Memory and Amnesia

Nathan Spreng

Cognitive Neuroscience: PSY393

August 2, 2005

Amnesia at the movies

Remember Sammy Jankis?

Memory Lecture Summary• Memory

– Process and Definitions– Systems

• Medial Temporal Lobe & Classic Amnesia– Encoding & Retrieval– Case studies

• Frontal Lobes– Working Memory & DLPFC– Working with Memory – Case study

• Autobiographical Memory

Memory is...

• A group of mechanisms or processes by which experience shapes us, changing our brain and behaviour

• The product of learning

Memory involves...

• Acquisition

• Retention

• Ability to retrieve– information– personal experiences– procedures (skills and habits).

Memory enables...

• Adaptation to the environment

• Improvement of our interactions with the outside world

• Intergenerational transfer of knowledge

Short and Long Term Memory

• Memory can be divided into– Time (seconds to minutes to years)– Contents (7 plus minus 2)– Systems by type of information

Memory processes

1. Registration

2. Encoding

3. Consolidation

4. Storage

5. Retrieval

6. Re-encoding

Sensory perception in sensory brain areas

Initial processing (association with previous information) - Trace

Deeper processing: Engram formation

Stable representation in central nervous system

Reproduction of previously stored information: Recollection

Re-encoding through retrieval; initial trace (engram) changes

Memory Systems

Memory Systems

• Implicit Memory: Memory without awareness– Skills, priming, etc (spared in amnesia)

• Explicit Memory/Declarative Memory– Memory accompanied by an awareness of

recollection. May be “declared” or verbally reported

Amnesia

Definition: “An abnormal mental state in which memory and learning are effected out of all proportion to other cognitive functions in an otherwise alert and responsive patient” Kopelman (2002)

• Memory can be compromised in isolation from other cognitive abilities

• Amnesia is selective, effecting certain capacities, showing that there are many systems of memory

Temporal Extent of Amnesia• Anterograde amnesia

– Deficit in new learning– Inability to form new memories AFTER time of

injury

• Retrograde amnesia– impairment of memory of information PRIOR

to onset of amnesia– temporal gradient, effecting recent > remote

Temporal Extent of Amnesia

• Ribot’s Law (1882): “The progression of the destruction of memory follows a logical order. It begins with the most recent recollections, being rarely repeated, and having no permanent associations”

• Greater compromise of recent memory over remote

Temporal Extent of Amnesia

The case of H.M.

• HM - surgery for intractable epilepsy.

• Resection of hippocampus, parahippocampal gyrus, amygdala & uncus.

• HM could not form new memories (anterograde amnesia).

• Retrograde amnesia (11 years)

• Right: HM vs. 66-yr old Control

(Corkin et al., 1997)

Anterior

Posterior

Etiology of Amnesia

• Korsakoff’s syndrome (Jimmy)

• Herpes encephalitis (Clive)

• Severe hypoxia

• Vascular disorders

• Head Injury (K.C.)

• Dementia (J.S.)

• Transient global amnesia (fugue state)

Amnesia

• Inability to form new long term memories

• Assessed with– Free recall (no info)– Cued recall (starting with “c”)– Recognition (target and lures used)

• Savings in relearning (also impaired in amnesia)

Memory Systems

Impaired Spared

Implicit Memory

• “Memory without awareness”

• Spared in classical amnesia

• Priming – Primary Sensory Cortex

• Procedural Memory - Striate

Implicit Memory

• Gollin Incomplete Pictures task

• Repetition Priming

• Bias to previous exposure

Implicit Memory

• Eye movements to assess implicit memory

• Top: Initial exposure, eye movements over 3 items

• Bottom: 2nd exposure, eye movements over where one item would be

Implicit Memory

• Procedural Memory

• Improvement in performance without recollection of the material

• Spared in amnesia

Mirror Reading Task

Declarative Memory• Semantic Memory: “Knowing”

– Knowledge of words and their meanings, objects, concepts and facts.

