Cognitive Neuroscience

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Cognitive Neuroscience

• The Brain Story
• by
• Vaia Lestou

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A brief History of Cognitive Neuroscience

• Ancient humans although they wondered extensively
  about the nature of human feelings, memories,
  attention, communication, motion and many other
  cognitive functions, they had one big problem.
• Problem
• They did not have the ability to systematically
  explore the mind through experimentation.

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A brief History of Cognitive Neuroscience

• But if you can observe, manipulate measure then
  you can start to determine how the brain gets its
  job done
• Debrück (1986) Mind From Matter?
• If you want to understand how a biological system
  works then a laboratory is needed and experiments
  are essential.

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A brief History of Cognitive Neuroscience

• Enigma of whether the brain works in concert or
  parts of the brain work independently is still
  the focus of contemporary research
• face area
• specialised only for faces?
• or objects as well?

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A brief History of Cognitive Neuroscience

• Franz Joseph Gall J.G. Spurzheim claimed that
  the brain was organised into 35 specific
  functions
• founders of phrenology in the early 19th century
• Functions ranged from language and colour
  perception to hope and self-esteem
• If a person used one of the faculties more than
  the others the brain representation area grew
  (bump in the skull idea!)

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A brief History of Cognitive Neuroscience

• Gall and colleagues believed that by studying
  carefully the skull of a person you could go a
  long way in describing the personality of the
  person inside the skull
• Anatomical Personology

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A brief History of Cognitive Neuroscience

• P.J.M. Flourens (1794-1867) challenged Galls
  localisation views
• bird experiments
• According to Flourens(1824) All sensations, all
  perceptions and all volitions occupy the same
  seat in these (cerebral) organs. The faculty of
  sensation, percept and volition is then
  essentially one faculty.

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A brief History of Cognitive Neuroscience

• In France Paul Broca treated a man who had
  suffered from stroke
• the patient could understand language but could
  not speak
• the patients left frontal lobe was damaged
• Brocas area

3D MRI of human brain with Broca's area
highlighted in red
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A brief History of Cognitive Neuroscience

• The German Neuroloist Carl Wernicke in 1876
  reported a stroke victim who could talk freely
  but what he said made little sense
• Patient could not understand spoken or written
  language
• Wernickes area

3D MRI of human brain with Wernicke's area
highlighted in blue
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A brief History of Cognitive Neuroscience

• The most famous of all physiologists was Brodmann
  who analysed the cellular organisation of the
  cortex and characterised fifty two distinct
  regions
• It was soon discovered that the
  cytoarchitectonically described brain areas
  represent distinct brain regions

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A brief History of Cognitive Neuroscience

• The revolution in our understanding of the
  nervous system was brought by Camillo Golgi
  (Italy) and Ramon y Cajal (Spain)
• Golgi developed a stain that impregnated
  individual neurons
• Cajal found that neurons are discrete entities
• He was also the first to suggest that neurons
  transmit electrical information in only one
  directions from the dendrites to the axonal tip

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A brief History of Cognitive Neuroscience

• In the 20th century physiologist and neurologists
  continued the debate over the holistic processing
  or the functional localisation conflict in the
  field.
• And while the medical profession pioneered most
  of the studies of how the brain worked,
  psychologists began to claim that they could
  measure behaviours and indeed study the mind.

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A brief History of Cognitive Neuroscience

• The term Cognitive Neuroscience was first coined
  in a taxi in the 70s and by that time a new
  mission was clearly required
• neuroscientists were discovering how the cerebral
  cortex was organised and functioned in response
  to simple stimuli
• specific mechanisms were described, such as those
  relating to visual perception by Hubel Wiesel
• models were build to describe how single cells
  interact to produce percepts
• and psychologists started to abandon the ideas of
  learning and associationism and believed that the
  behaviours they were interested in had biological
  origin and instantiation.

