THE SYSTEMS NEUROSCIENCE

OF HUMAN MEMORY

Rik Henson
 Overview
 A taxonomy of memory

 For each type of memory:

 Definition and Common tests

 Neuropsychological evidence

 Neuroimaging evidence

 Summary
 Taxonomy of Memory
Cohen and Squire, 1980 Memory

Declarative Non-declarative
 Taxonomy of Memory
Cohen and Squire, 1980 Memory

Declarative Non-declarative

 Available to conscious retrieval  Experience-induced change in behaviour

 Can be declared (propositional)

 Cannot be declared (procedural)

 Examples  Examples
 “What did I eat for breakfast?” (episodic)  Subliminal advertising?
 “What is the capital of Spain?”
(semantic) (priming)
 “What did I just say?” (working)  How to ride a bicycle (skills)
 Phobias (conditioning)
 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working

 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working

 Episodic Memory
 Memory for personally experienced events that occurred in particular place at a specific
time (defined by Tulving, 1972)

 Contextual, spatiotemporal, autobiographical, “remembering”

 “Direct” memory tests:

Encoding Retrieval

Free recall CAT ?

DOG ?

Cued recall CAT – DOG EAGLE- ?

EAGLE – NEST CAT- ?

Recognition CAT CAT 

DOG SUN X

Source Memory CAT CAT bold

DOG DOG italics
 Episodic Memory

PATIENTS CONTROLS

Copy

Delayed
Recall
(15 mins)

Rempel-Clower et al., 1996

Episodic Memory - Neuropsychology
 Organic Amnesia
 Intact: semantic memory (e.g, language)
working memory (e.g, <5 mins)
nondeclarative memory
memories

Retrograde Anterograde
Episodic

Amnesia Amnesia

“Ribot” gradient Trauma time

Hippocampal / MTL memories ‘consolidated’ into neocortex over time, and

become hippocampal-independent (Marr 1971; Alvarez & Squire, 1995)
Episodic Memory - Neuropsychology
• Large lesions of bilateral Hippocampi, Amygdalae, and Rhinal Cortex produce
severe antero- and retro-grade amnesia, eg, HM (Scoville & Milner, 1957)

• Circumscribed lesions of CA1 of Hippocampus produce significant anterograde

amnesia (Zola-Morgan et al 1986)

• Korsakoff’s Patients with diffuse damage to Diencephalon, Medial Thalamus,

Mammillary Nuclei show varied amnesia (Press et al., 1989)

• Alzheimer’s patients show early signs of amnesia, with first lesions in Medial
Temporal Lobe (Hyman et al 1984)

• Frontal Patients show confabulation (Burgess & Shallice, 1996), impaired source
memory (Janowsky et al., 1989) and interference (Shimamura et al., 1995)
Episodic Memory - Neuroimaging
• MTL activations during episodic encoding (Tulving et al 1996) and retrieval
(Schacter et al. 1996)
Anterior-Posterior dissociation? (Lepage et al. 1998; Schacter et al. 1999)
• Left Frontal during Encoding (Shallice et al., 1994), right during Retrieval
“HERA: Hemispheric Encoding Retrieval Asymmetry” (Tulving et al., 1994)
• Posterior cingulate / Precuneus (Fletcher et al., 1996)
• Left lateral inferior parietal cortex (Henson et al., 1999)

Network of Frontal - Medial Temporal – Posterior areas all involved:

Frontal areas control encoding and retrieval of memories?
Posterior association areas store components of memories?
Medial Temporal regions (temporarily) bind different components?

• Finer spatial resolution (fMRI) beginning to dissociate MTL regions, eg

Hippocampus / Perirhinal for “Recollection / familiarity”? (Aggleton & Brown, 1999)
 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working

 Semantic Memory
 Memory for facts, general knowledge, word meanings

Acontextual: Independent of where or when the information was encoded

• Common Tests:

Object Naming e.g. “What is this?”

Semantic Judgements

“Which bottom picture goes best with the top one?”

Category Fluency Pyramid and Palm Tree Test

(Howard & Patterson 1992)
“Name as many dog breeds as possible in 1 minute”
German Shepard, golden retriever, . . .
Semantic Memory - Neuropsychology
• Modality-specific visual Agnosia after Left Temporal damage (Warrington, 1975)

• Category-specific, amodal Agnosia following Left Medial/Middle Temporal damage,

eg, living vs. nonliving (Warrington & Shallice, 1984)

category effects reflect visual vs functional information?

