PSY 368 Human
Memory
Neuropsychology & Memory
Announcements
• Experiment 2 due today
• Focus Questions for Weldon and Roediger (1987)
Due Monday March 26th
• Exam 2 a week from Wednesday (March 28)
Neuropsychology of Memory
• Where is memory?
• Methods of study
• Neurons and Brains
• Role of the hippocampus
• Memory Disorders
• Amnesia
• Alzheimer’s Disease
Memory
Mapping memory in 3D
Neurons and Memory
• Connections between neurons change based on
experiences
• Brain is less ‘hard-wired’ than we used to believe
• Lashley provided evidence of plasticity in monkeys in
the 1920’s but not widely accepted until 1960’s
• Neuroplasticity is fundamental property of brain (nervous
system)
•
Capacity of nervous system to modify its organization
•
Changes in structure and function as a result of experience
•
Changes largely within the synapses
Neurons and Memory
• Synaptic changes that could store memories
• Current dominant theory: Long-term potentiation (LTP)
• Persistent increase in synaptic strength following high-frequency
stimulation
• “the molecular and cellular changes mediating the induction of LTP in the
hippocampus are widely considered to provide a basis for memory”
(McGaugh, 2000)
• Not all learning-related changes involve changes in
synaptic strength (Martin & Morris, 2002)
• Neurogenesis – new evidence suggest that new neurons are
formed in some regions of the brain
• Changes in neuronal excitability – changes in the firing threshold
The Brain: networks of neurons
• “There are many steps between synaptic change and
behavioral memory.” Squire (pg 8, 1987)
• Lots of interesting questions
•
Does “memory” reside in single neurons, or in networks of
neurons?
•
Are all of the networks the same, or are there differences
(i.e., do different regions of the brain deal with different
kinds of things)?
The Brain
Vital Statistics
• Adult weight: about 3 pounds
• Adult size: a medium cauliflower
• Number of neurons:
100,000,000,000 (100
billion)
• Number of synapses
(the gap between
neurons):
100,000,000,000,000
(100 trillion)
• These neurons are connected, organized into networks of neurons
Structure of the brain
• Cortex - four lobes
• Occipital - vision
Frontal Lobe
• Parietal - sensation
• Temporal – memory,
hearing
• Frontal - reasoning,
memory
Parietal
Lobe
Occipital
Lobe
Temporal
Lobe
Brain and Memory
Other Crucial Parts
• Limbic system: controls emotions and
instinctive behavior (includes the hippocampus
and parts of the cortex)
• Thalamus: receives sensory and limbic
information and sends to cerebral cortex
• Hypothalamus: monitors certain activities and
controls body’s internal clock
• Hippocampus: where short-term memories are
converted to long-term memories
The Brain: networks of neurons
• Networks of neurons hold memories
Neurobiological systems regulating the
consolidation of memory
• “… memory consolidation involves
interactions among neural systems
as well as cellular changes within
specific systems, and that the
amygdala is critical for modulating
consolidation in other brain
regions”
McGaugh, 2000
The Brain: networks of neurons
• So where is memory? It is complicated
• Multiple brain regions are involved in encoding (as shown
by fMRI) -term memory.
Brain and Memory
• So where is memory? It is complicated
• Multiple brain regions are involved in encoding (as shown
by fMRI)
• For recalling pictures, the right prefrontal cortex and
parahippocampal cortex in both hemispheres are activated.
• For recalling words, the left prefrontal cortex and the left
parahippocampal cortex are activated.
• Consolidation of memory involves the hippocampus but the
hippocampal system does not store long-term memory.
• LTM storage occurs in the cortex, near where the memory was first
processed and held in short-term memory.
