Richard G. Petty, MD

Genes, Culture and Aging

The study of genetics is becoming ever more interesting. Not only have we gone well beyond the nature/nurture debate, but also there is more and more interest in genetic influences on culture and vice versa: the way in which culture impacts gene expression. It is also clear that our brains are amazingly plastic: nutrition, emotional environment, education and experience all impact brain development.

Now it appears that culture does indeed affect the brain.

Westerners and East Asian people process visual information differently: Westerners preferentially process objects, while Asians tend to pay more attention to contextual information. In studies of semantic organization, Asians associate pictures based on functional relationships, for instance grouping together a mother and her child based on maternal relationship. Westerners based their associations on physical features and categorical membership, such as grouping together a woman and a man because they are adults. These differences may be changing as young people in Asian cultures are becoming more westernized.

New research has found that the aging brain reflects cultural differences in the way that it processes visual information. This study “Age and culture modulate object processing and object-scene binding in the ventral visual area” is published this month in the journal Cognitive, Affective & Behavioral Neuroscience. This paper (which can be downloaded here) and another published by the same group in 2006 are the first to demonstrate that culture can alter the brain’s perceptive mechanisms.

The research is the result of a collaboration between Denise Park’s group from the University of Illinois and Michael W. Chee, of the Cognitive Neuroscience Laboratory, SingHealth, in Singapore. The researchers conducted an array of cognitive tests on study subjects at their facilities in the U.S. and Singapore, and used identical functional Magnetic Resonance Imaging (fMRI) scanners at both sites. Their analysis involved 37 young and old East Asians, and 38 young and old Westerners. They found significant cultural differences in how the older adults’ brains responded to visual stimuli.

As Professor Park said,

“These are the first studies to show that culture is sculpting the brain. The effect is seen not so much in structural changes, but at the level of perception.”

We have known for decades that East Asians and Westerners process visual information differently. A paper in 1972 reported that East Asians are more likely to pay attention to the context and relationships in a picture than are Westerners, who more often notice physical features or groupings of similar subjects.

More recent research, which analyzed the eye movements of East Asians and Westerners viewing identical images, found that Westerners were more attentive to central, or dominant, objects, while East Asians paid more attention to the background, or scene.

Last year the team reported differing patterns of neural activation in the brains of East Asians and Americans shown identical pictures. The Americans showed more activity in brain regions associated with object processing than the East Asians, whose brains showed more activity in areas involved in processing background information.

The new study takes this work further, comparing neural responses to visual stimuli in young and old adults in both cultures. These are some of the pictures they used in the experimenets:

The researchers found that all four groups – young and old East Asians; young and old Americans – processed background information in part of the brain called the parahippocampal gyrus: a region that is vital to memory encoding and retrieval. As expected, older adults in both cultures had less ability to use “binding mechanisms” – the ability to connect a particular object to its background – in the hippocampus. The older people also had diminished object processing in the lateral occipital cortex.

The most striking finding was that the “object areas” of the brains of older East Asian subjects responded much more weakly to novel stimuli than did those same brain regions in the older Americans. For the older East Asians, a lifetime of attention to the backgrounds, or context, of pictures eventually showed up as a diminished response in the part of the brain that keeps track of foreground objects.

One of the best ways of keeping the brain healthy is with cognitive cross training: doing things like crossword puzzles, but also doing things that exercise other cognitive muscles, like playing the piano. This research would suggest that the exact strategies that we should use will be different in native-born Asian and western-born people. Something to factor in the next time that we get some advice about how to keep the brain young for as long as possible.


Memory is a Key to Visualization

Most of us have been told something about the potential benefits of visualizing an outcome, and I know from working with many athletes, chess players, dancers and even surgeons, that most are very good at visualizing exactly what they want and where they are going to be.

I have recently talked about the ways in which encoding of memory for faces and the crucial role of memory in creating images of the future.

