Learning and Memory
Learning and Memory
What is learning?
– Changes in our nervous system as a result of experiences
What is memory?
– How these changes are maintained over time and how they are expressed
(recall)
Are they different?
– Yes, but they are interconnected…
You can’t have memory if you have not learned anything
But, can we have learning if we have no memory?
– Perhaps only at birth?
My thoughts:
– Learning and memory make up who we are
– We are who we are because of all of the experiences we have had
throughout our lives that have changed us…for better or worse
How we study Learning & Memory
Amnesia: The loss of memory, incapable of
remembering
– Retrograde Amnesia
Inability to remember events prior to injury (i.e., some
sort of damage to your brain)
Can’t remember your past
– Anterograde Amnesia
Inability to remember events after injury
Can’t form new memories
Injury
Retrograde Amnesia
Anterograde Amnesia
Time-line of events in one’s life
The Case of HM
Bilateral Medial
Temporal Lobectomy
– Removed his medial
temporal lobes (MTL)
bilaterally to alleviate
serious epilepsy (1953)
Hippocampus
Amygdala
Rhinal Cortical Areas
– Epilepsy improved
– He was last patient to
receive this treatment
Why, you might ask?
The Case of HM
After surgery:
– Intellect was above average
IQ actually improved from 104 to 118
– Normal perceptual and motor abilities
– Well-adjusted individual
– BUT,
He was left with very poor memory abilities
– Mild retrograde amnesia (~ 2 years prior to surgery)
– Profound anterograde amnesia
The Case of HM
Brenda Milner (1965)
– “As far as we can tell, this man retained little if
anything of events subsequent to the operation…
Ten months before I examined him, his family had
moved from their old house to a new one a few blocks
away on the same street. He still had not learned the
new address (though remembering the old one
perfectly), nor could he be trusted to find his way
home alone. He did not know where objects in
constant use were kept, and his mother stated that he
would read the same magazines over and over again
without finding their contents familiar… Forgetting
occurred the instant the patient’s focus of
attention shifted.”
The Case of HM
HM is the most famous patient in the history of
neuroscience research.
He has served as an invaluable teacher of the
neurobiology of memory and has been
extensively tested for over 50 years.
Demonstrated that the medial temporal lobe is
critical for forming new memories.
But, what can HM do?
Many Forms of Memory
How Long the Memory Lasts
Short-Term Memory
(seconds – minutes)
Working Memory
(active maintenance)
Long-Term Memory
(hours – years)
What Can HM Do?
Remember a list of 6-7 digits
– Digit-Span + 1 Test
– Performance in normal range
Tap a sequence of 5 blocks
– Block-Tapping Memory Span Test
– Performance in normal range
So, HM has relatively intact short-term memory
Milner (1965): “… Forgetting occurred the instant the
patient’s focus of attention shifted.”
Many Forms of Memory
How Long the Memory Lasts
Short-Term Memory
(seconds – minutes)
Long-Term Memory
(hours – years)
Working Memory
(active maintenance)
Not OK in HM?
OK in HM
Many Forms of Memory
Long-Term Memory
Declarative (explicit): things
you know that you can tell
others
Episodic:
breakfast this
morning
Semantic: the
name of the
44th president
OBAMA!
Procedural (non-declarative,
implicit): things you know that you
can show by doing
Skill
Learning:
skiing, riding
a bike
Priming:
more likely
to use a
word you
heard
recently
Conditioning:
salivating
when I see a
nice steak!
What Can HM Do?
HM can learn new behavioral
skills
Mirror-Drawing Task
HM’s performance improves
with training sessions
– Normal sensory-motor
learning
He has no conscious
recollection of ever performing
it before
What Can HM Do?
HM can learn new behavioral
skills
Rotary-Pursuit Test
HM’s performance improves
with training sessions
– Normal sensory-motor
learning
He has no conscious
recollection of ever performing
it before
What Can HM Do?
