Richard G. Petty, MD

Jazz and the Brain

It is remarkable how good the brain is at coordinating multiple regions at once. A new study published in today's issue of the journal Public Library of Science (PLoS) One has used functional magnetic resonance scanning (fMRI) to examine musicians engaged in highly creative and spontaneous jazz improvisation. They found that a large region of the brain involved in monitoring one's performance is shut down, while a small region involved in organizing self-initiated thoughts and behaviors is highly activated. The researchers propose that this and several related patterns are likely to be key indicators of a brain that is engaged in highly creative thought.

During the study, six highly trained jazz musicians played keyboard under two conditions. In the first scenario, called the Scale paradigm, the music was based on a simple C major scale. Using only their right hand, the volunteers first played the scale up and down in quarter notes. Next, they were asked to improvise, though they were limited to playing quarter notes within the C major scale.

The second scenario, called the Jazz paradigm, examined higher-level musical improvisation. This paradigm was based on a novel blues melody that the volunteers had memorized beforehand, and had been written by one of the researchers. Again, using only their right hand, the musicians played the tune exactly as they had memorized it, only this time accompanied through headphones by a pre-recorded jazz quartet. When they were asked to improvise, the musicians listened to the same audio background, but they were free to spontaneously play whatever notes they wished.

The brain scans were nearly identical for the low-level and high-level forms of improvisation, supporting the idea that the change in neural activity was due to creativity and not the complexity of the task.

Much of the change between improvisation and memorization occurred in the prefrontal cortex, the region of the frontal lobe of the brain that helps us think and problem-solve. It is also involved in generating the sense of self. The dorsolateral prefrontal cortex is responsible for monitoring our own performance and it shuts down completely during improvisation, while the much smaller, centrally located region at the foremost part of the brain – the medial prefrontal cortex - increases in activity. The medial prefrontal cortex is believed to be involved in self-initiated thoughts and behaviors, and it becomes very active when a person describes an event that has happened to him or makes up a story.

The suppression of inhibitory, self-monitoring brain mechanisms helps to promote the free flow of novel ideas and impulses. This is an unusual pattern of brain activity that closely resembles the pattern seen in people when they are dreaming.

Another unusual finding was that there was increased neural activity in each of the sensory areas during improvisation, including those responsible for touch, hearing and vision, despite the fact that there were no significant differences in what individuals were hearing, touching and seeing during both memorized and improvised conditions. This suggests that when the brain wants to be creative, a whole range of sensorimotor processing is increased. At the same time systems that regulate emotion were also engaged during improvisation.

As someone who has done a lot of brain imaging, and has spent many hours inside scanners, this whole piece of work is dazzling from a technical point of view. The hardy musicians had to lie on their backs with their heads and torsos inside the scanner and their knees bent upward. They had to use a plastic keyboard, which was shortened to fit inside the scanner and which rested on their knees. A mirror placed over the volunteers' eyes, together with the headphones, helped the musicians see and hear what they were playing.

Just thinking about it makes me queasy.

“Words are the children of reason and, therefore, can't explain it. They really can't translate feeling because they're not part of it. That's why it bugs me when people try to analyze jazz as an intellectual theorem. It's not. It's feeling.”
--Bill Evans (American Jazz Pianist, 1929-1980)

“Jazz tickles your muscles, symphonies stretch your soul.”
--Paul Whiteman (American Musician and Bandleader, called the King of Jazz for popularizing a musical style that helped to introduce jazz to mainstream audiences during the 1920s and 1930s, 1890-1967)

“Jazz music is an intensified feeling of nonchalance.”
--Françoise Sagan (French Novelist and Dramatist, 1935-2004)

Violence and Diet

We have talked before about the link between nutrition and violence.

The evidence has continued to mount and I was pleased to see that the Wellcome Trust is funding trials in three British prisons to investigate the link between nutrition and behavior. This is a placebo study that will examine which nutrients are most important and at what dosage.

Volunteers from three young offenders institutions housing male prisoners aged 16 to 21 will take nutritional supplements in addition to their normal choice of food to ensure they receive the necessary vitamins, minerals and essential fatty acids to meet daily guidelines. The investigators will monitor how levels of nutrients affect a range of behaviors including violence, drug-related offences and incidents of self-harm.

The new trials build on previous research published in the British Journal of Psychiatry that was conducted at the then maximum security Young Offenders Institution in Aylesbury, Buckinghamshire. That study was funded by Natural Justice, a research charity that investigates the social and physical causes of offending behavior. Nutritional supplements  - 2 grams per day of the omega-3 fatty acids EPA and DHA for three months - were given to ensure that inmates' diets reached recommended UK dietary standards. The researchers found that the prisoners who consumed the active nutrient capsule committed on average 26% fewer disciplinary offenses overall than those taking the placebo and 37% fewer violent offenses.

The most likely reason why supplements can have such a large effect is because the proper functioning of nerve cell membranes and signaling molecules depends upon adequate amounts of minerals, vitamins and essential fatty acids in the diet.

This is extremely important work. Clearly nutrition is not the only driver of violence but it has been wondered for a long time whether the industrialization of our diets has contributed to the enormous rise in violent crime between the 1950s and 1970s.