Brain and Memory
• So where is memory? It is complicated
• Seven Sins of Memory
• Hippocampus and nearby structures related to sin of transience
• Parts of the frontal lobe related to transience, but even more
central to absent-mindedness and misattribution (and maybe
suggestibility)
• Area near front of temporal lobe related to blocking
• Amygdala closely related to persistence
• Not much is known about bias
Brain and Memory
• Hippocampus
• Important for formation of new episodic memories
• Important for encoding perceptual aspects of memories
• Novel events, places, and stimuli
• Important for declarative memory
• Especially as part of medial temporal lobe
• Supported by case of HM
• Video (location, 1 min)
Brain and Memory
• Hippocampus
• Recollection vs. Knowing
(familiarity)
• Eldridge et al have shown the
hippocampus is selectively
involved in R, not with K.
• Verfaelle & Treadwell (1993),
using process dissociation
procedure showed similar
pattern (discussed in detail in
your textbook)
(Eldridge et al., Nature Neuroscience 2000)
Brain and Memory: Amnesia
• Diencephalic amnesia damage to the medial
thalamus and mammillary
nuclei
• Medial temporal lobe
amnesia - damage to the
hippocampal formation, uncus,
amygdala, and surrounding
cortical areas
• Other implicated regions
include Anterior Lateral
Temporal Lobe and Frontal
Lobes
Amnesia
• Loss of memory ability - usually due to lesion or
surgical removal of various parts of the brain
• Relatively spared performance in other domains
• A pure amnesia is relatively rare
• video (#18, 10 mins)
• Video (~ 7 mins)
• Video 3 (Clive Wearing, 7 mins)
Amnesia
• Loss of memory ability - usually due to lesion or
surgical removal of various parts of the brain
• Three different kinds of classifications
• Source of the disease (e.g., illness, injury)
• Location of the area of damage
• Functional deficit (i.e., what kind of memory is impaired)
• This mixed way of categorizing amnesia causes some
difficulties
Amnesia
• Loss of memory ability - usually due to lesion or
surgical removal of various parts of the brain
• Two broad categories:
• Retrograde: loss of memories for events prior to damage
• Anterograde: loss of ability to store new memories of events
after damage
Injury
Time
Causes of Amnesia
•
•
•
•
Korsakoff ’s syndrome
Traumatic Brain Injury (TBI) (Concussion)
Alzheimer’s disease
Other causes include
• Specific brain lesions (i.e.
surgical removal)
• Psychological
• Dissociative Fugue
• Psychogenic
• Migraines
• Hypoglycemia
• Epilepsy
• Electroconvulsive shock
therapy
• Drugs (esp. anesthetics)
• Infection
• Nutritional deficiency
Amnesia
• Korsakoff ’s syndrome:
• Results from chronic alcoholism and consequent
thiamine deficiency
• Lesions to Medial Thalamus
• Neuropathology: most sources attribute the amnesia to
combined lesions in two diencephalic structures: the
dorsomedial nucleus of the thalamus and the mammillary bodies
of the hypothalamus
Amnesia
• Korsakoff ’s syndrome
• Generally preserved IQ, including a normal digit span.
• Personality changes, the most common of which is apathy,
passivity and indifference
• inability to formulate and follow through a series of plans
• Lack of insight into their condition.
• How can someone with a shattered memory remember that he
has become unable to remember?
Amnesia
• Korsakoff ’s syndrome
• Retrograde amnesia with a temporal gradient
• Anterograde amnesia
• Confabulation, which is a tendency to "fill in the gaps" of
one's memories with plausible made-up stories.
• confabulations are rare among chronic Korsakoff patients
who've had the disease for more than 5 years. Patients in the
chronic stage are more likely to say "I don't know" or remain
silent when faced with memory failures rather than to invent
stories.
Amnesia
• Korsakoff ’s syndrome
• Worst impairments are on episodic memory tests,
including list learning of words, figures, or faces,
paragraph recall.