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Mission Statement of Cognitive NeuroscienceHow
the brain actually does enable the mind
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Anatomy of the Brain

• Brain Cerebral Cortex
• Has two symmetrical Hemispheres
• Each hemisphere consists of large sheets of
  layered neurons
• The human cortex is highly folded to pack more
  cortical surface into the skull.
• The surface area of the average human cerebral
  cortex is about 2200 to 2400cm2
• The infolding of the cortical sheets are the
  sulci and the crowns of the folded tissue are
  called the gyri

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Anatomy of the Brain

• The cortex has a high density of cell bodies, the
  grey matter
• The underlying region is composed primarily by
  axons of neurons and is known as the white
  matter, they connect the neurons of the cerebral
  cortex to other locations in the brain

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Anatomy of the Brain

• Cerebral Hemispheres have four main subdivisions
• Frontal
• Parietal
• Temporal
• Occipital

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The methods of Cognitive Neuroscience

• 1. Neuroanatomy
• 2. Neurophysiology
• 3. Neurology
• 4. Functional Neurosurgery
• 5. Cognitive Psychology
• 6. Computer Modelling
• 7. Converging Methods

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1. Neuroanatomy

• Studies the nervous systems structure
• Describes how the parts are connected
• Descriptions can be made at many levels
• For the neuroanatomist investigations occur at
  two levels
• gross neuroanatomy general structures and
  connections
• fine neuroanatomy main task is to desribe
  componenents of individual neurons
• Histology is the study of tissue structure
  through dissection, and is essential for
  neuroanatomists to know

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1. Neuroanatomy

• Primary concern of neuroanatomy is the pattern of
  connectivity in the nervous system that allows
  information to get from one site to another
• problem made difficult by
• fact that neurons are not wired together in a
  simple fashion
• often innervated with many neurons
• Solution Refinement of New Stains
• stains for cell bodies
• stains for axons
• have the characteristic that they are absorbed
  from specific chemicals and therefore colour
  specific targets

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1. Neuroanatomy

• Interested in describing the structure of
  different neurons
• Neurons are heterogeneous, varying in shape and
  size

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2. Neurophysiology

• Structure is closely tied to function
• We cannot understand brain function from
  neuroanatomy alone
• Neural function depends on electrochemical
  processes and numerous techniques exist to
  measure and manipulate neuron activity
• Some record cell activity in passive or active
  conditions and other manipulate activity by
  electrical stimulation or chemical induction
• a. Electrical Stimulation
• b. Single Cell Recording
• c. Lesions

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A. Electrical Stimulation

• Early insights to cortical organisation were made
  by directly stimulating the cortex of awake
  humans undergoing neurosurgery
• Pioneers, Penfield jaspers (1954) explored the
  effect of small electrical currents applied to
  the cortical surface

Stimulation of the motor cortex movement
Stimulation of the somatosensory area somatic
sensation
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B. Single-Cell Recording

• The most important technological advance in
  neurophysiology has been the development of
  methods to record directly the activity of single
  neurons in laboratory animals.
• An thin electrode is inserted into an animals
  brain (brain does not hurt!)
• The primary goal of single cell recording
  experiments is to determine experimental
  manipulations that produce a consistent change in
  the response rate of a single neuron

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C. Lesions

• Neurophysiologists have studied how behaviour is
  altered by selectively removing one or more of
  brain components.
• Logic if a brain structure contributes to a task
  then removing that structure should impair
  performance in that task.
• Human cannot be subjected to such procedures, so
  human neuropsychology requires patients with
  naturally occuring lesions.

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MRI scan of a normal and lesioned brain
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3. Neurology

• Human pathology has provided key insights to the
  relation between the brain and behaviour
• Postmortem studies by early neurologists such as
  Broca and Wernicke were instrumental in linking
  the left hemisphere with language functions
• By selecting patients with a single neurological
  impairment, we can best link brain structures to
  specific cognitive functions.
• Sometimes patients have diffused damage and then
  conclusions are harder to draw.
• Structural imaging of neurological damage (CT)
  helps define the damage (advanced method of x-ray
  studies)
• Causes of Neurological Disorders
• vascular disorders (ie strokes)
• tumours
• degenerative and infectious diseases (MS,
  Huntingtons Disease)
• trauma
• Functional Neurosurgery (lobectomy)

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Phineas Gage Case

• Most famous patient who survived severe brain
  damage
• He was a railway construction worker who got
  injured by an accidental explosion
• Severe personality change after the accident

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4. Cognitive Psychology

• Cognitive Psychology assumes that our
  perceptions, thoughts and actions depend on
  internal transformations or computations
• Mental Representation and Transformations
• information processing depends on internal
  representation
• ball rolls down a hill -pictorial representation
  better than one that encompasses the laws of
  physics
• mental representations undergo transformations
• imagine two letters presented in a screen one
  vertical the other one rotated in order to decide
  if they are the same or different you transform
  them to be into the same position
• Constrains on Information Processing
• exploring the limitation in task performance
• Stroop task

