Transcript AJA Teaching - Neuroscience

Xavier
Phineas Gage
In the 1840s, an unfortunate man by the name of Phineas Gage
was laying railway tracks in the midwestern United States. He
was pressing down a charge of dynamite into a rock formation
using a tamping rod, when the charge suddenly exploded. This
caused the tamping rod to shoot through his head, from
underneath his cheekbone into the frontal lobe of his brain and
out through the top of his skull. Partly because the rod passed
through so rapidly, probably cauterizing the tissue on its way, the
damage to Gauge’s brain was not very widespread, only a
relatively small area of frontal tissue was affected. Gage did not
even lose consciousness and he made a rapid physical recovery.
Before the accident Gage had been the foreman of his team.
He was regarded as a reliable character and was highly valued
by his employers. However, his physician made the following
observation:
The equilibrium or balance, so to speak, between his
intellectual faculties and animal propensities, seems to have
been destroyed. He is fitful, irreverent, indulging at times in the
grossest profanity (which was not previously his custom),
manifesting but little deference to his fellows, impatient of
restraint or advice when it conflicts with his desires, at times
pertinaciously obstinate, yet capricious and vacillating,
devising many plans for future operations, which are no sooner
arranged than they are abandoned. … In this regard his mind
was radically changed, so decidedly that his friends and
acquaintances said that he was ‘no longer Gage’.
A biological approach
regards the brain as a
substrate of the mind,
but the mind is more
than just the brain
Cellular Architecture of the Brain





About 10 billion neurons (109)
Each individual neuron makes a synaptic connection
with approximately 60,000 to 100,000 other neurons
The total number of synaptic connections is in the
range of 1027
The functional unit of mental activity is not a single
neuron but a circuit of interconnected activated
neurons
Clusters of neurons with similar functions are known as
nuclei
Synapses
Neurons are connected to one another via
synapses. The axon of one neuron links up with
a dendrite of another neuron. At the place where
these meet there is a small gap, called synapse.
This gap is breached by molecules, called
neurotransmitters
Synapse Illustration
Neurotransmitters


There are a variety of neurotransmitters, each
with a different profile and distribution
Acetylcholine: first known neurotransmitter,
lacking in Alzheimer Disease, broken down by
enzyme acetylcholinesterase (nerve gas blocking
this enzyme, now used therapeutically in
treatment of Alzheimer Dementia)
Neurotransmitters




Noradrenaline: Arousal: feeling alert, hyperactive, pain
sensitivity, sexual arousal
Dopamine: involved in movements, also in
Schizphrenia; Parkinson’s Disease when lack of
dopamine production
Serotonin: Pain control, Sleep, mood elevation
Gamma-aminobutyric Acid (GABA): inhibitory,
suppresses unwanted activity (e.g. epilepsy, anxiety
symptoms); Benzodiazepines enhance GABA effects
Neuronal Networks



Interactions with the environment cause
neurons to wire into circuits, so called neural
networks
Recognition occurs when we encounter
something that evokes a neural pattern similar to
one already preserved
Hebb’s rule (1949): Cells that fire together wire
together (creating neuronal pathways)
Neuronal Network
Neuronal Network
Neuronal Plasticity






Plasticity of the brain is a central concept
Some neuronal circuits may be hard-wired (i.e. genetically
determined or fixated very early on in life)
There are sensitive windows of time in the development of
neuronal circuits (early childhood, adolescence)
Neuronal pruning: neuronal pathways, which are no longer used
later in life, become inactivated (use it or lose it principle).
Regularly used pathways provide ‘templates’ of activity
Analysis can change neuronal pathways, i.e. new connections
(new ways of thinking and emotional experience) can develop,
old ones breaking up
Memory




Neural representation of information to which a
person was previously exposed and which can
be reactivated for use in the present
Iconic Memory: short sense impression
Working Memory (short-term memory)
Long-term Memory
Memory
Explicit/Declarative
Implicit/ non-declarative
Semantic
Episodic
Priming
Procedural
Emotional
Facts, Knowledge
Autobiographical
Shapes, Forms,
Sounds
Motor skills,
cognitive (grammar)
Fear
Basal Ganglia
Amygdala
Hippocampus
Working Memory





Held for only few minutes (erasable work space)
Dependent on pre-frontal cortex
Responsible for the search and retrieval of information
from long-term memory that is involved in many
higher cognitive functions
Emotionally arousing information and personally
relevant information is more likely to be encoded
Memory is state-dependent: memory retrieval is
enhanced by degree of similarity between encoding
situation and retrieval situation.
Memory – Further Comments




