PYB304 Memory: Learning, Memory, and Amnesia - Comprehensive Notes

Overview of Human Memory Systems

• Short-term Memory vs. Long-term Memory
• Declarative vs. Non-declarative Memories
• Relevant Brain Anatomy

Amnesia

• MTL Amnesia: Amnesia related to the Medial Temporal Lobe.
• Memory Consolidation: The process by which memories become stable.
• Roles of non-MTL Structures in Learning and Memory: The involvement of brain structures outside the Medial Temporal Lobe.
• Non-MTL Amnesia: Amnesia not directly related to MTL damage.
• Striatum: A structure implicated in implicit learning and memory.

Cellular Bases of Learning and Memory

• Long-Term Potentiation (LTP): A process relating to the strengthening of synaptic connections.

Memory Systems

• Short-Term Memory (Working Memory):
  • Keeps information active while you're using it.
  • Information is lost quickly without active rehearsal.
• Long-Term Memory:
  • Enduring storage of information.
• Declarative Memory (Explicit Memory):
• Non-declarative Memory (Implicit Memory)

Components of Memory

• Declarative (Explicit) Memory:
  • Facts.
  • Events.
• Nondeclarative (Implicit) Memory:
  • Skills and habits.
  • Priming.
  • Nonassociative learning.
  • Simple classical conditioning.

Declarative Memory System: Explicit Memory

• Involves intentional recollection of previous experiences.
• Conscious and accessed directly.
• Includes factual information (words, definitions, names, concepts, and ideas).
• Episodic Memory:
  • Events, chronological or temporally dated recollections of personal experiences (e.g., record of your activities).
• Semantic Memory:
  • Facts, contains general knowledge that is not tied to the time when the information was encoded (e.g., Christmas is in December, Sun rises in the east).

Non-Declarative: Implicit Memory

• Apparent when retention is exhibited on a task that does not require intentional remembering.
• Unconscious and accessed indirectly (i.e., driving a car for a number of years, riding a bike).
• Procedural: Skills and habits.
• Priming.
• Simple Classical Conditioning.
• Non-Associative Learning.

Long-Term Memory Types

• Nondeclarative (Implicit):
  • Cannot explicitly describe what was learned.
  • Change in task performance indicates memory acquisition.
  • Examples: motor skills, driving a car, riding a bike.
  • Relevant Structures: Striatum, Cerebellum
• Declarative (Explicit):
  • Facts (Neocortex, Medial Temporal Lobe, Diencephalon).
  • Events (Medial Temporal Lobe, Diencephalon).
• Procedural (Skills and Habits): Striatum.
• Priming: Neocortex.
• Simple Classical Conditioning:
  • Emotional Responses (Amygdala).
  • Skeletal Musculature (Cerebellum).
• Nonassociative Learning: Reflex Pathways.

Episodic vs. Semantic Memory

• Patient KC:
  • Diffuse brain damage from a motorcycle accident.
  • Intact semantic memory (general knowledge/facts).
  • Lost episodic memories (particular events of life).
  • Unique case of amnesia.
  • Details in Rosenbaum et al. (2005).

Amnesia

• Pathological Loss of Memory
• Can be caused by:
  • Head trauma.
  • Brain surgery (e.g., temporal lobectomy).
  • Chronic alcoholism (e.g., Korsakoff’s syndrome).
  • Brain infections (e.g., encephalitis).
  • Ischemia (lack of blood flow).
  • Hypoxia (lack of oxygen).
  • Dementia (e.g., Alzheimer’s disease).

Memory Loss Types

1. Retrograde Amnesia: Loss of memories for events before the onset of amnesia.
2. Anterograde Amnesia: Loss of memories for events after the onset of amnesia.

• Retrograde Amnesia: Loss of memory for events that occurred before the injury.
• Anterograde Amnesia: Inability to learn new things.

Medial Temporal Lobe (MTL)

• Structures:
  • Hippocampus.
  • Amygdala.
  • Perirhinal cortex.
  • Entorhinal cortex.
  • Parahippocampal cortex.
  • Anterior Thalamic Nuclei.
  • Mammillary Body.
  • Fornix.

Bilateral Medial Temporal Lobe

• H.M. Case:
  • Epileptic seizures from age 16.
  • Bilateral medial temporal lobectomy (removal), including parts of amygdala & hippocampus.
  • Minor retrograde amnesia for preceding 3 years.
  • Severe anterograde amnesia.

Formal Assessment of H.M.

• Tests Used to Assess H.M.’s Anterograde Amnesia:
  • Unconscious memory: H.M. demonstrated retention of tasks without conscious recollection.
  • Mirror-drawing.
  • Incomplete-pictures.
  • Matching to sample.
  • Pavlovian conditioning.
  • Digit span +1.
  • Block-tapping memory-span test.

Mirror Tracing Test

• H. M. had no conscious recollection of having performed the task before.

