Learning and Memory

Learning and Memory

Learning and Memory • What is learning? • Changes in our nervous system as a result of experiences • What is memory? • How these changes are maintained over time and how they are expressed (recall) • Are they different? • Yes, but they are interconnected… • You can’t have memory if you have not learned anything • But, can we have learning if we have no memory? • Perhaps only at birth? • My thoughts: • Learning and memory make up who we are • We are who we are because of all of the experiences we have had throughout our lives that have changed us…for better or worse

How we study Learning & Memory • Amnesia: The loss of memory, incapable of remembering • Retrograde Amnesia • Inability to remember events prior to injury (i.e., some sort of damage to your brain) • Can’t remember your past • Anterograde Amnesia • Inability to remember events after injury • Can’t form new memories Injury Retrograde Amnesia Anterograde Amnesia Time-line of events in one’s life

The Case of HM • Bilateral Medial Temporal Lobectomy • Removed his medial temporal lobes (MTL) bilaterally to alleviate serious epilepsy (1953) • Hippocampus • Amygdala • Rhinal Cortical Areas • Epilepsy improved • He was last patient to receive this treatment • Why, you might ask?

The Case of HM • After surgery: • Intellect was above average • IQ actually improved from 104 to 118 • Normal perceptual and motor abilities • Well-adjusted individual • BUT, • He was left with very poor memory abilities • Mild retrograde amnesia (~ 2 years prior to surgery) • Profound anterograde amnesia

The Case of HM • Brenda Milner (1965) • “As far as we can tell, this man retained little if anything of events subsequent to the operation… Ten months before I examined him, his family had moved from their old house to a new one a few blocks away on the same street. He still had not learned the new address (though remembering the old one perfectly), nor could he be trusted to find his way home alone. He did not know where objects in constant use were kept, and his mother stated that he would read the same magazines over and over again without finding their contents familiar… Forgetting occurred the instant the patient’s focus of attention shifted.”

The Case of HM • HM is the most famous patient in the history of neuroscience research. • He has served as an invaluable teacher of the neurobiology of memory and has been extensively tested for over 50 years. • Demonstrated that the medial temporal lobe is critical for forming new memories. • But, what can HM do?

Many Forms of Memory How Long the Memory Lasts Short-Term Memory (seconds – minutes) Long-Term Memory (hours – years) Working Memory (active maintenance)

What Can HM Do? • Remember a list of 6-7 digits • Digit-Span + 1 Test • Performance in normal range • Tap a sequence of 5 blocks • Block-Tapping Memory Span Test • Performance in normal range So, HM has relatively intact short-term memory Milner (1965): “… Forgetting occurred the instant the patient’s focus of attention shifted.”

Many Forms of Memory How Long the Memory Lasts Short-Term Memory (seconds – minutes) Long-Term Memory (hours – years) Not OK in HM? Working Memory (active maintenance) OK in HM

Many Forms of Memory Long-Term Memory Declarative (explicit): things you know that you can tell others Procedural (non-declarative, implicit): things you know that you can show by doing Conditioning:salivating when I see a nice steak! Priming:more likely to use a word you heard recently Skill Learning:skiing, riding a bike Semantic:the name of the 44th president Episodic:breakfast this morning OBAMA!

What Can HM Do? • HM can learn new behavioral skills • Mirror-Drawing Task • HM’s performance improves with training sessions • Normal sensory-motor learning • He has no conscious recollection of ever performing it before

What Can HM Do? • HM can learn new behavioral skills • Rotary-Pursuit Test • HM’s performance improves with training sessions • Normal sensory-motor learning • He has no conscious recollection of ever performing it before

What Can HM Do? • HM can show normal priming • More likely to use a word if you have heard it recently • Repetition Priming Test • He has no conscious recollection of the words on the original list Examine List of Words: Puppy Mushroom Pancake Salsa Spicy Fill in the Blanks: __us__r__o__m

What Can HM Do? Recognition • HM can show normal recognition memory and priming • Incomplete Pictures Test

What Can HM Do? Priming Recognition • HM can show normal recognition memory and priming • Incomplete Pictures Test

What Can HM Do? • HM can learn conditioning tasks • Pavlovian Conditioning • HM’s performance improves with training sessions • He has no conscious recollection of ever performing it before Prior to Eye-Blink Conditioning: Tone (CS) ≠ Eye Blink (UR) Training: Tone (CS) + Air Puff (US) = Eye Blink (UR) Conditioned State: Present Tone (CS) alone = Eye Blink (CR)

Many Forms of Memory How Long the Memory Lasts Short-Term Memory (seconds – minutes) Long-Term Memory (hours – years) Not OK in HM? Working Memory (active maintenance) …sort of, but he can form some kinds of long-term memories… OK in HM

Many Forms of Memory Long-Term Memory Declarative (explicit): things you know that you can tell others Procedural (non-declarative, implicit): things you know that you can show by doing Conditioning:salivating when I see a nice steak! Priming:more likely to use a word you heard recently Skill Learning:skiing, riding a bike Semantic:the name of the 44rd president Episodic:breakfast this morning OK! OK! OK! OK! Impaired

What has HM Taught US? • Supported ideas that there are many different kinds of memory • Different brain regions seem to be more important for some kinds of memory, but not others • Forming (consolidating) new episodic memories is dependent on MTL

Multiple Memory Systems? Long-Term Memory • Why do we need 2 parallel memory systems? • Although subjects with MTL amnesia can form procedural (implicit) memories, they can not transfer that memory to a new or different context (situation) • Two parallel memory systems enables us to use the information we have gathered more flexibly. Declarative (explicit): things you know that you can tell others Procedural (non-declarative, implicit): things you know that you can show by doing