• Relatively preserved semantic memory, including normal
verbal fluency, vocabulary, rules of syntax, and basic
arithmetic operations
• Intact sensori-motor memory (mirror tracing, mirror
reading, pursuit rotor)
• Intact performance on perceptual tasks (e.g., perceptual
identification, generating category exemplars)
Amnesia
• Post-traumatic amnesia
• Damage due to lesions as well as twisting and tearing
of microstructure of brain
• Symptomology
• After severe TBI, individuals typically lose consciousness
• After they begin to regain consciousness, there is often a
gradual recovery during which patients have difficulty
keeping tracking of and remembering on-going events,
though there may be islands of lucidity and memory
• In the news
• Football (ESPN video)
• Soldiers (6 part video series)
Amnesia
Injury
Time
• Retrograde amnesia
• Refers to difficulty remembering events that occurred
prior to injury
• The duration of amnesia varies but can extend back for
several years
• Rare, short-lived
• Typically due to brain trauma
• Case Study: Doug Bruce (Unknown White Male)
• His case is exceptional (the extent and persistence of the
memory loss)
Amnesia
Injury
Time
• Retrograde amnesia
• Duration of retrograde amnesia typically shrinks as time passes
• e.g., Russell (1959) described case of TBI as a result of a motorcycle
accident
• 1 week post accident patient had lost 11 years of memory extending back
from injury
• 2 weeks post accident patient had last 2 years of memory
• about 10 weeks post injury memories of the last two years gradually
returned
• This pattern of results suggests that retrograde amnesia is a
retrieval problem
• The pattern of damage/recovery -- from most distant to most
recent -- has been argued by some to reflect a failure of
consolidation (Ribot’s Law)
Amnesia
Injury
Time
• Retrograde amnesia
Percent recall
• Butters & Cermak (1986) reported a case study of an
eminent scientist (born 1914) who had written his
autobiography only two years prior to becoming
amnesic
• Tested him by asking him questions all drawn from his
autobiography
Recall of information from PZ autobiography
80
70
60
50
40
30
20
10
0
Recall
19161930
19301940
19401950
19501960
19601970
19701980
Amnesia
• Anterograde amnesia
• Refers to problems of learning new facts
• Specific to episodic memories
• Procedural memories intact
• Implicit memory performance normal
• Famous Cases:
• H.M.
• N.A.
• Clive Wearing
• Video 3a, b, c, d (each ~10 mins)
Injury
Time
Amnesia Case Study: HM
• Henry Molaison (Patient H. M.) (brief news video following his death)
• Suffered from extreme epilepsy
• Bilateral mesial
temporal lobe resection
extending 8 cm. back
from the temporal tips,
including the uncus and
amygdala, and
destroying the anterior
two-thirds of the
hippocampus and
hippocampal gyrus
• Scoville & Milner (1957)
Amnesia Case Study: HM
• Henry Molaison (Patient H. M.)
• prototype of amnesia attributable to hippocampal
damage
• Surgery led to a permanent, severe anterograde amnesia,
limited retrograde amnesia, and normal intelligence.
Amnesia Case Study: HM
• Henry Molaison (Patient H. M.)
• Functional characteristics
• 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, stimulusresponse, and motor memory; not affected by anterograde amnesia; these
control behavior; cannot always be described in words
Amnesia Case Study: HM
• Henry Molaison (Patient H. M.)
• Functional characteristics
• Episodic memory is impaired
• Both autobiographical and nonautobiographical episodic
memory
• even for emotionally charged information such as the death of
his favorite uncle
• Verbal learning is disrupted in anterograde amnesia
• e.g. H.M. did not learn any new words after his surgery
(biodegradable = “two grades”)
Amnesia Case Study: HM
• Henry Molaison (Patient H. M.)
• Functional characteristics
• Perceptual learning
• e.g. recognize broken drawings; also faces and melodies
• Stimulus-response learning
• Can acquire a classical conditioned eyeblink response
• Working memory is intact
• Essentially normal STM, seen on the Brown-Peterson
task, digit span, and conversation
• Semantic memory is spared
• Procedural memory is intact
Amnesia Case Study: HM
• HM shows normal procedural
and implicit memory despite
extensive declarative and
explicit memory deficits.