There is some important confirmatory research from the Wellcome Trust Centre for Neuroimaging, University College in London. A study led by Dr Eleanor Maguire has just been published in the Proceedings of the National Academy of Sciences. It involved five participants with dense amnesia caused by damage to the hippocampus on both sides of the brain.

The researchers asked the participants – and a control group without amnesia – to imagine several future scenarios, such as visiting a beach, a museum and a castle, and then to describe what the experience would be like. They then analyzed the subjects’ comments sentence by sentence, scoring each statement based on whether it involved references to spatial relationships, emotions or specific objects.

All but one of the people with amnesia were worse at imagining future events than people with normal memory. Their visualizations of future events were more likely to be disorganized and lacking in emotion.

Here is a quotation from one of the subjects:"It’s not very real. It’s just not happening. My imagination isn’t…well, I’m not imagining it, let’s put it that way."

The hippocampus does not simply relive past experiences, it also supports our ability to imagine any kind of experience including possible future events.

This is yet more evidence against the idea that memory works like a kind of video camera, passively recording your life. It is a far more dynamic process that include your own beliefs, emotions and expectations.

“A rock-pile ceases to be a rock-pile the moment a single man contemplates it, bearing within him the image of a cathedral.”
–Antoine de Saint-Exupéry (French Aviator and Writer, 1900-1944)

“All acts performed in the world begin in the imagination.”
–Barbara Grizzuti Harrison (Italian-America Journalist, Essayist and Author, 1934-2002)

“I visualize things in my mind before I have to do them. It’s like having a mental workshop.”
–Jack Youngblood (American Football Player and Member of the Pro Football Hall of Fame, 1950-)

Brain Gain

We have previously discussed how a relatively small number of strategies can dramatically reduce your risk of cognitive decline as you get older.

Our recommendations are firmly buttressed by a most important article available for free download at the website of the Journal of the American Medical Association.

We already knew that cognitive training can improve cognitive abilities in older adults but nobody had established the effects of cognitive training on everyday function.

Sherry Willis of Pennsylvania State University led a team of scientists that followed a group of 2,832 adults, aged 65 and older -mean age 73.6 years – who were still living independently between 1998 and 2004. The seniors came from all walks of life, races, and parts of the country, including Birmingham, Alabama; Detroit, Michigan; Boston, Massachusetts and three other major cities. They all had one thing in common when the study commenced: they had no signs of cognitive impairment.

The researchers divided them into four groups of roughly 700 each: three groups that would receive training in either memory (verbal episodic memory), inductive reasoning or speed of processing (visual search and identification) with 4-session booster training at 11 and 35 months after training, and one that would serve as a control.

The memory training program consisted of mnemonic strategies for remembering word lists or texts, such as associating various words, visualizing them or organizing them in specific ways. Reasoning training taught the participants how to spot the pattern in a series, such as “a c e g i… .” The researchers boosted the subjects’ processing speed via practice, practice, practice in identifying an object on a screen after increasingly short exposures.

Over the course of the next five years the researchers asked participants to appraise their skills and to report whether the training had helped with everyday tasks. They also independently evaluated the subjects’ skills in things like finding items in a medicine cabinet. After training, 87 percent of the speed trainees, 74 percent of the reason trainees and 26 percent of memory trainees showed immediate improvement. That advantage over their untrained peers persisted over the next five years.

The training seemed to largely offset the cognitive decline suffered by nearly all of the controls as the years wore on. By the fifth year, significant skill gaps had opened between the people who had done the training and their untrained peers.

It is not enough to continue to do the crossword or sudoku puzzles. The brain must be continually stretched and challenged. It seems that to drive this effect, you have to practice things that you don’t like or things you don’t regularly practice.

Many of us have spent years working on new training strategies, and this research shows just how valuable cognitive training can be for all of us.

