
E.g. attending to 1 complex stimulus, or a few simple stimuli but you cannot attend to all of the stimuli
Biologically unclear - where is the perceptual load or how is it being divided
Posner Cueing task
Attention improves performance, cognition, behaviour, etc.
central target being attended to, then presented a visual cue
Goal is to maintain fixation onto the target (often fixation cross) - cue appears and must identify where the target is after a given amount of time
IV: whether the cue accurately predicts where the target is (valid) or if the cue is not where the target is (invalid)
For the invalid variable -> must make it so the cue is generally where the target is
DV: identify where the target is
Result: attention is important and has a beneficial effect on our ability to navigate our world -> higher levels of target detection even at low contrast or fast stimuli and reaction time decreases
Studies often control for eye movement as you must maintain eyes on target
But our eyes are always moving
Overt attention
our eye movements track to where we are paying attention to
We may more attention to where there are faces
Covert attention
shift in attention but we have not moved eyes -> We can have attention at something we are not looking at
Endogenous attention
you consciously decide to shift attention to some aspect of the environment
Aka Voluntary attention - driven my voluntary conscious decision
Aka Top-down attention
exogenous attention
external stimuli in the environment - directing attention to salient stimuli
Aka reflexive attention - driven by brains interest in salient stimuli
Aka bottom-up attention - focusing on individual features first and then expanding into larger perception
Consequences of attention
Attention means we are processing information differently - dedicating more of our brain to processing info
Some neurons may be more sensitive to certain stimuli
Brain activity will change as a consequence of the attention
Some brain areas are targets of attention
Some brain areas are modified by attention (consequence) -> some brain areas are affected by the guidance of attentio
mechanisms of attention
Need parts of our brain that are doing the shifting in attention
Some brain areas that determine what we will attend to (sources of attention) -> these brain areas guide our attention -> sources of attention
Areas important for attention: e.g. posterior parietal cortex (mechanism)
Consequences of attention: Attention enhances and tunes neural function
Seen at larger (brain area) scales
can see whole different areas fire differently
When different parts were cued, there would be different levels of sensitivity in different parts of the visual cortex (occipital lobe)
Train the monkey to focus on one particular part of the stimuli - ask to attend to one region
If asked to pay attention to different places on visual field, different parts would become active
If asked to pay attention to 2 different places that are different parts of your visual field, both of those places will becomes somewhat more sensitive
Suggests that our attention is not just one spotlight
Consequences of attention: Attention enhances and tunes neural function
Seen at smaller (single neuron) scales
Intracellular/extracellular recording -> electrode in brain
At Low levels of stimulation
Increase overall baseline level of firing within some neurons
Increase in gain/amplitude seems universally accepted
In some cases, neurons becomes insensitive to irrelevant stimuli and maintain sensitivity to relevant stimuli
Narrowing tuning so that you are only interested in one orientation - less interested in other orientations of light
Optimal stimuli firing more and related stimuli firing less
If you ask an animal model to attend to a specific orientation of stimuli, you may see some neurons will change their orientation preference
May see change in orientation preference
Change in receptive field also observed -> shift in stimulus that you are paying attention to
Sometimes called “position tuning”
Does tuning (narrowing/tuning for stimuli) actually occur? in PFC
Definitely occurs for arousal/vigilance in PFC -> narrowing response to stimuli
Specifically in catecholamine release (dopamine, norepinephrine) will narrow the range in which PFC neurons will fire
At low levels of arousal, it will fire for everything and at optimal levels of arousal, it will have a more tuned narrow firing
attention V4 neuron
For attention, first evidence seems to be from Spitzer et al. 1988 in V4 neuron
Narrowing and tuning of firing in 1988
McAdams & Maunsell find evidence for gain but not tuning in V4 in 1999
They could not replicate findings of V4
Subsequent work (Reynolds & Heeger 2009, suggests differences for attending to a space (gain) versus attending to a feature (tuning) in MT
(Martinez-Trujillo & Treue 2004) and V4, and areas related to movement
There is slight difference in the consequences of attention
If there is attention on spatial orientation of firing (attending to location), there will be obvious changes in gain but not changes in tuning
But if you ask the participant to attend to certain features (e.g. orientation of movement) instead of the whole space, there will be a tuning effect of the neurons and suppressing related stimuli
Discussion on gain vs. tuning even today
Crick & Koch theory of neural synchrony -> another proposed mechanism of attention
GABA interneurons coordinating and modulating oscillations within brains activity
Brain will take asynchronous signals and synchronise them together into very specifically timed actions -> EPSPs sum up to increase APs
Attending to something of interest will cause…
Attending to something of interest will cause pronounced firing - but when there are distractor stimuli that are also presented, it can cause suppression of firing
V4 neurons are particularly interested in colour and have a larger receptive field
Receptive field generally get larger and larger
As your attention shifts away, there are differences in level of firing
When asking animal to attend to certain parts of the environment -> there are shifts in the receptive field itself in response to the attention shift
4th consequence of attention at a smaller scale
Mechanisms of attention: Attention driven by multiple brain areas
The pulvinar
huge nucleus in the thalamus) -> strong connectivity to visual cortex and with a variety of other areas
Thalamus is often communicating with the cortex in a bidirectional manner => cortico thalamic loops
Lesions to the pulvinar can also lead to contralateral neglect
Important in shifting of mechanism of attention
Salience maps: priorities we are looking for in the environments -> what we should pay attention to in the environment
Priority maps
Inhibition of return
Mechanisms of attention: Attention driven by multiple brain areas Superior colliculus (midbrain)
down-up reflexive attention/eye movement/orientation
Mechanisms of attention: Attention driven by multiple brain areas
The frontal eye fields
involved in top-down guidance of movement
Strongly stimulate the frontal eye field -> causes eyes to move
Low levels of stimulation will cause a shift in covert attention -> increase in activity in the perceptual neurons
Frontal eye field guiding shifts in attention
Mechanisms of attention: Attention driven by multiple brain areas
Posterior parietal cortex
(blanket term for large area)
The lateral intraparietal area (non-human primates)
The intraparietal sulcus (humans) -> this tissue is especially important in the guidance of attention
Inputs are both top-down (PFC) and bottom-up (perceptual systems)
Lesions to these regions can lead to contralateral neglect or ataxia in some cases
Mechanisms of attention: Attention driven by multiple brain areas
