1. The Neurology and Dysfunctions associated with Learning and Memory
NEUROPSYCHOLOGY
The Neurology and Dysfunctions associated with Learning and Memory
Dr. Malcolm Hughes

2. Localised or diffuse Representation of Memory
Pavlov (early 20th Century) pioneered the investigation of classical conditioning in which a stimulus comes to elicit a response similar to the response produced by some other stimulus:
Led to the recognition of the terms
Conditioned stimulus (CS) and unconditioned stimulus (UCS);
Conditioned response (CR) and unconditioned response (UCR)
As a development from this, Skinner evolved the idea of operant conditioning – individual’s response is followed by some form of reinforcement (positive or negative)
Pavlov believed that classical conditioning reflected a strengthened connection between a brain area that represents CS activity and a brain area representing UCS activity.

3. Lashley (1929; 1950) set out to test this hypothesis – sought an ENGRAM, the physical representation of learning:
Considered that if learning depended on new or strengthened connections between two brain areas, then severing sections of the brain should interrupt that connection and abolish the learned response.
Rats were trained to run a number of mazes and a brightness discrimination task – then had one or more deep cuts made in varying locations of the rats’ cerebral cortexes. However, none of the knife cuts impaired the rats’ performance i.e. the types of learning studied did not depend on strengthened connections across the cortex.
Eventually researchers discovered that Lashley’s work reflected two unnecessary conclusions:-
That the best place to search for an engram is the cerebral cortex
2. That all kinds of memory are physiologically the same

4. Pavlov’s view of the physiology of learning – (a) UCS excites UCS centre which then triggers the UCR centre. After training (b), excitation in the CS centre flows into the UCS centre thus eliciting the same response as the UCS.
Map of the cuts that Lashley made in the brains of various rats to see which one(s) would interfere with memory of learning a maze.
None of the cuts interfered with that memory.

5. Short-Term Memory vs Long-Term Memory
It is possible to draw an unlimited number of distinctions among different types of memory – memory of recent events (short-term) vs. a memory of older events (long-term).
A question arises as to how such distinctions (if any) are “natural” ones and which distinctions are not?
It appears likely that two functions can be physiologically different if some procedure (e.g. damage to a specific brain area) impairs one function, while some other procedure impairs another function.
However, no researcher has found any procedure that impairs one type of memory without equally impairing the other.
Hebb (1949)distinguished between short-term and long-term memory:
Short-term memory – memory for events that have just occurred.
Long-term memory – past events that must be retrieved from storage – events not currently occupying the person’s attention.

6. Individuals with damage to the hippocampus can form new short-term memories, but have difficulty developing new long-term memories.
Individuals with certain kinds of head trauma forget the events that occurred immediately before the trauma (events in short-term memory) without forgetting earlier events (that were in the long-term memory).
Short-term memory has several properties that differ from those of long-term memory e.g. literary recall.
Consolidation of Long-Term Memories
On a daily basis, information passes into the short-term memory. Of that, a tiny fraction becomes readily available long-term memory, while a larger fraction becomes harder-to-recall long-term memory.
i.e. there is a tendency to consolidate or strengthen some short-term memories into long-term memories, but the degree of consolidation varies.

7. Physiological basis of long-term memory:
Reason a person can remember more effectively an exciting experience than a dull experience is that the former arouses the sympathetic nervous system – increases secretion of epinephrine (adrenaline) into the bloodstream (McGaugh, 1990).
Excessive epinephrine can have a less beneficial effect – people in panic often have trouble remembering details of the situation later.
Epinephrine effect: does not enhance memory by stimulating nerve synapses – very little epinephrine crosses the blood-brain barrier.
Now recognised that epinephrine converts stored glycogen to glucose and thus raises the level of blood glucose that is available to the brain (Gold, 1987; Hall & Gold, 1990).
The high glucose level brought about by high epinephrine levels does facilitate memory.
Injecting glucose (to bypass the epinephrine stage) shortly after a specific experience enhances future memory of that experience.

8. Explicit Memory vs. Implicit Memory
Explicit memory is a memory for facts or specific events.
Implicit memory is a memory that does not require any recollection of a specific event e.g. when you tie shoelaces, you make use of implicit motor-skill memories.
The distinction between explicit-implicit memory effects is useful as certain types of brain damage impair explicit memory without affecting implicit memory.
Some psychologists distinguish between declarative memory and procedural memory (as a preference to explicit-implicit memories).
Declarative memory - memory that a person can state in words.
Procedural memory – a memory consisting largely of motor skills.
Declarative memories are largely explicit; procedural memories are mostly implicit.

