Module 11 - Learning, Memory, and amnesia

Neuroplastic processes

Learning and memory, deal with the ability of the brain to change its functioning in response to experience.

Learning

The brain’s ability to change in response to experience

Memory

The brain’s ability to store and access the learned effects of experiences. Deals with how changes are stored and subsequently reactivated

Amnesia

Any pathological loss of memory, supports the research about the various brain structures involved in the processes of learning and memory

H.M’s memory changes

Medial portions of his temporal lobes were removed. Instrumental in the achievement of our current understanding of the neural bases of memory.

Bilateral medial temporal lobectomy

The removal of the medial portions of both temporal lobes, including the hippocampus, amygdala, and adjacent cortex

Lobectomy

An operation in which a lobe, or a major portion of one, is removed from the brain.

Lobotomy

An operation in which a lobe, or a major part of one, is separated from the rest of the brain via a large cut, but is not removed.

H.M’s treatment of seizures

Successful bilateral medial temporal lobectomy was successful in eliminating generalized seizures, focal seizures 1x per day, even though anticonvulsant medication was reduced. Left surgery with still normal perceptual and motor abilities, normal intelligence.

Retrograde amnesia

Backward acting, loss of memory for events or information learned before the amnesia-inducing brain injury.

Anterograde amnesia

Loss of memory for events occurring after the amnesia-inducing brain injury. Can influence short-term or long-term memory.

H.M’s memory loss

Mild retrograde amnesia for events in 2 years before surgery. Profound anterograde long-term amnesia. Could not form new memories of address, new people, events, etc.

Characterizing H.M’s anterograde memory problems

Digit span +1 with each new trial test: (could not get to 8 digits after 25 trials, most people can repeat 15 accurately after 25 trials)

Block-tapping test: (Tap a sequence of blocks, could not learn to touch a sequence of 6, even after 12 trials, most can)

Mirror drawing test: His performance on a task of tracing the shape of a star on a mirror improved after consecutive days, but did not recall ever having completed the task.

Incomplete-pictures test: Non-sensorimotor test, presented with fragments of pictures and need to identify the complete image. His recognition improved without conscious memory of doing the task.

Pavlovian conditioning: learned an eye-blink association at a slower rate. Retained two years later

Global amnesia

Amnesia for all information presented in all sensory modalities

H.M’s contributions: medial temporal lobes play an important role in memory

Challenged the prevalent view that memory functions are diffusely and equivalently distributed throughout the brain. Renewed efforts to relate individual brain structure to specific mnemonic (memory related) processes. Spawned research on clarifying the functions of the hippocampus and other medial temporal lobe structures.

Remote memory

Memory for experiences in the distant past.

Memory consolidation

The transfer of short-term memories to long-term storage.

H.M’s contributions: bilateral medial temporal lobectomy abolished H.M’s ability to form long-term memories without disrupting performance on short-term or remote memory

Supported the theory that there are different modes of storage for short-term, long-term, and remote memory. H.M had difficulty in memory consolidation (short-term to long-term)

H.M’s contributions: Revealed an amnesic patient may have no recollection of a previous experience while demonstrating a memory for it with improved performance

The mirror-drawing test and incomplete pictures test proved he did not have conscious recollection (explicit memories) of the learning events, and these long-term memories demonstrated by improved test performance without conscious awareness became known as implicit memories.

Medial temporal lobe amnesia

Amnesia associated with bilateral damage to the medial temporal lobes, its major features are anterograde and retrograde amnesia for explicit memories with preserved intellectual functioning.

Repetition priming tests

Assess implicit memory, ie. incomplete pictures and the mirror drawing test. Those that involve word memory are more common, shown fragments. Participants with amnesia often perform as well as controls, even though they have no explicit memory of seeing the original list.

Advantage of having two parallel memory systems (unconscious and conscious)

Flexibility — experiment on monkeys — amnesic subjects learned an implicit learning task as well as control subjects but could not use implicit knowledge in a different way/context. Explicit memory allows for flexible uses of information

Semantic memories

Explicit memories for general facts or knowledge, form of explicit long-term memories

Episodic memories

Explicit memories for specific moments in ones life. People with medial temporal lobe amnesia have particular difficiculty with it. In general amnesiacs tend to struggle with either episodic memory or semantic memory.

