Posts Tagged ‘medial prefrontal cortex’

Alzheimer’s Disease (AD)

September 24, 2019

This post is based on an important book by Scott D. Slotnick titled “Cognitive Neuroscience of Memory.” Remember to consult the website http://www.brainfacts.org/
to see the anatomical information referred to in this post.

As AD progresses from earlier to later stages, atrophy starts in the medial temporal lobe, extends to the parietal lobe, and finally includes the frontal lobe. The long-term memory impairment in early AD patients can be attributed to the disrupted processing in the hippocampus and parietal cortex, to regions that have been associated with this cognitive process. As the disease progresses, other cognitive processes are disrupted such as attention and language, which both depend on the dorsolateral prefrontal cortex.

In early AD patients, as atrophy begins in the parietal cortex and the frontal cortex, there have also been reports of increases in fMRI activity within cortical regions. It is unknown whether these increases in cortical fMRI activity reflect a compensatory mechanism, which is often assumed to be the case, or reflect non-compensatory hyperactivity due to neural disruption.

In addition to brain atrophy, AD patients have abnormal high levels of proteins in different brain regions. In the medial temporal lobe, the accumulation of tau protein leads to neurofibrillary tangles. In cortical regions, such as the parietal cortex in early AD, the accumulation of amyloid-B protein leads to amyloid plaques. The neurofibrillary tangles in the medial temporal lobe and amyloid plaques in cortical regions can be assumed to disrupt neural processing in these regions.

Dr. Slotnick writes, “There is an influential hypothesis that there is a causal relationship between default network activity that leads to deposition of amyloid that results in atrophy and disrupted metabolic activity, which impairs long-term memory in AD patients. The regions in the default network are active when participants are not engaged in a task and include the dorsolateral prefrontal cortex, the medial prefrontal cortex, the inferior prefrontal cortex and the medial parietal cortex. In AD patients, amyloid deposition occurs in the same regions, which suggest the default network activity may lead to amyloid deposition. Dr. Slotnick suggests that perhaps higher level of amyloid deposition, which occurs in late AD patients, is necessary to produce atrophy in the frontal cortex.

Healthy memory readers should recognize the similarity between the default network and Kahneman’s System 1 processing. System 1 processing is the default network that needs to be disrupted to engage in System 2 processing, better known as thinking.

Dr. Slotnick continues, “If high amyloid deposition is a causal factor in developing AD, older adults with low levels of amyloid should be at decreased risk for developing this disease. There is some evidence that cognitive engagement and exercise throughout life may reduce the amyloid level in the brains of healthy older adults as a function of cognitive engagement (System 2 processing), and this was compared to the cortical amyloid levels . Participants rated the frequency which they engaged in cognitively demanding tasks such as reading, writing, going to the library, or playing games at five different ages (6, 12, 18, 40, and their current age). Healthy older adults with greater cognitive engagement throughout their lifetime, as measured by the average cognitive activity at the five ages, had lower levels of amyloid in default network regions. Moreover, the healthy older adults in the lowest one-third of lifetime engagement had amyloid levels that were equivalent to AD patients, and the healthy older adults in the highest one-third of lifetime cognitive engagement had amyloid levels that were equivalent to young adults.

It should also be noted that many have died who upon autopsy had levels of amyloid plaque and neurofibrillary tangles definitive of AD, but who never exhibited any of the behavioral or cognitive symptoms characteristics of the disease. The explanation typically offered for these individuals is that they had built a cognitive reserve as a result of the mental activities they had engaged in during their lifetimes.

There is a wide variety of products sold to prevent AD, such as computer games and pills that increase short-term memory. But it should be clear from the posts on cognitive science that the entire brain is involved. That is why the healthy memory blog strongly recommends growth mindsets with continual learning throughout the lifespan. These make heavy use of System 2 processing. Of course, a healthy lifestyle that includes physical exercise must also be part of the mix.

The Happiness U-Curve

March 16, 2017

This post is based on a section with the same subtitle in “The Cognitive Upside of Aging” an article by Alexandra Michel in the February 2017 “Observer”, a publication of the Association of Psychological Science (APS).

Despite all the negative components of aging, researchers consistently find a happiness paradox:  As the body declines, happiness tends to increase.  Across the lifespan this “Positivity effect” follows a U-shaped pattern:  happiness starts out high in late adolescence, bottoms out in middle age, and reaches a second zenith in old age.

A 2011 Gallup analysis of 500,000 phone interviews found that “a septuagenarian is far more likely than someone in their 30s to have high emotional health.  This happiness advantage held true even after controlling for demographic factors, including gender, race, education, marital status, employment, and regional location.

This happiness U-shape appears across the world.  Economists Andrew Oswald and David G. Blanchfower documented this pattern in more than 500,000 people living in more than 70 different countries.  Their analysis concluded that from Azerbaijan to Zimbabwe, people around the world tend to be happiest in their old age regardless of their nationality.

Oswald says, “Only in their 50s do most people emerge from the low period.  But encouragingly, by the time you are 70, if you are still physically fit then on average you are as happy and mentally healthy as a 20 year old.  Perhaps realizing that such feelings are completely normal in midlife might even help individuals survive this phase better.”

This universality of happiness U-curve implies the aging may play a positive role in the brain.  A team of Australian researchers led by Leanne Williams, who is now at the Stanford University School of Medicine, argues that a combination of neurological changes and life experiences account for this phenomenon.  Using functional magnetic resonance imaging (fMRI) to monitor emotional processing as people of various ages viewed photographs of different facial expressions, the researchers found that older people were more emotionally stable and less reactive to negative emotional stimuli than younger people.