• Temporal Pole lesions cause deficits in person-naming; Left Middle Inferior in

animal-naming and Left Posterior Inferior in tool-naming (Damasio et al 1996)

• Semantic Dementia (SD) following anterior/inferior Temporal atrophy, with

reverse Ribot gradients (Graham et al., 2000)

• SD patients demonstrate graded deterioration of knowledge (Hodges et al., 1992)

Semantic Memory - Neuroimaging
• Common activation in Left Inferior Frontal,
Inferior Temporal, Angular gyrus and
Temporal pole for semantic judgments to
words and pictures (Vandenberghe et al 1996)

• Left Inferior Temporal activations for animal

and tool naming, Temporal Pole for people
naming (Damasio et al., 1996)

• Left Inferior Temporal activation for category-

versus letter-fluency (Mummery et al 1996)

• Left Middle Temporal and Premotor activations

for tool vs animal naming, Left Middle Occipital
for animal vs tool naming (Martin et al 1996)

Distributed representations, with activations

reflecting object’s interaction with world? McClelland and Rogers, 2003
E.g., tool naming activates motor regions
 Episodic vs Semantic debate
• Are episodic/semantic memory just a continuum? (Watkins, 1974)

• Does Global Anterograde Amnesia exist?

Inability to acquire new semantic memories (Gabrieli et al, 1998)...
...yet intact development of semantic memory despite
hippocampal damage (Vargha-Khadem et al. 1998)

Hippocampus proper underlies true episodic memory?

Additional Medial Temporal areas underlie anterograde semantic
memory impairment?
 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working

 Working Memory
 The ability to hold information “on-line” for current task (e.g. for comprehension, planning, problem solving, Baddeley 1992)

 Short-term memory (cf. long-term episodic / semantic memory)

 Verbal vs Visuospatial Maintenance vs Manipulation
 Spatial vs Object Storage vs Rehearsal

• Common Tests

• Memory Span (maintenance)

Digit span “Repeat back: 8,5,3,2,7,9”
Corsi Block span
• (Sternberg) probe task (maintenance)

… …

• N-back task (manipulation)

...$%^!*&*+
Working Memory - Neuropsychology
• Auditory-Verbal maintenance deficit following Left Supramarginal / Inferior
Parietal lesions, eg KF (Warrington & Shallice, 1969)

• Visual-spatial maintenance deficit following Right Inferior Parietal lesion, eg

ELD (Hanley et al 1991)

• Frontal patients impaired on manipulating information in Working Memory on

tasks such as card sorting (Milner, 1963) and selection-without-repetition
(Petrides & Milner, 1982)

• Age-related Working Memory deficits following frontal-striatal decline

(Gabrieli, 1996)

Modality-specific, passive stores in posterior parietal/temporal cortex

Common executive processes in frontal cortex
Working Memory - Neuroimaging
• Left Inferior Parietal activation during verbal storage; Left Inferior Frontal
and Premotor activation during verbal rehearsal (Paulesu et al. 1993)

• Right Inferior Parietal, Inferior Frontal, Anterior Occipital, and Premotor

Cortex activated during spatial maintenance (Jonides et al. 1993)

• Left inferior temporal and inferior parietal activated when object compared
to spatial maintenance (Smith et al. 1995)

• Dorsolateral Frontal Cortex activated in N-back task when manipulation

required by N>1 (Cohen et al 1997), for both verbal and spatial material
(Owen et al 1998)

Ventrolateral (Inferior) Frontal Cortex involved in maintaining

information on-line in current form
Dorsolateral Frontal Cortex involved in manipulating information into
new forms (Owen 1997; Postle & D’Esposito, 1999)
 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working Priming Procedural Conditioning

 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working Priming Procedural Conditioning

 Priming
 A change in speed, accuracy or bias of processing a Perceptual Priming
stimulus owing to prior exposure to that stimulus (Gollin Figures)
 Perceptual vs Conceptual

 Example “Indirect” Memory Tests:

Perceptual Identification – Gollin Figures ->

Stem/Fragment Completion
(SMILE) SMI_ _
S_ _ L _

Word Association
(ROSE) FLOWER - ?

Speeded Decisions
(APPLE) Concrete/Abstract? Warrington & Weiskrantz, 1970
 Priming - Neuropsychology
 Amnesics with Medial Temporal damage show intact Perceptual
Priming (Warrington & Weiskrantz 1970) and intact Conceptual
Priming (Graf et al 1985)

 Huntington’s patients with Basal Ganglia damage show intact

priming (Heindel et al 1989)

 Alzheimer’s patients with diffuse Temporal Lobe damage show

intact perceptual priming but impaired conceptual priming (Keane
et al 1995)

 Patients with right occipital lesions show no perceptual priming,

but intact conceptual priming (Gabrieli et al 1995)
 Priming - Neuroimaging
 Reduced activity in bilateral occipito-temporal regions in word-stem completion
(Buckner et al. 1995), independent of explicit memory (Schott et al, 2005)

 Reduced activity in left frontal cortex in word-association (Blaxton et al 1996)

 Subliminal priming “right thru” to motor cortex (Dehaene et al, 2001); though
issues of stimulus vs response priming (Dobbins et al, 2004)

Left frontal cortex involved in conceptual/semantic priming

Occipito-temporal cortex involved in visual perceptual priming

Priming deactivations localised in same areas that performed initial

processing (Schacter & Buckner, 1998)