Explicit Memory does not emerge before the age of 3
(immaturity of hippocampus and prefrontal cortex)
In early trauma dissociation between emotion (fear
reaction) and conscious memory of trauma
High levels of emotional arousal can flood
hippocampus with cortisol, which results in
hippocampal damage and further impairment of
declarative memory
‘Neutral’ cues may result in strong emotional reaction
due to implicit memory retrieval
Damasio: Kinds of Self



Proto-Self: Representing the state of the organism
(biochemical milieu, blood pressure, oxygen) moment
by moment – unconscious, processes information from
within the body; mainly brainstem structures involved
Core-Self: Conscious awareness of changes to the
system, non-verbal, based on images, no memory, no
external observer (‘you are in the music while the music
lasts’)
Autobiographical Self: Record of core-self
experiences, explicit, partially modifiable with further
experience; requires core consciousness; life experience
The Unconscious Mind




David (Good Guy, Bad Guy Experiment)
Claparède
Split Brain Patients
Libet
Claparède (1911)
A female patient with brain damage, which today
we assume included circuits involving the medial
temporal lobe, was unable to form new
memories. Each time Claparède visited her, he
had to reintroduce himself. One day he
experimented. While reintroducing himself
along with his usual handshake, he held a pin in
his hand. Although on subsequent occasions the
woman still could not consciously remember
him, she refused to shake his hand
Split Brain Patients
In her television series on the brain, Susan Greenfield presented Joe, who had
undergone a split-brain operation as a desperate measure to cure his epilepsy.
This means that the right and the left half of Joe’s brain do not communicate
with one another. Joe was given the word ‘glass’ to his left hemisphere and
the word ‘hour’ to his right hemisphere. He was asked to draw, what he had
been shown. He drew an hourglass, even though he did not know why. He
only had conscious knowledge of having been shown the word glass. This
shows that information had been processed unconsciously. This is the
biological basis for the psychotherapeutic experience that the unconscious
knows more. We permanently receive information and process it, even
though this information never reaches the level of consciousness. This
unconscious information is stored in neuronal circuits, probably for short
periods of time. It can be accessed in the way of association and intuition.
We do not know, where the knowledge came from, but it was suddenly there
all be it in a rather vague and hazy fashion.
Benjamin Libet (1983)



Brain wave activity (Readiness Potential) occurs
anywhere between 500 and 1,000ms before we
consciously decide to move our arm or hand
The cerebral initiation of what becomes a free
voluntary act begins unconsciously or before there is
any subjective consciousness or awareness that the
decision to act has already been activated in the cerebral
cortex.
This suggests that the brain initiates the process
towards a movement before the ‘mind’ or
consciousness is cognizant of the decision.
Jaak Panksepp: Basic-Emotion
Command Systems





Based mainly on animal research but close correlates in humans.
Basic-emotion command systems can be stimulated or reduced
(drugs, surgical elimination, direct stimulation)
Universal affective reactions represent basic emotions. They
seem to be ‘hardwired’ connections based mainly in the
brainstem and limbic system.
Shared evolutionary heritage embodying the primal experiences
of our ancestors
Basic emotions define a set of common biological ‘values’ that
unite us all in our struggle with the tasks of life.
Basic Emotions


SEEKING: curiosity, interest, expectation; provides
arousal and energy that activates our interest in the
world around us; need-detector; strongly activated
during sexual arousal, hunger thirst, craving; dopamine
as predominant neurotransmitter, reward; Seeking
system is unspecific, does not know what it is seeking,
‘just something’
LUST: dominated by consumption (reciprocal
relationship between SEEKING and LUST); orgasmic
feelings; endorphins as main neurotransmitters; related
to addictive behaviour
Basic Emotions (2)





RAGE: fighting behaviour (as opposed to flight);
aggression, irritability; linked to amygdala
FEAR: high alertness for danger, flight response;
amygdala
PANIC: separation distress system, feelings of loss and
sorrow; located in anterior cingulate gyrus; related to
maternal behaviour
CARE system: morphine, oxytocin; mothering, social
interactions
PLAY: social emotions
Basic Emotions (3)