Other Case Studies • Patient RB • Ischemic brain injury during surgery • Suffered from MTL amnesia (similar to HM) • Killed cells in CA1 subfield of hippocampus • Perhaps it is just CA1 subfield of hippocampus that is important for forming new long-term episodic memories

Other Case Studies • Patient NA • Stabbed up the nose with a miniature fencing foil • Resulted in slight retrograde amnesia which got better over time • Also had anterograde episodic amnesia, but this was less consistent • Past events would spontaneously enter his consciousness • Damage restricted to medial diencephalon • Mammilary bodies of the hypothalamus • Mediodorsal thalamic nucleus

Other Case Studies • Korsakoff’s Syndrome • Observed in chronic alcoholics (vitamin deficiency) • Similar memory impairments as in MTL amnesia • Prominent anterograde amnesia (declarative memories) • But, severe retrograde amnesia develops later on in the course of the disorder • Damaged areas: • Mammilary bodies, mediodorsal thalamus, neocortex, hippocampus, & cerebellum

Other Case Studies • Alzheimer’s Disease • Memory deterioration greater than what is seen in a normal ageing population • More general than seen with MTL amnesia & Korsakoff’s Syndrome • Progressive and Terminal: eventually loose abilities to perform simple activities (eating, speaking, recognizing family, bladder control) • Anterograde & Retrograde amnesia for explicit memory • Impaired short-term memory & implicit memory for verbal and perceptual material • Sensory motor learning intact

Other Case Studies • Alzheimer’s Disease • Degeneration of acetylcholine-producing cells in basal forebrain • Amyloid plaques • Neurofibrillary tangles • Twisted fibers within neurons • Widespread cortical damage

Another Case Study • Clive Wearing • Herpes Encephalitis • Primary damage to hippocampus • Some damage to amygdala, temporal, and frontal lobes http://www.youtube.com/watch?v=5ObnErfTblY

Storing Memories • Overall, we have now seen that amnesia results from the inability to form new memories, or store them over time • But, what do we mean by storing a memory? • Memory Storage = Memory Consolidation • Change the memory from a labile/vulnerable state to a stronger, more permanent state • Donald Hebb (late 1940’s) • Postulated that memories are held in a short-term reverberating circuit until they are consolidated to last over a long period of time

Post-traumatic Amnesia: Evidence for Memory Consolidation • Concussion or Coma • Usually results in amnesia for events occurring just after regaining consciousness • Failure to convert short-term memories to long-term memories • Permanent retrograde amnesia for events just prior to the injury • Older memories are spared! • Suggests that these memories have been protected by some mechanism and are stronger than newly formed memories

Memory Consolidation • Electroconvulsive Shock (ECS) • Used to study memory consolidation with the assumption that disrupting neural activity would erase the memories that had not been consolidated yet • One-trial learning • Thirsty rats allowed to discover the location of water spout • ECS applied more than 1 hour after training did not disrupt memory for the location of water spout • Suggests that consolidation takes place within 1 hour

Memory Consolidation • Human studies show that ECS (used to treat severe depression) can disrupt memories up to 3 years old • Why are memories up to 3 years old affected by ECS?

Memory Consolidation • Human studies show that ECS (used to treat severe depression) can disrupt memories up to 3 years old • Suggests consolidation is a longer, ongoing process that takes more time than a short-term reverberating circuit would allow • Hebb’s basic postulate is likely incorrect • Reconsolidation: recalling a memory seems to put that memory into a more labile state that can still be disrupted before it is consolidated again

Reconsolidation Failures:Misinformation Effect • Loftus, Miller, & Burns (1978) • Subjects watched a video of a car accident. A sports car stopped at a yield sign. • Subjects were then interviewed 20 min – 1 week later • Consistent Condition: “Did another car pass the sports car while it was stopped at the yield sign?” • Neutral Condition: “Did another car pass the sports car while it was stopped?” • Inconsistent Condition: “Did another car pass the sports car while it was stopped at the stop sign?” • Subjects then shown pictures of a stop sign and a yield sign. Subjects had to point to the sign they saw in the video.

Reconsolidation Failures:Misinformation Effect • Loftus, Miller, & Burns (1978) • Consistent questions reinforced the correct memory • Inconsistent question deteriorated the correct memory • Biased subjects towards reconsolidating the incorrect memory!

Hippocampus and Consolidation • HM: • Temporally graded retrograde amnesia and severe anterograde episodic amnesia • Suggests that hippocampus and related cortical areas are important for consolidating episodic memories for long-term storage in other cortical areas • Over time, memories are stored in distributed networks of cortical areas and become less and less connected to the hippocampus • Engram – the change in the brain that represents a memory • The search for the Engram: Where is the memory stored? • Need to systematically test which brain areas are important for memory storage

Animal Models of Memory • Delayed Nonmatch-to-Sample Task: monkey version • Test of object recognition memory

Delayed Nonmatch-to-Sample Task • Monkey results are inconclusive • Damaged hippocampus, amygdala, and rhinal cortex • Rodent studies only damage small portions of parietal cortex, leaving rhinal cortex intact

Animal Models of Memory • Delayed Nonmatch-to-Sample Task: rodent version • Mumby Box • Test of object recognition memory

Object Recognition Engram? • Rodent studies suggest that recognition memory for objects is dependent on rhinal cortex, not hippocampus or amygdala • What is the hippocampus important for?

Hippocampus and Spatial Memory Morris Water Maze Pool “Hidden” Platform

Learning and Memory