1. The MTH System: Episodic Memory, Semantic Memory, and Ribot’s Law17
The MTH System: Episodic Memory, Semantic Memory, and Ribot’s Law

2. Divisions of Declarative Memory
Semantic memory supports our memory for facts and our ability to make generalizations from multiple experiences so that you can answer questions like is a violin a musical instrument or an automobile, or what is your mothers birthday?
To do this requires intentional retrieval and explicit recollection. However, the content of semantic memory is said to be context free—not tied to the place where it was acquired.

3. Two Views of the Role of the Hippocampus in Episodic and Semantic Memory
(A) The unitary view of the medial temporal hippocampal (MTH) system. Supporters of this view believe that the system is needed to support both episodic and semantic memory. (B) The modular view. Supporters of this view believe that the entire system, including the hippocampal formation, is required for episodic memory but that semantic memory does not require the hippocampus.

4. A Modular MTH System: Growing up without a Hippocampus
Farneh Vargha-Khadem and her colleagues studied children that had experienced an anoxic- ischemic insult that bilaterally damaged their hippocampus.
They were between the age of 4 and 9 years when the damage occurred.
These children had very impaired episodic memory but developed normal language and social skills.
They were able to read and write and acquire new factual information.

5. A Modular MTH System: Recognition Memory, Primates
Monkeys with damage to the hippocampus can recognize the sample object in the DNMS task. Humans with damage to the hippocampus can also use a familiarity based recognition system but do depend on the hippocampus to recollect the supporting information. This result suggests a modular organization of the MTH system.

6. A Modular MTH System: Recognition Memory, Rodents
Rodents with damage to the hippocampus recognize previously experienced objects but cannot remember the context in which an object was experienced. This result suggests a modular organization of the MTH system.

7. What Happens When Memories Age?
What happens to episodic memories as they age? Should they stay or should they go?
In some cases the memory trace is likely lost.
However, in some cases the trace might endure or even strengthen.
The outcome depends in part on the content.
Much of what is initially stored is of no significance and can be lost without any consequence.

8. Ribot’s Law
Ribot’s Law: Ribot also proposed that old memories are more resistant to disease/disruption than new memories.

9. The MTH System and Ribot’s Law
Ribot’s Law suggests that as memories age they become resistant to disruption (see Chapter 1). By itself this claim is not surprising because (a) the experience that produced the initial memory is more likely to be repeated and (b) older memories, compared to new memories, are more likely to have been recalled a few times. Both of these factors would increase the strength of the memory. However, in the modern era, Ribot’s Law has been nuanced to give an explicit role for the MTH system in protecting old memories from disruption. So, we will examine this position.

10. The Standard Model of Systems Consolidation
David Marr (center) was the first neuroscientist to suggest a role for the hippocampal system.
However, Squire, Cohen, and Nadel (1984) are primarily responsible for the spread of this idea.
Based primarily on the patient H.M, who was originally thought to have a temporally limited retrograde amnesia, they proposed what is now called the standard model of systems consolidation.

11. The Standard Model of Systems Consolidation
A schematic representation of the standard model of systems consolidation. Initially the memory trace consists of weakly connected neocortical representations of the features (purple circles) of the experience held together by their temporary connections with the medial temporal hippocampal (MTH) system. New memories require the MTH system for retrieval. As the memory ages, intrinsic processes result in the consolidation or strengthening of the connections among the neocortical representations. Because of the strengthened connections the memory can now be retrieved without the hippocampus.

12. Cellular and Systems Consolidation
Two types of processes are thought to contribute to the consolidation of long-term stability of memories.

13. Challenges to the Standard Model
These graphs illustrate patterns of results that would either support or be evidence against the standard model of systems consolidation. (A) This pattern would support the model because it shows that damage to the hippocampus results in temporally graded retrograde amnesia. (B) This pattern would be evidence against the standard model because it shows that damage to the hippocampus produces a flat retrograde amnesia.

14. Challenges to the Standard Model
After reviewing the post H.M. patient literature, Lynn Nadel and Morris Moscovitch concluded that both old and new episodic memory always depend on the hippocampus. This is because patients with almost complete damage to the hippocampus could not recall either new or old episodic memories. Some evidence for old episodic memories was found in patients with only partial damage to the hippocampus.

15. Patient V.C
This figure illustrates V.C.’s flat retrograde amnesia for recall of famous public events. This memory test was conducted in Control subjects were chosen to match V.C.’s age and educational level.

16. Patient H.M. Revisited
When Suzanne Corkin reexamined Henry Molaison, she found that his old episodic memories were not spare.

17.   Multiple Trace Theory
The assumptions of the multiple trace theory of systems consolidation. Old memories still depend on the hippocampus but are more resistant to disruption because they have had more opportunity to be reactivated than new memories, and each reactivation generates another index in the hippocampus. Because these copies are distributed, the memory can survive partial but not complete damage to the hippocampus and will be more resistant to other insults such as a brain concussion.

