April 25, 2021
PSY 340 Brain and Behavior
Class 32 Learning, Memory, and Memory Loss
Localized Representations in Memory
Our experiences in life teach us things: putting our finger into a flame or an electrical socket will hurt, eating ice cream will usually taste really good, smiling at our boy- or girl-friend is more likely to keep them around than a frown, and failing to show up at work will usually get us fired. It seems as if learning connects one thing to another.
In the late 19th and first half of the 20th century, behavioral psychologists developed elaborate theories that we learn such connections because of our experiences.
Karl Lashley's FAILED Search for the Engram
University of Chicago and, later, Harvard physiologist and psychologist, Karl Lashley, wanted to find where learning resided in the brain. In the period from roughly 1920 to 1955, Lashley searched after the "engram" -- the physical representation (or memory trace) in the brain of what has been learned.
To do so, Lashley performed two general types of experiments.
Cortical Cuts. First, he trained rats to learn how to find food in mazes. When they had learned this, he performed operation on the rats by cutting areas of the cortex. He theorized that, if there was a link between two areas of the brain as a result of learning, he might pinpoint that link by making the cuts. The diagrom on the right shows you the different places where he cut the rat brain. When each rat recovered from the operation and put back into the maze, they didn't show any evidence of loss of learning.
Tissue Ablation. The second experiments involved maze learning as well. When the rats had learned to manouver in the maze, he performed a "tissue ablation" -- that is, he cut different amounts of tissue from the rat's cortex. The rats later on did more poorly in running the maze. But, it appears to be the amount of lost brain tissue, not the place where the tissue was removed that was related to poorer performance.
Lashley's Principles for the Nervous System. Lashley rejected the notion of localized learning. Rather he proposed two principles:
- Equipotentiality: All parts of the cortex contribute equally to learning; one part can substitute for another part.
- Mass Action: The cortex works as a whole; performance improves when more of the cortex is involved.
We know that Lashley was wrong about both of these principles? Why? He assumed (1) the engram (memory trace) is only in the cortex and (2) all memories are the same physiologically.
The Modern Search for the Engram: Conditioning & the Lateral Pontine Nucleus of the Cerebellum
II. Types of Memory
Short- and Long-Term Memory
Donald O. Hebb proposed in the late 1940s a model of memory with two different components:
- short-term memory (STM; up to 20 seconds)
- Keeping items in STM requires regular rehearsal (actively calling items to mind) or else they will fade.
- George Miller noted, the storage capacity of STM is limited: 7 +/- 2 chunks of information. More recent research suggests that it is really more likely about 4 +/- 2 chunks.
- long-term memory (LTM; 20-60 seconds to a lifetime): anything that happened in the past which you can remember
- Hebb also proposed that all information enters into STM and stays there until the brain consolidates that information as LTM. Hebb argued that the shift from STM to LTM came with the "consolidation" of memories by means of a reverberating circuit within the nervous system. As the memory reverberates around the circuit, it gradually causes some type of permanent change in the chemical or structural make-up of the nervous system.
Changing Views of Consolidation
Earlier view: Consolidation is a general & simple process leading to a permanent long-term memory. But, this is no longer a viable option because
Alan Baddeley's "Working Memory": A Modern Advance
- Time for consolidation varies considerably: may take from an instant (for emotional memories) to hours (for memorizing facts). Something more than "simple" consolidation is taking place, e.g., cortisol in short term enhances consolidation, but may hinder consolidation if person is stressed for long periods.
- Memories are labile (changeable or vulnerable to alteration). When memories are recalled, they are frequently reconsolidated, that is, subtly changed or altered by new information, e.g., parent recalls a detail and child adds that detail to their memory; or, a policeman makes a remark about what a witness might have seen and the witness incorporates that remark into their memory
In the early 1990s, Alan Baddeley (U York, UK) and his colleagues proposed a newer model of memory: working memory. This was revised in 2000-2001 and now includes 4 elements:
- phonological rehearsal loop: auditory & linguistic information
- visuospatial sketch pad
- episodic buffer: temporary storage of multimodal-coded information drawn from long-term memory and presented as an episodic representation (a scene)
- central executive control system: directs attention toward one or another stimuli and decides what will be put into the working memory
We may also have working memory systems for the other senses (touch, taste, smell), but not much research has been done on them.
Testing the "working memory" model uses delayed response tasks = respond to a stimulus that was seen or heard a short time ago with a time delay inserted between the perception and the response.
What parts of the brain are active during the delay, that is, while the working memory is rehearsing or holding the memory? Most active appears to be the dorsolateral prefrontal cortex. However, multiple other areas of the prefrontal cortex are involved in other aspects of working memory besides rehearsal.
III. Memory Loss (Amnesia)
A. Korsakoff's Syndrome & Other Prefrontal Damage
Wernicke's encephalopathy (WE) is an acute brain disorder in which a patient has profound global confusion, difficulty in coordinating muscle movements (ataxia), and problems using their eyes. It is fatal in 10-20% of cases coming to a hospital. It is caused by a deficiency of thiamine (vitamin B-1). 80% of patients surviving Wernicke's encephalopathy develop Korsakoff's Syndrome (KS). WE often, but not exclusively, develops in individuals with alcoholism
KS is a chronic
brain disorder characterized by severe memory problems: both
anterograde and retrograde memory is usually damaged. Patients
also show apathy and confusion.
The brain area damaged includes the mammillary bodies (beneath the hypothalamus) and the dorosmedial (or mediodorsal) thalamus (nucleus connected to pre-frontal cortex).