Right temporoparietal junction (TPJ)
convenient and important for anatomical locations
Left temporal parietal junction = wernicke’s area (important in comprehension of language)
Damage can lead to impairments in theory of mind
Right TPJ is Important in the guidance of attention and self-monitoring
Lesion can lead to outer body experiences
Attending to self in the world
Mechanisms of attention: Attention driven by multiple brain areas
The dorsal frontoparietal system
(more activity to voluntary endogenous control of attention)
Activity in dorsolateral prefrontal cortex, some TPJ activity, medial frontal activity
Mechanisms of attention: Attention driven by multiple brain areas
The right temporoparietal system
(more activity to exogenously controlled aspects of attention)
some TPJ activity
Disorders of attention: dysfunction of the mechanisms (not consequences) of attention
Contralateral neglect
Lost ability to pay attention to some part of the world
NOT Visual BUT attentional impairment
Related to posterior parietal damage and pulvinar
aka hemispatial neglect, aka left neglect
Disorders of attention: dysfunction of the mechanisms (not consequences) of attention
Simultagnosia
can attend to individual features in the world but cannot attend to multiple features at the same time (cannot make bigger picture)
Often bilateral posterior parietal and large amounts of damage (multiple strokes in the same region)
One aspect of valuence syndrome
Consciousness
Consciousness poses the most baffling problem in the science of the mind. There is nothing that we know more intimately than conscious experience, but there is nothing that is harder to explain. - David Chalmers, 1995
Not a single one of the cells that compose you knows who you are, or cares. -Daniel Dennett, 2005
Brain activity does not generate consciousness; brain activity is consciousness
Features of consciousness
Subjectivity -> personally experienced and not easily quantifiable or measurable
Resistant to direct measurement
Consciousness can vary in terms of our mood, etc
Intentionality -> focused or directed at something
Unity -> not easily fragmented; cannot simultaneously experience things in two different ways
Selectivity -> we have attention; we filter out other aspects of the world constantly
Transience -> stream of consciousness; mind is constantly wandering
Likely due to limited nature of our nervous system (working memory is limited -> contents of conscious experience is often working memory)
Aspects of conscious experience
- Body awareness
- agency
- theory of mind
- self-awareness
- metacognition
Body awareness
knowing you have a body
E.g. if a rat gets hurt, the rat will protect that part of the body -> nurse and tend to wounds
Demonstrate Body awareness
agency
understand you are separate from the rest of the world
Agency and mental health -> understanding yourself as separate from the world is compromised in some mental health conditions (E.g. schizophrenia)
theory of mind
understanding that contents of my mind is different from the contents of other people’s minds
Emerges gradually (3-4 yrs old)
E.g. crow buries something in the ground and when a buddy crow is around, the crow will guard that spot on the ground
When the stranger crow comes around, the crow does not defend the spot because he knows that the stranger crow did not see him bury his stash
Crow understands that the contents of his knowledge is different from the contents of others’ knowledge
self-awareness
experiencing your experiences -> aware that you exist
E.g. mirror recognition test: chimpanzees over time start to recognize themself and notice and self-inspect itself the paint spot on their forehead
Dolphins, elephants, pigeon display this
Dogs often fails this
metacognition
thinking about yourself thinking
E.g. test the ability for an organism to monitor its own performance
People with severe brain injuries, meta-cognition is compromised
Consciousness sometimes seems inscrutable
Easy problem vs. hard problem
Easy problem: map brain activity conscious experience -> activity = conscious experience
No quality in brain activity
E.g. migrating birds will align themselves even with very little environmental cues -> they have knowledge of magnetic fields and the direction
Can show brain activity but difficult to imagine if one has never experienced it
Hard problem: difficult to understand why these brain activities result in a conscious subjective experience and colour/quality of the experience which is difficult to explain or understand fully
Materialism
everything in the universe has a material basis
brain activity does not generate consciousness, brain activity is consciousness
Brain activity is consciousness
dualist language
that the mind and body is separate -> no evidence
for consiousness
The neural correlates of consciousness (NCCs)
looking for patterns of activity that is only seen when a conscious experience occurs
A comparative problem: What is life?
Drawing line between when a cell is alive and when a cell is dead is extremely difficult and fuzzy
the élan vital / vitalism: traditional view that there was a vital substance that results in life -> no evidence
As we solve easy problems the hard problems will dissolve by understanding the functions relating to consciousness
Consciousness vs. selective attention
Selective attention is a major component of consciousness but it is not the entire consciousness
Consciousness vs. wakefulness (and sleep)
In order to be conscious, the brain activity must be connect (evidence in disconnection experiments)
Even if most of our brain activity is intact, if you are not able to generate a waking state, you will not have full consciousness
Need baseline level of arousal related to reticular formation
Wakefulness is a necessary component of consciousness
Exception: Persistent vegetative state: appear awake but do not show evidence of consciousness
Consciousness vs. perception
Perception: Organising noisy world into something that makes sense
Higher level perception is the conscious experience of an object
Consciousness vs. explicit memory
Explicit memory, we are drawing information that is in storage
Memory can be useful for imagining what may happen in the future
Consciousness vs. decision making
Many of the decisions we make seem to be conscious in nature
Consciousness in some forms are playing a role
A number of studies suggest that consciousness may not doing anything but rather is an product of the activity - epiphenomenon
Many decisions we make are not consciously made, rather done before you even realise
Consciousness vs. the self
Clearest part of who you are is the part you have conscious access to
But there are parts of our personality that we may not be consciously aware of
Aspects of personality driven by parts of our brain that we do not have conscious access to
Reasonable starting points in studying the neuroscience of consciousness
Consciousness is another word for brain activity
Brian activity is the psychological language for describing something that is happening at the neurobiological level (materialist)
BUT there is plenty of brain activity outside of our consciousness
Brian activity does not constitute consciousness
Reasonable starting points in studying the neuroscience of consciousness
- Consciousness is another word for brain activity
- Consciousness is how we describe the activity of some (but not all) neurons
- Consciousness seems especially related to activity in the cortex, and somewhat related to activity in the subcortical structures of the telencephalon (frontal cortex, hippocampus, amygdala) and the thalamus (diencephalon)
(Damage to the thalamus can lead to some disorders of consciousness)