“Violence is the last resort of the incompetent.”
Isaac Asimov (Russian-born American Biochemist and Writer, 1920-1992)

“Blessings crown the head of the righteous, but violence overwhelms the mouth of the wicked.”
--The Bible (Proverbs 10:6)

“Peace cannot be achieved through violence, it can only be attained through understanding.”
--Ralph Waldo Emerson (American Poet and Essayist, 1803-1882)

Judah Folkman R.I.P.

I just heard that Judah Folkman just passed away at the age of 74. That is a name that is not widely known outside the scientific world, although a couple of years ago an excellent book –Dr. Folkman’s War - was written about him and his work.

His major work and his enduring legacy was in the field of angiogenesis: the production of new blood vessels. In the 1960s he came up with the idea that a way to kill tumors was to starve them of the blood supply that they need to survive. He was initially ridiculed, but history is now proving him correct. I got to know him twenty years ago after publishing a paper in which I described the discovery of a growth factor that is involved in the production of new blood vessels at the back of the eye in people with diabetes. Judah was very supportive and we had many good discussions about the potential role of angiogenesis not only in tumors and diabetic retinopathy, but also in diseases like rheumatoid arthritis and psoriasis.

Last November, at the 12th Annual Society for Neuro-Oncology Meeting in Dallas, researchers from the University of Virginia and several other leading brain tumor centers in the United States presented data on the successful use of an inhibitor of angiogenesis in the treatment of glioblastoma multiforme (GBM), the most common form of primary brain cancer. It is hard to treat, and if it recurred after surgery, radiation and/or chemotherapy there was often not much to be done.

Building on Judah’s work, they wanted to see if they could inhibit vascular endothelial growth factor (VEGF) that has an important role in the disease. VEGF fosters the growth of a tumor by stimulating the growth of new blood vessels to feed it. According to earlier studies, bevacizumab (BV) (Avastatin), a humanized monoclonal antibody that specifically targets VEGF, in combination with irinotecan (also called CPT-11) could have a role in recurrent glioblastoma multiforme. The researcher was an attempt to establish the clinical benefit of BV, both alone and in combination with CPT-11, in a multicenter, randomized phase II trial.

The results were very promising, substantially exceeded the pre-specified thresholds set for this work.

They looked at 6-month progression-free survival (PFS) defined as no clinical or MRI tumor growth and the objective response rate (ORR), which measures tumor shrinkage. Secondary endpoints included safety and survival. Response assessments were conducted by an independent radiographic facility that did not know which patients had been treated. All patients were followed for 24 weeks to determine efficacy and safety.

When taking BV, 35.6 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 21.2 percent on average.

The combination of BV and CPT was even more effective, with results of 51 percent and 34.1 percent, respectively.

The investigator group found similar results when they evaluated the patients. Those results showed that 44.7 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 38.8 percent on average. The combination therapy yielded results of 60.9 percent and 46.3 percent, respectively.

The surviving patients have remained in the study and are still being treated and followed, so we shall be seeing some longer-term results in the future.

In the United States bevacizumab has already been approved for the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer.

This is very encouraging research and a fitting tribute to a genuine medical pioneer.

Music, Language and the Brain

For more than two centuries neurologists and others interested in music and language have wondered whether or not language and music depend on common processes in the mind. It has been known that some aspects of language and music are represented in different regions of the brain, but there are also many areas of crossover.

Now, researchers at Georgetown University Medical Center have published evidence in the journal NeuroImage, that the processing of music and language do indeed depend on some of the same brain systems.

Their findings suggest that two different aspects of both music and language depend on the same two memory systems in the brain. One brain system, based in the temporal lobes, helps us to memorize information in both language and music, for example words and meanings in language and familiar melodies in music. The other memory system is focused in the frontal lobes, and this one helps us to learn “unconsciously” and use the rules that underlie both language and music, such as the rules of syntax in sentences, and the rules of harmony in music.

The study involved 64 adults and the researchers used a technique called event-related potentials, in which they measured the brain's electrical activity using electrodes placed on the scalp.

The subjects listened to 180 snippets of melodies. Half of the melodies were segments from tunes that most participants would know, such as "Three Blind Mice" and "Twinkle, Twinkle Little Star." The other half included novel tunes composed by one of the researchers. Three versions of each well-known and novel melody were created: melodies containing an in-key deviant note that could only be detected if the melody was familiar, and therefore memorized; melodies that contained an out-of-key deviant note that violated rules of harmony; the original melodies that acted as the “controls”

They found that violations of rules and memory in music corresponded to the two patterns of brain waves seen in previous studies of rule and memory violations in language. In-key violations of familiar melodies led to a brain-wave pattern similar to one called an "N400" that has previously been found with violations of words. One example that the authors gave: :I'll have my coffee with milk and concrete.” Out-of-key violations of both familiar and novel melodies generated electrical activity over the frontal lobe similar to the patterns previously found for violations of rules in both language and music. Out-of-key violations of familiar melodies also led to an N400-like pattern of brain activity, as expected because these are violations of memory as well as rules.

This research opens up new ways of thinking about the relationships between language and music, and may have implications for speech and language therapy.