Matching-to-Sample Test

• No problem with letters after 40-second delay.
• Demonstrates H.M.’s reliance on verbal rehearsal.
• Could not match shapes after 5-second delay.
• Demonstrates further deficit for non-verbal material.

Incomplete-Pictures Test

• Although H.M. improved performance when he was retested, he had no conscious awareness of having previously seen the items.

Global Memory Deficit of H.M.

• H.M.’s anterograde amnesia is not total.
• Normal immediate digit span but:
  • Digit Span + 1 test: Attained only 7 digits, most normals get 15 digits.
  • Block-Tapping Memory-Span test: Attained 5 blocks, normal range, but could not get 6 blocks even after 12 trials.
• Demonstrates amnesia for non-verbal material

Medial Temporal Lobe (MTL) Amnesia

• Distinction between long-term and short-term memory.
• Distinction between declarative (explicit) and non-declarative memory (implicit).
• Role of the MTL in long-term declarative memory.
  • Recent memories are dependent on the MTL.
  • Remote memories are stored somewhere outside the MTL (memory consolidation).
• No loss of:
  • Remote (i.e., old) memories.
  • Short-term memory.
  • Non-declarative memory (implicit).

Memory Consolidation

• Patients with MTL amnesia often have lifelong anterograde amnesia, but their retrograde amnesia tends to affect a short time period only.
• This tells us three things about the MTL’s role in long-term declarative memory:
  1. MTL is important for forming new long-term memories.
  2. Newly formed memories are dependent on the MTL.
  3. MTL is not a permanent storage site for long-term memories.

Delayed Nonmatching to Sample Task

• Animal Studies: Focus on object recognition deficits in anterograde amnesia (e.g., Gaffan, 1974).
• Applied in research with monkeys, rats, & humans.
• Phase I:
  • Learn where desired object is (food underneath).
  • Variable delay.
• Test Phase:
  • Learn to select new (nonrecurring) item where desired object will be found.

Findings

• Normal monkeys: 90% correct performance with short retention intervals (less than a few minutes).
• Monkeys with bilateral medial temporal lobe lesions: performance falls to chance level with delays of a few minutes.
• Finding mirrors that with medial temporal lobe amnesia in patients.

Non-Medial Temporal Lobe Amnesia

• Korsakoff's Syndrome.
• NA Case Study.
• Alzheimer's Disease.
• Post-Trauma.

Korsakoff’s Syndrome

• Occurs as a consequence of alcohol abuse.
• Results in a range of problems:
  • Sensory and motor problems.
  • Disorientation and confusion.
  • Confabulation.
  • Personality changes.
  • Liver, gastrointestinal or heart disorders.
• Characterised by gradual onset and progressive decline in cognitive function.
• Severe retrograde and anterograde amnesia.

Korsakoff’s Syndrome Detail

• Degenerated diencephalon.
  • Particularly dorsomedial nucleus of thalamus and medial hypothalamus.
• Thiamine deficiency.
• Severe retrograde AND anterograde amnesia (mainly episodic).
• Slow development: amnesia onset?
• Temporally graded retrograde amnesia.
• Deficit in explicit memory.
• Damage can extend to frontal lobes (Squire, 1982): deficit in temporal ordering.

Brain Damage in N.A.

• Small fencing foil up his nose.
• Damage to hypothalamus and mammillary bodies.
• Verbal deficits.
• Inability to understand language and communication.

Alzheimer’s Disease.

• Pathology: neurofibrillary tangles & amyloid plaques, reductions in neurotransmitters.
• Reduction in cholinergic activity (degeneration of neurons in basal forebrain).
• Progressive and terminal → dementia.
• Deficits:
  • Progressive amnesia (anterograde and retrograde).
  • Explicit memory deficits and some implicit memory deficits (verbal and perceptual).
  • Sensorimotor learning ok.

Alzheimer’s Disease II

• More General Symptoms
  • Can involve short term as well as long term memory.
  • Declarative and episodic.
  • Generally procedural and sensorimotor learning.
• Initially, mild loss of memory (Predementia Alzheimer’s), both anterograde and retrograde amnesia.
• Short-term and implicit memory deficits.
• Eventually incapacitates patient.
• Brain damage is diffuse across the brain

Post-Traumatic Amnesia

• Confusion on regaining consciousness
• Cannot remember time right before incident (retrograde).
• Things that happened in and since onset of confusion (anterograde).
• Confusion period lasts longer than time spent in coma
• Coma: after severe blow to head, can loose consciousness for seconds, minutes or weeks
• Concussion: temporary disturbance of consciousness produced by non- penetrating head injury

Post-Traumatic Amnesia

• Loss of consciousness & shrinking (but permanent) retrograde amnesia, & anterograde amnesia.
• Also seen following ECS (Electroconvulsive shock) treatment.