Deactivations reflect less neural activity (lowered thresholds, synaptic

change, residual activation)? Priming-related increases? (Henson, 2003)
 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working Priming Procedural Conditioning

 Procedural Memory
 Skill learning (e.g. riding a bicycle)

 Requires multiple trials

 Indexed by improved accuracy or RTs

Serial Reaction Task Rotary–Pursuit Mirror Tracing

(e.g. Hazeltine et al., 1997) (e.g. Gabrieli et al., 1997) (e.g. Corkin, 1968)
Procedural - Neuropsychology
 Amnesic patients show intact:
 Rotary Pursuit (Corkin 1968)
 Serial Reaction Task (Nissen & Bullemer 1987)

 Alzheimer’s patients show intact:

 Rotary Pursuit (Gabrieli et al 1993)
 Mirror Tracing (Heindel et al 1989)

 Parkinson’s patients impaired on:

 Rotary Pursuit (Heindel et al 1989)
 Serial Reaction Task (Ferraro et al 1993)

 Huntington’s patients impaired on:

 Rotary Pursuit (Gabrieli et al 1997)
 Serial Reaction Task (Willingham & Koroshetz 1993)
but not:
 Mirror Tracing (Gabrieli et al 1997)

 Cerebellar lesions impair Mirror Tracing (Sanes et al 1990)

 Procedural - Neuroimaging
 Rotary Pursuit learning correlates with activity in Primary and Secondary Motor
Cortex (Grafton et al 1992)

 Serial Reaction Task correlates with activity in Primary and Secondary Motor
Cortex, and Basal Ganglia (Hazeltine et al 1997)

 Two hypotheses:

1. Learning repetitive sequence involves Basal Ganglia-Thalamic-Motor Cortical loop

Learning new visual-motor mappings involves Cerebellar-Motor Cortical loop

2. Open-loop learning (minimal feedback): Basal Ganglia-Thalamic-Motor Cortical loop

Closed-loop learning (continual feedback): Cerebellar-Motor Cortical loop

 Rotary Pursuit and Serial Reaction Task involve open-loop motor learning with
little visual feedback (impaired by Basal Ganglia lesions)

 Mirror Tracing involves much visual feedback (impaired by Cerebellar lesions)

Need to examine nonvisual feedback

 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working Priming Procedural Conditioning

 Classical Conditioning
 Changes in response (R) to conditioned stimulus (CS) after repeated
conditioned – unconditioned stimulus (US) pairing

 Example:
Existing: e.g. air puff to eye (US) – blink reflex (R)

Training: e.g. tone in ear (CS) – air puff to eye (US)

Result: tone in ear (CS) – blink reflex (R)

Delay Conditioning: US starts after a CS but they co-occur

CS
US

Trace Conditioning: US starts after CS but they do NOT co-occur

CS
US

Fear Conditioning: CS is neutral (e.g. a light), US is aversive (e.g. shock)

R is behavioural/physiological (e.g. Galvanic skin response)
 Conditioning - Neuropsychology
 Delay conditioning (eye-blink):
Abolished with Cerebellar lesions (Daum et al 1993)
Abolished in Alzheimer’s Disease: diffuse damage? (Woodruff-Pak et al 1990)
Impaired in Korsakoff’s amnesics: diffuse damage (McGlinchey-Berroth et al 1995)
Intact despite Basal-Ganglia lesions in Huntington’s (Woodruff-Pak & Papka 1996)
Intact in Medial-Temporal amnesics (Gabrieli et al 1995b; Clark & Squire, 1998)

 Trace conditioning:
Impaired in Medial-Temporal amnesics (McGlinchey-Berroth et al 1997)

 Fear conditioning:
Impaired following amygdala resection, despite intact declarative memory for
contingency (LeBar et al 1995)
Intact in amnesics despite impaired declarative memory for contingency (Bechara et al
1995)
 Conditioning - Neuroimaging
 Cerebellar activity correlated with CR during Delay Conditioning
(Logan & Grafton 1995)

 Hippocampus (and amygdala) shows transient involvement in Fear

Trace Conditioning (Buechel et al., 1999)

 Amygdala activity correlates with CS during Fear conditioning (Morris

et al 1998)

Cerebellum implicated in delay conditioning

Amygdala implicated in fear conditioning
Hippocampus may be involved in trace conditioning
(development of declarative memory for contingency?)

Future research may benefit from analyses of effective

connectivity (Buechel et al 1998)
 Taxonomy of Memory
Memory

Declarative Non-declarative

Episodic Semantic Working Priming Procedural Conditioning

What did I What is the What did I Facilitated How to ride Reflex response
have for capital of just say? processing a bicycle to new stimuli
breakfast? France?

Lateral Frontal Many cortical

Medial temporal Lateral Parietal and regions… Basal Ganglia
Temporal / Cerebellum Cerebellum/
Diencephalon occipital
Frontal lobes Motor cortex Amygdala
Mammillary bodies (MTL?)
Frontal lobe
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