Endel Tulving’s patient K.C

Struggled with lack of an episodic memory (autobiographical memory), couldn’t revisit personal moments in his life and play them out event though he retained good cognitive ability and semantic memories.

Challenges in spotting episodic memory deficits

Neuropsychologists have no way of knowing true events of a patients life and the patients are usually effective at providing semantic answers to episodic questions.

Global cerebral ischemia

An interruption of blood supply to the entire brain. Patients who have suffered from it often have a medial

Pyramidal cell layer

One of the major layers of cell bodies in the hippocampus

CA1 subfield

A region of the hippocampus that is commonly damaged by cerebral ischemia. R.B’s damage was restricted to a pyramidal cell layer of here, had more selective (less extensive) damage than H.M, less severe amnesia, suggests that hippocampal damage alone can produce amnesia.

Transient global amnesia

A sudden onset severe anterograde amnesia and moderate retrograde amnesia for explicit memory that is transient — typically lasting between 4-6 hours. Strongest evidence that selective hippocampal damage can cause medial temporal lobe amnesia. Usually caused by stroke

The process of memory consolidation

The relatively slow process of storing fast, episodic memories into slow semantic memories (which are more robust and can be used as a building block).

Dual-trace theory

Is the standard consolidation theory, that suggests learning creates two memory traces: a detailed, but fragile short-term trace (STM) for quick recall, and a stable, but less detailed long-term trace (LTM) that consolidates over time.

Alternative theory for memory consolidation

The hippocampus is solely responsible for episodic memories. It hinges on the question of if there is a temporal gradient

How does Korsakoff’s syndrome occur

Disorder of memory that is most common in people who have consumed large amounts of alcohol. Attributable to brain dysfunction associated with thiamine deficiency

Korsakoff’s syndrome affected brain regions

Lesions in the medial diencephalon, diffuse damage to several other brain structures, notably the neocortex, hippocampus, and cerebellum

Amnesia present in Korsakoff’s syndrome

During early stages:

• anterograde amnesia for explicit episodic memory

As disorder progresses:

• retrograde amnesia can eventually extend back into childhood can develop

Mediodorsal nuclei

A pair of thalamic nuclei, damage to which is thought to be responsible for many of the memory deficits associated with Korsakoff’s syndrome

Medial diencephalic amnesia

Associated with damage to the medial diencephalon (e.g Korsakoff’s amnesia)

Alzheimer’s disease

Another major cause of amnesia. First sign is mild deterioration of memory. Progressive disease, terminal.

Predementia alzheimers patients

More general than medial temporal lobe damage, medial diencephalic damage, or Korsakoff’s syndrome. Patients often display deficits in short term memory and some implicit memories (for verbal and perceptual material, not sensorimotor learning)

Structures involved in alzheimers

Levels of acetylcholine are reduced (resulting from degeneration of the basal forebrain, a midline area of the forebrain, located just in front of and above the hypothalamus, the brain’s main source of acetylcholine). Brain damage is diffuse, involves many areas including the medial temporal lobes and prefrontal cortex.

Neuronal damage in Alzheimer’s disease

Progressive neuronal loss and buildup of neurofibrillary tangles and amyloid plaques. Symptoms start with mild memory loss and end with incapacitation and death. tangles and plaques concentrate in the PFC, PPC, and MTL.

Semantic dementia

Loss of long-term, explicit, semantic memory, like faces and concepts. Also known as frontotemporal dementia. Exemplars are progressively lost to prototypes. Involves anterior temporal lobe atrophy.

Closed head traumatic brain injuries

Injuries produced by blows to the head that do not penetrate the skull, most common cause of amnesia. Injuries post event are called posttraumatic amnesia

Coma

Pathological state of unconsciousness, following a severe blow to the head usually lasts seconds to minutes but can last up to weeks. After regaining consciousness, usually a period of confusion.

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

Gradients of retrograde amnesia after a closed-head TBI

Provide evidence for memory consolidation. Closed head TBIs preferentially disrupt recent memories, suggests that older memories have been strengthened.