“When I hear music, I fear no danger. I am invulnerable. I see no foe. I am related to the earliest times, and to the latest.”
--Henry David Thoreau (American Essayist and Philosopher, 1817-1862)

“There is nothing better than music as a means for uplifting the soul.”
--Hazrat Inayat Khan (Founder of the Sufi Order of the West, 1882-1927)

“There are more love songs than anything else. If songs could make you do something we'd all love one another.”
--Frank Zappa (American Composer, Guitarist, Satirist and Song Writer, 1940-1993)

“Since music is a language with some meaning at least for the immense majority of mankind, although only a tiny minority of people are capable of formulating a meaning in it, and since it is the only language with the contradictory attributes of being at once intelligible and untranslatable, the musical creator is a being comparable to the gods, and music itself the supreme mystery of the science of man, a mystery that all the various disciplines come up against and which holds the key to their progress.”
--Claude Lévi-Strauss (Belgian-born French Social Anthropologist, 1908-)

Brain Mapping and ADHD

It is amazing how many people remain resistant to the idea that Attention Deficit Hyperactivity Disorder (ADHD) is a genuine problem. It is likely becoming more common as we live in a progressively more demanding world in which our inner resources can easily become overwhelmed. It is a “real” problem since if it is severe it can cause suffering and second, ADHD can also be associated with a range of other difficulties. There is also more and more evidence that it is associated with robust disturbances in the structure and functioning of the brain.

There is an important study published in Human Brain Mapping that reveals an association between ADHD and a decrease in cortical volume, surface area and folding throughout the brain. Researchers from the Kennedy Krieger Institute in Baltimore, Maryland, found that children with ADHD has decreased total brain volume and decreased volume throughout the cerebral cortex. What is new is that the reduction in cortical volume seems to be the result of decreased folding in the cortex. This in turn suggests that folding – a process that starts around the 14th-16th weeks of pregnancy and continues into infancy - is the key structural brain feature associated with ADHD.

The investigators examined 21 children with ADHD aged 8-12 years, and a control group of 35 unaffected children matched for age and gender. The children with ADHD had more than 7 percent reduction in total cerebral volume compared with the control group.

One of the design problems in human beings is that the brain is encased in a hard skull that moves little. So once the brain has grown to fill the skull, the only way to increase the surface area of the brain is for the cortex to become more folded. The whole process of cortical folding is crucial to increasing the structural and functional capacity of the brain.

This is of great interest, particularly in light of the study just published in the Proceedings of the National Academies of Sciences that indicates that the brain of people with ADHD can catch up later. That study did not look at brain folding, so it will be interesting to see exactly how the brain can catch up, and how we might be able to give it a helping hand.

Mature Plasticity in the Human Brain

The more we look, the more we understand that the human brain retains a remarkable ability to learn and re-fashion itself well into old age. The old idea that young brains are flexible, but that age causes us to become “hard-wired” and inflexible is not correct.

This has been confirmed in some new research that has just been published in the journal Neuron by investigators from Johns Hopkins who have shown that adult neurons are not glued in place as rigidly as had been thought.

The investigators led by David Linden used a new technique known as two-photon microscopy that allowed them to living neurons at work in the intact brain. The researchers injected fluorescent dye into the brains of mice to illuminate a subset of neurons and then viewed these neurons through a window in the skull of living, anesthetized mice.

They examined neurons that extend axons to the cerebellum, a region of the brain involved in coordinating motor and sensory information. These axons have a primary trunk that runs upward and several smaller branches that sprout out to the sides.

While the main trunk was firmly connected to other target neurons in the cerebellum, the side branches were mobile: Linden describes them like this:

"The side branches swayed like kite tails in the wind."

Over the course of a few hours, individual side branches would highly dynamic behavior, elongating, retracting and morphing. These side branches also failed to make conventional synaptic connections with adjacent neurons. The motion of the side branches was arrested stalled by a drug that produced strong electrical currents in the axons.

Why the brain would want such motile, non-connected branches remains a mystery.

They may provide a second mechanism for conveying information beyond traditional synapses. Alternatively they may be involved in nerve regeneration.

Whatever the final answer, it is clear that the adult brain remains a remarkably plastic, fluid and flexible structure.

Excellent news for all of us!

“That which is flexible and flowing will prosper and grow. That which is rigid and blocked will wither and die.”
--Tao D Ching

“When a noble life has prepared old age, it is not decay that it reveals, but the first days of immortality.”
--Muriel Spark (Scottish Writer, 1918-)

"You will stay young as long as you learn, form new habits and don’t mind being contradicted.”
--Marie, Baronin von Ebner-Eschenbach (a.k.a. Baroness Marie von Ebner-Eschenbach, Austrian Writer, 1830-1916)

Attention Deficit Disorder and the Growing Brain

An extremely important article by researchers from the National Institute of Mental Health has just been published in the Proceedings of the National Academies of Sciences. It suggests that children with Attention Deficit Hyperactivity Disorder (ADHD) have brains that develop more slowly than those of children without ADHD. However in most cases they still follow a normal pattern of development.

In a study of 450 children, 225 of whom had ADHD, the researchers found that the cerebral cortex of children with ADHD developed about three years more slowly.