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5. Computer Modelling

• Models are explicit
• they can be analysed in detail, the way the
  computer represents the process must be
  completely specified
• Representation in Computer Models
• models differ greatly in their representations
  (ie. symbolic of object recognition would have
  units that represent visual features such as
  corners)
• Models lead to Testable Predictions
• Limitations with computer models
• radically simplified and limited in their scope
• some of their requirements come in contrast with
  what we know about living organisms
• restricted to narrow problems
• modelling often also occurs in isolation to
  current theories

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7. Converging Methods

• Cognitive Deficits Following Brain Damage
• Single and Double Dissociations
• Groups versus individuals
• Imaging the Healthy Brain

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Single and Double Dissociations

• Single dissociation
• Two groups differ on one critical behavioral task
  
• One group has a particular brain lesion, the
  other doesn't (the other group is usually a
  control group who is considered healthy and
  without any known brain abnormality)
• We then tentatively conclude that the difference
  on the behavioral task is due to the brain lesion
  
• This, in turn, suggests that the brain region
  that is lesioned probably was responsible for
  some aspect of the behavior being studied
• However, this connection is not guaranteed to be
  the case

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Single and Double Dissociations

• Problems with interpreting a single dissociation
  
• The task measuring the behaviour may not be
  sensitive to the true underlying behaviour that
  is disrupted
• The task may reflect something similar to, or a
  derivative of, or part of the real behaviour that
  brain region is involved in, but it may not be a
  completely accurate measure
• The behavioural change, though apparently narrow
  in scope, may be part of a broader behavioural
  change that we haven't yet identified
• The lesioned brain area may also affect other
  brain areas responsible for producing this and
  related behaviours

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Single and Double Dissociations

• Double dissociation
• Two groups differ, in different ways, on two
  different behavioral tasks
• Usually, the two groups each have different types
  of brain lesions
• For example, one patient with Broca's area
  damaged and another patient with Wernicke's area
  damaged
• The first patient shows difficulty producing
  speech, while speech comprehension is apparently
  normal
• The second patient shows difficulty comprehending
  speech, while speech production is apparently
  normal
• We conclude, fairly confidently, that Broca's
  area is responsible for speech production while
  Wernicke's area is responsible for speech
  comprehension

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Single and Double Dissociations

• Double dissociations are more powerful than
  single dissociations because we can isolate
  fairly specific behaviours that change with one
  type of lesion but don't change with a different
  type of lesion
• The problems with the task (how sensitive it is
  to the actual behavioural change) are still a
  concern, but we are more confident with
  conclusions about brain localization when there
  are double dissociations

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Groups versus individuals

• Individual case studies
• Study one individual carefully with a known brain
  deficit
• If there is a specific behavioural deficit (after
  careful testing), it can be correlated with the
  known brain deficit
• And if two case studies are compared, each with
  different lesions, and double dissociations are
  found, we have strong confirmation for the link
  between behavior and brain region
• We are, of course, concerned that one individual
  case study may not reflect a larger population
• If you are familiar with statistical analysis,
  you should know that one research subject (N1)
  is not very useful in statistical analyses
• We cannot know for sure that the behavioural
  deviations from normality are due to the brain
  deficit and not just because this person was
  different (with or without the brain deficit)

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Groups versus individuals

• Group studies
• In this approach, we compare groups of people
  with similar brain deficits and determine if they
  show a consistent pattern of behavioural deficits
  
• This minimizes the chance that individual
  differences are masking the results of brain
  damage
• The bottom row shows the proportion of overlap
  for a given brain region
• So we would be fairly confident that the areas of
  highest overlap were most likely involved in
  producing the behavioral deficit
• Comparing across brains is not trivial, however,
  because of individual variation
• To accomplish this, individual brains are matched
  to a "standard" brain
• The common technique is to use the Talairach
  brain--the brain of a French woman
• After matching certain landmark features, the
  image of a brain is distorted until it matches
  the Talairach brain
• Then all the brains are compared from this
  common, standard brain image

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Imaging the Healthy Brain

• Transcranial magnetic stimulation (TMS)
• The goal of this technique is to intentionally
  induce a temporary "lesion"
• As far as we know, the brain is not damaged in
  any way, but a region is temporarily deactivated
• A strong electrical signal is sent to a region of
  the scalp
• We don't exactly know how this works, but it
  seems to disrupt neural function
• So for a very brief period of time, the
  behaviours associated with the focus of the TMS
  should be impaired
• There is some control over the location of the
  "lesion," but the precision is limited
• The device that administers the electrical pulse
  is fairly large
• It is usually held in place manually, lacking
  much precision