Consciousness is how we describe the activity of some (but not all) neurons
Some neurons are related to consciousness and others are not
Consciousness and the forebrain Visual perception (cortex)
Visual perception:
Some forms of vision is accessible to conscious knowledge
Ventral pathway through thalamus, V1, and frontal cortex
Consciousness and the forebrain
blindsight (midbrain)
blindsight (midbrain)
Brain can get visual information outside of conscious experience
Secondary Visual cortex damage -> some individuals will report that they do not have any conscious visual perception
but if asked to guess what card they are holding up, they will report with greater than chance accuracy the correct card
Top-down (FEF) vs. bottom-up (superior colliculus) eye movement
bottom-up (superior colliculus) -> uses sensory information to cause motor changes
If superior colliculus is preserved during cortex damage - patients may exhibit blindsight
Even without conscious visual perception, patients can navigate around a room full of objects
Reflexively moving eyes
Top-down (FEF) -> consciously moving eyes
Pavlovian conditioning, the cerebellum, and the hippocampus
thalamus and consciousness
Learning can occur prior to conscious experience
Loss of function and gain of function in the thalamus
Thalamic damage can lead to disorders of consciousness
Mixed results depending on patient and the severity of damage
Some people with highly damaged thalamus who get their thalamus stimulated with electrodes can improve their consciousness to some extent
e.g. Eyeblink conditioning
Eyeblink conditioning
Airpuff onto eye will cause eye to blink
By associating tone with the puff of air
When there is a time gap between the tone and the airpuff in eye, animals with a lesion to the hippocampus often cannot learn this (trace condition)
Damage to hippocampus -> no trace condition learning
If there is no gap between tone and airpuff, you do not need hippocampus to learn this association -> instead the cerebellum would be needed
Some areas can learn without consciousness (e.g. cerebellum)
Research methods that probe the neuroscience of consciousness
- Bistable images
- Binocular rivalry
- Present relevant stimuli for a given brain area or neuron
- Comparing the brains of conscious vs. nonconscious individuals
Bistable images
content is the same but the conscious experience/perception is changing
E.g. seeing a duck and a bunny in the same image
Necker cube: perspective of which side is the front of the wire cube
Binocular rivalry
radical different image in different eyes
Altering what we see from one eye and the other eye
Holding the content of visual cue constant but the conscious experience is changing
Present relevant stimuli for a given brain area or neuron
Show a bunch of different stimuli to the neuron/brain area, and what every stimuli causes more firing -> find related images and show images to measure firing again
Comparing the brains of conscious vs. nonconscious individuals
Waking brain vs. sleeping brain
Someone who is in different states of consciousness
Visual awareness studies point to sensory association cortex for NCCs
i.e. the ventral stream of the visual system
Binocular rivalry in non-human primates (extracellular recording)
The inferotemporal cortex (IT)
Upper levels of visual processing is related to consciousness
Parahippocampal gyrus (parahippocampal place area PPA) -> stronger activity for places in primates
Binocular rivalry in humans (fMRI)
Note: results are more diffuse using fMRI
The inferotemporal cortex (IT)
inferior temporal gyrus, sometimes the medial temporal gyrus and the fusiform gyrus Fusiform gyrus (FFA)
Fusiform gyrus (FFA)
Minimal activity when there is random shape image
Minimal activity when random shape is mixed with primate face image
Binocular rivalry image (shape image in one eye and primate face in other eye)
When the monkey consciously reports seeing a face, there is higher levels of activity
When they are consciously reporting seeing the shape, there is minimal activity
Binocular rivalry in humans (fMRI)
When people’s visual perception change from seeing a face to seeing a house, the BOLD response shows a decrease in activity in the FFA and increase in activity in the PPA (and vice versa)
Note: results are more diffuse using fMRI
Slower temporal resolution
It has been suggested that lower visual perception areas are related to consciousness as well but the evidence is weaker with fMRI
Concept cells
The Halle Berry neuron, this time with dolphins!
Done on patients with epilepsy in the medial temporal lobe (hippocampus, sometimes in the amygdala and surrounding cortex) -> removing tissue where seizures are occurring with electrodes in the brain
Neuron is firing for things related to dolphins even the word dolphin written down
Concept cells
Sydney Opera House
Neuron fired whenever the participant was seeing the sydney opera house
The neuron would fire for the sydney opera house or when the participant mistook other buildings as the sydney opera house
The resting brain is not idle
fMRI
performing a task reflects increases and decreases in brain activity
fMRI pulses magnetic field and disturbs all of your atoms and realigns which is measured
Some decrease is related to task, some not
i.e. The brain has resting state brain activity
Measure via resting-state functional-connectivity MRI (rsfcMRI)
resting state brain activity
The brain has resting state brain activity
Brains were much more active when the participants were not doing a specific task
There was a pattern of BOLD response during resting state activity -> high correlation of activity in the PFC and posterior cingulate cortex
Measure via resting-state functional-connectivity MRI (rsfcMRI)
Seeing that when one area is active, the other area is inactive while another area is active
Key finding: the default mode network
mPFC, posterior parietal cortex, PCC, precuneus (directly adjacent to the PCC)
PCC and precuneus is especially important for autobiographical consciousness (thinking about self)
And sometimes hippocampus, lateral temporal cortex
DMN: not just at rest - can be generated under certain task conditions
DMN thought to underlie spontaneous cognition -> mind-wandering
DMN-like activity also observed in monkeys and rats!
Sentinel hypothesis
Internal mentation hypothesis
Together: sort of suggests what consciousness is doing when not selectively attending to world
DMN represents our conscious introspection and reflection when we’re not selectively attending to external world
Sentinel hypothesis
even when we are doing nothing, we must still pay a little attention to the world
E.g. if you ask a participant to get ready for an event to occur but do not tell them where it is occurring -> activity increase in default mode network
Whereas if asked to get ready for an event to occur in one region of their environment -> more activity in attentional regions
Internal mentation hypothesis
(mind wandering/daydreaming)
Fundamental role of DMN
Very related to consciousness
Comparing the brains of conscious vs. non-conscious individuals
Non-conscious individuals: sleep, anaesthesia severe head injuries
Some aspects of sleep are considered a type of consciousness especially vivid dreaming
Overlapping MRI studies: Structural MRI of many participants and overlay on top of each other and look for common areas that have been damaged for individuals with disorders of consciousness
Main results: overlap with selective attention (i.e. that frontoparietal network; dorsal attentional networks), plus DMN areas (e.g. mPFC, posterior cingulate cortex) related to disorders of consciousness
Persistent vegetative states: Sometimes conscious!
How do we know that the individuals are conscious?
