Neurobiology of Memory and Classic Cases

Question 1

Atkinson & Shiffrin (1968)

Answer 1

• Proposed information flows through sensory form, into short-term storage and then short-term memory
• Sensory information is subject to decay (disappear if due to lack of attention)
• Storgae of sensory information is only possible through attention and then stored in short-term storage
• Information is pushed out of short-term storage by more information or rehearsed and retained in long-term storage
• Long-term storage is lost due to interference - confuse information with other information

Question 2

Warrington and Shallice (1969) - Patient K.F

Answer 2

• Brain damage demonstrated certain incompatibilities with Atkinson and Shiffrin (1968) model
• K.F had a digit span of 2 (normal is 6-8 items)
• Difficulty in short-term storage but was able to remember long-term information
• Had normal learning abilities
• The idea of flow from short-term storage to long-term storage is incompatible with K.F

Question 3

H.M patient overview

Answer 3

• Epiletic who had left and right medial temporal lobes removed: bilateral medial temporal lobectomy
• His seizures were dramatically reduced but so was his long-term memory
• Experienced both mild retrograde amnesia and severe anterograde amnesia
• While H.M was unable to form most types of new long-term memories (LTM), his short-term memory (STM) was intact and also had procedural memory.

Question 4

Retrograde amnesia

Answer 4

• Unable to remember the past (before H.M surgery)

Question 5

Anterograde amnesia

Answer 5

• Unable to form new memories

Question 6

Assessing H.M - Short Term Memory

Answer 6

• Digit Span
  
  • If he was asked to read a series of number, he could repeat them back in order, providing that the time between them being read to him and him having to repeat them back was within a duration of short-term memory (immediate essentially)
  • H.M. could repeat digit provided time between learning and recall is within the duration of STM i.e. Immediate recall
• Block-tapping memory-span test
  
  • Demonstrated H.M STM fucntion was good for spatial information - with immediate recall
• Short-term/working memory okay for both verbal and visual spatial information

Question 7

Assessing H.M - Long Term Memory

Answer 7

• Digit Span: does not benefit from repeated testing
• Block-tapping memory-span test: does not benefit from repeating testing
• Suggesting amnesia is global, not limited to one sensory modality when it comes to LTM

Question 8

Evidence of new learning - H.M patient tasks

Answer 8

• Mirror tracing
• Rotary pursuit
• Incomplete pictures

Question 9

Evidence of new learning H.M - Mirror Tracing

Answer 9

• Required to trace between two lines, an outline of an image. Difficult to do when you can’t see what you’re drawing or where your pencil is, except through feedback from a meter
• H.M. was able to do this task with some effort and then showed improvement after a number of trials
• When H.M. came back and was tested again and again, he wasn’t starting at baseline. He had learned and was producing less errors and took less time than he had the first time, performance improved over the course of the day.
• So he was performing and learning this new skill normaly, so retained that learning.

Question 10

Evidence of new learning H.M - Pursuit rotor task

Answer 10

• You have to keep a stylus on a rotating target.
• He could also do that and improved over a learning trial period
• HM cerebellum was not damaged by the operation that might be of importance.

Question 11

Evidence of new learning H.M - Incomplete pictures task

Answer 11

• Shown a series of images that are in a degraded form. So they’re just basic outline shapes that you didn’t really know what this is.
• Then you’re showing them again and again until a point at which you can identify them and then for those that you’ve been unable to identify your shown more until you can’t identify them.
• Then people are showing them again and can identify them at a lesser stage because they’ve been exposed to them before
• He’s making a number of errors when seen in the degraded forms and less errors when he’s being shown the fuller forms and then when he is retested he’s making fewer errors on the very degraded form, so he’s making more identification and then fewer errors and the second most degraded forms and so on.

Question 12

Scientific contributions of H.M.’s case

Answer 12

• Medial temporal lobes are involved in memory
• STM and LTM are distinctly separate - H.M. Is unable to move memories from STM and LTM, a problem with memory consolidation
  
  • Double dissociation with K.F.
• Memory may exist but not be recalled - as when H.M. exhibits a skill he does not know he has learned (dissociation between explicit and implicit memory

Question 13

Episodic and semantic Memory

Answer 13

• Unlike episodic memory, semantic memory does not involve conscious recollection of the past
• Extent of amnesia effects on each is different
  
  • Episodic memory generally suffers more greatly (e.g., Spiers et al., 2001; Tulving, 2002; Vargha-Khadem et al., 1997)
  • But some patients show more specifically semantic memory deficits (e.g., Yasuda et al., 1997)
• Different involvement of brain areas during encoding and retrieval (Wheeler et al., 1997)

Question 14

Autobiographical Memory

Answer 14

• A double dissociation between impairments of personal and semantic memory has been observed (Dalla Barba et al., 1990; De Renzi et al., 1987; Hodges & McCarthy, 1993)
• Neuroimaging data suggest that:
  
  • Visual imagery and emotion centres in the brain, as well as frontal areas involved in self-referential processing, are important for autobiographical memories (Cabeza et al., 2004; Conway et al., 2003; Greenberg et al., 2005)

Question 15

Amnesia: A Modal Model

Answer 15

• Baddeley (see 2001) summarised a ‘modal model’ that accounted for most of the findings:
  
  • Episodic memory learning involves associating items with their context using ‘mnemonic glue’ to tie episodes to context
  • Recall and recognition involve the same underlying storage processes
  • Semantic memory built from episodic memory

Question 16

A Problem for the Modal Model of Amnesia?