HM can show normal
priming
– More likely to use a word
if you have heard it
recently
Repetition Priming Test
He has no conscious
recollection of the words
on the original list
Examine List
of Words:
Puppy
Mushroom
Pancake
Salsa
Spicy
Fill in the Blanks:
__us__r__o__m
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
Priming
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
Priming
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
Priming
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
Priming
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
Priming
What Can HM Do?
Recognition
HM can show
normal recognition
memory and
priming
Incomplete
Pictures Test
Priming
What Can HM Do?
HM can learn
conditioning tasks
Prior to Eye-Blink Conditioning:
Pavlovian Conditioning
HM’s performance
improves with training
sessions
Tone (CS) ≠ Eye Blink (UR)
Training:
Tone (CS) + Air Puff (US) = Eye Blink (UR)
Conditioned State:
He has no conscious
recollection of ever
performing it before
Present Tone (CS) alone = Eye Blink (CR)
Many Forms of Memory
How Long the Memory Lasts
Short-Term Memory
(seconds – minutes)
Working Memory
(active maintenance)
OK in HM
Long-Term Memory
(hours – years)
Not OK in HM?
…sort of, but he can form some
kinds of long-term memories…
Many Forms of Memory
Long-Term Memory
Declarative (explicit): things
you know that you can tell
others
Episodic:
breakfast this
morning
Impaired
Procedural (non-declarative,
implicit): things you know that you
can show by doing
Semantic: the
name of the
44rd president
Skill
Learning:
skiing, riding
a bike
OK!
OK!
Priming:
more likely
to use a
word you
heard
recently
OK!
Conditioning:
salivating
when I see a
nice steak!
OK!
What has HM Taught US?
Supported ideas that
there are many different
kinds of memory
Different brain regions
seem to be more
important for some kinds
of memory, but not others
Forming (consolidating)
new episodic memories is
dependent on MTL
Multiple Memory Systems?
Long-Term Memory
Declarative (explicit): things
you know that you can tell
others
Procedural (non-declarative,
implicit): things you know that you
can show by doing
Why do we need 2 parallel memory systems?
Although subjects with MTL amnesia can form
procedural (implicit) memories, they can not transfer that
memory to a new or different context (situation)
Two parallel memory systems enables us to use the
information we have gathered more flexibly.
Other Case Studies
Patient RB
– Ischemic brain injury during
surgery
– Suffered from MTL
amnesia (similar to HM)
– Killed cells in CA1 subfield
of hippocampus
– Perhaps it is just CA1
subfield of hippocampus
that is important for forming
new long-term episodic
memories
Other Case Studies
Patient NA
– Stabbed up the nose with a
miniature fencing foil
– Resulted in slight retrograde
amnesia which got better over
time
– Also had anterograde episodic
amnesia, but this was less
consistent
Past events would
spontaneously enter his
consciousness
– Damage restricted to medial
diencephalon
Mammilary bodies of the
hypothalamus
Mediodorsal thalamic nucleus
Other Case Studies
Korsakoff’s Syndrome
– Observed in chronic alcoholics (vitamin deficiency)
– Similar memory impairments as in MTL amnesia
Prominent anterograde amnesia (declarative memories)
– But, severe retrograde amnesia develops later on in
the course of the disorder
– Damaged areas:
Mammilary bodies, mediodorsal thalamus, neocortex,
hippocampus, & cerebellum
Other Case Studies
Alzheimer’s Disease
– Memory deterioration greater than what is seen in a
normal ageing population
More general than seen with MTL amnesia & Korsakoff’s
Syndrome
– Progressive and Terminal: eventually loose abilities to
perform simple activities (eating, speaking,
recognizing family, bladder control)
– Anterograde & Retrograde amnesia for explicit
memory
– Impaired short-term memory & implicit memory for
verbal and perceptual material
– Sensory motor learning intact
Other Case Studies
Alzheimer’s Disease
– Degeneration of
acetylcholineproducing cells in
basal forebrain
– Amyloid plaques
– Neurofibrillary tangles
Twisted fibers within
neurons
– Widespread cortical
damage
Another Case Study
Clive Wearing
– Herpes Encephalitis
– Primary damage to hippocampus
Some damage to amygdala, temporal, and frontal
lobes
http://www.youtube.com/watch?v=5ObnErfTblY
Storing Memories
Overall, we have now seen that amnesia results from the
inability to form new memories, or store them over time
– But, what do we mean by storing a memory?