9. Brain Damage and Impairment of Implicit Memory
Implicit memory includes
conditioned responses
learned motor skills
certain kinds of perceptual learning
priming effects (hearing certain words “primes” the individual to use them later).
Thompson (1985) found cells in one nucleus of the cerebellum – the lateral interpositus nucleus became increasingly active as a learning activity takes place (conditioned response).
Damage to the lateral interpositus nucleus causes a permanent loss of the conditioned response.
There is however evidence that certain kinds of implicit memory may depend on other brain areas as well e.g. thalamus and auditory sections of the cerebral cortex which can change their responsiveness to various stimuli and such changes could contribute to learning.

10. Brain Damage and Impairments of Explicit Memory
Occasionally, patients complain about a loss of motor skills – refer to it as a loss of co-ordination rather than a loss of (implicit) memory.
If the memory loss is explicit, then this often manifests itself in a form of AMNESIA.
Hippocampal Damage effects: (HM).
Focus on the hippocampus re. memory function relates to studies of a man referred to a “HM” (Milner, 1959).
HM suffered severe epileptic seizures – unresponsive to treatment. As a consequence, neurosurgeons removed his hippocampus from both sides of his brain as the seizures appeared to emanate from this structure.
Following surgery, seizures decreased in frequency and severity – his personality and intellect remained the same and I.Q. increased.
However, he suffered moderate retrograde amnesia – could not recall events that happened during the last 1 to 3 years prior to his operation but could recall events prior to that time.

11. Location of the hippocampus in the human brain.

12. Photo showing part of the hippocampus which curves into the interior of each hemisphere; not the hippocampus curves around over the thalamus and under the cerebral cortex

13. HM also suffered massive anterograde amnesia (loss of memory for events that happened after brain damage) – could store new information briefly, but had difficulty in recalling it after any distraction.
In one test of HM’s memory, Milner asked him to remember the number 584. after a 15 minute delay without distractions, he was able to recall the number correctly. He explained how he did so.
“It’s easy. You just remember 8. You see, 5, 8 and 4 add up to 17. You remember 8, subtract it from 17, that leaves 9. Divide 9 in half and it come to 5 and 4, and there you are – 584. Easy”.
A moment later HM’s attention had shifted to another subject, he had forgotten both the number and the complicated line of thought he had associated with it.
In 1980, he moved to a nursing home. Four years later, he could not say where he lived or who cared for him, He could only recall a few fragments of events since 1953.
Although he could not remember new facts, he could learn new skills without any apparent difficulty.

14. Korsakoff’s Syndrome and Frontal lobe Damage
Is a type of brain damage due to thiamine deficiency and occurs almost exclusively among severe alcoholics who go weeks eating only occasionally and drinking only alcoholic beverages – become deficient in Vitamin B1 which the brain requires to metabolise glucose.
Prolonged thiamine deficiency leads to shrinkage of neurones throughout the brain, notably part of the hypothalamus and part of the pre-frontal cortex.
Consequently, the symptoms are similar to those of people with damage to the pre-frontal cortex, including apathy, confusion and memory impairment.
Treatment with thiamine can sometimes improve the condition, but the longer the person has been thiamine-deficient before treatment, the poorer the chances of recovery.
Most Korsakoff’s syndrome patients have both retrograde and anterograde amnesia, yet often show signs of implicit memory despite severe impairment of their explicit memories.

15. Alzheimer’s Disease
Condition that becomes more prevalent with increasing age – can occur among a small group before they are 40 or 50 years of age.
By the age of 65 – 74 : less than 5% affected
Among those aged 85+: approx. 50% affected
Symptoms begin with minor episodes of forgetfulness. Later symptoms include:
Serious memory loss, confusion, depression, restlessness, hallucinations, delusions and disturbances of eating, sleeping and other daily activities.
Alzheimer’s disease is associated with a widespread atrophy of the cerebral cortex, hippocampus and other areas.
The most heavily damaged is the entorhinal cortex, the portion of the crebral cortex that conducts the greatest amount of communication with the hippocampus – acetylcholine producing neurones degenerate and plaques (degenerated axons and dendrites) appear in the damaged areas.

16. Progressive deterioration of neurones in the prefrontal cortex during Alzheimer’s Disease. (a) a normal nerve cell (b) cells from the same area of the cortex during different stages of deterioration.