Hebb’s theory

Classic theory of memory consolidation, memories of experience are stored in the short term by neural activity reverberating in closed circuits which may be susceptible to disruption but eventually induce structural changes in involved synapses.

Electroconvulsive shock

Intense, brief, diffuse, seizure-inducing current administered through large electrodes attached to the scalp. Studies memory consolidation by disrupting neural activity and erasing from storage memories not yet converted to structural synaptic changes. Length of period of retrograde amnesia produced by an ECS provides an estimate for amount of time needed for memory consolidation.

Current view of memory consolidation

It continues for a very long time, if not indefinitely. Lasting memories become more and more resistant to disruption throughout a person’s life. Each time a memory is activated, it is updated and linked to additional memories, increasing their resistance to cerebral trauma.

Engram

A change in the brain that stores a memory. Every time a similar experience occurs or the original memory is recalled, a new engram is established and links to the original engram.

Reconsolidation

The theory that each time a memory is retrieved from long-term storage, it is temporarily held in a labile (changeable/unstable) state where it is susceptible to posttraumatic amnesia until reconsolidated.

Delayed nonmatching-to-sample test

A test in which the subject is presented with an unfamiliar sample object and then after a delay presented with a choice between the sample object and an unfamiliar object, where the correct choice is the unfamiliar object.

Monkey testing using delayed nonmatching to sample test

A monkey is presented with an object under which it finds food, then must remember the object after a screen is lowered between it and the object. Well trained moneys perfrom correctly 90% of the time when the retention intervals were less than a few minutes. Monkeys with bilateral medial temporal lobe lesions had major object-recognition deficits. Susceptible to distration, fell off after a few minutes between events

Medial temporal cortex

Cortex in the medial temporal lobe that lies adjacent to the hippocampus and amygdala. Implicated with the amygdala and hippocampus in memory of delayed nonmatching to sample tests.

Nootropics

Pseudo psychology — drugs told to enhance memory in humans, however research tends to be poorly conducted and cannot be replicated. Shows that the drugs have no memory-enhancing effects.

The delayed nonmatching-to-sample test in Rats (the mumby box)

Extraneous damage from aspirations is limited to a small area of the parietal neocortex — rhinal cortex, the hippocampus is lesioned electrolytically, produces less extraneous damage. Rat version of the test yields similar responses, performing the complex test with delays up to 1 minute

Challenges to the theory that the hippocampus is a main source of memory

Explicit memory deficits in object recognition were found to be much worse following medial temporal lobectomis than hippocampectomy. There were severe and permanent deficits after MTL removal, but only model deficits following bilateral hippocampus removal, and none after bilateral amygdala removal. Yet, profound impairment in e.g., spatial, autobiographical memory following hippocampal removal. Apparent contradiction likely reflects specialization of MTL memory structures in particular types of explicit memory.

Place cells

Neurons that respond only when the subject is in specific locations. Consistent with the view that the hippocampus plays a role in spatial processing.

Remapping of place cells

• The spatial sensitivity of hippocampal place cells will, on occasion spontaneously shift to a new profile

• The shift appears to be driven by a change in context

• Possibly evidence of a new “situation” that demands its own memory representation

Entorhinal cortex

An area of the medial temporal cortex that is a major source of neural signals to the hippocampus. Gives a possible answer to how hippocampal place cells obtain their spatial information from grid cells in the entorhinal cortex

Grid cells

Entorhinal neurons that each have an array of evenly spaced place fields, producing a pattern reminiscent of graph paper. Produces spatially relevant neurons.