Evolutionary advantage of inherited emotionally driven
behavioural stereotypes
However: open to influence by learning mechanisms;
basic emotions need adjustment depending on the
environment; phobias may be hardwired manifestations
of the FEAR system
Inhibition and control of basic emotions is achieved by
inhibitory cortical systems, mainly of the ventromesial
and orbital frontal areas (cf. Phineas Gage)
‘Our brains resemble old museums
that contain many of the archetypal
markings of our evolutionary past....
Our brains are full of ancestral
memories and processes that guide
our actions and dreams but rarely
emerge unadulterated by corticocultural influences during our
everyday activities.’ (Panksepp,
“Affective Neuroscience”, p. 75)
‘The collective
unconscious contains the
whole spiritual heritage of
mankind’s evolution, born
anew in the brain structure
of every individual.’ (CW8,
342)
Distributed Midbrain - Diencephalic - Basal Forebrain
Chemoarchitectures for Prototype Emotions (Extracted from
Panksepp, 1998)
Affective
Behavior
Structures/Neural Networks
Neuromodulators
Non-Specific
Motivational
Arousal –
Seeking &
Exploratory
Behavior
Rage/Anger –
("Affective
Attack")
Ventral Tegmental Area (VTA) to more
dorsolateral hypothalamic to PAG, with
diffuse mesolimbic and mesocortical
“extensions:” nucleus accumbens as basal
ganglia processor for emotional “habit”
systems
DA (+), glutamate (+), many
neuropeptides including
opiods, neurotensin, CCK
Medial amygdala to bed nucleus of stria
terminalis (BNST) to anterior and
ventromedial and perifornical hypothalamic
to more dorsal PAG
Lateral & central amygdala to medial and
anterior hypothalamic to more dorsal PAG
to nucleus reticularis pontine caudalis
BNST and corticomedial amygdala to
preoptic and ventromedial hypothalamus to
ventral PAG
Anterior cingulate to bed nucleus of stria
terminalis (BNST) to preoptic hypothalamic
to VTA to ventral PAG
anterior cingulate/anterior thalamus to
BNST/ventral septum to midline &
dorsomedial thalamus to dorsal preoptic
hypothalamic to dorsal PAG (close to
circuits for physical pain)
Parafascicular/centromedian thalamus,
dorsomedial thalamus, posterior thalamus,
to ventral PAG (septum inhibitory re: play)
Not clear if separate from activation of play
systems and inhibition of fear systems?
Substance P (+) (? ACh,
glutamate (+) as nonspecific
modulators?)
Fear
Sexuality
Nurturance/
maternal care
Separation
Distress/
Social
Bonding
Play/Joy/
Social
Affection
? Social
Dominance
Glutamate (+), neuropeptides
including DBI, CRF, CCK,
alpha MSH, NPY
Steroids (+), vasopressin and
oxytocin
Oxytocin (+), prolactin (+),
dopamine, opiods,
Opiods (-/+) oxytocin (-/+),
prolactin (-/+) CRF (+) for
separation distress
Opiods (+ in small amounts, in larger amounts), muscarine
(+), nicotine (+)
‘The concept of basic emotions
accounts for the similarity of basic
emotional expression across
individuals and cultures and display
rules take care of many differences....
Many emotions are products of
evolutionary wisdom, which probably
has more intelligence than all human
minds together’. (LeDoux, “The
Emotional Brain” p 36 & 118)
‘The brain does not begin its day as a
tabula rasa. The brain is imbued by the
sort of life with knowledge regarding how
the organism should be managed, namely
how the life process should be run and
how a variety of events in the external
environment should be handled.... In brief,
the brain brings along innate knowledge
and automated know how....’ (Damasio,
”Looking for Spinoza” p 205)
Dreams

Allan Hobson



Dreaming is a creative process in the brain and any meaning
that results is absolutely transparent (not disguised as
suggested by Freud)
Dreaming is another form of consciousness. The ‘chaotic
electrochemical state may reflect our emotional
preoccupations, and reflecting on those preoccupations can
provide insight’
‘There must be some kind of reworking of memory going on,
but it isn’t buried stuff you can’t manage. It’s probably just
the opposite: in dreaming we’re trying to integrate and come
to terms with the difficulties of having emotions’
Dreaming (2)

Jonathan Winson



What’s going on during REM in both animals and humans is
that the brain is literally being wired
Dreaming in humans evolved from a mechanism inherited
from lower species in which both genetically encoded,
survival-related data and crucial information drawn from daily
experience are processed in the brain during REM sleep
In man, dreams are a window on the neural process whereby,
from early childhood on, strategies for behaviour are being
set down, modified, or consulted
Dreams (3)