The primary measure that they used was the peak thickness of the brain, which is normally taken to be a sign of maturity. Half of the children with ADHD reached peak thickness when they were an average of 10.5 years old, compared with 7.5 years among children without ADHD.

Even if the brain is developing more slowly, the fact that it appears to grow normally is reassuring, and may explain why a substantial proportion of children with ADHD do grow out of it as they get older. Though it still leaves us with several questions:

• Why does the delay occur at all?
• Why do so many people NOT grow out of it, and have persistent symptoms in adulthood?
• Is the brain really “catching up?” The brains of people without ADHD also continue to develop and grow

The National Institute of Mental Health has also published a nice press release that includes a video of brain maturation. You can find it here.

Close Your Eyes and I’ll…

Every young neuroscience student learns about a classic experiment that was published in 1956 by Raul Hernandez-Peon, in which he had an electrode in the acoustic nerve of a cat, while a metronome was ticking. Every tick caused a pulse of electricity in the nerve. But as soon as the cat saw or smelled a mouse, the electrical activity plummeted: now all of his attention was on lunch, and his brain damped down the unnecessary ticking of the metronome. Something similar happens with the “Cocktail Party Phenomenon:” our ability to focus our listening attention on a single talker and ignoring other conversations that are going on.

A study by researchers from Wake Forest University Baptist Medical Center and the University of North Carolina was presented at the Society for Neuroscience conference in San Diego this week, suggesting that our brains can turn down our ability to see, so that we are better able to listen and focus on music and complex sounds.

The research used functional Magnetic Resonance Imaging in 20 non-musicians and 20 musical conductors aged 28-40, and found that both groups diverted brain activity away from visual areas during listening tasks. The activity fell in the visual regions areas as it rose in auditory ones. But during harder tasks the changes were less marked for conductors than for non-musicians.

While being scanned the subjects were asked to listen to two different musical tones played a few thousandths of a second apart and identify which was played first. The task was made harder for the professional musicians than for the non-musicians, to allow for the differences in their background.

As the task was made progressively more difficult, the non-musicians carried on diverting more and more activity away from the visual parts of the brain to the auditory, as they struggled to concentrate on the music. However, the conductors did not suppress their brains, suggesting that their years of training had given them an advantage in the way that their brains were organized and functioning. They are less likely to be distracted and are highly tuned to musical sounds.

This is like closing your eyes to listen to music and the advantage of the trained musicians is similar to the advantage that we see in the brain of the chess master compared with the amateur. Years of study and practice enable the chess player to move without much conscious thought.

It shows how well we are able to divert activity from one part of the brain to another as needed. It is that ability to be flexible and to recruit more brain when we need it that lies at the heart of the neurocognitive revolution that is changing the way that we think about the brain and mind.

Minocycline and Neurological Disease

We recently talked about the fascinating new data on the use of the antibiotic minocycline for treating stroke. The reason is that minocycline is also an anti-inflammatory and it also prevents “apoptosis” or programmed cell death. It has been found to be neuroprotective in animal models of stroke, traumatic brain injury and neurodegenerative disorders. Minocycline also prolongs survival and reduces the loss of motor neurons in transgenic mouse models of amyotrophic lateral sclerosis (ALS), a.k.a. motor neuron disease, a.k.a. Lou Gehrig's disease.

But as with any new research, we always have to go back and re-check and replicate everything. How many times have you heard a news item about some major breakthrough, and then you never again hear anything about it?

An article in today’s issue of the Lancet has indicated that minocycline may be harmful to people with ALS. This is important and will have implications for several clinical trials that are either planned or in progress for trying minocycline in people with dementia, stroke, Huntington's disease and multiple sclerosis.

The United States Western ALS Study Group based at Columbia University in New York, undertook a randomized phase III trial to test the efficacy of minocycline as a treatment for ALS in 412 patients. Patients who took minocycline deteriorated at a 25% faster rate compared with people on placebo.

Therefore the authors suggest that trials of minocycline in other neurological diseases should be reassessed. It is possible that minocycline might be detrimental in patients with other neurological diseases as well.

There is also an editorial comment by Mike Swash, who was once one of my teachers. He talks about the importance of early diagnosis in ALS:

"Clinicians and patients alike would prefer ALS therapy to be tested as early as possible, but there are unresolved difficulties with accurate early diagnosis, particularly the absence of a specific diagnostic test. Might some of the compounds that have failed in clinical trials show benefit if tested at disease onset in human beings?" He concludes that the time has come for new approaches to trial design: "The aim must be to design informative, short, inexpensive, and sensitive phase I/II studies before large phase III studies are attempted".

This is another one of those examples where a medicine introduced for one indication may have many others. In contrast to an antibiotic being used to treat neurological problems, there has recently also been a great deal of interest in the antibiotic potential of some medicines used to treat depression and psychosis.

There is a mountain of new information on this topic, which promises to revolutionize many of our concepts of health and disease. I shall keep you posted as more material is published.

Rewiring the Dyslexic Brain

Dyslexia can be a real difficulty for many children, although for many it has been a gift: they have succeeded very well in life by mobilizing other psychological and neurological resources. Sir Richard Branson, the founder of Virgin Enterprises, Thomas Edison and Albert Einstein are all said to have had dyslexia.