Scale along the long axis in the hippocampus

• The scale of spatial representation varies along the hippocampal long axis

• Colleagues and prof have argued that this translates to effects in episodic memory pertaining to “gist” and detail

• Episodic gist is a slippery construct

Head-direction cells

Monitor head direction

Spatial view cells

Respond to where the subject is looking

Border cells

Monitor if the subject is near a spatial border

Function of specialized storage

• Each memory is stored diffusely throughout the brain structures that were involved in its formation

• Structures typically active at both encoding and retrieval

• Some structures are nonetheless associated with particular aspects of memory

Entorhinal and parahippocampal cortex

Associated with spatial memory

Perirhinal cortex

Associated with objects and recognition

Hippocampus

Associated with episodic memory

Inferotemporal cortex

Associated with visual memory

Amygdala

Associated with emotional learning/memory

Prefrontal cortex and its many sub-areas

Associated with working memory and temporal order of events and responses

Cerebellum and striatum

Associated with implicit memories of sensorimotor learning and habit learning

Concept cells

Neurons that respond to ideas or concepts rather than to particulars. May respond to more than one concept if the two have an obvious relationship (ie. jennifer aniston and lisa kudrow)

Optogenetics

A tool biopsychologists use, neuroscientists insert an opsin gene into particular neurons, then use a light to hyperpolarize or depolarize them. Used as a tool to study learning and memory in mice (particularly engram cells)

Engram cells

Neurons that maintain an engram, undergo a persistent change as the result of experience such that when they are subsequently activated or inhibited, the retrieval of the original experience is triggered or suppressed

Tagging stage

The first stage of identification of an engram cell, neurons active during the learning task are induced to express opsins while an animal engages in a particular learning task

Manipulate stage

Second stage of the identification of an engram cell, previously active neurons are either inhibited or excited by using light to influence the activity of the opsin-tagged neurons.

Conclusions made from studies on where memories are stored

1. Memories are stored diffusely in the brain and thus can survive destruction of any single structure

2. memories become more resistant to disruption over time

Hebb

Argued that enduring changes in the efficiency of synaptic transmission were the basis of long-term memory. The search for neural bases of learning and memory has since been focused almost exclusively on the synapse

Long term potentiation

The enduring facilitation of synaptic transmission that occurs following activation of synapses by high-intensity, high-frequency stimulation of presynaptic neurons

Two key properties of LTP

• can last a long time

• only develops if there is a co-occurrence of activity in the presynaptic and postsynaptic neurons

Observations about LTP

1. LTP can be elicited by low levels of stimulation that mimic normal neural activity

2. LTP effects are most prominent in structures that have been implicated in learning and memory, such as the hippcampus

3. learning can produce LTP-like changes in the hippocampus

4. Many drugs that influence learning and memory can have parallel effects on LTP

5. disruption of LTP impairs memory performance on many behavioural tasks

6. behavioural changes (appears to be memories) can be induced in mice via LTP

7. LTP occurs at specific synapses that have been shown to participate in learning and memory in simple invertebrate nervous systems

Induction

Mechanism of LTP, first part. The processes by which high-frequency stimulations induce LTP

Maintenance

Mechanism of LTP, second part. The changes responsible for the maintenance of LTP.

Expression

Mechanism of LTP, third part. The changes that allow it to be expressed during the test

NMDA receptor

Prominent at LTP synapses. The receptor for glutamate, main excitatory neurotransmitter of the brain. Responds maximally only when glutamate binds to it and the postsynaptic neuron is already partially depolarized (so that calcium channels open wide when glutamate binds)

Dendritic spines function in LTP

Allows specificity in LTP mechanisms, keeping events at one set of synapses on a postsynaptic neuron, calcium ions that enter a dendritic spine do not pass readily out of it, and thus exert their effects locally.

Maintenance of LTP involves structural changes

Structure of neurons and neural circuits was previously assumed to be static. Changes can include: increases in number and size of synapses, postsynaptic dendritic spines, changes in pre and postsynaptic membranes, changes in dendritic branching. Include more frequently than was once assumed.

Transcription factors

Intracellular proteins that bind to DNA and influence the operation of particular genes. Were activated by neural activity

DNA Methylation

As an epigenetic mechanism, serves a role in memory storage.

Definition of LTP as a synaptic mechanism

• Generally defined as a strengthening between synapses

  • Only occurs if presynaptic firing is followed by postsynaptic firing

  • Can last indefinitely

Long term depression

Occurs in response to prolonged low-frequency stimulation of presynaptic neurons

Metaplasticity

The modulation of long term potentiation/ LTD induction by prior synaptic activity