• Episodic Memory: “Remembering”– Re-experiencing of an event that

occurred in the past including time and place of original encoding episode…mental time travel.

The case of K.C.

• TBI • Bilateral hippocampus

& frontal lobe damage• Severe RA and AA• No episodic memory• Intact semantic

memory

K.C.

normal

Memory Circuit

(Mayes, 2000)

Main memory structures & connections

MTL

Diencephalon

Mamillary bodies

Hippocampal formation

3. Parahippocampal cortex

2. Entorhinal cortex

1. Perirhinal cortex

Structures of the Medial Temporal Lobe

SubiculumCA1CA2CA3Dentate gyrus

1-3 = Parahippocampus

Medial Temporal Lobe• Hippocampus as Convergence zone

• Memories are not stored within the hippocampus

• Hippocampus acts as an “indexor” and lays trace of memories.

• Memories are stored in sensory cortex

• Hippocampus has access to all sensory information

• Relational Memory

Medial Temporal Lobe

• Morris Water Maze

• Hippocampal lesions

• Deficits in learning and remembering spatial relations

Medial Temporal Lobe

• Hippocampal Lesions: Material specific memory disorder

• Unilateral– Left: verbal impairment– Right: nonverbal

impairment

• Bilateral - Global impairment

• fMRI Hippocampus: Material dependent activity at encoding

• Verbal - Left

• Nonverbal - Right

Medial Temporal Lobe

• Hippocampal activity predicts successful recall– During encoding– During retrieval (Nyberg, et al., 1996)

• “Subsequent Memory Effect”

Medial Temporal Lobe

• While memories are young, they depend upon an intact hippocampus

• Are old episodic memories independent hippocampus once consolidated?

Medial Temporal Lobe

• fMRI: Robustness of hippocampal activity during retrieval related to vividness of memory, not age (Gilboa, 2003)

• H.M. possesses some remote memories.– Are they episodic? Depends on measure– lack episodic content, “semanticized” (Steinvorth &

Corkin, submitted)

Medial Temporal Lobe

• How does the hippocampus bind information?

• LTP– Hebb’s Law

• Connectivity

(Rolls, 2000)

• Same brain regions activated for perception and retrieval

• Regions– fusiform gyrus (a)

– superior temporal gyri (d)

• Retrieval of pictures and sounds, respectively

(2004) Proc. Natl. Acad. Sci. USA 101, 5181

MTL & Emotion

• Emotionality enhances memory performance

• Mediated by the Basolateral limbic circuit• Parahippocampus and perirhinal cortex

connect with the amygdala• Orbitofrontal cortex involved in processing

salience at encoding • Emotion enhances attention

Main memory structures & connections

Mayes, 2000

Amyg-dala

Basolateral limbiccircuit

Want Slides?Please provide email address

Video: NoT cue 17-27 minutes

Video: Tulving/Milner – Clive cue 6-18 minutes

Clive Wearing• R-handed

• Above average IQ

• Prominent Musician

• Herpes Simplex Encephalitis

• Bilateral temporal lobe degeneration L>R

• Dense Anterograde Amnesia

(Wilson & Wearing, 1995)

Clive Wearing

Frontal Lobes

• Tennessee Williams:

“Life is all memory except for the present moment that flies by so quickly that you can

hardly catch it going by”

• WM: moment

• LTM: past

Working Memory• Central Executive: Attentional

control of the slave systems:– Visuo-spatial sketchpad

– Phonological loop

• Both derive and feed information to and from LTM

• WM is a combination of maintenance and manipulation operations and works in close interaction with LTM

Baddeley & Wilson, 2002Video: cue @ 27-33 min

Basic WM paradigms• Delayed response• Delayed alternation• Object alternation• Go No-Go• Reversal• Delayed match to sample• Delayed non-match to sample

– Recurring stimuli (recall most recent presentation)– Trial-unique stimuli (distinguish familiar from novel)

Component processes of WM

• Mnemonic

– Register (encode)