Memory Molecules

There are still a great many mysteries about memory:

  • The molecules in neurons are constantly changing, as are many of the connections between cells. So how can memory be maintained for a lifetime in an environment that is in a constant state of flux?
  • Why is it that you can remove large regions of the brain yet memories are not lost? Even in the late stages of Alzheimer’s disease, some long-term memories are maintained even when much of the brain is taken over by plaques and tangles.
  • How much memory is there outside the brain and in the body?
  • Is some memory maintained not in the brain itself but in fields associated with the body?


Gradually some questions are being answered not just by technology, but by asking new questions and bringing new types of expertise to bear on these problems.

A very interesting new study was published last week in the Journal of Neuroscience. The paper was not by neurologists, but by two mathematicians from the Brain Institute at the University of Utah. Their research suggests that memories are held in our brains because certain proteins serve as anchors, holding other proteins in place to strengthen the connections between nerve cells known as synapses. The anchors keep proteins in place, and these proteins in turn determine how strong a synapse is. And the strength of the synapse is a key to forming and retaining memories.

Synapses function by electrical activity in a neuron releasing a chemical neurotransmitter that affects another neuron or an organ.

One of the primary neurotransmitters involved in learning and memory is called glutamate, that binds to a number of receptors. But the most important for memory are the "AMPA receptors" that are embedded in the receiving ends of neurons. The AMPA receptors are held in place by special scaffolding molecules.

The mathematicians were able to make several predictions about the way in which AMPA receptors stay in place and how repeatedly learning something strengthens the connections between neurons.

The key to learning and remembering is anchoring AMPA receptors on our neurons.

I went into the technical side a bit, because this finding may help us get closer to understanding what goes wrong in Alzheimer’s disease.

It also ties in with some other research out this week in the journal Neuron. A team from the Univesity of Oxford has been trying to work out why adults may find learning more difficult than children. The young learn things more easily, but older brains stiore information more efficiently. They also focused on synapses, and  seem to have found the mechanisms involved.

Young brains have many "silent" synapses that don’t do anything unless called upon to learn something. Older brains have to reuse synapses that have already been used, boosting the strength of connections with increased amounts of neurotransmitters.

So as we get older, our brains adopt different strategies for learning new material, and we should get ever better at organizing and integrating information.

That also fits with the strategies that we have used for improving people’s ability to learn and remember. We use connections as in Mind mapping, multiple sensory associations inclusing music, color and smells, and a sophisticated method for asking constant questions to see if new information fits with material that we have already asimilated.

A Possible Test for Alzheimer's Disease

I was very pleased for some of my former colleagues from the Institute of Psychiatry at the Maudsely in London.

Years of work by the researchers and unstinting support from pateints and their families seems to be bearing fruit.

Professor Simon Lovestone and his team have published an important paper in this month’s edition of the journal Brain, which is commemorating the centenary of the first description of Alzheimer’s disease. It is very hard to get a paper in to the journal, and the fact that the researchers did, speaks volumes about the quality and importance of their work. The entire article is available online. That was made possible by the Alzheimer’s Research Trust who also funded this work: kudos to them for backing this work and for publicizing the results.

What they have done is to develop a blood test that may be able to pick up signs of Alzheimer’s disease before people start to show symptoms. They used a process called proteomics – the study of proteins – and found levels of two types of protein in the blood that were only present if people had the condition. We do not yet know exactly what the proteins are.

The researchers are quite rightly being cautious at this point. Nobody wants yet again to raise false hopes. There is also the knotty ethical problem of being able to test for people with the earliest stages of the illness. There is the theoretical risk that medical insurers may deny coverage if someone’s test is positive.

But if confirmed, this is of enormous importance: we already know that the earlier that treatment is started the better. And by treatment I certainly do not simply mean medications: controlling blood pressure, glucose and lipids; maintaining optimal nutrition; and taking physical and mental exercise may all slow progression of the illness.

It’s wonderful to have some good news about this often devastating illness.

Erasing Your Neurological Hard Drive

Did you ever see the movie Total Recall, and wondered if it might really be possible to erase someone’s memory and implant a new one? Well, that might just be a little closer than most people realize.

