Lecture 15, 16: Memory Flashcards
Review: Name the parts pointed in the image below.
- A: Pyriform cortex
- B: Rhinal Sulcus
- C: Entorhinal Cortex
- D: Parahippocampal cortex
- E: Hippocampal sulcus
- F: Collateral sulcus
- G: Occipito-temporal sulcus
- H: Fusiform gyrus
- A, B, C together: Parahippocampal gyrus
Before the 1950’s how was the limbic medial temporal lobe called?
Rhinencephalon
(nose brain)
Where is the perihinal cortex?
Within the lateral bank of the rhinal sulcus.
In yellow in the image below.
How can you know where the entorhinal cortex ends and where the parahippocampal cortex begins?
The Perirhinal cortex ends at the same point where the retorhinal cortex ends.
Here is an image of the MTL in a Monkey.
What is the red line highlighting? And the blue?
Red: Amygdala
Blue: Hippocampus
What does MTL stand for?
Medial Temporal Lobes
What is the area of the brain which is most commonly found to be the focus/source for epileptic patients?
MTL
What is an alternative solution for epileptic patients whose medication is not enough?
Surgically remove the focus from where the epilepsy originates
The procedure which involves removing the focus from where epilepsy originates in patients was known as?
The Montreal procedure (thanks to Dr. Penfield at the MNI)
True or False
Since most epileptic patients had as source the MTL, it was common to do a bilateral anterior temporal lobe removal. Most patients would then recover and the seizures could be controlled with medication.
False.
Most procedures were unilateral removal of the anterior temporal lobe. H.M. had a bilateral removal which caused him to be unable to recover correctly.
True or False
Before H.M. no one had performed bilateral anterior temporal surgeries.
False, Sr. Scoville had performed the surgery although rarely.
Who was the doctor who operated on H.M.?
Dr. Scoville
What was the salient symptom of H.M.’s unsuccessful recovery?
He was unable to consolidate new memories
What was H.M.’s diagnosis?
Anterograde amnesia
True or False
Limbic MTLs are important for consolidation to long term memory but NOT for storage.
True
How did H.M.’s IQ was affected by the procedure?
H.M.’s IQ increased after the procedure. It is thought that since the seizures diminished to the point of them being able to be medically controlled, now the brain had enough resources to use its full potential.
Did H.M. lose all of his memories?
No, he could remember everything pre-operation although up to 1 or 2 years before the operation is more blurred.
Which parts of H.M.’s cognition were intact after the surgery?
Language, perception, motor control, attention
Who was Brenda Milner?
- PhD student of Hebb
- Tested Penfield’s patients at the MNI
- Worked with H.M. for 50 years (until his death)
What test with Milner made H.M. do which allowed her to test his motor learning abilities? What were the results and Milner’s conclusion?
- Mirror-drawing task
- Results:
- H.M. couldn’t recall having done the task previously but was improving every day
- Conclusion:
- Memory comes in different forms
What is the Mirror-drawing task?
- Consists of using the reflection of a mirror to draw within the lines of a star
- healthy people get better each day
What is declarative memory?
Declarative memory is episodic. It has to do with events, semantics, facts and knowledge.
Relies on the Limbic MTLs for consolidation
What is procedural memory?
- Procedural memory is a more general circuit that doesn’t only involve motor memory but also habits formation.
- It has to do with the behavioural response to a stimulus
- Depends on simple stimulus-response reward feedback.
- Relies on the Basal ganglia structures (reward)
- DOES NOT rely on the limbic MTLs for consolidation
What structures are involved in procedural memory?
-
Striatum
- Putamen
- Caudate Nucleus
- Globus Pallidus
-
Basal ganglia
- Striatum
- Amygdala
- other structures important for motor learning and procedural memory
What type of connections were identified to support procedural memory?
- Cortico-striatal pathway
- Unidirectional connections from cortex to all over the caudate nucleus
During the summer, your friend invited you to go on a bicycle ride. At this, you remember that your sister taught you on an old red bicycle your grandpa owned. To your surprise, after years of learning and not being on a bicycle, you still remember how to ride it.
Which aspects of your memory are procedural and which ones are declarative?
- Declarative:
- bicycle and bicycle ride (what it is/semantic)
- red, old bicycle
- sister taught you
- Procedural:
- know how to ride the bicycle
Given what you know about declarative knowledge and H.M. procedure, what can you conclude?