Memory Storage = Memory Consolidation
– Change the memory from a labile/vulnerable state to a stronger,
more permanent state
Donald Hebb (late 1940’s)
– Postulated that memories are held in a short-term reverberating
circuit until they are consolidated to last over a long period of
time
Post-traumatic Amnesia: Evidence
for Memory Consolidation
Concussion or Coma
– Usually results in amnesia for events occurring just
after regaining consciousness
Failure to convert short-term memories to long-term
memories
– Permanent retrograde amnesia for events just prior to
the injury
– Older memories are spared!
Suggests that these memories have been protected by some
mechanism and are stronger than newly formed memories
Memory Consolidation
Electroconvulsive Shock
(ECS)
– Used to study memory
consolidation with the
assumption that disrupting
neural activity would erase the
memories that had not been
consolidated yet
One-trial learning
– Thirsty rats allowed to
discover the location of water
spout
– ECS applied more than 1 hour
after training did not disrupt
memory for the location of
water spout
– Suggests that consolidation
takes place within 1 hour
Memory Consolidation
Human studies show
that ECS (used to
treat severe
depression) can
disrupt memories up
to 3 years old
Why are memories up
to 3 years old affected
by ECS?
Memory Consolidation
Human studies show that ECS (used to treat severe
depression) can disrupt memories up to 3 years old
Suggests consolidation is a longer, ongoing process that
takes more time than a short-term reverberating circuit
would allow
Hebb’s basic postulate is likely incorrect
Reconsolidation: recalling a memory seems to put that
memory into a more labile state that can still be
disrupted before it is consolidated again
Reconsolidation Failures:
Misinformation Effect
Loftus, Miller, & Burns (1978)
– Subjects watched a video of a car accident. A sports car stopped at a
yield sign.
– Subjects were then interviewed 20 min – 1 week later
Consistent Condition: “Did another car pass the sports car while it was
stopped at the yield sign?”
Neutral Condition: “Did another car pass the sports car while it was
stopped?”
Inconsistent Condition: “Did another car pass the sports car while it was
stopped at the stop sign?”
– Subjects then shown pictures of a stop sign and a yield sign. Subjects
had to point to the sign they saw in the video.
Reconsolidation Failures:
Misinformation Effect
– Biased subjects towards
reconsolidating the
incorrect memory!
60
40
Percent Correct
Neutral Info
Inconsistent Info
20
Inconsistent question
deteriorated the correct
memory
Consistent Info
0
Consistent questions
reinforced the correct
memory
80
100
Loftus, Miller, & Burns
(1978)
0 20
1
min. day
2
days
Retention Interval
1
week
Hippocampus and Consolidation
HM:
– Temporally graded retrograde amnesia and severe anterograde
episodic amnesia
– Suggests that hippocampus and related cortical areas are
important for consolidating episodic memories for long-term
storage in other cortical areas
Over time, memories are stored in distributed networks of
cortical areas and become less and less connected to the
hippocampus
– Engram – the change in the brain that represents a memory
The search for the Engram: Where is the memory stored?
Need to systematically test which brain areas are important
for memory storage
Animal Models of Memory
Delayed Nonmatchto-Sample Task:
monkey version
– Test of object
recognition memory
Delayed Nonmatch-to-Sample Task
Monkey results are
inconclusive
– Damaged
hippocampus,
amygdala, and rhinal
cortex
Rodent studies only
damage small
portions of parietal
cortex, leaving rhinal
cortex intact
Animal Models of Memory
Delayed Nonmatchto-Sample Task:
rodent version
– Mumby Box
– Test of object
recognition memory
Object Recognition Engram?
Rodent studies suggest that recognition
memory for objects is dependent on rhinal
cortex, not hippocampus or amygdala
What is the hippocampus important for?
