Components of amnesia

• Anterograde amnesia: after onset of amnesia

• Retrograde amnesia: prior to onset of amnesia.

Anterograde amnesia

• I. Selective impairment of long-term memory

• Working memory is intact!!!!!

Working memory is intact!!!

• Digit span (7 digits)

• 6-5-8-3-2-4-9

• Extended digit span (8+ digits)

• 6-5-8-3-2-4-9-1

Anterograde amnesia

• II. Global nature

• free recall

• recognition

• cued recall

• visual, auditory, somesthetic, olfactory

• material specific memory disorders

Anterograde amnesia

• III. Profound impairment for new events/facts

• cannot report personal events since injury

• cannot report public events since injury

• paired-associate learning

– obey-inch, crush-dark

Anterograde amnesia

• IV. Spared acquisition and expression of skills performance

• skill learning

– mirror tracing

– mirror-image reading task

– Tower of Hanoi puzzle

• repetition priming

Mirror-image reading (Cohen & Squire, 1980)

Tower of Hanoi (Cohen et al., 1985)

Repetition priming (Warrington et al., 1970)

Word-stem completion (Graf, Squire, Mandler, 1984)

• Motel, cyclone (stem)

• cued recall

– poor performance among amnesics

• word-stem completion

– “mot” what is the first word that comes to mind?

Preserved skill learning

• No recollection of training events

• No recall of the test materials

• Poor insight into the nature of the newly acquired skills

Anterograde amnesia

• V. Sparing of information acquired in an inflexible manner

• if “normal learning occurs, it is inflexible”

• expressed only in narrow range

• hyperspecific

Retrograde amnesia

• I. Variations in temporal extent

• II. Temporal gradient

• III. Retrograde amnesia never affects ALL long-term memory

• IV. Skill performance is spared

I. Temporal extent

• Temporally extensive retrograde amnesia

– Korsakoffs, Alzheimers

– encephalitis, anoxia

Butters (1970), Squire (1981)

Temporal extent

• Temporally limited retrograde amnesia

– ECT, closed head injury

Squire & Cohen (1979)

II. Temporal gradient

• Recent memories are affected more than remote memories

• Shrinking retrograde amnesia

• Ribot’s Law (1881, 1882)

Shrinking retrograde amnesia

III. Sparing of information learned early in life

• Intact knowledge about world

• Preserved language

• Perceptual and social skills

• Spared General Intelligence

IV. Sparing of skilled performance

• Dissociation between impaired free recall and priming.

• Squire et al., (1984)

– ECT

– Mirror-image text before and after ECT

Where does amnesia exert effect?

• Encoding of memory

• Storage, maintenance, or consolidation

• Retrieval of memories

Encoding

• Retrograde amnesia: disruption of memories that were previously encoded normally.

Consolidation

• Anterograde amnesia

• Temporally graded retrograde amnesia

Retrieval

• Failure to retrieve

• Loss of stored memories

Multiple Memory Systems

• I. Direct and indirect

• II. Declarative and procedural

• III. Episodic and semantic

Explicit and Implicit memory

• Direct (explicit) tests of memory

– conscious recollection required

– What did you have for breakfast yesterday?

• Indirect (implicit) tests of memory

– conscious recollection not required

– Report the first word that comes to mind that completes the stem mot____.

Direct and indirect

• Problems

• conscious recollection still possible for remote memories after lesion of hippocampus

• conscious recollection is not the critical determinant of whether memory performance is spared or impaired.

Direct and indirect

• GRE vocabulary study (Gabrieli et al, 1988)

• tyro and cupidity

• implicit memory tests

• choose definition

• choose synonym

• choose sentence frames

• HM’s performance profoundly impaired

Declarative and Procedural

• Declarative memory

• requires memory for arbitrary relationships

• relational

• flexible

Declarative memory Table 9.2

Declarative memory - neural structures

• Hippocampal system and related structures

– receives input from all neocortical (sensory, motor, and limbic) processors in brain.

• recipient of info about people, objects, temporal and spatial contexts

Procedural memory

• Procedural memory is:

• inflexible

• dedicated

• can be retrieved and expressed only when original processing operations are engaged

Procedural memory

• Exert influence only when original learning situation is repeated.

Procedural memory (Table 9.2)

Episodic and semantic memory

• Episodic memory

– autobiographical records of personally experienced events occurring in specifiable temporal and spatial contexts

– circumstances of buying the textbook involves episodic memory

Episodic and semantic memory

• Semantic memory

– world-knowledge stored in a context free fashion

– ability to remember various facts about neuropsychology gleaned for lecture and textbook

Episodic memory

• Amnesia during tasks that require memory for specific episode

• memory for relationship between certain items and their original context

• relational

• episodic memory is a subset of declarative memory

Semantic memory

• Amnesia patients have deficits in semantic (world) knowledge:

• new vocabulary, public events, identity of famous persons

• this too involves relational memory

• semantic memory is a subset of declarative memory

Semantic memory

• Semantic knowledge overlearned early in life remains intact for amnesia patients!

