CHAPTER 12

Learning and Memory

Learning deficiencies, dementias and Intellectual Disorders

Memory loss and aging

• For many years – researchers believed deficits in the elderly caused by a

substantial loss of neurons, especially from the cortex and the hippocampus.

• More recent investigations – the number of hippocampal neurons was not diminished

in aged rats– Even rats with memory deficits show little neuronal loss– What neuronal loss occurs from cortical areas was

relatively minor.

• BUT: certain circuits in the hippocampus do lose synapses and NMDA receptors as animals age.

dementias

• Dementia – ubstantial loss of memory and other cognitive abilities – Typically in elderly – 50% of those over 80 show some signs of dementia

• Alzheimer’s disease – most common cause of dementia is– characterized by progressive brain deterioration, impaired memory, loss of

other mental abilities.– earliest and most severe symptom = impaired declarative memory.– Language, visual-spatial functioning, and reasoning are particularly affected– Behavioral problems such as aggressiveness and wandering away from home.– Alzheimer’s affects nearly 10% of people over 65 years of age, and nearly half

of those over 85.

• Other dementias:– Frontal-temporal dementia; Lewy Body Dementia– Vascular dementias– Dementias from illness such as stroke/heart attack

• There are two notable characteristics of the Alzheimer’s brain, though they are not unique to the disease.– Plaques– Neurofibrillary tangles

• Plaques = clumps of amyloid, – a type of protein Beta Amyloid peptide, which congregates

together– cluster among axon terminals – interfere with neural transmission and are toxic to the neuron

• neurofibrillary tangles – Abnormal accumulations of the protein tau – form complexes inside neurons. – Tangles are associated with the death of brain cells.

Brain changes in dementia

• In the Alzheimer’s brain, – gyri are smaller – sulci are wider than in the normal brain.

• Pathology of Alzheimers believed to be death of groups of neurons particularly in the nucleus basialis– Because of their location, they effectively isolate the

hippocampus from its inputs and outputs, – Particularly affect ACETYLCHOLINE neurons, but also

serotonin and norephinephrine neurons.– this partially explains the early memory loss.

• Plaques and tangles in the frontal lobes account for– additional memory problems – attention and motor difficulties.

Dementia and brain changes

Figure 12.15 Alzheimer’s brain (left) and a normal brainThe illustrations show the most obvious differences, the reduced size of gyri and increased size of sulci produced by cell loss in the diseased brain.

• Acetylcholine:– Neural systems in various parts of the brain that produce acetylcholine are

critical for cognitive functions– including attention and learning.

– Degredation of Ach:• Ach----------------------Acetate + Choline

AChE Enzyme(acetylcholine esterase)

• Acetylcholine-releasing neurons are among the victims of degeneration in Alzheimer’s disease.

• The majority of treatment efforts have focused on restoring acetylcholine functioning.– E.g., cognex (Tacrine), aricept (Donezepil), exelon– Also use anti-inflammatories early on, such as ibuprofen

Ach and memory

• Currently five drugs approved by the FDA for the treatment of Alzheimer’s.– Four of them improve acetylcholine neurotransmission

by preventing the breakdown of acetylcholine at the synapses.

– drugs provide only modest relief for both memory and behavioral symptoms in mild cases of Alzheimer’s

– little or no help when degeneration is advanced.

• Other drug treatment– Psychotropic drugs to control behavioral symptoms,

reduce hallucinations– Antiseizure medications to control onset of seizures– tranqulizers

Drugs for dementia

• Memantine – The fifth dementia drug– first approved for use in patients with moderate and severe

symptoms.

• Some neuron loss in Alzheimer’s occurs when dying neurons trigger the release of the excitatory transmitter glutamate.– The excess glutamate overstimulates NMDA receptors and kills

neurons, a phenomenon known as excitotoxicity.– Memantine limits the neuron’s sensitivity to glutamate, reducing

further cell death.

• Studies indicate moderate slowing of deterioration and improvement in symptoms.

Newer dementia drug

• Korsakoff’s syndrome – Another form of dementia is, brain deterioration – almost always caused by chronic alcoholism.

• The deterioration results from a deficiency in the vitamin thiamine (B1), which has two causes:1. The alcoholic consumes large quantities of

calories in the form of alcohol in place of an adequate diet.

2. The alcohol reduces absorption of thiamine in the stomach.

Korsakoff’s syndrome

• The most pronounced symptom : anterograde amnesia– retrograde amnesia is also severe.– Impairment is to declarative memory, while nondeclarative

memory remains intact.