Hippocampus and Spatial Memory
Morris Water Maze
Pool
“Hidden”
Platform
Hippocampus and Spatial Memory
Morris Water Maze
Hippocampal
Lesion Rat
Pool
Control Rat
“Hidden”
Platform
Hippocampal lesions impair rats’ ability to learn the location of the platform
Eight Arm Radial Maze
Hungry rats will learn
which arms contain
rewards
– Reference Memory
Where
should I
go???
Rats will learn to not
enter an arm more
than once on a given
day
– Working Memory
Hippocampal lesions
produce major deficits
on reference and
working memory
measures
Hippocampus and Spatial Memory
Hippocampus seems to be
critical for spatial memory, but
why is this?
Place Cells!
– Cells that fire when the subject
occupies a particular location
in the environment
Place cells seem to represent
a cognitive component of the
environment
– If the cells fire in a certain
pattern, the rat will behave a
certain way
Hippocampus and Spatial Memory
Theories of Hippocampal Function
– Cognitive Map Hypothesis
Hippocampus contains a cognitive map of allocentric space that can
be used to navigate to locations in an environment
– Configural Association Theory
Hippocampus is critical for learning the significance of combinations
of stimuli (i.e., you will be learning about biopsychology in this room,
not any other topic)
– Spatial Arrangements
Hippocampus is important for recognizing the arrangement of
objects relative to one another (i.e., the layout of your living room)
Milner (1965): “… He still had not learned the new
address (though remembering the old one perfectly), nor
could he be trusted to find his way home alone. He
did not know where objects in constant use were
kept…”
Evolutionary Perspectives
Hippocampus is
important for spatial
memory in Food Caching
Birds
Larger hippocampi than
non-food caching birds
Hippocampus grows
when food caching
behaviors begin
– Developmental changes
– Seasonal changes
Evolutionary Perspectives
Hippocampus is important for spatial memory in Nonhuman Primates
Spatial view cells in monkey hippocampus
– Fire if monkey is looking at a particular location in the
environment
– Analogous to place cells
Hippocampal damage produces deficits on some spatial
tasks
Inconsistent results likely due to the fact that monkeys
are not allowed to freely move around during
experiments
Evolutionary Perspectives
Hippocampus is
important for spatial
memory in Humans
Hippocampal activation
during performance of
virtual navigation tasks
Place-like cells recorded
in humans performing
similar virtual tasks
Evolutionary Perspectives
Hippocampus is important for spatial memory in
Humans
London Taxi cab drivers have larger hippocampi
than normal subjects
Milner (1965)
– “… He still had not learned the new address (though
remembering the old one perfectly), nor could he be
trusted to find his way home alone. He did not
know where objects in constant use were kept…”
Hippocampus: Imagining the Future?
Do you remember Clive Wearing???
The Truth About Learning and Memory:
There’s a lot more to it!
Mediodorsal
Thalamus & Basal
Forebrain
– Alzheimer’s Disease
– Korsakoff’s Syndrome
– Patient NA
The Truth About Learning and Memory:
There’s a lot more to it!
Inferotemporal Cortex
– Visual patterns
“What” component of
visual system
– Visual Recognition Memory
– Prosopagnosia
The Truth About Learning and Memory:
There’s a lot more to it!
Amygdala
– Emotional memory (fear
conditioning)
– Lesions disrupt ability to
learn CS-Shock
associations
– Rodent and Human data
are very consistent
– Imposter Syndrome
The Truth About Learning and Memory:
There’s a lot more to it!
Prefrontal Cortex
– Temporal order of
events (i.e., steps
involved in cooking)
– Short-term and
Working Memory
The Truth About Learning and Memory:
There’s a lot more to it!
Cerebellum
– Implicit sensorymotor
tasks (eyeblink
conditioning)
– Motor Learning
Feedback loop
“Efference Copy”
The Truth About Learning and Memory:
There’s a lot more to it!
Striatum
– Part of Extrapyramidal
Sensory Motor system
– Important for
“allowing” appropriate
movements to occur
– Implicit sensory motor
tasks (habit formation)
– Affected in Parkinson’s
disease