Where is long-term memory stored?

• Hippocampal system is not the site!

• Lashley (1950) “In search of the Engram”

– mass action

– equipotentiality

Long-term memory

• Penfield & Penfield (1963)

• electrical stimulation of temporal lobe

• elicited memories that unfolded in time

• temporal lobe must be the repository!

• Similar to tape back-up

Long-term memory

• Bickford et al (1958)

• implanted electrodes in depths of temporal lobes

• reported retrograde and anterograde amnesia during delivery of current

• extent of retrograde amnesia related to duration of current

• failed to create new memories

Long-term memory

• Problems

• memories from Penfield’s study were not verified

• patients incorporated OR staff into memories

• removal of temporal lobe did not result in loss of memories

Storage of declarative memory

• Hippocampus is not the site!

• Various elements of given scene are processed by CORTICAL processors

– specialized for visual, auditory, linguistic, spatial

• rich, reciprocal connections between hippocampus and cortical areas

Storage of declarative memory

• Visual aspects of memory: visual processing areas

• Linguistic aspects of memory: language areas

• Memory for whole event is distributed

Supporting evidence

• Ventral stream or inferotemporal cortex

• long-term storage for visual objects

• So, Lashley was right?

– Memory is stored in a distributed fashion?

• Penfield was right?

– Specific brain regions associated with memories?

Storage of procedural memory

• Does not require hippocampal participation

• Depends only on cortical systems engaged in the task

Evidence

• Cortical reorganization in somatosensory cortex or primary auditory cortex in response to learning (Merzenich et al., 1990)

• Changes in receptive field

Evidence

• PET and fMRI for humans

– repetitions of words in priming results in changes in visual processing areas (Ungerlieder, 1994)

– learning of finger-movement sequences results in changes in activation in motor cortex and cerebellum (Kim et al., 1994).

– Semantic encoding of words results in changes in left prefrontal cortex (Demb et al., 1995)

Evidence

• Damage to right occipital lobe can result in selective deficits of visual word priming (Keane et al., 1992)

Working memory

• Working memory deficits

– dorsolateral prefrontal cortical areas

• Not impaired in long-term memory areas

• Working memory works in parallel to long-term memory

• deficits are tied closely to individual information-processing systems

Working memory (Baddely, 1986)

• Auditory-verbal working memory

– input phonological buffer

– output phonological buffer

• Visual-verbal working memory

– visuospatial scratch pad

Executive Function (10)

• Case of Dr. P.

– minor facial surgery

– complications resulted in anoxia

– brain damage

– planning, adaptation, acting independently

Executive Function

• Dr. P.

– IQ tests constant, superior range

– failed to do simple day-to-day activities

• change clothes

– unable to appreciate deficits

– employed as delivery truck driver

– unconcerned, uninterested in basics of life

Executive functions

• plan actions toward a goal

• use information flexibly

• realize ramifications of behavior

• make reasonable inferences

Executive functions

• Lobotomy

Executive function

I. Initiation, cessation, and control of action

A. Psychological inertia

1. Difficulty starting behavior

ex: verbal fluency

2. Difficulty stopping behavior (perseveration)

ex: circle, square, triangle test

ex: Wisconsin Card Sorting Test

Ex: Environmental dependency syndrome

Executive function

II. Abstract and concrete thinking.

A. Concrete thinking

ex: apple and orange

ex: modified card sorting

Executive function

III. Cognitive Estimation

A. Length (ex: woman’s spine)

B. Price (ex: washing machine)

C. Temporal domain

“How often” and “when”

Ex: Brief Test of Attention

Executive function

IV. Cognitive flexibility & response to novelty

A. Fluency tests (initiation & flexibility)

ex: supermarket items

Categorical naming

Executive function

V. Goal-directed behaviors

making a peanut butter and jelly sandwich

A. Ability to sequence

1. Appreciation of the sequence

ex: recency judgment task (Milner, 19820

Executive function

A. Ability to sequence

2. Generating the sequence

ex: self-ordered pointing task

Lesions: left frontal lobe damage

Executive function

A. Ability to sequence

3. Choose best sequence or strategy

ex: Tower of London

Executive function

SPECT (Morris et al., 1993)

control: passive

experimental: active

left prefrontal region

left superior frontal region

Executive function

V. Goal directed behaviors

A. Ability to sequence

B. Ability to shift set and modify strategies

ex: conceptual shifts

Executive function

V. Goal directed behavior

C. Use of contingencies to guide behavior

ex: advance information paradigm

Executive function

V. Goal-directed behavior

D. Self-criticism or self-monitoring

“How am I doing?”