There are many types of dyslexia, but in the most common - developmental dyslexia – children confuse letters and syllables when they read.

It now appears that some children with dyslexia struggle to read because their brains are not correctly wired to process fast-changing sounds, according to a study published this month in the journal Restorative Neurology and Neuroscience.   

However sound training using computer exercises was able to rewire children's brains, correcting the sound processing problem and improving reading.

More than 30 years ago Paula Tallal of Rutgers University proposed that children with dyslexia might have an underlying problem processing sound, but it has never been tested using brain imaging. The researchers used functional MRI imaging (fMRI) to examine how the brains of twenty two 9- to 12-year old children with developmental dyslexia, and normal readers, responded to sounds, both before and after using educational software called Fast ForWord Language.

The first test involved measuring how the children's brains responded to either fast-changing or slow-changing sounds that resembled speech. The fast-changing sounds altered in pitch or other acoustic qualities quickly. In just tens of milliseconds, as occurs in normal speech. The slow-changing sounds changed over only hundreds of milliseconds.

In normal readers, 11 brain areas became more active when the children listened to fast changing, compared to slow changing, sounds. In dyslexic children, the fast-changing sounds did not stimulate high levels of activity in these regions of the brain. Instead, dyslexic children processed the fast-changing sounds as if they were slow changing. They used the same regions of the brain but at lower intensity.

We know that infants must correctly process fast-changing sounds as they learn language. They use sound processing to create a sound map of their native language. If they are unable to analyze fast-changing sounds, their sound map may become confused. The idea is that they run into trouble when they first see printed letters because the children's brains now try to match their internal sound map to letters that they see on the page. Linking normal letters to confused sounds may lead to syllable-confused reading.

But the brains of the children with dyslexia changed after completing exercises in a computer program known as

The Fast ForWord Language program does not involve reading at all, but only listening to sounds, starting with simple, changing noises, like chirps that swooped up in pitch. The children then have to respond with a clicker when the chirp's pitch goes up or down. At first the sounds are played slowly, but they gradually speed up, becoming more challenging for dyslexic children. The exercises are then repeated with increasingly complex sounds: syllables, words, and finally, sentences.

The fMRI study showed that these repetitive exercises appeared to rewire the dyslexic children's brains: after eight weeks of daily sessions - about 60 hours in total - their brains responded more like the brains of typical readers when they were processing fast-changing sounds, and at the same time their reading improved.

It is still early days for this research, and we do not yet know whether the improvements in reading and in the brain will be sustained.

This research may make it possible to identify children at risk of dyslexia even before they start learning to read. It is also possible that other approaches to learning sounds, such as learning to sing or play an instrument may be effective, since most of us learn music with gradual, repetitive, and intense listening and move up to faster changing sounds.

Decision Making and Internal Balance

Many of us run into problems when we try to make decisions. In a special section in the October 26 issue of the journal Science, Martin Paulus who is a professor in the Department of Psychiatry at the University of California in San Diego, has marshaled a growing body of evidence that human decision-making is inextricably linked to an individuals' need to maintain a homeostatic balance.

He goes on to suggest that psychiatrists may need to approach the treatment of psychiatric patients from a new direction: by understanding that such individuals' behavior and decision-making are based on an attempt to reach an inner equilibrium, in the same way that we try to being our temperature or blood pressure back to a set point. And if the thermostat is broken we may see mental illness and substance abuse.

This makes good sense: in the past decision-making process as a considered series of options and values, but that is not what we see in the clinic. People with addictions and some mental illnesses keep making bad choices, despite being intelligent and insightful.

Recent neuroimaging research shows strong support for the homeostatic nature of decision-making:
The insula is involved in processing interoceptive information: the body's internal state or sense of balance
Damage to the insula stops addiction to cigarettes
Some of the same brain structures implicated in the urge to take drugs are involved in other biological urges

The question addressed in part by this paper are whether changes in decision-making behavior and associated brain functions are a result of pre-existing characteristics - which may predispose individuals to use drugs - or occur as a consequence of long-term use. 

This is certainly an interesting idea, and we shall have to see how it fits as we collect further data.

“The quality of a decision is like the well-timed swoop of a falcon which enables it to strike and destroy its victim.”
--Sun Tzu (Chinese Military Strategist and Author of the “Art of War”, c.400-c.430 B.C.E.)

“The risk of a wrong decision is preferable to the terror of indecision.”
--Maimonides (a.k.a. Rabbi Moses ben Maimon, Spanish-born Jewish Philosopher and Physician, 1135-1204)

“All you have to decide is what to do with the time that is given you.”
--J.R.R. Tolkien (South African-born English Writer, Linguist, Oxford Don and a Member of C.S. Lewis’ Literary Group, “The Inklings,” 1892-1973)

“Decisions are doorway to change and change starts from a moment of decision. One decision can change your life forever!”
--Tony Robbins (American Motivational Speaker and Writer, 1960-)

“Nothing is more difficult, and therefore more precious, than to be able to decide.”
--Napoleon Bonaparte (Corsican-born French Military Strategist, General and, from 1804-1814, Emperor of the French, 1769-1821)

Optimism and the Brain

Humans have a wonderful ability to expect positive events in the future, even when there is no shred of evidence to support them. One of the key components of resilience is optimism. Though there is data to show that there is a genetic contribution to optimism, it is also a psychological attribute that can flow from life experiences as well as attitude that can be developed. Though the motivational coaches who tell us that putting on a happy face will make you happy and optimistic are probably overstating the truth! A lack of optimism is often a sign of clinical depression so learning more about it, is not just an academic exercise.

