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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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)
FACTS (Semantic)
Recognition
Visual-paired comparison
Delayed non-matching to sample
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
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
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
Sensory Input
Frontal Lobe (short term)
Hippocampus (long-term)
Cortex (long-term memory storage
Part II: Overview
FACTS (Semantic)
RecognitionRecall
Multiple choice
Free-response
Characterization of Damage
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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
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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
Recognition (Multiple Choice)
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
Delayed non-matching to sample
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)
Cortex (long-term memory storage
Recognition Memory
Recall Memory
Summary (a way to look at the information)
Lost Memory
Lost Memory
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
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
Recognition (Multiple Choice)
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
Cortex (long-term memory storage
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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