Matthew Wilson


Tore Nielsen


The brain is constantly evaluating new experience to figure out hot it fits
into the mental model built through previous memories, testing to see
how well that model is working to predict novel occurrences and to guide
decisions. Much of this revision appears to occur during sleep.
Dreaming may serve as a kind of internal therapist, helping us to integrate
emotional experiences from the day.
Rosalind Cartwright

For most people, dreams in the first REM period of the night contain the
most negative emotion, an in each successive REM period, dreams
become both more positive emotionally and also incorporate elements of
autobiographical memory
Dreams (4)

Eric Nofzinger


Ernest Hartmann


Dreams seem to be taking emotionally charged information from the
daytime and connecting it with a larger body of information in the cortex
that’s species specific or that comes from each individual’s personal base
of experience
As connections are made between the recent disturbing event and
previous experiences, the emotion becomes less overwhelming and the
trauma is gradually integrated
Bill Domhoff

Jung’s observation of some commonality in dream content across
individuals and cultures is plausibly encompassed by the idea that
metaphorical concepts are acquired through both developmental
experiences shared by all human beings and gradual linguistic socialisation
into the huge treasure trove of conceptual metaphors that are part of our
cultural heritage
Dreams (5)

Stephen LaBerge


Dreams are the worlds we have created from the contents of
our minds. Dreams may not be messages, but they are our
own most intimately personal creations. As such, they are
unmistakably coloured by who and what we are, and could
become
Allan Hobson

Dreaming may be our most creative conscious state, one in
which the chaotic, spontaneous recombination of cognitive
elements produces novel configurations of information: new
ideas. While many or even most of these ideas may be
nonsensical, if even a few of its fanciful products are truly
useful, our dream time will not have been wasted
Mirror Neurons


Distinctive class of neurons that discharge both
when a monkey executes a motor act and when
it observes another individual performing the
same or a similar motor act
Significance and role
Imitation and learning
 Understanding the actions of others (Autism)
 Emotions and Empathy (Countertransference)
 Language Evolution

Mirror Neuron Distribution
Ventral
premotor
cortex
Inferior parietal
lobe
Mirror Neurons - Future
Watch

this space!
www.scholarpedia.org/article/Mirror_neurons
Epigenetics 1
Traces of Dutch 'Hunger Winter' in genetic material
 Conditions in the uterus can give rise to life-long changes in genetic material. People in
their sixties who were conceived during the Hunger Winter of 1944-45 in the
Netherlands have been found to have a different molecular setting for a gene which
influences growth. Researchers from the LUMC are the first to demonstrate this
effect. They published their findings this week in PNAS Online Early Edition, together
with colleagues from Columbia University.
Epigenetics
 During the Hunger Winter (the Dutch famine of 1944-1945) the west of the
Netherlands suffered from an extreme lack of food. It now appears that the limited
food intake of mothers who were pregnant during this period altered the genetic
material of embryos in the early stages of development. The effects of this can still be
observed some sixty years later. These alterations are not changes in the genetic code,
but a different setting for the code which indicates whether a gene is on or off. This is
known as epigenetics. One of the main processes in epigenetics is connecting the small
molecule methyl to DNA.
Epigenetics 2
Vulnerable

The researchers compared the degree of methylation of a piece of DNA, the IGF2 gene, of
people who were conceived in the Hunger Winter with that of their brothers and sisters. They
chose this particular gene because it plays an important role during gestation. People in their
sixties who were conceived during the Hunger Winter have less methyl groups on the IGF2 gene
than their siblings. This did not apply to children of the Hunger Winter who were in later stages
of gestation when the famine occurred. They did have a lower birth weight than their siblings, but
the IGF2 gene was not 'packaged' differently. This indicates that epigenetic information is
particularly vulnerable in the early stages of pregnancy.
More economical level

‘The next question is whether the epigenetic change which has been identified is a 'scar' on the
DNA because of lack of food, or a specific adaptation to the shortage of food,' comments Prof
Eline Slagboom. Researcher Dr Bas Heijmans: ‘Epigenetics could be a mechanism which allows
an individual to adapt rapidly to changed circumstances. Changes in the DNA sequence occur by
chance and it takes generations before a favourable mutation spreads throughout the population.
By then, a temporary famine is long past. It could be that the metabolism of children of the
Hunger Winter has been set at a more economical level, driven by epigenetic changes.' This could
explain why children of the Hunger Winter suffer more frequently from obesity and cardiovascular diseases.
Epigenetic Mechanisms