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Imaging the Healthy Brain

• Scalp recordings
• Electroencephalogram (EEG)
• Passively measure electrical activity from
  neurons that reaches the scalp
• Place electrodes on the scalp to record
  electrical activity
• Hook the electrodes to an amplifier to boost the
  signal (very little neurally generated
  electricity will reach the scalp)
• Have a representation of global neural activity
• Very useful for determining sleep patterns

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Imaging the Healthy Brain

• Event-related potential (ERP)
• The development of ERPs is when the EEG became
  useful as an experimental tool
• The procedure involves time-locking an EEG
  recording to the onset of a particular stimulus
  or behaviour
• One EEG reading is very noisy i.e. the
  electrical signal is very chaotic and variable
• But if we measure EEG multiple events of the same
  type, all time-locked to the onset of the event,
  and average them together, a smooth pattern
  arises

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Imaging the Healthy Brain

• Magnetoencephalogram (MEG)
• The methodology of MEG is very similar to the
  methodology for ERP
• The sensors for MEG are actually measuring
  magnetic fields produced by neurons, not
  electrical signals
• The inverse problem still exists for MEG, but
  because there is less distortion of the magnetic
  signal than there is for the electrical signal,
  the solutions end up being more accurate, on the
  whole
• However, this technique is extremely expensive
  (1 million for a reasonably good set-up)

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Imaging the Healthy Brain

• Positron-emission tomography (PET)
• Methodology
• Water labelled with radioactive oxygen, is
  injected into a subject
• Brain cells require oxygen (and glucose) for
  energy
• The radioactive oxygen is unstable enough that
  protons break off and collide with electrons in
  the brain
• These collisions are measured by a PET scanner
• With this technique, we do not directly measure
  neural activity
• It is assumed that the higher concentration of
  radioactive isotopes reflects higher neural
  activity
• The more active a neuron is, the more energy it
  should need to replenish and the more likely the
  radioactive oxygen will enter into that brain
  region

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Imaging the Healthy Brain

• We use the subtraction method to determine
  relative levels of neural activity
• PET scans are taken separately for two
  experimental conditions
• The two conditions are identical except for one
  feature--the behavior being studied
• Then one PET images are subtracted from the
  other, so the resulting difference should reflect
  the defining feature
• So if Task 1 required Processes A, B and C, and
  Task 2 required Processes A, B, C and D, the
  difference between the PET images for Tasks 1 and
  2 should reflect the activity unique to Process D
  
• One consideration when using PET as an
  experimental technique is that it takes 20-45
  minutes for the radioactive isotope to get
  flushed out of the brain
• So each experimental condition takes that long,
  meaning it is impossible to compare too many
  conditions in one PET experiment

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Imaging the Healthy Brain

• Functional magnetic resonance imaging (fMRI)
• The BOLD response
• BOLD stands for Blood Oxygen Level Dependent
• What is measured is dependent on the levels of
  oxygen in the blood for any local region of the
  brain
• When oxygen is used by cells, the result is the
  blood becomes more deoxygenated
• Deoxygenated hemoglobin is more ferromagnetic
  (the iron in the blood is more prominent), which
  is what the MRI scanner can measure
• Basically, fMRI measures the ratio of
  deoxygenated to oxygenated hemoglobin

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Imaging the Healthy Brain

• Subtraction method is one technique also used
  with fMRI
• Present variations of a task that each differ in
  one respect
• These differences may be different levels of a
  single cognitive dimension (e.g., different
  amounts of visual information presented) or they
  could be completely different cognitive functions
  
• Contrast the fMRI signal from these conditions
  with each other and with the signal from a
  control condition, when the extra cognitive
  function was not present (but everything else
  was)
• These subtractive differences are reported as
  correlating with changes in behavior
• Many different variations are possible with fMRI,
  unlike PET, because it is not necessary to wait
  minutes between conditions
• We can use alternating epochs of a fixed length
  of time doing each variation of the task

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Concluding Remarks

• Advances in science are often fueled by
  technological developments
• The maturation of cognitive neuroscience as a
  scientific field provides a tremendous impetus
  for the development of new methods
• The questions we ask are constrained by the
  methods available but new research tools are
  promoted by the questions we ask.