Relational Learning and Amnesia

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Chapter 14

• Relational Learning and Amnesia

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Human Anterograde Amnesia

• Anterograde amnesia - difficulty in learning new
  information, due to head injury or certain
  degenerative brain diseases pure form is rare
• Retrograde amnesia inability to remember events
  that occurred prior to brain damage
• Korsakoffs syndrome permanent anterograde
  amnesia caused by brain damage resulting from
  chronic alcoholism or malnutrition (due to
  thiamine deficiency) also have confabulations
  (reporting of memories that did not occur,
  without the intention to deceive)
• Anterograde amnesia can be caused by damage to
  temporal lobes
• e.g. patient H.M. bilateral removal of medial
  temporal lobe to alleviate epilepsy resulted in
  severe anterograde amnesia

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Human Anterograde Amnesia

• Basic description
• Results from study with H.M.
• The hippocampus is not the location of long-term
  memory (LTM) nor is it necessary for the
  retrieval of LTM
• The hippocampus is not the location for
  short-term memory (STM)
• The hippocampus is involved in converting STM
  into LTM
• These results are too simple anterograde amnesia
  is actually much more complex
• Learning consists of at least 2 stages
• STM immediate memory for events, which may or
  may not be consolidated into LTM can only hold a
  limited amount of info
• LTM relatively stable memory of events that
  occurred in the more distant past, as opposed to
  STM no limit on amount of info
• Consolidation the process by which STM are
  converted into LTM

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Simple model of memory process

• Sensory info enters STM
• Rehearsal keeps that info in STM
• Eventually, info will move into LTM via
  consolidation

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Human Anterograde Amnesia

• Spared learning abilities
• Still capable of
• Perceptual learning
• e.g. recognize broken drawings also faces and
  melodies
• Stimulus-response learning
• Can acquire a classical conditioned eyeblink
  response
• Motor learning
• Mirror drawing task subjects required to trace
  the outline of a figure while looking at the
  figure in a mirror

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Human Anterograde Amnesia

• Declarative and nondeclarative memories
• Although patients can learn other tasks, they
  cannot recall ever learning them
• Learning and memory involve different processes
• 2 major categories of memories
• Declarative memories memory that can be
  verbally expressed, such as memory for events,
  facts, or specific stimuli this is impaired with
  anterograde amnesia
• Nondeclarative memories memory whose formation
  does not depend on the hippocampal formation a
  collective term for perceptual,
  stimulus-response, and motor memory not affected
  by anterograde amnesia these control behavior
  cannot always be described in words

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Human Anterograde Amnesia

• Failure of relational learning
• Verbal learning is disrupted in anterograde
  amnesia
• e.g. H.M. did not learn any new words after his
  surgery (biodegradable two grades)
• Episodic memories most complex form of
  declarative memory memory of a collection of
  perceptions of events organized in time and
  identified by a particular context
• e.g. explain what you did this morning after
  waking up
• The hippocampal formation enables us to learn the
  relationship b/t the stimuli that were present at
  the time of an event (i.e. context) and then
  events themselves

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Human Anterograde Amnesia

• Anatomy of anterograde amnesia
• Damage to the hippocampus or to regions that
  supply its inputs and receive its outputs causes
  anterograde amnesia
• The most important input to the hippocampal
  formation is the entorhinal cortex, which
  receives inputs from the limbic cortex either
  directly or via the perirhinal cortex or the
  parahippocampal cortex
• How does the hippocampus form new declarative
  memories?
• Hippocampus receives info about what is going on
  from sensory and motor assc. cortex and from some
  subcortical regions
• It processes this info and then modifies the
  memories being consolidated by efferent
  connections back to these regions
• Experiences that lead to declarative memories
  activate the hippocampal formation
• Patient R.B., suffered brain damage that lead to
  anterograde amnesia after autopsy, found that
  field CA1 of the hippocampal formation was
  completely destroyed

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Limbic cortex
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Human Anterograde Amnesia

• Anatomy of anterograde amnesia
• Damage to other subcortical regions that connect
  with the hippocampus can cause memory impairments
• Limbic cortex of the medial temporal lobe
• Semantic memories a memory of facts and general
  info different from episodic memory
• Destruction of hippocampus alone disrupts
  episodic memory only must have damage to limbic
  cortex of medial temporal lobe to also impair
  semantic memory (and thus all declarative memory)
• Fornix and mammillary bodies
• Patients with Korsakoffs syndrome suffer
  degeneration of the mammillary bodies
• Most of the efferent axons of the fornix
  terminate in the mammillary bodies
• Damage to any part of the neural circuit that
  includes the hippocampus, fornix, mammillary
  bodies and anterior thalamus cause memory
  impairments

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Human Anterograde Amnesia

• Role of the medial temporal lobe in spatial
  memory
• Individuals with anterograde amnesia are unable
  to consolidate info about the location of rooms,
  corridors, buildings, roads, and other important
  items in their envt
• Bilateral medial temporal lobe lesions produce
  the most profound impairment on spatial memory,
  but enough damage to only the R hemisphere is
  sufficient
• R hippocampal formation is activated when a
  person is remembering or performing a
  navigational task
• Damage to this area also impairs ability to learn
  spatial arrangement of objects