One of the mechanisms of the storage of memories in the brain is thought ot involve a process known as long-term potentiation (LTP), that strengthens synaptic connections between neurons. The mechanism of LTP has been a mystery, but recently it was discovered that there is a biochemical pathway that utliizes something called an atypical protein kinase C isoform,  protein kinase Mzeta (PKMz), that seems to be a key player in LTP.

New research from a team at  SUNY Downstate Medical Center, in Brooklyn, New York, using a PKMz inhibitor reverses LTP and produces persistent loss of 1-day-old spatial information, proving that PKMz is crucial to laying down memories in the brain.

There are many ways of losing memory. Apart from being belabored about the head and shoulders with a stout cudgel, alcohol and benzodiazepines are all fairly reliable ways of causing transient memory loss. But they also may fail, and each may have other unpleasant consequences.

But this is different: undestanding the basic mechanism of memory formation may enable us to obliterate unpleasant or wanwanted memories in conditions like chronic pain and posttraumatic stress disorder. It may also help us understand something more about the mysteries of illnesses like Alzheimer’s and Dementia of Lewy Body type, in which memory can be lost.

But it is also important to keep an eye on this research. I would not like either a government or a corporation to have a way reliably to erase our memories.

Though I’ve often thought that I’d quite like to have one of those little Neutralizers that they had in Men in Black…..

Labor Day Trivia With a Twist

The English language must be one of the oddest. Well actually I know that it is. Except perhaps for those few languages that have managed to get by with hardly any words for emotion. Or the ones that have hundreds of ways of describing snow.

In English there are more than one thousand words describing groups of things, usually animals. Many of these words go back to the Middle Ages: fun to look up on a wet English afternoon. And many have been taking up some of my precious neural storage space for a very long time.

In today’s trivia corner, the question came up as to what name is given to a group of cats? I knew that one, it’s a clowder, and if they’re kittens, it’s a kyndyll, also spelt kindle.

Then I started putting together a few others that I remembered, and looked up a couple more. If you type “Collective nouns” into Google you’ll get hundreds, but I’m not sure about some of them!

Here are a few fun ones:
Army of frogs or ants

Bale of turtles 

Band of gorillas 

Baren of mules
Bed of clams or oysters 

Bevy of quail or swans 

Brace of ducks 

Brood of chicks
Business of ferrets
Cast of hawks 

Cete of badgers 

Charm of goldfinches or hummingbirds
Chine of polecats
Cloud of gnats
Clutch of chicks
Colony of rabbits, ants, gulls and bats
Company of wigeons (they’re dabbling ducks found all over North America)

Congregation of plovers
Convocation of eagles 

Covert of coots 

Covey of quail or partridge
Cry of hounds
Down of hares 

Draft of fish (That one’s rarely used these days)
Dryft (drift) of tame swine 

Drove of cattle, sheep, pigs 
(In the Middle Ages, cows were also called kine or kyne)
Exaltation of larks 

Fall of woodcocks
Flange of baboons
Flight of birds 

Flock of sheep, geese, ducks 

Gaggle of geese 

Gam of whales 

Gang of elk 

Grist of bees
Harras of horses 

Herd of cattle, deer, elephants, horses, and sheep
Hive of bees
Horde of gnats 

Hover of trout 

Husk of hares 

Kettle of hawks
Labor of moles
Lepe or leap of leopards 

Leash of foxes 

Litter of pigs, cats, dogs 

Murder of crows 

Murmuration of starlings 

Muster of peacocks 

Mute of hounds 

Nest of rabbits, vipers, turtles and hornets
Nide, or nye of pheasants 

Pack of dogs, hounds, wolves, and mules
Parliament of rooks or owls 

Pod of dolphins, whales or seals
Pride of lions
Raft of ducks (paddling around on water) 

Rafter of turkeys 

Rag of colts
Route of wolves
School of fish (At one time they were called shoals of fish)
Scold of jays
Sculk of foxes
Sedge of cranes, bitterns, herons 
shoal of bass
Singular of boars
Shrewdness of apes 