• In particular, he shows normal
motor priming on pursuitrotor and mirror tracing tasks
• (Milner video start 5:45)
Amnesia
• Anatomy of anterograde amnesia
• Damage to the hippocampus or to regions that supply its
inputs and receive its outputs causes anterograde amnesia
• 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
• The hippocampal formation enables us to learn the relationship
between the stimuli that were present at the time of an event (i.e.
context) and then events themselves
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 Korsakoff’s syndrome suffer degeneration of the
mammillary bodies where 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
Amnesia
• Theoretical implications of amnesia
• Provides evidence for STM versus LTM distinction
• Supports the notion that there are different systems
mediating explicit (episodic) and implicit (procedural
memory)
• May indicate that semantic and episodic memory can
be fractionated
• May provide insight into nature of consciousness
Alzheimer’s Disease
• Alzheimer’s disease (video clip # 19, ~7mins)
• cortical, progressive dementia
• disease is associated with the development of neurofibrillary tangles and plaques
• The brain has billions of neurons, each with
an axon and many dendrites.
• To stay healthy, neurons must communicate
with each other, carry out metabolism, and
repair themselves.
• AD disrupts all three of these essential jobs.
Alzheimer’s Disease
• Alzheimer’s disease
Preclinical AD
• Signs of AD are first noticed in
the entorhinal cortex, then
proceed to the hippocampus.
• Affected regions begin to
shrink as nerve cells die.
• Changes can begin 10-20 years
before symptoms appear.
• Memory loss is the first sign of
AD.
Alzheimer’s Disease
Mild to Moderate AD
• Alzheimer’s disease
• AD spreads through the brain. The
cerebral cortex begins to shrink as
more and more neurons stop working
and die.
• Mild AD signs can include memory
loss, confusion, trouble handling
money, poor judgment, mood changes,
and increased anxiety.
• Moderate AD signs can include
increased memory loss and confusion,
problems recognizing people, difficulty
with language and thoughts,
restlessness, agitation, wandering, and
repetitive statements.
Alzheimer’s Disease
Severe ADs
• Alzheimer’s disease
• In severe AD, extreme shrinkage
occurs in the brain. Patients are
completely dependent on others for
care.
• Symptoms can include weight loss,
seizures, skin infections, groaning,
moaning, or grunting, increased
sleeping, loss of bladder and bowel
control.
• Death usually occurs from aspiration
pneumonia or other infections.
Caregivers can turn to a hospice for
help and palliative care.
Alzheimer’s Disease
• Alzheimer’s disease
Alzheimer’s Disease
Pet Scan of
Normal Brain
Pet Scan of Alzheimer’s
Disease Brain
Alzheimer’s Disease
• Criteria
• deficit in two or more areas of cognition, at least one of
which is memory
• interferes with social or occupational functioning
• decline from premorbid level
• gradually progressive course
• rule out other causes
Alzheimer’s Disease
• The Hallmarks of AD
• The brains of people with AD have an abundance of
two abnormal structures:
• Beta-amyloid plaques
• Dense deposits of protein and
cellular material that accumulate
outside and around nerve cells
An actual AD plaque
• Neurofibrillary tangles
• Twisted fibers that build up inside
the nerve cell
An actual AD tangle
Alzheimer’s Disease
Beta-amyloid Plaques
Amyloid precursor protein (APP) is the
precursor to amyloid plaque.
• Alzheimer’s disease
1. APP sticks through the neuron
membrane.
2. Enzymes cut the APP into fragments
of protein, including beta-amyloid.
3. Beta-amyloid fragments come
together
in clumps to form
plaques.
In AD, many of these clumps form,
disrupting the work of neurons. This
affects the hippocampus and other
areas of the cerebral cortex.
Alzheimer’s Disease
• Alzheimer’s disease
• three types of memory problems
• episodic memory impaired (e.g., free recall)
• executive function (Baddeley appears to be affected)
• semantic memory is also impaired
• note: pure amnesics do not have the latter two
impairments
Alzheimer’s Disease
• AD
• semantic memory
• system for storing, organizing, and manipulating
information pertaining to the meaning of words, concepts,
and their associations
• conceptualized as a broadly distributed network
• enables judgments about the properties and functions of
items
Semantic Memory
Performance in AD
• naming and word generation to semantic cues both
require semantic memory, both impaired in AD
• Explanations:
• degradation of the semantic network?