Since declarative memory relies on the Limbic MTLs to consolidate memories, it makes sense that H.M. couldn’t consolidate new declarative memories. On the other hand, given that the Striatum and the Basal ganglia were unaffected, H.M. was able to use his procedural memory and was capable of motor learning.
True or False
Global amnesia can be caused by unilateral and bilateral damage to the limbic MTL region.
False
Global amnesia only results from bilateral damage to limbic MTL region.
What does unilateral limbic MTL damage result in?
-
Material Specific impairment
- Verbal memory impairment (left)
- Nonverbal memory impairment (right)
Hebb came up with a way to test the short term memory span, what was it?
-
Reoccuring digit sequence test
- Hebb gave many numerical sequences that were of the length student’s span + 1. One of the sequences was repeated every so often.
- He noticed that the students would eventually memorize a sequence.
What did Philip Corsi do to test left unilateral limbic temporal damage?
- Establish the patient’s span
- Controlled for difficulty level by giving sequences that were span + 1
- One of the sequences was repeated every so often
- Results:
- LTh: as good as controls
- LTH: severely impaired
What do LTh and LTH mean?
- LTh:
- Lesion on:
- Temporal pole
- Amygdala
- very anterior hippocampus
- Lesion on:
- LTH:
- Lesion on:
- temporal pole
- amygdala
- much more hippocampus
- Lesion on:
True or False
Patient H.M. had an LTH lesion.
False,
LTH patients are capable of learning the sequence. They are just very slow at learning and require many repetitions.
What did Philip Corsi do to test right unilateral limbic temporal damage?
- Called spatial tapping sequence
- Procedure:
- Established the span for each patient
- Tested the patients on span + 1 sequences
- The experimenter would tap a sequence of blocks and the participant had to tap back the same sequence to the examiner
- Results:
- RTh: as good as controls
- RTH: severely impaired
What do RTh and RTH mean?
- RTh:
- Lesions on:
- Temporal pole
- amygdala
- anterior hippocampus
- Lesions on:
- RTH:
- Lesions on:
- Temporal pole
- amygdala
- much more hippocampus
- Lesions on:
How can we quantify the deficit of right limbic MTL damage?
With the spatial tapping sequence we could quantify the deficit based on the number of repetitions needed to learn a sequence.
Name another spatial memory task for unilateral MTL patients and who tested it?
- Dr. Mary-Lou Smith
- Procedure:
- Arrangement of dollar store objects on a table
- Patients had to point and name the objects and estimate the real-life price
- This was made to make sure that they attended to the objects
- The objects were then removed from the table, and after a delay, participants were asked to put them in the correct place
- Results:
- Left MTL: as good as controls
- Right MTL: RTH > RTh impaired
Remember:
- Scoville had operated bilaterally on the anterior temporal lobes and his patients had not had amnesia
- Each component of the limbic medial temporal lobes contributes to the consolidation process.
Notice that most damages to the hippocampus were not isolated, it was a larger area that was damaged. What did Mishkin suggested?
Maybe it is a combination of damages that causes the problem
In order to investigate this, animal studies were carried out.
What does H+ mean?
Hippocampus and overlaying cortex
What does A+ mean?
Amygdala and overlaying cortex
What did Mortimer Mishkin study regarding bilateral H+A+ lesions?
- Goal: determine the role of the hippocampus in the consolidation of declarative memory
- He imitated patients H.M.’s damage on animals and tested them on visual discrimination tasks
- They were able to learn this task!
What was the procedure of the test that Mishkin used to investigate the consolidation of declarative memory in bilateral H+A+ damage patients?
- Day 1:
- Show objects A and B, A hides food.
- Show objects C and D, D hides food
- Show objects E and F, E hides food
- Day 2:
- Exactly the same as day 1
- Day 3:
- Exactly the same as day 1
The initial test that Mishkin implemented to test declarative memory didn’t work. Why? What was he really testing?
- The task involved simple reward-feedback learning
- Procedural memory
What new test did Mishkin develop to really test declarative memory? What is the procedure?
- Called Delayed non-matching to sample task (DNMS task)
- Day 1:
- Trial 1:
- Show Object A
- Delay
- Show Object A and B, B has the food
- Trial 2:
- Show Object C
- Delay
- Show Object C and D, D has the food
- Trial 3:
- Show Object E
- Delay
- Show Object E and F, F has the food
- Trial 1:
How are we sure that DNMS tests declarative memory?
- The animal needs to remember what was presented before the delay
- Since objects are not repeated, the procedural memory is not used
Mishkin performed a variety of different bilateral lesions and observed the results.
Which lesions did he test and what were the results?
