impaired recognition memory in monkeys after damage limited to the hippocampal region zola sm,...

Impaired recognition memory in monkeys after damage limited to the hippocampal region

Zola SM, Squire LR, Teng E, Stefanacci L, Buffalo EA, Clark RE

Semantic memory and the human hippocampus

Manns JR, Hopkins RO, Squire LR

Hippocampal Damage and Semantic Memory

Semantic Memory

MEMORY

DECLARATIVE(EXPLICIT)

EVENTS(Episodic)

MEDIAL TEMPORAL

LOBE

Milner B, Squire LR, Kandel ER: "Cognitive neuroscience and the study of memory". Neuron 1998, 20:445-468.

FACTS (Semantic)

RecognitionRecall

Visual-paired comparison

Delayed non-matching to sample

Multiple choice

Free-response

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MTL lesion

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Medial Temporal Lobe (MTL)

1) Hippocampus

3) Perirhinal Cortex

2) Entorhinal cortex

4) Parahippocampal Cortices

What is the Role of the Hippocampus Semantic Memory?

How might you test your hypothesis?

Some Examples:

Lesion studies

Stroke damage in humans. Chemical lesion in animals.

Record Activity

fMRI, electrical recording

Stimulation

Electrical stimulation (e.g. Penfield)

Part IFormation of long-term semantic

memory after monkey hippocampal lesions

FACTS (Semantic)

Recognition

Visual-paired comparison


Multiple choice

Sensory Input

Frontal Lobe (short term)

Hippocampus (long-term)

Cortex (long-term memory storage

Part I: Overview

Part I: Goal

Study the role of the hippocampus in recognition (semantic) memory with a highly localized lesion.

Natural ischemia (loss of blood supply) may produce undesired side effects

Ibotenic acid (IBO) selectively destroys cell bodies and leaves surrounding white matter intact

Radiofrequency (RF) and ischemia (ISC) lesions were also analyzed

Characterize the lesion

Delayed nonmatching to sample (recognition memory)

Standard Setup

1. Animals are presented with an object for a period of time.

2. The animal is blocked from viewing the object.

3. After a delay, they are presented with the original object and a new one.

4. The animal has to choose the new object to get a food reward.

8 sec - 40 min delay

Delayed nonmatching to sample (recognition memory)

IBO = ibotenic acid; RF = radiorequency; ISC = ischemia

Visual paired-comparison task (recognition memory)

Animals have a natural tendency to look at new images more often than familiar images

1 sec - 40 min delay

25 sec of viewing time

FAMILIARIZATION

5 sec5 sec

1 sec delay

TESTING

Visual paired-comparison task (recognition memory)

Combined data for all forms of hippocampal lesions (recognition memory)

Part I Conclusions

The hippocampal region is crucial for the formation of recognition (semantic) memory after a period of time

But this period might vary depending on the task. Possible role for other structures, attention, food deprivation in semantic memory formation? Difficult to tell with a lesion alone

Part IIThe storage of long-term

recognition and recall memory after hippocampal lesions in

humans

Sensory Input

Frontal Lobe (short term)

Hippocampus (long-term)


Part II: Overview

FACTS (Semantic)

RecognitionRecall

Multiple choice

Free-response

Characterization of Damage



Controls

13.4 ± 3.3 yrs52 ± 3.3 yrsControls (n=12)

13.7 ± 3.3 yrs48.5 ± 5.1 yrsPatients (n=6)

Years of EducationAverage AgeGroup

Each patient was matched with 2-3 controls

Recall Task

Data was analyzed in five year intervals starting from the onset of amnesia (e.g. J.S. from 1999-1994, 1993-

1988, etc.)

Questions ranged from 1950 to present

Sample Questions that might apply to 22 year olds: Who was the famous rock musician

that committed suicide in 1994? Which famous rapper remarried his

ex wife and then filed for divorce 3 months later?

Recall Task



Years Before Onset of Amnesia

Patients with hippocampal damage (H) were impaired at learning notable news events compared to controls (CON).

However, recall of more remote memories was unaffected by hippocampal damage.