Activity in some brain areas predicts consciousness
Adrian owen’s research
fMRI: yes = imagine playing tennis (primary/secondary motor areas); no = imagine walking through house (parahippocampal gyrus/place area)
20% of individuals in these minimally conscious states (Persistent vegetative states) are able to accurately answer questions
Changes patient care and how the patients are treated
The curious case of Crick and the claustrum
Claustrum: a little grey matter
Claustrum has extensive connectivity to the telencephalon and diencephalon, thalamus, basal ganglia, and all over the cortex -> every single lobe has interconnectivity with the neurons of the claustrum
Many of the claustrum has very long branches and prolific input layers
Plays a role in synchrony and plays some role in consciousness
Electrical stimulation of claustrum
Electrical stimulation of claustrum and nearby areas (e.g. basal ganglia) caused loss of consciousness in human case study (similar to epilepsy seizure)various altered consciousness in animal models
claustrum also implicated in…
stress responses, addiction, slow wave sleep, epilepsy, and more
In mice that were exposed to chronic stress -> caustrum lesion would lead to less pronounced stress responses
Animals with cocaine addiction, reenforcing effects of drug addiction are related to the claustrum
When claustrum was lesioned, behavioural responses were diminished and the animals were less likely to administer cocaine
Some of the slow wave sleep may be driven in part by the claustrum
Claustrum related to the generation of seizures and the eplieptic processes in disordered brain
when claustrum removed with tumour, or lesioned
no loss of consciousness when claustrum removed with tumour, or lesioned
Some individuals who had their claustrum removed due to epilepsy seem to be fine in terms of consciousness
Executive functions
The prefrontal cortex; role of executive functions in many cases are critical for consciousness
The contents of consciousness are often determined by these executive function
Executive function as higher-order cognitive processes (incl. metacognition) that control and organise lower-level cognitive processes
Executive function as supervisory system (we are systems built on systems built on systems)
Competing motivational demands built in to different parts of the brain
Features of executive function: shifting, updating, inhibiting
The more switching required in a task -> the more mentally tiring the task is (cognitive mental effort)
Updating -> behavioural rigidity or cognitive rigidity
The most cognitively successful people are extremely cognitively flexible -> adapt to new information coming in
Inhibiting -> moment to moment controls are outside of conscious access
A lot of tasks are driven by skills and habits and learning
Prefrontal cortex is sometimes referred to as the breaks of subcortical/automatic processes
Executive dysfunction impairs these abilities
The way in which you think and frame the world is related to the PFC
Brain rhythms and EEG
EEG waves aren’t necessarily reflective of brain activity/APs but they are reflective of voltage changes on the neurons (EPSPs/IPSPs)
Harken back to the EEG: gamma waves (high frequency observations on EEG)
Some studies suggest that brain rhythms especially gamma waves are related to action potential
Rhythm Synchronises activity across many different parts of the brain all at once
Different aspects of the same stimulus is processed by different parts of the brain
Expert mediators have high gamma -> gamma waves are thought to be focusing on higher cognitive processes
binding problem
Different aspects of the same stimulus is processed by different parts of the brain
Individual action potentials across the brain are all related to the same stimulus -> must bind of the features together (binding problem)
People believe that rhythm can bind together the APs of the stimulus and the conscious experience
Bandleader
neuron firing in a pattern that synchronises all the other neurons within a network or circuit
Jamband
the instruments are firing together, they feed and interplay off each others inputs and outputs
Both jamband and bandleader is probably the case
Some neurons depending on whether or not the _____ seems to be synchronising with itself
thalamic gate is open
a two-neuron oscillator
A model of rhythms: a two-neuron oscillator: one neuron has an excitatory projection and the other neuron has an inhibitory projection
The excitatory one would have activate the inhibitory one -> The inhibitory one would inhibit the excitatory one for a moment
Results in cells firing in a rhythmic way
Seen in thalamus and other areas
The thalamus as pacemaker for rhythms
Neurons that are pacemaking - setting patterns of firing
Two neurons can generate its own oscillations/pattern
cortico-thalamic loops
Recurrent thalamo-cortical resonance, aka cortico-thalamic loops
The cortex and the thalamus (sensory) are connected forming many closed loops
Cortex projects to new parts of the thalamus and send information to new parts of the cortex -> closed loop
The loops are ascending through various levels of processing systems
cortico-thalamic loops Mouse model with A1 (auditory cortex), V1 (visual cortex), S1(somatosensory cortex), M1 (primary motor cortex), ALM (secondary motor cortex in mice)
Projecting from thalamus to these cortical regions -> where some layers (e.g. layer 6) are projecting back to the thalamus forming perfect closed loop
Some layers (e.g. layer 5) projects to different parts of the the thalamus and this new part of the thalamus is going to project to a new part of the cortex
These processes eventually guide and shape our movement to navigate to world
TRN: thalamic reticular nuclei (subregion of the thalamus)
Under slow wave sleep or REM conditions, the thalamus is not getting the reticular input from RAS => the loops do not occur
The disruption of these loops are leading to the disruption of consciousness (aka closing of thalamic gates)
BUT the cortex can still have lots of activity elicited
Thalamic damage often implicated in disorders of consciousness
Consciousness is not binary (there is a spectrum of consciousness)
VS: unresponsive wakefulness syndrome
LIS: locked in syndrome
MCS: minimally conscious states; more lucid and connected to reality but not fully conscious
EMCS: someone who had exited a minimally conscious state
Can we quantify conscious brain activity?
perturbational complexity index, PCI
perturbational complexity index, PCI
Record with EEG, perturb with TMS by transcranial magnetic stimulation, measure perturbation effect (patterns of ripples of activity all across the brain)
Take TMS and pulse one part of the cortex
Conscious: diffuse, longer-lasting response across brain -> More conscious individuals have higher PCI
Non-conscious: e.g. NREM, anaesthetics, disorders of consciousness: local, shorter-lasting response -> lower PCI value
Suggests that thalamic gating is allowing for synchrony across the brain, which is related to consciousness - integrated across many brain regions
Likely mediated by those corticothalamic loops!
Consciousness reflects complex, integrated brain activity Sci-fi implications?
The reason we are conscious is because of the complicated integrated system of activity suggesting that there are many things that are nonbiological that may have similar properties of integration and diffusion of these signals that may end up being conscious as well
Consciousness
Summary
Consciousness is a challenging, but not insurmountable, problem -> start with easy problems and solve harder ones
Consciousness is a psychological construct that describes activity in some brain areas (notably DMN, association cortex, and thalamus) but not others
Consciousness is also reflected by some types of brain activity in these regions (e.g. DMN, cortico-thalamic loops, gamma) but not others
READING: A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behaviour
The PCI could allow tracking of consciousness in individual patients.
The values ranged from 0.44 to 0.67 in 32 awake healthy people, but fell to 0.18 to 0.28 during nonrapid eye movement (NREM) sleep
‘‘unconscious’’ values for the PCI: midazolam deep sedation, 0.23 to 0.31; propofol, 0.13 to 0.30; and xenon, 0.12 to 0.31
The PCI values from these patients clearly reflected the state of their consciousness, with the six patients in a vegetative state clearly unconscious (0.19 to 0.31), the two with locked-in syndrome clearly aware (0.51 to 0.62), and those in a minimally conscious state showing intermediate values (0.32 to 0.49).