New research just published in the journal Nature indicates that there are two regions of the brain linked to optimism.

The team from New York University and University College, London, says that the act of imagining a positive future event, for example winning an award or receiving a large sum of money, activates two brain areas: the amygdala and the rostral anterior cingulated cortex (rACC). The finding ties in with earlier studies that suggested that these brain regions malfunction in depression. (1,2)

The investigators first measured how optimistic 15 volunteers were using a standard questionnaire. They were then scanned using functional magnetic resonance imaging (fMRI) while reflecting on one of a number of potential scenarios.

In one part of the trial, subjects followed specific instructions to recall a negative event in the past, such a funeral that they had attended in the past five years. In another experiment they had to imagine what it would be like to be involved in a car crash in the near future. At other points in the study subjects had to reflect on positive events such as winning an award in the past or receiving a large sum of money in the future.

Reflecting on both past and future events activated the amygdala and the rACC regions of the brain. However, positive events, and particularly those imagined in the future, generated a significantly larger response in these regions than reflecting on negative events.

When imagining happy events, the more pessimistic subjects in the trial had less activation of these brain areas than their optimistic counterparts when imagining happy events.

For some time now, many researchers have assumed that the amygdala and rACC are only involved in negative thoughts and negative reactions, but this research indicates that they have an important role in signaling cheerful thoughts. And, what is more, these are also regions of the brain that have been implicated in depression. Previous research has suggested that patients with depression have decreased nerve signaling and fewer cells in the rACC and amygdala.

Is this why people with depression find it so hard to generate positive thoughts?

This is important work that will likely have a great many practical applications.

“Children are born optimists and we slowly educate them out of their heresy.”
--Louise Imogen Guiney (American-born English Poet, 1861-1920)

“Although the world is full of suffering, it is full also of the overcoming of it.”
--Helen Keller (American Blind and Deaf Swedenborgian Philosopher, 1880-1968)

“No man is so old as not to think he can live one year more.”
--Marcus Tullius Cicero (Roman Political Figure and Orator, c.106-43 B.C.E.)

"The way to become happy
Is to think

And to feel

That the very best is yet to come.”
--Sri Chinmoy (a.k.a. Chinmoy Kumar Ghose, Indian Philosopher and Spiritual Teacher, 1931-2007)

The Neurology of Fibromyalgia

Fibromyalgia can be a particularly nasty illness, not least because people who suffer from it have often been misdiagnosed and occasionally even accused of malingering. But the pain can be very real and very severe. There are some very good reasons for believing that it is a neurological problem involving regions of the brain and spinal cord that are involved in modulating pain.

A new study from the University of Bath and Royal National Hospital for Rheumatic Diseases in England has raised some intriguing possibilities for treatment. A year ago, researchers from the same institution reported that there is a reorganization of the sensory regions of the brain n people with chronic pain.

In this new study, researchers asked patients to look at a reflection of one arm while moving their other arm in a different direction that was hidden behind a mirror positioned in front of them at a right angle. So one limb was obscured from view behind the mirror while they could clearly see the other limb and its reflection.

This simple experiment created a mismatch between what the brain sees from sensory input and what it feels through the motor system that controls movement.

Of the 29 fibromyalgia patients involved in the study, 26 reported feeling a transient increase in pain, temperature change or heaviness in their hidden limb - all symptoms of a flare up of their condition.

This suggests that a mismatch between sensory and motor neurons could be at the root of the fibromyalgia.

This study adds to the growing body of evidence that many of the symptoms of fibromyalgia may be triggered or perpetuated by a sensory-motor conflict.

That opens up all kinds of new possibilities for treatment.

Sleep Deprivation and Emotional Instability

Most of the time we are in control of our moods, rather than our moods being in control of us. One of the main things that we learn as we get older is not simply to damp down our emotional reactions, but to make them “contextually relevant:” we produce the right emotional response for the right situation. Yet we also know that there are exceptions: times when our emotions over-run any attempts at our control.

Second, we all know that sleep deprivation can be a Bad Thing. It is known to impair a range of mental and physical activities, including immune function, metabolic control and many cognitive processes, including learning and memory.

It has long been suspected that sleep deprivation can have significant effect on mood. Many of us feel irritable and distractible if we haven’t slept enough, and you may have had the experience of being up all night and feeling a little bit “high” in the morning. It has also been known for centuries that mood disorders are very commonly associated with sleep disturbances, and sleep disturbance is often the first sign that someone with mood problems is running into trouble. So mood and sleep must be linked in some way.

Despite these common observations, there has never been that much empirical evidence for the impact of sleep deprivation on mood, and in particular the effects of sleep deprivation on the brain.