“Have I reached the goal?”

Developmental Neuropsychology

• Dan (12 years old)

• stuggling with spelling and reading

• Full Scale IQ is average

• Performance IQ above average

• Verbal IQ below average

• form = farm, grieve as great

Changes in the brain

• Plasticity: the ability to change

Neuronal migration

• Radial glia

• chemoaffinity hypothesis (Sperry)

– newt experiment

– optic fibers

– 180 degree rotation

Synaptogenesis

• Synapses increase more than 10 fold

Changes con’t

• Neurons do not proliferate after birth

• Glial cells do proliferate

• oligodendrocytes (4th gestational month and 1st year of life)

• myelination continues through late teens

– example: corpus callosum

EEG changes

• First 2 years : delta (<3.5Hz)

• 1 year and 5 years : theta (4-7Hz)

• 5 years: alpha is discernible (8-13Hz)

• 10-13 years: alpha is similar to adults

• 10-13 years: beta activity is discernible (>14Hz)

Change con’t

• Programmed cell death

– vast numbers of neurons die at specific stages

• mice lose 30% of neurons during development

• Elimination of synapses

– could be the mechanism for fine tuning

Behavioral Changes

• Basic reflexes

• rooting

• grasping

• Babinski

• Cortical inhibition

Environmental Influences

• Enriched environment (Rosenweig et al., 1972)

• dendrites become bushier, synapses increase

Sensitive periods

• Crossed-eyes

– binocular columns

• Language

– before 5-7 years of age

– after 15, poorest aquisition

Developmental Disorders

I. Learning disabilities

neuropsych definition: difficulty acquiring skill in a certain area

educational definition: significant difference between IQ score and scores on achievement tests

Learning disabilities

A. Verbal learning disabilities

1. Dyslexia: inability to read

a. Other cognitive areas intact

b. 5% of all children

c. 85% have difficulty linking letter to sound

d. 15% have difficulty with visual- spatial

Learning disabilities

e. Therapy

1. Phonological route

2. Direct route

f. Clear neurologic picture is uncertain

1. Genetic

2. Males

3. Left-handed

Learning disabilities

2. Developmental aphasia

a. Disorder of expressive language

b. Expressive and receptive difficulties

c. Origin unknown??

Learning disabilities

B. Nonverbal learning disabilities

1. Average verbal IQ

2. Deficits in perception, imagery, telling time, arithmetic

3. Neurologic impairment: tremors, poor coordination on left side.

Learning disabilities

4. Social and emotional deficits

a. facial expression and gesture

b. tone of voice

c. Speech is flat or monotone

d. Lack of empathy

e. Anxiety, withdrawal, depression

Developmental Disorders

II. Autism and Pervasive Developmental Dis

A. Qualitative impairment in social interaction.

B. Delays and abnormalities in language

C. Restricted, repetitive, stereotyped patterns of behavior

D. Onset before age three

Autism con’t

E. Most autistic children are mentally retarded.

F. The profound social deficits distinguish them from common mental retardation.

Autism con’t

G. Cause: unknown, likely heterogenous

many structures implicated

(cerebellum, brain stem, thalamus, etc)

F. Asperger’s Syndrome

Developmental Disorders

III. Attention-Deficit Disorder (ADD)

A. Impulsivity

B. Poor attention span

C. Can’t do more than a couple of things.

Developmental Disorders

IV. Mental Retardation

A. Categories

Mild: 50-55 - 70

Moderate: 35-40 - 50-55

Severe: 20-25 - 35-40

Profound: <20-25

IV. Mental Retardation

B. Causes

1. Infection (e.g., herpes virus)

2. Genetic disorders

a. Down’s syndrome

(trisomy 21)

b. Fragile X syndrome

Down’s and Fragile X

Causes Con’t

2. Genetic disorders

c. Turner syndrome (XO)

Overall intelligence normal

Spatial and perceptual skills below average

Accuracy Scores

Causes Con’t

2. Genetic disorders

d. Phenylketonuria (PKU)

lack of phenylalanine hydroxylase

phenylalaline converted to tyrosine

tyrosine is a precursor to dopamine

result: mental retardation

Causes Con’t

3. Toxins

a. Fetal Alcohol Syndrome (FAS)

1. Leading cause of MR

2. Hyperactivity, poor attention,

retarded physical growth, abnormalities of face and cranium

Causes Con’t

3. Toxins

a. Fetal Alcohol Syndrome (FAS)

3. Fetal alcohol effects

Causes Con’t

3. Toxins

b. Cocaine

1.??????

Causes Con’t

4. Anoxia

a. Damage to placenta

b. Umbilical cord

can cause mental retardation OR

cerebal palsy