• Several brain changes:– hippocampus and temporal lobes are unaffected.– mammillary bodies and the medial part of the thalamus are

reduced in size– structural and functional abnormalities occur in the frontal lobes.

• Thiamine therapy can relieve the symptoms if the disorder is not too advanced,

• Brain damage itself it irreversible.

Korsakoff’s syndrome

• Confabulation – Some Korsakoff’s patients show a particularly interesting

characteristic in their behavior– Many other dementia patients, particularly frontal-temporal

lobe also show this– They fabricate stories and facts to make up for those missing

from their memories.– Depends on abnormal activity in the frontal lobes;

confabulating patients usually have lesions there.

• Confabulating amnesic patients– Trouble suppressing irrelevant information they have learned

earlier.– Why? confabulation is due to an inability to distinguish

between current reality and earlier memories.

Korsakoff’s symptoms

What is Intelligence?

• Intelligence is – the ability to reason, – to understand, – to profit from experience.

• Binet, 1905: Intellingence tests for educational purposes– Large sample average levels or norms– Mental age vs. Chronological Age

• The measure of intelligence is typically expressed as the intelligence quotient (IQ).– (Mental age /chronological age) * 100– Currently: IQ norm = 100;; Standard deviation = 15 poins– 68% of people have IQ between 85 and 115

• Remember: IQ = score on test!

What is Intelligence?

• Wechsler Intelligence tests– Several types of these tests– Wechsler Adult Intelligence Scale : WAIS-III– Wechsler Intelligence Scale for Children: WISC-IV– Wechsler Preschool and Primary Scale of Intelligence:

WPPSI

Divides test up by age groupings and by type of task:– Verbal scales– performance scales

Kinds of Intelligence

• Spearman’s G: general intelligence- just one kind

• Crystallized Intelligence:– Skills, knowledge

• Fluid Intelligence– Information processing– Reasoning ability– Memory

• Sternberg: practical and emotional intelligence– Every day living skills– Ability to perceive, process, use emtions

The Biological Origins of Intelligence

• Intelligence research has tended to rely on data obtained from individuals with compromised intelligence, particularly those with frontal lobe damage

• Frontal lobe damage :– impairs general intelligence more than performance on

traditional IQ tests, – These tests emphasize crystallized intelligence (skills and

information learned earlier).– Makes sense: Frontal areas involved in working memory

and executive control of problem solving

The Biological Origins of Intelligence

• Brain size itself does not determine intelligence.

• What IS important? Ratio of the brain’s size to body size.– Using ratio adjusts for the proportion of the brain to body size– Adjusts brain area needed for managing the body – Tells us how much is left over for intellectual functions.– Ratio for humans is one of the highest.

• MRI Twin studies: Is intelligence “genetic”– Fraternal versus identical twins – General intelligence correlated with both volume of gray matter

and the volume of white matter.– Volume of gray matter in the frontal area appears to be

particularly important to general intelligence.

• IQ scores also correlated with nerve conduction velocity– Nerve conduction velocity: Speed with which nerve impulses

transmitted• Related to size of axon• Degree of myelination, etc.

– Higher IQ correlated with faster nerve conduction velocity– How examine? Speed of processing tasks on intelligence tests.

• People with higher IQ scores excel on tasks in which stimuli presented for an extremely short interval and on tasks that require choices.– Both tasks: processing speed is important – Assume that higher nerve conduction velocity contributes to the

more intelligent person’s superior performance.– Thus: processing speed factors into IQ

Rate of processing important

• How make brain more efficient? – greater efficiency through enhanced myelination of its

neurons.– Also insulates neurons form each other.– reduces “crosstalk” that would interfere with accurate

processing.– Remember, though: brain not have to be optimal or

perfect, just “good enough”

• Humans have a greater proportion of white matter (myelinated processes) to gray matter than other animals– appears IQ is related to the degree of myelination

among individuals.– Animals such as elephants, marine mammals, dogs,

other nonhuman primates also have high degree of myelination

– Sea Aplysia has No myelination!

Nerve conduction speed: increased efficiency

• Increased nerve conduction velocity may particularly enhance efficiency of working memory.– Working memory correlated with white & gray matter volume, – Similar to correlation of white/gray matter and general

intelligence– Indeed, working memory correlated with intelligence!