The case of Jon

Answer 16

• Developmental amnesia due to premature birth and anoxia (deprived of oxygen), which resulted in specific, severe hippocampal damage
• Memory problems appeared obvious from age 5
• However, above average intelligence, good semantic memory
• Impaired recall, but largely intact recognition
• Does not retain or experience episodic memories and the idea that these episodic memories accumulate to create a semantic representation that just doesn’t seem to account for John.
• With double dissociations and the different temporal gradients, it seem to be evidence for dissociable, episodic and semantic systems within long-term memory
• Jon highlights is the importance of the hippocampus in episodic memory

Question 17

Effects of Cerebral Ischemia on the Hippocampus and Memory

Answer 17

• R.B patient is a consequence of an operation that went wrong. He had cerebral ischemia (his brain wasn’t supplied with blood, which damages cells).
• R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell layer) and developed amnesia
• R.B.’s case suggests that hippocampal damage alone can produce amnesia
• H.M.’s damage – and amnesia – was more severe than R.B.’s

Question 18

Amnesia after Concussion: Evidence for Consolidation

Answer 18

• Posttraumatic amnesia
  
  • Concussions may cause retrograde amnesia for the period before the blow and some anterograde amnesia after
  • The same is seen with comas, with the severity of the amnesia correlated with the duration of the coma
  • Period of anterograde amnesia suggests a temporary failure of memory consolidation

Question 19

Gradients of Retrograde Amnesia and Memory Consolidation

Answer 19

• Concussions disrupt consolation (storage) of recent memories
• Hebb’s theory - memories are stored in the short term by neural activity
• Interference with this activity prevents memory consolidation. Examples:
  
  • Blows to the head (i.e., concussion)
  • ECS (electroconvulsive shock)

1. A blow to the head produces coma
2. When victim regains consciousness there is a period of confusion
3. When confusion ends, the victim has retrograde emnesia for events that occured before blow and anterograde amnesia for events that occured during confusion

Question 20

The Hippocampus and Consolidation

Answer 20

• Proposal that the hippocampus stores memories temporarily (standard consolidation theory)
• Consistent with the temporally graded retrograde amnesia seen in experimental animals with temporal lobe lesions
• Or, perhaps the hippocampus is involved in establishing memories, but they become “stronger” and less dependent on hippocampus over time

Question 21

Neuroanatomy of Object-Recognition Memory

Answer 21

• Early animal models of amnesia involved implicit memory i.e recognition memory and assumed the hippocampus was key
• 1970s – monkeys with bilateral medial temporal lobectomies show LTM deficits in explicit memory, the delayed nonmatching-to-sample test
• Like H.M., performance was normal when memory needed to be held for only a few seconds (within the duration of STM)

Question 22

Delayed non-matching-to-sample test for monkeys

Answer 22

• Monkey is presented with an object and underneath the object is food and after a delay/ distraction
• The monkey then has two objects, one of which it saw before with food underneath it, and then also an unfamiliar one and in order to get a food reward, it has to recognize that it’s seen an object before and not use that object.
• But instead, look to the unfamiliar object in order to get food.
• In monkeys that didn’t have these bilateral medial temporal lobectomies, they can learn this task quite quickly. And in fact, when they were given lobectomies, they could perform this task initially as well. So when there was only a very brief interlude and no destruction than monkeys could do the task.
• But if you put in delays or even just a minute or so, if you had the distraction, then the demonstrated impairments (couldn’t go for unfamiliar object)

Question 23

Object-Recognition Deficits and Medial Temporal Lobectomy

Answer 23

• Neuroanatomical basis of resulting deficits:
  
  • Bilateral removal of the rhinal cortex consistently results in object-recognition deficits
  • Bilateral removal of the hippocampus produces no or moderate effects on object recognition
  • Bilateral removal of the amygdala has no effect on object recognition
• An explicit memory is being tapped and affected by surgery to the medial temporal cortex

Question 24

Hippocampus and Memory for Spatial Location (Morris water maze)

Answer 24

• Rats placed in pool filled with milky water
• Hidden platform that allows the rats to escape
• Healthy rates learn quickly where the platform is and swim directly to it, and are faster at learning on similar tasks
• Rats with hippocampal lesions never learn where the platform is and show no benefit on similar tasks

Question 25

Hippocampus and Memory for Spatial Location

Answer 25

• The rhinal cortex plays an important role in object recognition.
• The hippocampus plays a key role in memory for spatial location
  
  • Hippocampectomy produces deficits in Morris maze and radial arm maze performance.
• Many hippocampal cells are place cells, responding when a subject is in a particular place (and to other cues).
  