- A+ bilateral lesions:
- Could perform DNMS task
- A+H+ bilateral lesions
- Could not perform DNMS task
- H+ bilateral lesions
-
Could perform DNMS task
- This was surprising!
-
Could perform DNMS task
Mishkin performed a variety of different bilateral lesions and observed the results.
Which lesion caused discrimination impairment?
H+A+ only!
H+ did not caused an impairment!
What conclusion can you draw from Mishkin’s results after using the DNMS task?
The hippocampus is not the only responsible for memory
What was anatomically removed for each of Mishkin’s tests?
- A+
- 50% entorhinal/perihinal cortex removed
- H+
- 50% entorhinal/perihinal cortex removed
- H+A+
- Entire entorhinal/perihinal cortex removed
From the anatomy of Mishkin’s tests and the results he obtained from the DNMS task, what can you conclude?
- Hippocampus not most important for memory
- Maybe it is a combination of parts of the brain
Where is the Pes Hippocampus?
What results motivated the investigation of the entorhinal and perirhinal cortex? What did they find?
- Mishkin’s results
- Turns out that the entire neocortex has projections to the entorhinal/perirhinal cortex
What is the circuit that declarative memory follows?
- Neocortex → EC/PRC → Amygdala
OR - Neocortex → EC/PRC → Hippocampus
So EC/PRC is important for Processing familiarity of stimuli
True or False
Declarative memories are stored in the hippocampus
False
They are stored in the Neocortex
Who came up with the term cognitive map?
- John O’Keefe
- he found that specific neurons fire in the hippocampus when the rat is in a particular location
- Mapping the rat’s environment as the rat explores
- Conclusion:
- The hippocampus forms a spatial framework to which our experiences can be link
- NOTE:
- Not only where objects are but also spatial relations between objects
- NOTE:
- The hippocampus forms a spatial framework to which our experiences can be link
What the Olton noticed when he put rats with hippocampal lesions in the radial maze?
Rats couldn’t remember which branches they had previously visited.
With O’Keefe’s research, can we say that hippocampus in humans is JUST for spatial context?
No, since we have linguistic capabilities, it might be different from rodents.
Thus, a hypothesis is that the hippocampus is also important for language: semantic or linguistic context.
For example, names of landmarks, locations, etc…
So an extension to the hypothesis is that the left hippocampus is more linguistic context and right hippocampus more for non-linguistic/spatial context
As you walk through corridor B on your way to your class M you recognize a fellow student. You remember that they took class P with you and that their name is X. You also remember a feeling of anguish as he was a big bully.
What parts of declarative memory did you use?
- Hippocampus: left since remembering the name of the corridor and the class and right since you know that if you take corridor B you can get to your class.
- EC/PRC: since you recognize the student
- Amygdala: since you associate an emotion to the person
What are the structures involved in procedural memory?
-
Striatum
- Putamen
- Caudate Nucleus
- Globus Pallidus
-
Basal Ganglia
- Striatum
- Amygdala
- other structures important for motor learning and procedural memory
Note: cortex has unidirectional connections to all over the caudate nucleus (cortico-striatal pathway)
True or False
Procedural and Declarative memories are parallel processes
True
True or False
To learn tasks that involve reward, the animals rely on their amygdala to process the feeling of reward. Thus, animals that do not have an amygdala are unable to learn reward-based tasks.
False!!!
Turns out that the amygdala is not required for reward feedback. It only process the pleasurable aspects of reward.
Here is a table for you to distinguish VD task and DNMS task:
Postmortem examination of H.M.’s brain
Annese et al. 2014 (from class)
- Removed 14hours post-mortem (pertinent to mention this)
- In-vivo MRI, resolution not strong enough to show the surgical damage
- Post-mortem can be scanned for longer time
- Before cutting, embedded in gelatin at -40 degrees celsius
- Cut over 53 hrs
- section was 70µm thick
- 2401 sections
- For every section, a photo was taken
- anatomical images
3D reconstruction of H.M.’s brain
(Annese et al. 2014 from class)
- Reconstruction by putting images together
- reconstruct a 3D surface of the remaining hippocampus in each hemisphere
-
histological sections
- on glass slides and stained with Nissl stain to see cell bodies
What was revealed after the post-mortem analysis?
- More of the hippocampus was left intact than intended
- Most EC was removed in both hemispheres
- Hippocampus was cut off from the rest of the neocortical input
- Slight damage to the left orbitofrontal cortex
- probably due to insertion of surgical tool
