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April 25, 2021
  

[Brain Image]    

PSY 340 Brain and Behavior

Class 32 Learning, Memory, and Memory Loss

   

I. 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
            S. Lashley]Karl Lashley's FAILED Search for the Engram

[Lashley's 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:

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

[Lateral Pontine Nucleus] Richard Thompson

II. Types of Memory

[Donald O.
            Hebb]   Short- and Long-Term Memory

Donald O. Hebb proposed in the late 1940s a model of memory with two different components:

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

[Baddeley's
          Working Memory Model]   Alan Baddeley's "Working Memory": A Modern Advance
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:

Dorsolateral prefrontal cortexWe 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.

[Mammillary bodies]  [dorsomedial
            nucleus]

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

Auguste Deter -
            1st person to be diagnosed with ADB. 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 other disorders.

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.

Incidence of
            Ad among those over age 65AD 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.

  Genetic Factors

Progression of
          AD in the brain 

  brain tissue adCellular Pathology in AD

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.

  Brain Pathology in AD

AD: Normal vs.
        AD brain

  Infant Amnesia (Not responsible for this section; we won't be covering it)



References

Alzheimer'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/s41588-018-0311-9

Kolata, 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