  • Grid cells are also found in the entorhinal cortex.

Question 26

Brain structure that supports learning

Answer 26

Amygdala

Question 27

Classical Conditioning

Answer 27

• Amygdala is linked to different types of learning
• Classical conditioning changes the response of neurons to the conditioned stimulus and that change and neuron response is mediated by long-term potentiation
• We can see that when we inhibit long-term potentiation in the amygdala. Or lesion, the amygdala can inhibit classical conditioning
• Hippocampus is broadly understood to be instrumental in learning and memory

Question 28

Hebb (1949)

Answer 28

• Proposed that changes in synaptic efficiency are the basis of LTM
• Long-term learning comes about from cell assemblies (creation of links between cells and groups of cells and the building of relationships) thought to occur when cells are excited at the same time and that excitation can be communicated between them
• Simultaneous excitation of two or more cells
• “neurons that fire together wire together”! - establishment of connection through excitation that will give you a long-term relationship

Question 29

Synaptic Mechanisms of learning and memory

Answer 29

• Long-term potentiation (LTP) is consistent with the synaptic changes hypothesized by Hebb.
  
  • Synapses are effectively made stronger by repeated stimulation.
  • LTP can last for many weeks.
  • LTP only occurs if presynaptic firing is followed by postsynaptic firing.

Question 30

LTP as a Neural Mechanism of Learning and Memory

Answer 30

• Required intervention where they would place an electrode into an axon of cells that were terminating on cells of interest and the dentate gyrus of the rat
• Elicited by High-Frequency Electrical Stimulation of Presynaptic Neuron; Mimics Normal Neural Activity
• LTP effects are greatest in brain areas involved in learning and memory.
• Learning can produce LTP-like changes.
• Much indirect evidence supports a role for LTP in learning and memory.
• Observation of Associative LTP
• LTP can be viewed as a three-part process.
  
  • Induction (learning) - is when the stimulation and the associated processes happen that create the long-term potentiation
  • Maintenance (memory) - changes that happen in the cells
  • Expression (recall) - underlie the altered response in the cells

Question 31

Induction of LTP: Learning

Answer 31

• Requires activation of the synapses and depolarization of the postsynaptic neuron, so excitatory transmission where it is mostly studied in the hippocampus - occurs largely through glutamate receptors, AMPA and NMDA receptors
• Most Commonly Studied Where NMDA Glutamate Receptors Are Prominent
• NMDA receptors do not respond maximally unless glutamate binds and the neuron is already partially depolarized. - for NMDA receptors to respond maximally. And so that would be their peak response and allow calcium ions to flood into the cell.
• The glutamate has to bind to these receptors on the postsynaptic membrane has to be depolarized enough in order to displace magnesium ions that are otherwise clogging up the NMDA channels.
• Ca2+ channels do not open fully unless both conditions are met.
• Two requirements:
  
  • Glutamate has to bind
  • Depolarization of the cell has to be present

Question 32

When does Ca2+ occur

Answer 32

• If there is the co-occurrence that is needed for LTP, leading to the binding of glutamate at an NMDA receptor that is already depolarized.

Question 33

Ca2+ influx may activate

Answer 33

• Protein kinase C
• And CaM-KII
  
  • that induce changes, causing LTP.

Question 34

Explain this image:

Answer 34

• The influx of calcium ions through the channels and the NMDA receptors.
• When that happens it triggers then an action potential in the postsynaptic neuron.
• So you can see the difference in this image. And a cell that is not depolarized.
• The NMDA receptors are not allowing the calcium ions to come in.
• In a cell that is depolarized, then more calcium is enabled to come through the channels.
• There’s just more space and the large numbers of calcium ions that come in, they activate protein kinases (essentially enzymes are activated) and they strengthen existing AMPA receptors.
• Enables more AMPA receptors to be insert

Question 35

Maintenance and Expression of LTP: Storage and Recall

Answer 35

• Long-term changes occur in the Pre- and Postsynaptic Changes
• LTP is only seen in synapses where it was induced.
• Protein synthesis (structural changes) underlies long-term changes. - can increase the number of synapses and can change the membrane as well of the pre- and postsynaptic membranes
• LTP begins in the postsynaptic neuron, which signals the presynaptic neuron.
• How are presynaptic and postsynaptic changes coordinated?
  
  • Nitric oxide synthesized in postsynaptic neurons in response to Ca2+ influx may diffuse back to presynaptic neurons.
  • Structural changes are now a well-established consequence of LTP.

Question 36

Variability of LTP

Answer 36

• Fundamental to our understanding of these proposed cell assemblies that have put forward can happen.
• Most LTP research has focused on NMDA-receptor–mediated LTP in the hippocampus, but LTP is mediated by different mechanisms elsewhere.
• LTD (long-term depression) also exists - response to where there’s ongoing and repeated low-frequency stimulation from presynaptic neurons that has a different effect
• Much of LTP and the neural basis of memory is still a mystery, despite many research discoveries.