Skein of geese (In flight)
Skulk (sculk) of foxes 

Sloth or sleuth of bears 

Sounder of wild swine or boars  

Span of mules 

Spring of teal 

Stud of mares 

Swarm of bees
Team of ducks, horses, pigs, oxen 

Tribe of goats 

Troop of kangaroos or monkeys
Unkindness of ravens

Volary of birds 

Walk of snipe 

Watch of nightingales 

Wedge of swans 

Wing of plovers 

Yoke of oxen
Zeal of zebras

There are some very funny ones that can’t be genuine. Try these:
An addition of mathematicians
A brace of orthodontists
A bunch of florists
A clutch of car mechanics
A concert of yes-men
An expense of consultants
A flash of paparazzi
An intrigue of politicians
A prickle of hedgehogs
A rash of dermatologists
A tedium of golfers

This is all harmless fun. But there’s also a slightly more serious side to it. Developing your vocabulary, even for odd words like these, appears to reduce your risk of developing age-related cognitive decline and should help keep you mentally sharp.

And I’ve got the brain scans to prove it!

Dementia

I have written about Alzheimer’s disease in the past, but it is important for everyone to know that not all dementia, and certainly not all memory loss, is Alzheimer’s disease.

There is a brief article on the Psychiatric Resource Forum website that will point you toward some extra resources.

Our biggest interest is always in ensuring that someone who seems to be developing a dementing illness doesn’t actually have one of the large number of remediable causes of cognitive decline, such as depression, an underactive thyroid, vitamin B12 or folate deficiency, or an unusual condition called normal pressure hydrocephalus.

A New Way of Looking at – and Treating – Inflammation

Diseases of both large and small blood vessels are two of the biggest problem facing people with diabetes. Not only is it a huge clinical challenge, but also nature sometimes does our experiments for us. The high rates of coronary and peripheral vascular disease in diabetes can be seen as a kind of experiment of nature: a recognizable set of chemical abnormalities that might shed light on vascular diseases in general. It was those twin factors: a huge clinical problem, and an experiment of nature, that lead me to pick the topic of my research doctorate. 

When I was working on my research doctorate in the mid 1980s, I came across a lot of old research that seemed to show links between inflammatory and autoimmune conditions like systemic lupus erythematosus and rheumatic fever, and the eventual development of coronary artery disease. There was also a lot of old and largely forgotten research about the link between some viral infections and the development of coronary artery disease and acute coronary artery occlusions, because some infections can make blood more “sticky.” Inflammation evolved as one of the body’s defence mechanisms.

So I made the proposal – revolutionary at the time – that diabetes, coronary artery disease and a range of other illnesses might be inflammatory rather than degenerative. I soon found inflammatory markers in people with diabetes, that helped predict when someone was running into trouble with their eyes, kidneys or heart.  Even with stacks of data, I had to spend a lot of time defending that position, because it also implied that some illnesses thought to be irreversible might not be.

With the passage of time, it has tuned out that I was probably correct. Chronic inflammation, wherever it starts, mat have long-term effects on the body and on the mind. Chronic inflammation increases the risk of diseases of many blood vessels, as well as causing anemia, organic depression and cognitive impairment. Here is a partial list of common conditions in which inflammation is a prominent factor:
1.  Rheumatoid arthritis
2.  Systemic lupus erythematosus
3.  Fibromyalgia
4.  Chronic infections
5.  Insulin resistance or metabolic syndrome
6.  Arteriosclerosis
7.  Diabetes mellitus
8.  Hypertension
9.  Asthma
10. Inflammatory bowel disease
11. Psoriasis
12. Migraine
13. Peripheral neuropathy
14. Alzheimer’s disease
15. Autism
16. Gingivitis
17. Cystitis

The reason for raising the issue is not to say “told you so!”