• loss of access to preserved concepts?
• both?
Recapitulation during
retrieval
• Introduction
• Memory performance depends on the similarity of
conditions at encoding to those at retrieval. This finding
and memory others suggest that encoding and retrieval
processes are closely related to each other
• It is widely believed that the brain regions activated at
encoding will tend to be activated at retrieval
Recapitulation during
retrieval
• Purpose (Wheeler et al., 2000)
• To identify regions of brain associated with the retrieval
of vivid visual and auditory information
• To determine the extent to which these regions are
associated with the regions activated at the time of
encoding
Recapitulation during
retrieval
• Method
• Subjects a set of picture and sound items each of which
was paired with a descriptive label
• E.g., half Ss presented DOG with picture of dog; half
Ss presented DOG with sound of dog barking
• Ss performed task in which they perceived the sounds
and pictures or recalled the studied sounds and pictures
from memory when shown the label
Recapitulation during
retrieval
• Results
• Brain areas in the visual cortex are active during
retrieval of memories with visual content
• Brain areas in the auditory cortex are active during
retrieval of memories with auditory content
Recapitulation during
retrieval
• Discussion
• Sensory aspects of a multisensory event are stored in
some of the brain regions that were activated at
encoding
E. P.
• Suffered acute viral disease in brain
• Damage sustained in temporal lobes, notably the
hippocampus
• Displays anterograde amnesia
• Short term memory intact
• Lives in a permanent present
• What else can we infer from the interview seen?
Hypermnesia - S.
• “Photographic” extreme memory ability (a
mnemonist)
Hypermnesia - S.
• “Photographic” extreme memory ability (a
mnemonist)
• Able to recall complex test stimuli
Hypermnesia - S.
• S. used two “strategies” or abilities typical of
mnemonists:
• Rich synesthesia-like quality to his perception of
stimuli - leads to stronger associative links
• Vivid and elaborate mental imagery of things he should
remember
Hypermnesia - S.
• “ Even numbers remind me of images. Take the
number 1. This is a proud, well-built man; 2 is a
high-spirited woman; 3 a gloomy person (shy, I
don’t Know); 6 a man with a swollen foot...”
Luria, A.R. The mind of a mnemonist. 1968
Luria, A.R. The man with a shattered world. 1972
Neuropsychology of
Memory
• Consciousness
• Tulving has proposed that different memory systems
have associated with them different levels of
consciousness
• noetic -- awareness
• episodic memory -- autonoetic, self awareness
• semantic memory -- noetic, aware of the information, but
not aware of event
• procedural memory -- anoetic no conscious awareness
Neuropsychology of
Memory
Episodic
Autonoetic
Semantic
Noetic
Procedural
Anoetic
Neuropsychology
The Neuron
Nerual signal: The Action potential
• Positive chemicals flow
into axon, making it
positively charged
• Causes positive charge to
flow down cell to
terminal buttons
• Myelin sheath helps
Neuropsychology
Strong emotions can enhance memory formation and retrieval.
Many compounds participate: acetylcholine, epinephrine, norepinephrine,
vasopressin, the opioids, and GABA.
Drugs that are agonists or antagonists of these can be involved.
Dissociations
Good Neuropsychology studies look for dissociations:
Task 1
Brain Area 1
Brain Area 2
Activation
No Activation
Task 2
No Activation
Activation
Often found across patients
Example:
H.M. Intact Working Memory, poor ability to recall episodic memories
K.F. no problem recalling daily episodes, but digit span of 1
(Shallice and Warrington, 1970)
Amnesia
Injury
Time
Basic description
•
Results from study with H.M.
•
1.
The hippocampus is not the location of long-term memory (LTM);
nor is it necessary for the retrieval of LTM
2.
The hippocampus is not the location for short-term memory
(STM)
3.
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
Structure of the brain
• Video 3 (damage)
• Video 3a, b, c, d (Clive Wearing, damage)