– Store (maintain)

– Rehearse

• Non-Mnemonic

– Control interference (inhibit)

– Manipulate

– Select (retrieve, prepare)

– Respond (motor effector)

– Domain-specific sensory systems (spatial, object)

Working Memory

• Delayed Response Task:– Access spatial information

– Hold information on on-line during delay period

– Initiate motor response

• Delay tasks sensitive to principal suclus

• Impaired with lesions• Evidence for delay-

specific neurons

Working Memory

• Shared working memory circuit in humans– BA9/46 (DLPFC)– Posterior Parietal– Left Hemisphere

• Delayed response• Delayed alternation• Object alternation

• “Guide behavior in the absence of external cues”

Functional neuroimaging(D’Esposito et al., 2000; Fletcher & Henson, 2001)

• DLPFC– Encoding (supraspan) – Maintenance– Manipulation– Scanning

• VLPFC– Maintenance– Rehearsal– Inhibit, select

• Anterior PFC (Poles)– More complex manipulation

CUE DELAY RESPONSE

time

encoding manipulationscanning

maintenanceInhibition/selection

Frontal lobes and working with memory

• Associative retrieval: conscious recollection that are cue-driven– medial temporal lobes (MTL)

• Strategic Retrieval: problem solving approach to memory where – the frontal lobes work with memories– delivered through the medial temporal lobes

and posterior neocortex

Video: cue 35 minutes TRAIN

Frontal lobes and working with memory

Simons & Spires (2003)

• Frontal-medial temporal interactions– encoding– retrieval

Frontal lobes and working with memory

• Meta memory judgments

• Source amnesia– Dissociation between item and contextual information

(details of study episode)

• Judgment of recency (Milner, 1971)– Left-sided lesions affect verbal

– Right-sided lesions affect verbal and visual

• Temporal ordering (Milner, 1971)

Frontal lobes and working with memory

• Confabulation– Defined as an honest lying– Requires retrieval, sequencing,

output monitoring– Associative retrieval intact,

strategic retrieval impaired– “Source amnesia magnified and

extended to include an entire lifetime of experience” (Moscovitch, 1989)

Schnider, 2003

Patient J.S. Frontotemporal dementia

RR

R R LL

(McKinnon, et al., in preparation)

The case of JS: Confabulation

• MK: Can you tell me about Detroit again?

• JS: We were in this nice restaurant and a guy said I don’t think you guys should go outside. There’s a sniper on the roof outside. He said I think you had better stay in here. I’ve just called the cops. (laughter) He said there’s a sniper on the roof. He said you guys had better stay in here.

• MK: Then what happened?

• JS: Well the cops came. The cops got the guy. And they said okay guys you can leave now. That was all the help

and we went outside.

Autobiographical Memory

• Memory of, or relating to, the self

• Involves episodic memory (ie autonoetic awareness)

• Semantic memory

• Mental Time Travel

Autonoetic consciousnessWheeler, Stuss & Tulving (1996); Tulving (2002)

Awareness of the self as a continuous entity across time

"Remembrance is like a direct feeling; its object is suffused with warmth and intimacy to which no object of mere conception ever attains." James (1890)

"It's essence lies in the subjective feeling that the present experience is of an earlier, similar one, and in the belief that the self doing the experiencing now is the same self that did it originally." Wheeler, Stuss, & Tulving (1997)

Ascendancy of personal re-experiencing over childhood amnesia

Bruce et al., 2000

Mental Time Travel: Past & Future

Spreng & Levine (in press)

Autobiographical memory

a) Anteromedial prefrontal cortex

b) Superior medial prefrontal cortex

c) Ventrolateral prefrontal cortex

d) Temporoparietal junction

e) Posterior cingulate/Precuneus

f) Thalamus (anterior nucleus)

a

b

c

d

e

f

x = -4

y = -56

z = 5

Autobiographical recollection

Personal episodic versus personal semantic

Kopelman, 2002