An important new study by researchers from Harvard Medical School and the University of California at Berkeley has just been published in the journal Current Biology, and it is beginning to fill in some of the gaps in our knowledge.

The amygdala is known to be involved in processing of emotionally salient information, particularly unpleasant or aversive stimuli. In mature individuals, the emotional centers of the brain are usually controlled and modulated by an array of connected systems, mainly in the frontal regions of the brain. One particularly important part of the frontal lobes that is involved in controlling the amygdala is the medial-prefrontal cortex (MPFC). Under normal conditions the MPFC is supposed to exert an inhibitory, top-down control of the amygdala, so that we only generate appropriate emotional responses.

The scientists worked with 35 volunteers who were deprived of sleep for 35 hours. Blood flow can be used to deduce which specific regions of the brain are active. The researchers used functional magnetic resonance imaging (fMRI) to examine the blood flow – and therefore activity - in the brains of the volunteers in real time, both during and after sleep deprivation.

After going without sleep, the participants were asked to look at images that were designed to trigger angry or sad emotional responses. The investigators discovered that the amygdala showed 60% higher reactions to the images compared with people who are not sleep-deprived.

This is an extraordinarily large effect and implies that sleep deprivation knocks out the normal control mechanisms in the frontal lobes so that the sleep-deprived brain reverts to a more primitive pattern of activity. As a result we become unable to put emotional experiences into context and produce controlled, appropriate responses.

If we needed any more reasons to get a good night’s sleep, this one is very powerful. It also re-iterates something very important: if you or a loved one have had problems with mood, anger or anxiety, it is essential to watch your sleep pattern. Any change may be a harbinger or trouble, and is an excellent early warning that you or they need a hand to make sure that things stay on an even keel.

"Your brain shall be your servant instead of your master, you will rule it instead of allowing it to rule you.”
--Charles E. Popplestone (American Author of Every Man a Winner, 1936)

“Control your emotions or they will control you”
--Chinese Proverb

“For the uncontrolled there is no wisdom, nor for the uncontrolled is there the power of concentration; and for him without concentration there is no peace. And for the unpeaceful, how can there be happiness?”
--Bhagavad Gita (Ancient and Sacred Sanskrit Poem Incorporated into the Mahabharata)

“He who controls others may be powerful, but he who has mastered himself is mightier still.”
--Lao Tzu (Obscure Chinese Philosopher, Founder of Taoism and Alleged Author of the Tao-Te Ching, c. 604-c. 531 B.C.E.)

“ . . . let every man be swift to hear, slow to speak, slow to wrath.”
--The Bible, James 1:19

“When angry, count ten before you speak; if very angry, a hundred.”
--Thomas Jefferson (American Writer, Philosopher, Politician and, from 1801-1809, 3rd President of the United States, 1743-1826)

Dopamine, Drugs and Diabetes

We recently talked about the increasing evidence that insulin has many extremely important roles in the brain.

New research by investigators at the Center for Molecular Neuroscience and the Institute of Imaging Science at Vanderbilt University Medical Center researchers, working with colleagues in Texas, has found that insulin levels affect the brain's dopamine systems. These systems are involved in motivation, reward, salience, movement and emotional processing. Disturbances in dopamine pathways have been implicated in substance abuse, as well as schizophrenia, bipolar disorder and attention deficit hyperactivity disorder (ADHD). Drugs that interfere with the dopamine pathways may produce Parkinsonism as well as elevations of the hormone prolactin.

The psychostimulant drugs amphetamine and cocaine, as well as related medications for ADHD, block the reuptake of the neurotransmitter dopamine by dopamine transporters (DATs) thereby increasing the level of dopamine signaling. Some of these compounds also cause a massive surge of dopamine through DATs, resulting in high levels of synaptic dopamine that alter attention, increases motor activity and plays an important role in the addictive properties of psychostimulants.

The reason for examining a possible relationship between dopamine and insulin goes back to the 1970s, when it was reported that amphetamine had no effect on diabetic animals and in the 1980s it was shown that diabetic rats did not show the usual stereotyped behaviors when given amphetamine. There were also odd reports about disturbances in the enzyme dopamine-beta-hydroxylase in experimental diabetes and changes in dopamine D1 receptors in the brains of rats with induced diabetes.

These observations lead to this new research into a possible link between insulin signaling and amphetamine action.

They used a standard a rat model of type 1 diabetes in which insulin levels are massively depleted, and then assessed the function of the dopaminergic pathway in the striatum, an area of the brain rich in dopamine.

In the absence of insulin, amphetamine-induced dopamine signaling was disrupted: dopamine release in the striatum was severely impaired and expression of DAT on the surface of the nerve terminal was significantly reduced.

The lack of the DAT protein on the plasma membrane prevents the amphetamine-induced increase in extracellular dopamine, and in turn, amphetamine fails to activate the dopamine pathways that stimulate reward, attention and movement.

The researchers then gave insulin into the brains of the diabetic animals and found that the system returns to normal, indicating that the lack of insulin in the striatum directly affected amphetamine action.

They also developed a probe for brain DAT activity using functional magnetic resonance imaging (fMRI). In normal, healthy rats with plenty of insulin, amphetamine increased neural activity in the striatum. But in diabetic animals, activity in the striatum was suppressed.