• Working memory:– limited capacity: 7+/- 2– Contents decay rapidly (>20 seconds).– Must get info into long term memory quickly and efficiently

• Individuals with rapid neuronal conduction can:– complete manipulations more quickly– transfer information to long-term memory faster– All before decay occurs or short-term storage capacity is exceeded.

Working memory

• With low nerve conduction velocity:– information in STM or working memory is lost; person must restart the

process – Similar to when try to solve a problem and you not very alert – You have to review information over and over because you can’t store

it– Takes LONGER to process similar amount of information.

• Higher IQ correlated with use of less brain energy– lower rate of glucose metabolism during a challenging task– Remember is correlational, not causal– “hard” tasks not as hard; brain works less– Does support model of brain efficiency = higher

intelligence

Issues with low nerve conduction speed

• Linguistic– left frontal – Left temporal lobes.– Language based

• Logical-mathematical• Spatial ability depends on the interaction of somatosensory and

visual functions with parietal structures, • Mostly right hemisphere.

• Spatial– Mathematical ability in humans – depends on two distinct areas of the brain:

• left frontal region • both parietal lobes.

The Brain areas implicated in Intelligence

• Intelligence has a heritability of around 50%– At least 50% of variance for intelligence due to inherited

traits– Suggests large contribution of environment, however– Most important is likely the interaction between heredity

and environment

• Documented genetic influence on several of the functions that contribute to intelligence:– working memory, – processing speed– reaction time in making a choice.

Inheritability of intelligence

• Genetic factors appear to be slightly more important than environmental:– Most differences among individuals accounted for by genetic factors.– Estimated heritabilities in one twin study were

• 90% for brain volume• 82% for gray matter• 88% for white matter.

• General intelligence has higher heritability than more specific abilities– Less heritability for verbal and spatial abilities– Book suggests this provides additional argument for a biological basis

for g factor or general intelligence factor– Individual variations may influence specific intelligences

Inheritability of intelligence

Mental Retardation

• Limitations in intellectual functioning and adaptive skills– Two models: developmental and Different– are individuals jus slow to learn (hence word retarded)

or are they different physically (assume damage to brain produces different functioning).

• Levels of Retardation– Mild: IQ of 50 to 70– Moderate: IQ of 35 to 49– Severe: IQ of 20 to 34– Profound: IQ less than 20

• The criteria for retardation =arbitrary, and based on judgments about the abilities required to get along in our complex world.– In 1978, then 1994 the American Psychiatric Association set

the criteria for retardation as a combination of an IQ below 70 points and difficulty meeting routine needs like self-care.

– Prior to that, cut off was 85 – “cured” thousands of individuals

• Not only is any definition arbitrary, but it is situational and cultural as well.– A person considered retarded in our society might fare

reasonably well in a simpler environment.– 6-hour retarded child

Developmental disabiliteis and mental retardation

• MANY causes of retardation

• Retardation can be inherited or due to improper cell division– Fragile X– Tay Sachs– Williams Syndrome– Prader Willy– Down Syndrome: 3 instead of 2 of the 21 chromosome– Phenylketonuria or PKU:

• genetic condition in which there is a a toxic accumulation of phenylalanine• Faulty enzyme affects metabolism, causes neuron death

• Retardation can be caused by diseases contracted during infancy– Meningitis; infection, etc.– prenatal exposure to viruses such as rubella (measles).

Developmental disabiliteis and mental retardation

• Can be due to teratogen exposure– Maternal alcoholism is now the leading cause of mental

retardation– Other drugs

• Can be caused by prematurity– 50% of preterm infants have significant disability– Two most common: Cerebral palsy and mental retardation

• What about autism?– Used to be generically called retardation– Now identify it as separate disorder– Many of individual who would have been diagnosed as

retarded are now labeled autistic

Developmental disabiliteis and mental retardation

• Down syndrome usually caused by – the presence of an extra 21st chromosome, – Mosaicism: chromosome splits into many small parts– Trisomy 21: chromosonal split resembles presence of 3 21st chromosomes– Related to maternal age, but not necessarily caused by age

• Typically results in individuals with IQs in the 40 to 55 range.– Early intervention critical– Early that begin intervention, typically higher the IQ

• Amyloid precursor protein gene that involved in early-onset Alzheimer’s disease is located on chromosome 21– was discovered because Down syndrome individuals also develop amyloid

plaques.– 95% of people with Down syndrome have the entire extra chromosome– In a few cases: only an end portion is present, and attached to another

chromosome.