We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI).
PCI is calculated by:
- perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration)
- compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information).
implications of PCI
PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness.
PCI can potentially be used for objective determination of the level of consciousness at the bedside.
Neurophysiologically, these fundamental properties of subjective experience rely on the ability of multiple, functionally specialized areas of the thalamocortical system to interact rapidly and effectively to form an integrated whole
an emerging idea in theoretical neuroscience is that consciousness requires an optimal balance between functional integration and functional differentiation in thalamocortical networks, otherwise defined brain complexity
This complexity should be high when consciousness is present and low whenever consciousness is lost in sleep, anesthesia, or coma
compared to responses of conscious, wakeful individuals, brain responses of people who had lost consciousness became either …
local (suggesting a loss of integration) or global but stereotypical (suggesting a loss of differentiation).
determined the PCI in individual patients by performing several steps
- recording the brain’s early reaction (within the first 300 ms) to a direct TMS-induced cortical perturbation with high-density electroencephalography (hd-EEG)
- performing source modelling and nonparametric statistics to extract a binary matrix of significant sources that describes the spatiotemporal pattern of activation caused by the TMS perturbation
- compressing this matrix to calculate its information content with algorithmic complexity measures
- normalizing algorithmic complexity by the source entropy of SS
operationally, PCI is defined as the
normalized Lempel-Ziv complexity of the spatiotemporal pattern of cortical activation triggered by a direct TMS perturbation
PCI is expected to be low if there is reduced interaction among cortical areas (loss of integration), PCI
will also be low if many interacting areas all react to the perturbation in a stereotypic way (loss of differentiation) because the resulting matrix will be large but redundant and can be effectively compressed
PCI will be high only when the initial perturbation is transmitted to a large set of integrated areas that react differently, giving rise to a spatiotemporal pattern of activation that cannot be easily reduced.
PCI discriminates between consciousness and unconsciousness in healthy individuals
PCI was reduced to values between 0.12 and 0.31 when subjects lost consciousness, resulting in a clear-cut distinction between the distributions of the conscious and unconscious groups
PCI values in wakefulness were significantly higher than those in NREM sleep
No significant differences were found among PCI values for subjects who experienced loss of consciousness
the time course of PCI was reproducible -> During wakefulness, PCI grew substantially after 100 ms, whereas in all situations where consciousness was lost, the PCI plateaued at around the same latency.
the rate at which PCI increased was reproducible within and across subjects and changed only when the level of consciousness was altered
PCI is sensitive to graded changes in the level of consciousness
Loss of consciousness induced by anesthetic agents was graded with a score of 1 (no response to mild prodding/shaking) or 0 (no response to painful stimuli) as assessed by the Modified Observer’s Assessment of Alertness and Sedation (MOAAS) scale
In the intermediate condition, all subjects attained a MOAAS score between 3 (response only after name is called loudly and/or repeatedly) and 2 (response only to mild prodding/shaking) -> the PCI showed intermediate values between 0.34 and 0.42 that fell between the conscious and the unconscious values
PCI values at intermediate levels of propofol anesthesia were significantly lower than those during wakefulness (P = 0.001) and significantly higher than those obtained in deep sedation
PCI had an intermediate value (0.39) during the transition from wakefulness to sleep (sleep stage 1) and a value (0.46) within the conscious distribution during rapid eye movement (REM) sleep, upon awakening from which the subject reported having experienced a dream
PCI discriminates the level of consciousness in brain-injured patients
In six patients with a stable clinical diagnosis of vegetative state (VS) [called “unresponsive wakefulness syndrome], who were aroused but unaware, the PCI ranged from 0.19 to 0.31, falling within the distribution (0.12 to 0.31) observed in healthy subjects during NREM sleep and anaesthesia.
in two brain-injured patients who, at the time of recording, could communicate reliably only through vertical eye movements and who were diagnosed with locked-in syndrome (LIS), the PCIwas as high as in healthy awake subjects
PCI provides a data-driven metric that can discriminate level of consciousness in single subjects under different conditions
wakefulness; dreaming; the LIS (locked in syndrome); the MCS (minimally conscious states; more lucid and connected to reality but not fully conscious); the EMCS (someone who had exited a minimally conscious state)
intermediate levels of sedation; NREM sleep; midazolam-, xenon-, and propofol-induced loss of consciousness; and the vegetative/unresponsive wakefulness state
Various brain-based empirical measures have been proposed as potential neurophysiological markers of the level of consciousness -> These metrics belong to one of two general categorie
The first embraces methods that aim to quantify the information or spectral content of brain signals
second category includes methods that evaluate the spatial extent or synchronization of brain activations
Although each of these metrics tends to show group-level differences between specific conditions in which consciousness is absent or present, they are less reliable when it comes to detecting reproducible and graded changes in single individuals under different conditions (sleep, anaesthesia, and brain injury)
PCI, gauges at once both the information content and the integration of the overall output of the corticothalamic system by measuring ….
the algorithmic complexity of the brain’s response to a perturbation
Unlike other measures of complexity that are applied to spontaneous brain signals, PCI only assesses information that is generated through _____ ______within the thalamocortical system;..