ECS Treatment & Retrograde Amnesia

• ECS results in graded retrograde amnesia: greater for near events.
• At short intervals: suggests disruption of reverberating neural activity (Hebb, 1949) - prevents structural changes at synaptic level
• However, long gradients have been demonstrated. Nadel & Moscovitch (1997): hippocampal involvement, links critical circuits and provides spatial context

Non-Declarative Memory in the Brain

• There are many forms of non-declarative (implicit) memory, so many brain areas are involved in them
• Some examples:
  • Cerebellum: sensorimotor skills
  • Striatum: stimulus-response associations

Striatum

• Important for learning and retrieving;
• Specific responses that are to be made in response to specific stimuli
• Example: spatial navigation

Striatum and Spatial Navigation

• Identify object locations within a larger environmental framework
• Rapidly acquired, allows flexible behavior (e.g., short-cut), but requires conscious retrieval and susceptible to forgetting
• Similar to declarative memory
  • Mental map – Landmarks
  • Hippocampus also involved Place strategy
• Perform a specific sequence of action
• Slow to learn, only rigid behavior is possible, but does not require conscious awareness and much longer-lasting
• Similar to non-declarative memory
  • Response to a sequence of actions and cues – habit forming
  • Response = Reward Response strategy

Striatum and Spatial Navigation

• By selectively lesioning the MTL and caudate nucleus, we can manipulate which navigation strategy is used by animals (Packard & McGaugh, 1996)
• That is:
  • MTL: important for place strategy (declarative memory)
  • Caudate nucleus: important for response strategy (non- declarative memory)

Response Recognition (Caudate Nucleus)

• Memory for own response
• Reward only if turn made to same side of body as before

Hippocampus and Spatial Memory I

• Place cells
  • O’Keefe and Dostrovsky (1971)
  • Cells specific to hippocampus
  • Fire only when familiar with place, moving towards object, or object in specific location each cell acquires a place field
• Comparative studies
  • Larger hippocampi in food-caching species

Spatial Recognition (Hippocampus)

• Pre-training: Explore & find food at each end
• Study phase: run free
• Confinement period in centre [1-30sec]
• Test phase: open two arms. Food found only in recent arm.

Hippocampus and Spatial Memory II

• Cognitive Map Theory (O’Keefe & Nadel, 1978):
  • Hippocampus specialises in memories for spatial location, based on external location cues
• Configural Association Theory (Rudy & Sutherland, 1992):
  • Hippocampus plays a role in long-term retention of interrelations between cues.
  • Combination of cues, not individual cues

Long Term Memory Theory

• Hebb (1949): Theory on memory and in particular, long term memory
• Enduring changes in the efficiency of synaptic transmission are the basis of long-term memory
• Changes last for a long time
• Learning relies on co-occurrence of events
• IMPORTANT: pre-synaptic neuron must not only be active but must successfully produce a change in the post-synaptic neuron (Hebbian synapse)
• This co-occurrence results in progressively stronger synapses – i.e., learning

Cellular Bases of Learning and Memory

• Hebbian theory:
  • “neurons that fire together, wire together"
  • After repeated stimulation, synaptic transmission becomes more efficient
  • Hebb (1949) argued that this change is the basis of long-term memory
• Long-term potentiation (LTP)
  • Long-lasting facilitation of synaptic transmission

LTP and Memory

• The rate of growth in LTP is similar to the rate of behavioral improvement by learning
• LTP can be produced within seconds, and long- term declarative memory can be learned quickly too
• Both LTP and long-term memory can last for weeks (and longer)
• Organic level changes in the brain synapses
• Created following electrical pulse, stimulated “paths” (from pre-synaptic to post-synaptic neuron)

Long Term Potentiation

• Post synaptic neuron must be depolarized
• Glutamate: main excitatory neurotransmitter of the brain
• Glutamate must bind to NMDA receptor
• NMDA receptor: allows calcium ions (Ca^{+2}) through its central channel into post-synaptic neuron
• Calcium: activates protein kinases and sparks LTP
• Nitric oxide (NO): One possible retrograde signal from post-synaptic neuron to pre-synaptic neuron, signalling release of more neurotransmitters

Similarities Between LTP and Theorised LTM

Relationship Between LTP & Learning

• Can be stimulated by low level stimulation
• Primarily in the hippocampus
• Conditioning can produce LTP-like changes in hippocampal activity
• Drugs that affect memory and learning have like effects on LTP
• Rats with little LTP activity show poorer Morris maze learning
• LTP occurs at certain synapses implicated in learning in simple nervous systems

Memory Structures in the Brain

• Rhinal cortex: new LTM explicit memories (formation)
• Hippocampus: spatial information (formation)
• Amygdala: emotion
• Inferotemporal cortex: storage of visual patterns
• Cerebellum & striatum:
  • cerebellum: sensorimotor skills
  • Striatum (caudate nucleus & putamen; not shown): consistent mapping

Memory Structures in the Brain

• Prefrontal cortex:
  • temporal order
• Mediodorsal nuclei (thalamic nuclei)
  • Implicated in KS
• Basal forebrain
  • Implicated in AD