17. Brain atrophy in Alzheimer’s Disease (b) compared to the brain of a normal person (a);
Note that the cerebral cortex of the Alzheimic patient (right) has gyri that are clearly shrunken in comparison with those of a normal person. a. b.

18. Microscopic photo of the cerebral cortex of an Alzheimer’s patient
The small greyish spheres are plaques which are characteristic of Alzheimer patient’s brains; the larger dark areas are amyloid deposits which also sometimes appear.

19. The plaques contain deposits of a protein, β-amyloid – question as to whether this chemical is a cause of the condition or a symptom?
Studies have shown that injecting β-amyloid into a rat’s brain can damage neurones and cause symptoms similar to Alzheimer’s, but other studies have failed to replicate such findings.
Genetic basis of Alzheimer’s – disease found to run in some families but also occurs among people unrelated to Alzheimic patients.
Some evidence to support the genetic contribution is the fact that people with Down’s Syndrome almost invariably get Alzheimer’s disease if they survive into middle-age. (Have three copies of chromosome 21).
Those with early-onset of Alzheimer’s disease also appear to have mutations on chromosome 21, in or near the gene that that determines the structure of amyloid precursor protein (Murrell et al, 1991). The protein is interesting because fragments of it can become β-amyloid.
In other families with early onset of the condition, it is suspected that genes on chromosome 14 are involved (Schellenberg et al, 1992).

20. Role of the Hippocampus, Amygdala and Frontal Cortex
Recognising how hippocampal damage impaired the memory of HM and other patients led to further studies. Results suggest that:
a) New memories are not stored in the hippocampus itself;
b) Hippocampal damage makes it difficult to store new memories, but does not impair old memories.
Two hypotheses which account for hippocampal function in memory:
1. The hippocampus acts as a map of where memories are stored in the cerebral cortex. After damage to the hippocampus, the individual has trouble locating the memory that is correct at that moment and distinguishing it from memories stored in the past.
2. Hippocampal neurones maintain a temporary store of sensory information through their own continuous activity.

21. Contributions of the Prefrontal Cortex
Damage to the prefrontal cortex is similar to hippocampal damage; the hippocampus and amygdala send part of their output to the prefrontal area of the cerebral cortex, so the three areas are related.
Damage to the prefrontal cortex impairs performance on a variety of tasks, depending on the location of the damage.
e.g. damage to the ventral area of the prefrontal cortex leads to a phenomenon called perseveration: i.e. once a particular response is made, the individual tends to make the same response repeatedly even when they should suppress that response and choose something else (Mishkin & Manning, 1978).
Expts. based on the Wisconsin card-sorting test.

22. Brain and Memory in Old and Young
Question as to why some people have better memories that others? This is most noticeable among infants and older people.
The reality is that both infants and old people perform well on some memory tasks and poorly on others; e.g. infant amnesia when we remember few events from the first 4 to 5 years of our lives.
In the first 4 or 5 years, we learn many implicit memories but do not form many explicit ones.
In this instance, infant memories resemble those of people with hippocampal damage this is due to the hippocampus not yet having fully matured (Moscovitch, 1985).
Similarly, old people who have trouble with recent explicit memory still manage to learn new skills or adjust old skills.
The prefrontal cortex also deteriorates in old age – the deficits may be due in part to a declining number of dopamine and nor-epinephrine synapses in the prefrontal cortex.

23. Influence of Protein Synthesis on Learning and Memory.
Proteins are essential building blocks of the body; in relation to the nervous system, protein synthesis is necessary for:
growth of an axon or dendrite
increase or decrease in the production of neurotransmitters
alteration of any nerve receptor
It is recognised that the drugs which suppress protein synthesis also impair long-term storage of memory (in rats) although they do not impair short-term memory (Davis & Squire, 1984).

24. Acetylcholine synapses and Memory
Acetylcholine (+ glutamate) now recognised as essential for learning – degree of memory loss in old age correlates with decline in brain acetylcholine (Bartus et al, 1982; Davies, 1985).
Scopolamine expts.
In several experiments, young adult volunteers received injections of scopolamine, a drug that block acetylcholine synapses. Under the influence of the drug, they showed clear deficiencies on a variety of memory tasks. Their general pattern of performance resembled that of senile people and the memory tasks that they have trouble with (Beatty et al, 1986).
Question arises as to whether human memory could be enhanced by the administration of drugs such as physostigmine that prolong the effects of acetylcholine at the synapses? Unfortunately these drugs do cause side-effects so at present, would not be clinically useful.

25. Remember, for every glass you drink brain cells gradually atrophy