Down syndrome

• Traumatic Brain Injury– Occurs prenatally, at birth or in first few days/weeks of life

• Anoxia• Stroke• Other brain injury

– Results in brain that does not follow typical course of development

• Hydrocephalus– Water on the brain; occurs when cerebrospinal fluid builds up in the

cerebral ventricles.

– The increased fluid volume crowds out neural tissue, usually causing retardation.

– Hydrocephalus can be relatively easily treated if caught early• installing a shunt that prevents the accumulation of the excess cerebrospinal fluid.• Eliminate or greatly reduce likelihood of long term brain damage

Other causes of retardation

• Autism is a disorder that typically includes– compulsive, ritualistic behavior– impaired sociability– Language deficits– Often to usually: mental retardation.

• Autism is now combined category for what used to be 5 autism spectrum disorders– Autism, classic autism, high functioning autism – Autistic Disorder – Asperger Syndrome or Asperger's Disorder – Pervasive Developmental Disorder (PDD),– Autism Spectrum Disorder (ASD).

autism

• Autism:– Disorder of attention, socialization, intellectual functioning– Poor social interactions and lack of pretend play

• Does not make friends• Does not play interactive games

– Affects verbal and nonverbal communication• develops language slowly or not at all• Does not adjust gaze to look at objects that others are looking at

– Often lack sense of “self”• Does not refer to self correctly (for example, says "you want water" when the

child means "I want water")• Does not startle at loud noises

– Has heightened or low senses of sight, hearing, touch, smell, or taste

• Slower processing speed (sort of)– Often very low functioning in terms of academic and daily living skills– But: may show remarkable talent in a single area

Autism

• Whether retarded or not, autistic individuals share a common core of impairment in – Communication: often difficulty with communication– Imagination: very literal– Socialization: poor social skills

• May be mute or show delayed language development– have trouble understanding verbal and nonverbal communication.– Again, very literal and concrete

• Much of social behavior problem may be because autistic person lacks a theory of mind– ability to attribute mental states to oneself and to others.– An individual with autism cannot infer what other people are

thinking.

Autism: Common core of impairment

• Two hypotheses as to how we develop a theory of mind.– “theory theory:” We build hypotheses over time based on

our experience.– Simulation theory: We gain insight into people’s thoughts

and intentions by mentally mimicking the behavior of others.

• Data tends to support simulation view: – Existence of mirror neurons – Poor imitation skills in individuals with autism– Very different from Williams syndrome, another genetic

form of mental retardation.

Theory of mind

• Impaired mirror functions reduces the autistic person’s ability to – Empathize – learn language through imitation.

• For example, some individuals with autism show no mirror neuron activity while – imitating facial expressions – or when observing a model’s hand movements.

• Other studies show reduced activation in the inferior frontal cortex and motor cortex, – Suggests weakness in the dorsal stream connections – Provide important input to those areas containing mirror neurons.

How does poor mirror function affect intelligence?

• Subtle but widespread brain anomalies have been found,

• Especially in the – brain stem, – the cerebellum, – temporal lobes.– The location of damage is inconsistent, which may mean only

that there are various pathways to autism.

• What causes these brain defects?– is uncertain, – at least we know they occur early, during brain development– So: know where and when to look for the answer.– NOT caused by parental rejection!

Brain areas affected in autism

• Another form of mental retardation; typically moderate to severe retardation

• Is genetic misfiring: occurs randomly: deletion of approximately 25 genes from the 7th chromosome

• Symptoms: – include delayed speech early on, then exceptional speech– Strong learning by hearing; mimicking– Developmental delays, learning disorders and ADD– Variety of physical problems

• Personality traits: – very friendly– trusting strangers– fearing loud sounds or physical contact– being interested in music

• Interestingly: studies suggest that individuals with Williams Syndrom have a greater number of mirror neurons (compared to typically developing individuals)

Williams syndrome

• Use it or lose it!– Staying active keeps neural circuits active– Staying active enables brain to continue to make new connections

• General health important– Healthy people show less cognitive decline– Diet, exercise, general health contribute to brain health

• What you start with is important– If have higher cognitive function, will maintain throughout life time– Have more to work with, more to “lose”

• Most critical: using what you do have and maintaining it– Maintaining what cognitive abilities you do have– Making the most out of what abilities you have– Taking care of your brain!

Bottom line