Contrary to the ubiquitous negative stereotypes of declining memory and cognitive integrity, Williams and colleagues found emotional well-being may increase with normal aging.  Their study included 242 individuals (122 males and 120 females) divided up into four major age categories:  12-19 years, 20-29 years, 30-49 years, and 50-79 years.  Participants were assessed in the scanner for the neural activation evoked by emotions of threat and happiness depicted in facial expressions.  After being shown a photograph of a face, participants had to select the best option for identifying the emotion being displayed in the photograph.  They also rated on a 1-to-5 scale, the intensity of the emotion being displayed.
Rather than showing an inevitable decline across all functions, the images displayed a linear increase in emotional stability with age, meaning that people in their 70s ultimately experience better emotional well-being than most people in their 20s.

The fMRI results suggest that as we age, the way our brains process emotional stimuli  changes in ways that favor emotional stability.  The brain scans indicated that the medial prefrontal cortex (mPFC), which is a brain area involved in the governance of emotional functions, processed stimuli differently across the lifespan, contributing to better emotional stability for older adults.  As we age, the mPFC areas become increasingly active while processing negative emotions compared with positive ones, suggesting that older people were comparatively better at controlling negative emotions.

This article ends as follows: “Ultimately Williams and colleagues argue that as we age this combination of neural processing, as well as an accumulation of life experience, provides older adults with the neural tools to take life in stride—a capability their younger counterparts will just have to wait for.”

Can You Remember Things that Never Happened?

March 24, 2016

This post is based largely on portions of the fourth chapter in Elixir J. Sternberg’s Book “Neurologic and the Brain’s idea Rationale Behind Our Irrational Behavior.” The title of this post is the same as the title of Chapter 4.  Regular readers of the health memory blog should know the answer to the question posed in the title.  The answer is “yes.”  Elizabeth Loftus and others have done extensive research in this area.  They have a variety of methodologies for implanting false memories so that they are definitely believed.  I saw an example of one of these experiments on the PBS program NOVA.  In this case the research participants were convinced of a crime that they never had committed.  To find previous posts on this topic enter “Loftus” into the search block of the healthy memory blog.

Sternberg begins the chapter with a quote from Gabriel Garcia Marquez that largely captures the workings of our memories.  “He was still too young to know that the heart’s memory eliminates the bad and magnifies the good, and that thanks to artifice we manage to endure the burden of the past.”

A research group in Israel filmed a young woman, with no history of memory problems for two days straight.  Except for the cameras they were ordinary days.  At various intervals over the next few years she filled out questionnaires that tested her memories of those days.  The researchers used fMRI while she was filling out these questionnaires.  Over time the more distorted her memory became for the details.  What was especially interesting was how her brain activity changed over time while filling out the recall questionnaires.  As time passed and the memory errors accumulated, her memory appeared to be less endless reliant on the activity of the hippocampus.  The fMRI revealed reduced activation there as her recollection became more distant.  Other regions of the brain, including the medial prefrontal cortex and associated regions, became more and more active.  The medial prefrontal cortex is associated with self-centered thinking.  Her memory was accessing not simply a record from a neurological file, but a representation stored across multiple systems.  Her memory drifted away from accurately recording the details of that time period and instead became focused on her.

“To a large extent, our memories define us.  Our personal history forges our self-image and assembles our store of knowledge.  When the unconscious system in the brain encodes our memories, it is shaping who we are.  It doesn’t record our experiences impartially as a video camera would, because it focuses on our role in the story, on the aspects that we care about.   At any given moment, there is a context of how we are feeling, our emotions at that instant, what we are expecting or dreading, and what that moment means to us.  It is on that basis that the brain begins to compose its first draft.”

Three years after 9/11, two groups of New York City residents were enrolled in an experiment to learn how their emotions at the time of the attacks might have affected their memory.  The first group of people who were in downtown Manhattan that day close to the World Trade Center, and who personally witnessed the events of that day,  The second group consisted of people who were in midtown several miles away.  As would be expected, the downtown group rated their memories as being more vivid, more complete, and more emotional instances that the midtown group did.  And they had more confidence in the accuracy of their memories, but the neurological results revealed a different story.

The hippocampus is the area key to episodic memory, of which recalling 9/11 is a conspicuous example, but depending on the type of memory being accessed, other areas of the brain may be recruited to varying degrees.  For example, the amygdala may be activated when the memory is of an emotional nature, and the posterior parahippocampal cortex will become more involved when the brain attempts to access the more meticulous spatial details surrounding the event.  The members of the midtown group showed activation of the posterior  parahippocampal cortex as they recalled the details of 9/11, but only trivial amygdala activity.  It was just the opposite for the downtown group.  They exhibited striking activity in the amygdala but not in the posterior parahippocampal cortex.  This neuroimaging suggests that the downtown group recalled the events of the day for their emotional impact at the expense of remembering peripheral details.  Studies have revealed that the more emotionally  affected people are in recalling 9/11, the better they are at consistently describing the central events of what happened to them that day, but the worse they are at providing reliable description of the emotionally  neutral details.

There is a technical difference between telling a lie and confabulation.  A person telling a lie knows that he is telling a lie.  However, a person confabulating is trying to make a coherent story where substantial memory loss has occurred.  The chapter begins and ends with a man with both severe mental and addiction problems and a faulty memory.  He continually tries to put together a coherent story from the scraps of memory he can access, because he does not want to admit that he does not know.  Although his is a clinical case, we all work to make coherent stories from what memories we can find.  The unconscious system takes a self-centered egocentric approach to construct good narratives.