deterministic interactions; the resulting measured complexity is minimally affected by random processes, such as noise and muscle activity, or by patterns that are not genuinely integrated, such as those generated by isolated neuronal sources or common drivers
PCI behaved in the same way whether loss of consciousness was caused by a
physiological process (sleep) or by a pharmacological intervention with anesthetic agents (midazolam, xenon, and propofol) with different mechanisms of action, suggesting that our index captures a neural correlate of the level of consciousness that is general and reliable
an intermediate level of consciousness
Many patients emerge from coma and exhibit signs of an intermediate level of consciousness, ranging from simple visual fixation to a confused state in subjects with severe cognitive disability
PCI differs from TMS/EEG measures of effective connectivity
unable to detect graded changes in the level of consciousness
maximum value detected during loss of consciousness distinguishes PCI from measures of brain activation to sensory or verbal stimulation, which are characterized by a
significant rate of false negatives in brain-injured patients
PCI can be reliably calculated only if the TMS stimulation…
effectively elicits a significant cortical response
This problem can be avoided by using an imaging-guided TMS positioning system to avoid targeting damaged cortical sites
Psychopathology is vast and messy
- Mental illnesses (aka psychological disorders)
E.g. schizophrenia, major depressive disorders, BPD, etc - Neurological disorders
E.g. Neurological disorders that can lead to weak control of muscles or poor motor coordination, failing to get sensory information in (numbness), MS, epilepsy - Brain dysfunctions
Starting from what the damage is and what kind of symptoms emerge - Inevitably, if there is is some sort of deviation from normality in an individual, it is virtually guaranteed to show changes in their neurobiology
- Shifting societal norms inform our categories
Inevitably, if there is is some sort of deviation from normality in an individual, it is virtually guaranteed to show changes in their neurobiology
But what those biological differences mean is often harder to say
Pathology is reflected in our biology but so is every aspect of being human
Biological basis BUT Contrast these to individual differences
Shifting societal norms inform our categories
Deciding whether something is pathological or not is a societal distinction
Our determination of whether or not we have an illness is reflective of society itself -> there will be biological differences no matter what so we cannot look merely at biological differences to prove these people are atypical (we all have biological differences)
As societal norms shift, they are reflective of the society’s values and not just of the societies mental illness categorization
E.g. gender identity disorder - this was thought of as a disordered psychological thinking; these norms are shifting
Instead there is a category called gender dysphoria (the distress of not feeling like the gender assigned at birth is the disorder not the differing gender identity)
Psychopathology
people who have trouble navigating the world/society the way in which they are designed
BNS perspective: study changes to structure and function of brain, as related to symptoms
This is a lot easier in some disorders and not others
E.g. anorexia nervosa or obsessive compulsive disorder -> extremely challenging to model these in an animal model
The changes are slight or subtle because we are talking about people at the extreme ends of normal spectrum of brain function and chemistry
Principles of psychological disorders
- Etiology often unclear -> disease pathway is unclear
- Some types of polymorphism leads to increased risk
- Some (e.g. schizophrenia, psychopathy) best considered developmental in nature
Suggests there is a difference in the way these nervous systems have developed
Some (e.g. schizophrenia) might represent multiple disorders categorised together by symptoms
Schizophrenia patients show different symptoms and manifest differently
Each individual has a very different set of symptomatology
A bunch of processes can all lead to that outcome - Biological predispositions interact with environment
- Many likely represent the extreme ends of a normal spectrum of nervous system functioning
the diathesis stress model
Some individuals have predispositions that increase likelihood of manifesting disorders
The disorders may manifest during appropriate interaction between biological predispositions and some sort of external environmental pressure (e.g. stress)
Many likely represent the extreme ends of a normal spectrum of nervous system functioning
Patients may be at the extreme ends of the normal spectrum not that they are fundamentally different (e.g. extreme release of dopamine -> more dopamine release but not released in a fundamentally different way)
Psychological labels shape our experience
Psychological disorders and perpetrating crimes
There are a few mental disorders that lead to higher rates of violence
E.g. intermittent explosive disorder (people with extreme aggression and anger issues), drug addiction especially alcohol, people having delusions to being in imminent danger
Not really any consistent higher rate of crime or violence from individuals with schizophrenia
Those with mental disorders are disproportionately more often the ____ __ ____ than those non-mentally ill
victims of crime
Psychosis is not “dissociative identity disorder”
(multiple personality disorder -> patients with this disorder usually have very horrific things happen in their lives as consciousness is extremely resistant to fragmentation)
Psychosis ≠ Psychopathy
Psychosis is related to positive symptoms of schizophrenia (e.g. loss of touch with reality, hallucinations, delusions)
Psychopathy is a forensic (not psychological) assessment!
Self report of psychopathy is unreliable -> must look at case file
Psychopathy is not considered illness
What schizophrenia looks like
Positive symptoms
(hallucinations, delusions, disorganised thought, speech, behaviour)
Drugs that block dopamine functioning can provide benefits/reduce for these symptoms
These symptoms can be manifested by psychostimulant use -> doctors do not diagnose immediately
More somatosensory hallucinations
Commonly manifest in the beginning of the disease
Hallucinations are commonly auditory
What schizophrenia looks like
Negative symptoms
(absence or decrease in emotional expression, lack of motivation, lack of spontaneous speech)
Over time, often later on the negative symptoms emerge
Whether or not medication is given or not, these symptoms emerge
Medication is mostly targeted at positive symptoms
Motivation is related to dopamine function
What schizophrenia looks like
Cognitive symptoms
(decrease in attention, executive function, working memory) -> perhaps due to decrease in firing in the PFC - organising things into steps
They also miss subtle aspects of communicating with others
What schizophrenia looks like
Mood symptoms
(showing inappropriate emotions for certain contexts, depression)
Schizophrenia often is related to or coupled with mood disorders with them
Schizoaffective disorder: patient displays hallmarks of schizophrenia and major depressive disorders
schizophrenia overview
Symptom manifestation can be different among different individuals -> difficult to classify
Prevalence: 0.5-1.5%, slightly more common in men
Onset: teens to early 30s
Atypical behaviours even in younger children who will later manifest with schizophrenia (aka there are developmental predispositions for the disease) - indicators that disorder will manifest later on
Unemployment, poverty, homelessness common
What it doesn’t look like -> Dissociative identity disorder
Who gets schizophrenia/risk factors
Role of genetics:
Having a Twin with schizophrenia -> vastly increase chances (50-70)
Suggests strong genetics and/or biological/developmental component
Closer family members with schizophrenia, the higher risk of schizophrenia
no candidate gene for schizophrenia
Cannabis and psychostimulants (amphetamine, cocaine, etc) =correlation with=> rates of psychosis/schizophrenia by a bit (2-3)
Living in an urban environment increases risk of developing schizophrenia
Moving from urban to rural environment
Being born in the winter
Mother having some kind of in utero infection, commonly influenza in 1st and 2nd trimester
Brain changes in schizophrenia
Gross anatomical change can be seen in schizophrenia
Structural: widespread decreased grey matter, sometimes abnormal white matter patterns, enlarged ventricles (easiest to measure with lateral ventricle since they are so large)
Decrease in grey matter associated with the emergence of negative symptoms
Tissue organisation changes
Hippocampus: atypical layering structure, atypical neuronal shape and branching in unusual ways
PFC: fewer dendritic spines on pyramidal neurons (glutamatergic) and fewer GABAergic interneurons
Suggests developmental issue with macro and microscale changes
Brain changes in schizophrenia
Functional
abnormal (often hypoactive -> hypofrontality, which is measured with glucose PET) frontal and temporal lobes (incl. hippocampus), dysfunctional dopamine neurotransmission (pre- and postsynaptic; GABA + glutamate), less activity in TPJ, and more
Hypofrontality also seen in chronic stress, depression, schizophrenia, and some cases in BPD
Take-away: best considered a neurodevelopmental disorder
Pharmacological Treatments
The most common treatments (for positive symptoms of schizophrenia) are pharmacological:
antipsychotic drugs (aka neuroleptics) -> mitigates positive symptoms
There is usually less luck in treating the negative symptoms of schizophrenia
Most medication for negative symptoms is psychostimulants but this cannot be given to patients with schizophrenia as it will increase positive symptoms
Discovery of Neuroleptics
a surgeon noticed that the administration of chlorpromazine to his patients to counteract swelling had a calming effect.