Patients with KS often show
B. Alzheimer's Disease (AD) [Sheltens
et al. 2021]
AD is a form of
dementia. What is dementia? As the National Institute on Aging (2017) defines
it, "Dementia is the loss of cognitive functioning—thinking,
remembering, and reasoning—and behavioral abilities to such an
extent that it interferes with a person's daily life and
activities. These functions include memory, language
skills, visual perception, problem solving, self-management,
and the ability to focus and pay attention. Some people
with dementia cannot control their emotions, and their
personalities may change" (highlighting & italics added).
Not that "dementia" is not itself a disease but a broad term
specifying a range of symptoms found in multiple diseases like
AD, Parkinson's disease, fronto-termporal dementia, and several
The disorder was first
identified and diagnosed by the German psychiatrist and neuropathologist,
Dr. Alois Alzheimer (1864-1915) in 1906. A patient in the Frankfurt
psychiatric asylum, Frau Auguste Deter, who showed significant
behavioral symptoms including memory loss. When she died in
1906, Alzheimer analyzed her brain tissue after autopsy and
discovered the characteristic presence of amyloid plaques and
neurofibrillary tangles of tau (discussed below).
AD is a progressive
disorder which initially involves minor forgetfulness. Over the
course of about 8 to 10 years following diagnosis, AD patients
experience increasing symptoms including severe memory loss,
confusion, depression, hallucinations, delusions,
restlessness, sleeplessness, and loss of appetite.
Eventually, the disease will lead to death.
AD which develops among people over the age of
65 is described as "late onset" AD [LOAD]. This occurs
in more than 90% of cases of AD. However, about 5% of AD
occurs among people aged 30 to 65 and this is called "early
onset" AD [EOAD]. This form of the disease
appears to be strongly related to the presence of one of three
specific genetic variants on chromosomes 1, 14, and 21 and
other genetic risks. [https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet]
Prevalence and Incidence
of AD. What is the rate of Alzheimer’s disease
in the United States? Mendez (2019) reports that among those
who are 45 to 64 years old, early-onset AD [EOAD] is diagnosed
each year at a rate of about 6.3 per 100,000 with an overall
prevalence of 24.2 per 100,000. Thus, EOAD is actually a
fairly rare (though fatal) disorder. Note that people with
EOAD tend to die more quickly than in late-onset AD (LOAD)
which is why the prevalence rate remains steady.
But, as you see in the figure on the right,
beginning at the age of 60, the incidence rate of AD begins to
climb exponentially. It is 1% among those 60 to 64 years old,
and then it doubles in each 5 year period until age 85. After
85, however, the rate soars to between 30 and 40%.
The CDC estimates that in 2020 there were
5.8 million Americans with AD. And, that number is expected to
rise to 14 million by 2060. One cost estimate finds that the
extra expenses to treat people with AD in the last couple of
years of their life is about $250,000. That means that the
current population of the United States with AD will generate
about $1.45 trillion in expenses.
Cellular Pathology in
Amyloid plaques: amyloid precursor protein in the brain is incorrectly broken down into amyloid beta protein 42 (usually called A-beta by researchers). This substance accumulates with other amyloid beta proteins and damages the membranes of axons and dendrites as these clumps develop in the space between neurons.
Neurofibrillary tangles: the tau protein within the neuron usually supports the cell's structure, particularly the axon of neurons. However, abnormal forms of the tau protein collect inside the neuron and cause tangles to form within the neural cell.
- Many AD researchers believe that the tau protein tangles are not the cause of, but a result of other processes involved in the development of the disease.
- As you see in the figure above, the progression of AD in the brain begins usually in the temporal lobe (involving the hippocampus) and the inferior area of the frontal lobe. As the disease progresses the deterioration begins to spread widely throughout the brain.
Pathology in AD
Amnesia (Not responsible for this section; we won't be
ReferencesAlzheimer's Genetics Factsheet. (2015, August). Washington, DC: National Institutes of Health, National Institute on Aging. https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet
Carey, B. (2008, December 4). H.M., an unforgettable amnesiac, dies at 82. New York Times. [Obituary]
Couthard, E. J., & Love, S. (2018). A broader view of dementia: Multiple co-pathologies are the norm. Brain, 141(7), 1894-1897. doi: 10.1093/brain/awy153
Genoux, D., Haditsch. U., Knobloch, M., Michalon, A., Storm, D., & Mansuy, I. M. (2002). Protein phosphatase 1 is a molecular constraint on learning and memory. Nature, 418(6901), 970-975. [PubMed Abstract]
Jansen, I. E. et al. (2019) Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nature Genetics, 51, 404-413. https://doi.org/10.1038/s41588-018-0311-9Kolata, G. (2011, April 3). Vast gene study yields insights on Alzheimer's. New York Times. Retrieved from http://www.nytimes.com/2011/04/04/health/04alzheimer.html
Kolata, G. (2019, April 8). The diagnosis is Alzheimer's. But that's probably not the only problem. New York Times. Retrieved from https://www.nytimes.com/2019/04/08/health/alzheimers-dementia-stroke.html
Mendez, M. F. (2019) Early-onset Alzheimer disease and its variants. Continuum, 25(1), 34-51. https://dx.doi.org/0.1212/CON.0000000000000687
Mental Health: A Report of the Surgeon General. (1999). Chapter 5. Older Adults and Mental Health: Alzheimer's Disease. Washington, DC. Downloaded 04/17/05 from the Web site: http://www.surgeongeneral.gov/library/mentalhealth/chapter5/sec4.html
Newhouse, B. (2007, Feb 24). H.M.'s brain and the history of memory. Weekend Edition Saturday, National Public Radio. [incudes audio recording].
Robinson, J. L., Lee, E. B., Xie, S. X., Rennert, L., et al (2018). Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain, 141, 2181-2193.
Scheltens, P. et al. (2021). Alzheimer’s disease. Lancet, 397, 1557-1590. https://doi.org/10.1016/S0140-6736(20)32205-4
This page was first posted April 17, 2005