18. Other Evidence: Human Brain Imaging
The figure on the right illustrates the predictions that the standard model (SM) and multiple trace theory (MTT) of systems consolidation make about activation in the medial temporal hippocampal (MTH) system. Multiple trace theory predicts that retrieval of both new and old memories should activate the MTH system. The standard model predicts that the retrieval of only new memories should activate the system.
Figure 17.9 (A) In functional magnetic resonance imaging (fMRI) the participant’s head is placed in the center of a large magnet. A radiofrequency antenna coil is placed around the head to excite and record the magnetic resonance signal of hydrogen atoms. Stimuli can be presented to the subject using virtual reality video goggles and stereo headphones. fMRI is based on the fact that hemoglobin in the iron-containing, oxygen-transport metalloprotein in the red blood cells slightly distorts the magnetic resonance properties of hydrogen nuclei in the vicinity and the amount of magnetic distortion changes, depending on whether the hemoglobin has oxygen bound to it. When a brain area is activated by a specific task, it begins to use more oxygen and within seconds the brain microvasculature responds by increasing the flow of oxygen-rich blood to the active area. These changes in the concentration of oxygen and blood flow lead to what is called a blood-oxygenation level-dependent (BOLD) signal—changes in the magnetic resonance signal. (B) fMRI activity during a hand-motion task. Left hand activity is shown in yellow and right hand activity is shown in green. (Photo and images from Purves et al., 2012.)

19. Interpreting Imaging Data: A Caveat
The human imaging data supports the multiple trace theory. However, it does not rule out the standard model.
Suppose, as the standard model assumes, that an old memory is retrieved directly from the neocortical sites. Once these sites are activated they will project to the MTH system to cause activation there. If this happens, then the activity in the MTH system will not reflect retrieval of the memory through activating the existing index but instead will reflect the retrieval experience laying down a new copy of the trace—generating a new index.

20. Advantages of Animal Studies
Provide animals with a known behavioral experience
Vary the exact time between the experience and the occurrence of the brain damage
Vary the extent of the brain damage
It is also hold constant the length of time between when the brain is damaged and when the animals are tested.

21. Contextual Fear Studies Provide No Support for the Systems Consolidation View
(A) These images illustrate the extent of the damage to the hippocampus. (Images courtesy of Robert Sutherland.) (B) These data show that over the 6-month retention interval, control rats showed evidence of forgetting. Note, however, that there was no evidence that the 3-month and 6-month-old memories were protected from damage to the hippocampus.

22. Optogenetic Control of Remote Memories
Optogenetic inhibition
% Freezing
Cued Fear Memory
Old Contextual Fear Memory
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Light on 60 40 20 30 10
Optogenetic inhibition of CA1 neurons has no effect on retrieval of a cued fear memory, but blocks the retrieval of an old contextual fear memory. Implication: under normal conditions, hippocampal neurons are always involved in the retrieval of old contextual fear memories.

23. Distributed Conditioning Sessions Spare New Memories from Damage to the Hippocampus
In this contextual fear experiment, rats were shocked 3 times. In the 1-session group the rats were placed in the context and given all 3 shocks in a single session. In the 3-session condition the shocks were distributed over 3 sessions separated by 24 hours. Twenty-four hours after the trainings, the rats were assigned to either a sham surgery control condition or surgery that damaged the hippocampus. Several days later they were tested for contextual fear. Note that damage to the hippocampus did not impair contextual fear in rats in the 3 session condition.
Implication
This finding reinforces an important point: the hippocampus is required to rapidly form episodic memories. However, other brain regions also can capture representations of experience when the experience is often repeated or recalled.
Sham
Hippocampus
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1 Session sessions

24. The Complementary Learning System View
This view assumes that different learning systems evolved to serve different and sometimes incompatible functions. In this context, appropriate behavioral adaptations require one memory system that can rapidly acquire information about single episodes and another system that gradually collects information about repeated experiences to build representations of stable features of the environment. The complementary memory systems framework provides a natural way of understanding how memories can become independent of the MTH.

25. The Age of the Memory: Summary
Thus, this animal literature is consistent with the human literature, indicating that episodic memories always require the hippocampus. The hippocampus is required to retrieve new and old episodic memories. Nevertheless, neocortical regions can support memories for experiences that might also be captured by the hippocampal system. Such cortical representations may be the result of repeated experiences or repeated recall and can be retrieved without a functioning hippocampus, regardless of their age. This conclusion suggests that the age of a memory has limited value in explaining the resistance of a memory trace to disruption. Other variables such as repetition and frequency of reactivation or recall of the memory, which are more likely to be the case for old memories, are probably the important variables.