He subsequently suggested that it might have a calming effect on difficult-to-handle patients with psychosis.
Subsequent research showed that, after being administered for a period of 2-3 weeks, it alleviated (frequency and intensity) the symptoms of psychosis in many patients
Use of anti-psychotic drugs lead to parkinsonia -> displaying symptoms of parkinson’s disease with massive sedative effects in movement
Parkinsonian effects diminish and so does the positive symptoms over time
Hyperfunctioning dopamine system -> positive symptoms of schizophrenia
Dopamine Theory of Schizophrenia
The theory that schizophrenia is caused by too much activity at receptors for the neurotransmitter dopamin
Dopamine Theory of Schizophrenia
This theory was based on several findings:
- The brains of individuals with Parkinson’s disease have marked dopamine depletions; and antipsychotic drugs produce symptoms that are similar to Parkinson’s disease.
- Drugs known to increase dopamine levels (e.g., amphetamine, cocaine) produce positive symptoms of schizophrenia
- The efficacy of an antipsychotic drug is correlated with the degree to which it blocks activity at dopamine receptors
Dose of drug can vary quite dramatically depending on which drug you are getting
Drugs that bind more strongly to dopamine receptors are more effective at smaller doses
D2 receptor antagonists is especially important for schizophrenia
- Evidence suggests that individuals with schizophrenia have hypersensitive/ higher-than-usual dopamine release
Evidence suggests that individuals with schizophrenia have hypersensitive/ higher-than-usual dopamine release
PET Study: they gave participants a slight amount of amphetamine (psychostimulant drug that increases dopamine release)
Measure the amount of dopamine receptor availability using PET
Exaggerated release of DA from people who have schizophrenia (exaggerated response to the amphetamine drug)
More presynaptic activity
The bigger the change/the more severe the response to the amphetamine, the bigger change in a person’s positive symptoms
Problems with the dopamine theory
In the 80s and 90s, researchers began to realise that the theory had several major problems:
- The newer “atypical” antipsychotic drugs produce a wide variety of changes in the brain and were just as good as traditional antipsychotics at treating positive symptoms of schizophrenia
(NOTE: they were also just as bad even though they) (NOTE 2: drug differences might be exaggerated)
Atypical antipsychotic drugs had effects in many other neurotransmitter systems - It takes 2-3 weeks for antipsychotic drugs to work, yet their effects on dopamine receptor activity are immediate
- Most patients show no significant improvement to the first antipsychotic they are given
Glutamate Hypofunction Theory
Postulates that the dysfunction of glutamate NMDA receptors on GABAergic interneurons leads to a decrease in GABAergic transmission, especially in PFC
(Note, this theory also includes GABAergic dysfunction)
NMDAR -> mg2+ gated ionotropic glutamate receptors are dysfunctional
Glutamate is being released onto interneurons, which are going to release GABA -> synchronise and organise activity of neurons
Connectivity between excitatory and inhibitory systems to synchronise and organise connectivity
Glutamate Hypofunction Theory
support:
Post-mortem brains show fewer glutamate receptors in schizophrenia vs. control
Glutamate NMDAR antagonists like phencyclidine (PCP; angel dust) and ketamine (tranquilliser) can mimic symptoms and cognitive problems of schizophrenia
These other drugs acting on NMDAR can also have schizophrenia-like effects
NMDAR co-agonists (e.g. glycine, d-serine) which bind to another binding site on the NMDAR provide small improvement
D-serine normally released primarily by astrocytes which have some control over some functions of the NMDAR
Administration of glycine or d-serine can have small benefits in schizophrenia
CB1 receptor activation causes CB1-NMDAR internalisation
Chronic NMDAR antagonism (blocking NMDAR activity) changes DA transmission
Abnormal functioning in the dopamine system
Glutamate Hypofunction Theory
support:
CB1 receptor activation causes CB1-NMDAR internalisation
Cannabis is acting on our endocannabinoid systems which travel backwards
Tend to have inhibitory effect
Cannabis can be colocalized with NMDAR and get NMDAR and CB1 off membrane and into cell (internalised)
High doses can cause hypofunction of glutamate system and affect GABA releasing cells
Weakens connection with 2 different neurons
Very high doses of schizophrenia can exhibit psychotic-like states
Receptors that cannabis normally acts on (CB1) are often localised around NMDAR
Cannabis can pull down NMDAR from membrane which makes cell hypofunctional
Glutamate Hypofunction Theory
problems:
Positive symptoms fail to respond to glutamatergic medication
Perhaps because glutamate is used across the entire brain and may need to be targeted more specifically to PFC
Changes in glutamate functioning do not lead to changes in symptomatology
(Note, this theory also includes GABAergic dysfunction)
support for the idea that schizophrenia is an Autoimmune disorder
- Bone marrow transplant (BMT): “cured” schizophrenia!
- Another BMT: “caused” schizophrenia!
Bone marrow transplant (BMT): “cured” schizophrenia!
Usually schizophrenia will develop across a lifespan and symptoms will manifest pretty early in life
24 yr old male with treatment resistant schizophrenia with severe delusions and hallucinations who got a bone marrow transplant for leukaemia
Showed remarkable reduction in psychotic symptoms without administration of antipsychotic drugs and drastic improvement in social functioning
Surgery caused major changes to NS that they were no longer symptomatic
2-4 years after surgical intervention showed persistent beneficial effects
Another BMT: “caused” schizophrenia!
Another patient (67 yr old) who needed a bone marrow transplant -> only person who was a match was his brother who had schizophrenia Shortly after transplant, the patient started to develop the positive symptoms of schizophrenia
support for the idea that schizophrenia is an Autoimmune disorder
What’s happening here?