It is instead that we need to think about inflammation a little differently. There is a mountain of information about the physical aspects of inflammation. We can stop at the simple description of inflammation as a condition in which part of the body becomes reddened, swollen, hot, and usually painful, or we can look below the surface: we can examine inflammation not only as a physical problem, but also as a psychological, social, subtle and spiritual problem. Why bother? Because the deeper approach allows us to understand and to treat and transcend inflammation as never before.

I am going to write some more about specific ways to address inflammation and what it means in future articles. I would also like to direct you to the book Healing, Meaning and Purpose, in which I talk about specific approaches in more detail.

But I would like to start with this.

In Ayurvedic and homeopathic medicine, inflammation is a sign of an imbalance in the vital forces of the body, and the traditional Chinese system agrees: here inflammation is usually a manifestation of an excess of Yang Qi, or a deficiency of Yin Qi. Most of our lives are seriously out of balance: Yang Qi is like a rampaging lion that has been stimulated by:
Acidic foods;
Environmental toxins;
Unwanted sexual stimulation:
Noise;
Discordant music:
Constant demands from others:
Toxic relationships;
Years spent in front of television sets and limitless multi-tasking.

It should be no surprise to learn that all of these inflammatory conditions are increasing rapidly throughout the Western world. Not because we are getting better at identifying them, or we are living longer, but genuinely increasing.

It is wrong to put all the blame on poor diets or inadequate exercise. The problem is more subtle and is a reflection of distorted Information being fed to our bodies, minds, relationships, subtle systems and spiritual relationships.

The great news is that this simple conceptual shift gives us a whole load of new tools for handling these problems, and for using them as catalysts to growth.

In the next few weeks, I am going to drill down and give you some specific guidance that ties into the material in Healing, Meaning and Purpose and the next two that are on the launch pad.

Fasten your seat belt!

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Hunger and Memory

It’s always a good idea to see how new findings fit in with previous knowledge, and also to see if they make sense. We have previously met the hormone leptin, which is involved in decreasing appetite. Its twin is the hormone ghrelin. Discovered in 1999, ghrelin comes from some of the cells lining the stomach and acts in the hypothalamus to increase appetite. When the stomach is empty it is released into the circulation and travels to the brain where it activates receptors in many different regions. Some research has indicated that one of the reasons why gastric bypass surgery may be effective is because it reduces levels of ghrelin and therefore reduces appetite.

Research published in December 2004 showed that in healthy young men, sleep deprivation caused a decrease in leptin levels and an increase in ghrelin levels, which, as expected, was associated with an increase in hunger and appetite. This is one reason why getting less sleep than you need may cause you to gain weight.

A new study published in the journal Nature Neuroscience, has found an intriguing link between ghrelin and memory. I noticed that the BBC also picked up on this interesting story. Researchers at Yale have discovered that ghrelin acts in an ancient part of the brain known as the hippocampus: so named because it is shaped like a sea-horse. (As an amusing aside, the old German pathologists thought it looked like a silk worm, so that’s what they called it!) The hippocampus has a number of functions, but is most of all essential for learning new material.

The researchers showed that mice who lack the ghrelin gene had 25% fewer synaptic connections between their hippocampal neurons. They then did the next step, and injected normal mice with ghrelin. They promptly increased the number and density of their synaptic connections, which correlated with significant improvements in the animals’ performance on several tests of learning and memory.

So that means that a hormone produced by the stomach can control some brain functions, and this may represent a link between metabolism and the ability to learn. The more that we discover, the more we see the intimate interactions between the brain, intestines and heart.

This link makes good sense: we know that memory can be switched on and off by a range of factors. In order to help us come up with options for handling the environment and for remembering things to avoid, memory is often switched on at times of stress. Hunger is a form of stress, and it makes good biological sense that we might be more alert and better able to remember and to recall information when hungry. It stands to reason that this has enormous survival advantage. If our early ancestors had not had this hunger/memory link, they might well have died out in the competition for food.

This gives some credence to the old advice that it is best not to try to study or to take an exam on a full stomach. Just have enough food to make sure that you have ample fuel, and that you are not distracted by hunger pains.

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