AA = anterograde amnesia (inability to form new memories)

H = Patients (hippocampal damage)

CON = controls

Recognition (Multiple Choice)

Free Recall

Recall vs. recognition

1. Anterograde memory affected in both recall and recognition

2. The period when the hippocampus is important varies depending on the test.

3. Overall recognition memory is not statistically different from controls (69.3 ± 5% vs. 74.5 ± 5%)

Recognition vs.recall

semantic memory

Questions from year of damage to present

Part II conclusions

• The hippocampus is crucial for normal anterograde semantic memory.

• Different forms of semantic memory might be processed differently by the hippocampus

Discussion

• Were patients matched to controls only on age and years of education? Two patients became amnesiac after a drug overdose and associated respiratory failures!

• Differences between monkeys and humans?

• What if the hippocampus is just part of the pathway for recall?

Discussion

Above chanceYears before amnesia


Patients: 69.3 ± 5%

Controls: 74.5 ± 5%

Above chance

• Patients and monkeys with hippocampal damage retain some recognition memory skills

Summary

Semantic memory and the hippocampus:

• There is a period of time after the formation of long-term memory and before the storage of long-term memory that memories are directly associated with the hippocampus.

• This period can vary depending on the specific test of semantic memory

• It is difficult to account for these differences based solely on lesion studies.

Recall

Recognition

Semantic Memory Test

Long

Short

Amount of time in Hippocampus

X

Memory is more affected in

hippocampal lesion

Visual paired comparison task


Recognition Task

Short

Long

Amount of time in Frontal Lobe

X

Memory is more affected by

hippocampal lesion

Summary (a way to look at the information)

Sensory Input

Frontal Lobe

Hippocampus

Visual pairedDelayed non-matching to sample Higher Cortical Areas

(Consciousness)


Recognition Memory

Recall Memory

Summary (a way to look at the information)

Lost Memory

Lost Memory

Conclusion


are needed to see this picture.Hippo

Experiment B

Sample Questions: 1) Is Kurt Cobain famous? 2) If yes, is Kurt Cobain still alive? * In the experiment, all of the options who were famous were well known before 1970

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B

C

Experiment B

Other Interesting Results/Discussion

The size of the lesion does not correlate with the severity of recognition memory

It is possible that above a certain threshold (>20%) of damage, the hippocampus can no longer support recognition memory

“(the) process of forming associations and the ability to retain relational information across time that many have supposed is at the heart of declarative memory and in turn is the function of the hippocampal region in both humans and animals”

Ibotenic acid, which creates a more localized lesion, caused the same amount of memory deficit as other lesioning methods (e.g. ischemia).

This suggests that there is no “hidden damage” or neuronal dysfunction of visually/histologically unaffected portions of the brain.

Discussion

Does the term “semantic memory” have biological relevance? Does the area we call the hippocampus have behavioral relavence?

Are other structure involved in recognition memory? Is recognition memory a unique form of semantic memory?

Above chanceYears before amnesia


Patients: 69.3 ± 5%

Controls: 74.5 ± 5%

chance

Other Interesting Results/Discussion

No specific area of the hippocampus is important for recognition memory

Caudate nucleus damage, in addition to hippocampal damage, does not further disrupt recognition memory.

Experiment B (recognition)

It is generally accepted that the hippocampus is necessary for episodic memory.

What if episodic memory is enhancing for semantic memory for controls?

DECLARATIVE(EXPLICIT)

FACTS (Semantic)

EVENTS(Episodic)

Experiment B (recognition)

Is semantic memory augmented by episodic memory?

Controls were asked if they could remember the circumstances in which they heard of the individual’s death.

When data associated with episodic recall was removed, the patients were still impaired compared to the controls.

Sensory Information

Working Memory/Short term Memory

(Minutes)

Long Term Memory(Hours/Days/Years)

Sensory Input

Frontal Lobe

Hippocampus


Ebbinghaus Working Model

Short term

Long- term

What is the Role of the Hippocampus Semantic Memory?

Two tests for semantic memory commonly used under the lesion

model:

1. Free Recall

What are the four cortical lobes?

2. Recognition Tests

Multiple choice

Which person have you seen before?

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Sensory Information

Working Memory/Short term Memory

(Minutes)


Receptors (e.g photoreceptors)

Frontal Lobe

Hippocampus


Ebbinghaus Working Model

Short term

Long- term

impaired recognition memory in monkeys after damage limited to the hippocampal region zola sm,...

Documents

semantic memory slide

hippocampus semantic

delay slide

semantic memory formation

ischemia slide

study of memory

overview slide

humans slide