Hypothesis: BMT restores microglia function (immune function) may lead to improvement in function in patients schizophrenia
Something related to schizophrenia and immune function
Autoimmune disorders more prevalent in schizophrenia patients
as autoimmune disorders often target NMDAR which may be contributing to the development of schizophrenia (either damage, remove, or destroying NMDAR)
GAF = global assessment of functioning
Graph shows major changes in symptomatology
Psychopathy is (probably) not what you think
Not in the diagnostic at all
Serial killers: “partially successful” psychopaths
Many but not all serial killers would qualify as psychopaths (forensic term)
Partially successful: they are able to plan and evade getting captured
Probably many “successful” psychopaths in society
Successful: how well people are able to navigate through society with their personality disorder
But also many “unsuccessful” psychopaths (with criminal records)
Not able not able to navigate through society because the way in which they frame or think about the world
“Omnivorous criminals” (involved in all sorts of different criminal acts)
These criminals are not focused on one type of violent act
Psychopathy -> great emotional indifference for others; they did what they wanted in that moment
Some psychopaths are violent but in many cases, they are not violent at all (violence is associated but not a guarantee)
What psychopathy looks like: Cleckley’s Insights
Case studies: different than popular notion
Saw a number of cases where the people were diagnosed differently every time but had a unique set of symptoms
At first glance, psychopaths are rather charming and hold strong eye contact
Mask of sanity: from the surface they appear to have normal emotions but they’re emotions are artificial
They know all the words that they need to say
Talk therapy makes psychopaths better at hurting other people because they know what to say
Gives them better language and tools to get away with what they want to get away with
“Knows the words but not the music”
Often average or better intelligence, no obvious problems, BUT also “screw-ups”
Constant Lying, shameless for no particular reason
They lie because that is what they feel like doing in that moment
When they are caught, they feel no sense of shame but rather try to laugh it off
Bad at maintaining jobs
Something “off” but don’t seem mentally ill
Modern conception: The revised psychopathy checklist (PCL-R)
Robert Hare (UBC), adapted in part from Cleckley
Requires training, interview process, records check (case file)
Cannot ask individual because they will lie
Based on factor analysis
2 major factors with subcomponents in each factor
While the PCL-R is the “gold standard”, it has its issues (e.g. a predictor-criterion overlap)
One of the measures of PCL-R is criminal activity -> using criminal activity to predict criminal activity (problematic as it is quite obvious)
PCL-R: factors and facets
Psychopathy
Factor 1 (interpersonal affective) Factor 2 (impulsive antisocial; more behavioural)
Factor 1 (interpersonal affective) Interpersonal
Glib, superficial charm Grandiose self-worth Pathological lying (lying constantly for no benefit) Cunning/manipulation E.g. excessively cheating partner
Factor 1 (interpersonal affective) affective
Lack of remorse/guilt
When they fail at psychological test, they know remorse/guilt happens but it does not shape their behaviour in any way
Shallow emotional affective experience
Callous/lack of empathy
Failure to accept responsibility - never their own fault, it is always someone else’s fault
Factor 2 (impulsive antisocial; more behavioural) Impulsive
Need for stimulation/ proneness for boredom
Parasitic lifestyle
E.g. borrowing or stealing money from loved ones constantly
No realistic long-term goals
E.g. no plan for future or forethought on how their actions will lead to certain outcomes
Impulsivity
Irresponsibility
Factor 2 (impulsive antisocial; more behavioural) antisocial
Poor behavioural control Early behavioural problems Juvenile delinquency Revocation of conditional release E.g. they may be let out due to plead of guilt and then commit another criminal act shortly after Criminal versatility (omnivorous)
Checklist of 20 items of the PCL-R of on which you can score
Checklist of 20 items of the PCL-R of on which you can score 0,1, or 2 on each item
Minimum score = 0
Maximum score = 40
Usually 25 or 30 out of 40 -> psychopath
Average people will score a 2-3
If someone is at around a 20, there will be noticeable changes in their behaviour
Psychopathy prevalence
~1% in the general population (but difficult to estimate)
Less common in women
But some aspects of psychopathy may manifest differently between men and women
~3.5% of the business world
15-25% of the prison population -> qualify forensic diagnosis of psychopathy
~10% of violent criminal women
~30% of violent criminal men
57-97% of serial killers -> not many serial killers though (low N)
Present in all social strata
Thought to be a neurodevelopmental disorder
Most psychopathic professions
CEO Lawyer Media (TV/radio) Salesperson - manipulate people to buy things Surgeon Journalist Police officer Cleric Chef Civil servant
Least psychopathic professions
Care worker Nurse Therapist Craftsperson beautician/stylist Charity worker Teacher Creative artist Doctor accountant
Psychopathy vs. Antisocial personality disorder
Psychopathy is not in the DSM
Most psychopaths in criminal system would qualify for ASPD
BUT not all diagnosed ASPD are psychopaths on forensic diagnosis (missing affective interpersonal side); many ways to develop ASPD
ASPD: pervasive disregard and violation of rights of others
Lots of people are violents, ASPD people may have reasoning for their actions unlike psychopaths
Why care about psychopathy?
Enormous economic, societal burden
~ a trillion dollars for the cost of crime
Psychopaths are at increased risk for
Criminal and other disruptive activities
Violent crime
Recidivism rates are extremely high
If these individuals are let out, almost certainly they will be committing crimes again
History of Drug use and addiction to an extreme amount
Alcohol increases likelihood of violence
Physiological differences
People with psychopathy have extremely low levels of physiological arousal
There is still low arousal even when trying to arouse them
Low heart rate
Low EEG reactivity
Diminished augmentation of startle response by aversive stimuli
Diminished suppression of startle response by pleasant stimuli
Structural differences
Most research has focused on amygdala and vmPFC
Researchers when looking there due to the related nature of these brain areas to fear learning and planning
Underactive and less connected
Amygdala: decreased gray matter, decreased connectivity between amygdalar regions
vmPFC: decreased gray matter, reduced cortical thickness
Reduced structural (e.g. seen in DTI) and functional (i.e. seen in fMRI) connectivity between amygdala and vmPFC
Functional differences
No trouble with identifying moral violations BUT no brain response difference for moral vs. nonmoral stimuli
If you ask psychopaths to identify moral transgressions, they are able to recognize moral transgressions
While witnessing these socially transgressive acts, control people would show activation in the amygdala, or temporal lobe (in some cases) and vmPFC whereas
Psychopaths did not show activity in the emotional areas when exposed to moral transgressions
They know that it is wrong but do not have the emotional experience
Their bain activity correlated to the level of reward given -> hypersensitive responses to reward
Can psychopathy be measured in the general population?
Difficult, but some believe it can
Lilienfeld and Andrews: the Psychopathic Personality Inventory (PPI)
Potential problems (e.g. it’s self-report), but shows some validity
Some advantages over PCL-R (administration, training)
Like the PCL-R, it divides into factors
Fearless dominance
Self-centred impulsivity
Psychopathy and reward
As PPI scores go up, activity in the ventral striatum (aka nucleus accumbens) goes up
Reminder: NAcc is primary target of VTA dopamine
Are psychopaths hypersensitive to reward? Does this affect their decision making?