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Human Anterograde Amnesia

• Role of the medial temporal lobe in memory
  retrieval
• The hippocampal formation and its related
  structures also play a role in memory retrieval
• Anterograde amnesia is usually accompanied by
  retrograde amnesia brain damage can either cause
  loss of memories or loss of access to memories
• However, if damage is only limited to field CA1,
  patients do not show additional retrograde
  amnesia
• Semantic dementia loss of semantic memories
  caused by progressive degeneration of the
  neocortex of the lateral temporal lobes
• Impairment for meaning of words, and functions of
  common objects

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Human Anterograde Amnesia

• Confabulation
• May be a result of disruption of the normal
  functions of the prefrontal cortex
• Frontal lobes may be involved in distinguishing
  b/t real and imaginary memories may do this by
  helping us to distinguish items with general
  familiarity from specific items we have
  encountered before

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Relational learning in lab animals

• Lab animals with hippocampal formation lesions do
  not sow impairment in stimulus-response learning,
  but with relational learning tasks
• Remembering places visited
• Radial maze task food placed at end of each
  arm, rats did not go down arm that they had
  already collected food from lesions to
  hippocampus, fornix, or entorhinal cortex
  impaired this task animals must remember which
  arm they have collected from that exact day (as
  opposed to another testing day)

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Relational learning in lab animals

• Spatial perception and learning
• Lab animals with hippocampal lesions show
  problems with navigational tasks just as humans
  do
• Morris water maze task requires rat to find a
  particular location in the water drum, by means
  of visual cues external to the apparatus if rats
  wit hippocampal lesions are released from same
  position every testing time, they perform fine
  (e.g. S-R learning), but if they are started from
  a different place, they cannot complete the task
  correctly (e.g. relational learning)

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Relational learning in lab animals

• Spatial perception and learning
• Hippocampal lesions disrupt performance of homing
  pigeons
• Hippocampal formation of animals that normally
  store seeds or food in hidden caches and later
  retrieve them is larger than that in animals
  without this ability
• Role of hippocampal formation in memory
  consolidation
• Brain activity in the hippocampus is increased in
  mice learning a spatial task however, after 25
  days of testing, the activity there decreases,
  suggesting that the hippocampus is involved in
  consolidating spatial memories for only a limited
  time

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Relational learning in lab animals

• Place cells in the hippocampal formation
• When recording the activity of individual neurons
  in the hippocampus of an animals moving around
  its envt, some neurons fired at a high rate only
  when the rat was in a particular location
• The suggests evidence that different neurons have
  different spatial receptive fields (i.e. they
  responded when the animals were in different
  locations) these neurons were named place cells
• When placed on a circular platform that is
  rotated slowly within a larger chamber, rats will
  ignore local cues and orient themselves to face a
  cue card the place cells however, oriented
  themselves to the local cues
• When animals encounter new envts, they learn the
  layout and maps become established in their
  hippocampus an animals location within each
  envt is encoded by the pattern of firing of
  these neurons
• Place cells are guided by both visual stimuli and
  internal stimuli (e.g. proprioceptive feedback)
• Hippocampus receives spatial info via the
  entorhinal cortex

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Relational learning in lab animals

• Role of LTP in relational learning
• When place cells become active when an animal is
  present in a particular location, this causes
  changes in the excitability of neurons in the
  hippocampal formation
• Knockout mice for NMDA receptors specific for the
  field CA1 no establishment of LTP in field CA1,
  smaller and less focused spatial receptive
  fields, and learn Morris water maze task much
  slower
• NMDA mediated LTP appears to be required for the
  consolidation of spatial receptive fields in
  field CA1 pyramidal cells but not their
  short-term establishment
• Modulation of hippocampal functions
• Hippocampal formation receives input from ACh,
  NE, DA, and 5-HT neurons
• They appear to control the information-processing
  functions of the hippocampal formation
• 5-HT has suppressive effect on establishment of
  LTP in hipp. form.

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Relational learning in lab animals

• Modulation of hippocampal functions (cont)
• NE has a facilitator effect, particularly on
  synapses of terminals of entorhinal neurons of
  the dentate gyrus
• DA had excitatory effects on LTP and
  memory-related functions of the hippocampal
  formation
• Synaptic plasticity is induced by simultaneous
  depolarization of hippocampal neurons and
  activation of DA receptors on these neurons
• ACh neurons from medial septum project to
  hippocampus via fornix activity of these neurons
  is responsible for hippocampal theta rhythms
  (medium amplitude, medium frequency waves) that
  influence the establishment of LTP in the
  hippocampus
• If theta activity is disrupted, animals show
  deficits in learning tasks that are affected by
  hippocampal lesions
• Theta behaviors exploration or investigation
• Nontheta behaviors alert immobility, drinking,
  self-directed behaviors