So there is a powerful interplay between dopamine neurotransmitter systems and insulin signaling mechanisms. The results are some of the first to link insulin levels and dopamine function in the brain and hold several implications for human health and disease.

We need to have another look at the effect of diabetes on the brain. We have known that people with diabetes are at increased risk of cognitive impairment and depression, and we had assumed that it was because of hypoglycemia and vascular disease. Those assumptions may have been wrong.

The findings may also be important for diseases with altered dopamine signaling, such as schizophrenia and ADHD. Insulin may have something to do with the underlying brain disturbances in ADHD. Then control of insulin levels and neuronal responses to the hormone may help determine the efficacy of psychostimulants in people with ADHD.

Every now and then you see people on psychostimulant medications who need huge doses. Perhaps their problem lies with insulin rather than dopamine.

Memory and Emotion

Your humble reporter has had more than his fair share of major life events. As a sixteen year old I was a passenger in car that had a meeting with another vehicle driving down the wrong side of the road. This was in England, where folk always do drive on the “wrong” side, but the fellow who was kind enough to arrange the collision could never explain why he was driving on the “American” side.

The interesting thing is that the memory of the crash is seared into my memory: I can remember the license plate of the vehicle that hit us. Some people call that a “flashbulb memory.”

If you live in the United States you probably have clear and fairly accurate memories of where you were and what you were doing on September 11th 2001.

This kind of experience is not uncommon: most of us have noticed that events that occur during heightened states of emotional arousal, such as fear, anger, happiness and sex are far more memorable than less dramatic occurrences. The emotional “load” of an event is a key factor in remembering it. Previous studies have confirmed that heightened states of emotion can facilitate learning and memory.

This makes good evolutionary sense: emotionally charged events are likely to be the ones that we need to remember. From an evolutionary perspective, it is more important to remember where Mr. Saber-tooth Tiger lives, rather than the names of the Kings and Queens of England.

Therefore the regions of the brain that are responsible for the storage of memories need to distinguish between important experiences and those that less significant for survival. The brain must have some mechanisms for giving priority to emotionally charged memories, so that they are converted and stored in long-term memory.

The downside is that in some situations, for instance posttraumatic stress disorder (PTSD), this process can become pathological and people can be tormented by persistent vivid memories of traumatic events.

Writing in the journal Cell, researchers from Johns Hopkins University and their collaborators at Cold Spring Harbor Laboratory and New York University may have identified the biological basis for this phenomenon. Memories in the brain are held in neurological circuits and each new experience creates a new circuit. The investigators have found that the hormone norepinephrine, which is released during emotional arousal, serves to "prime" nerve cells to remember events. They do this by increasing the neurons’ chemical sensitivity at the precise sites where nerves rewire to form new memory circuits.

Norepinephrine is often described as one of the "fight or flight" hormones and it is likely also involved in the third type of response to a threat, which is “freeze.” In the brain norepinephrine energizes the circuit-building process by adding phosphate molecules to a nerve cell receptor called GluR1. The phosphates help guide the receptors to insert themselves next to a synapse.

So when the emotionally-charged brain needs to form a memory, the nerves have plenty of available receptors to quickly adjust the strength of the connection and lock that memory into place.

The researchers targeted the GluR1 receptor after discovering that if it is disrupted in mice, the little creatures develop spatial memory defects. They tested the idea by either injecting healthy mice with adrenaline or exposing them to fox urine, both of which increase norepinephrine levels in the brain.

They then analyzed the brains of the mice and found increased phosphates on the GluR1 receptors and an increased ability of these receptors to be recruited to synapses.

When the researchers put mice in a cage, gave a mild shock, took them out of that cage and put them back in it the next day, mice who had received adrenaline or fox urine were likely to "freeze" in fear, compared with mice who had not been exposed to the adrenaline or fox pee. This implies an enhancement of their memory of the cage and its unpleasant associations.

In a similar experiment with mice genetically engineered to have a defective GluR1 receptor, adrenaline injections had no effect on mouse memory. So this provides us with further evidence of the "priming" effect of norepinephrine on the receptor.

There has been a lot of recent interest in using medications like beta-adrenoreceptor blocker propranolol – which prevents some of the actions of norepinephrine -  to prevent the development of PTSD in people who have been exposed to extreme trauma, and this research may provide the scientific basis for this kind of therapy.

On the other hand, this research leads me to predict that people with overactive GluR1 receptors may be constantly curious about their environment, but also likely to be chronically anxious and more likely to develop PTSD.

We have known for years that propranolol and other beta-blockers may attenuate some of the physical symptoms associated with anxiety. Most people had assumed that the medicine worked by reducing heart rate, shaking and sweating. But experienced clinicians usually find that beta blockers that cross the blood/brain barrier work best, and it may well be that these drugs also have direct actions in the brain itself.

“Recollection is the only paradise from which we cannot be turned out.”
--John Paul (a.k.a. Johann Paul Friedrich Richter, German Novelist and Humorist, 1763-1825)

“The existence of forgetting has never been proved:  We only know that some things don't come to mind when we want them.”
--Friedrich Wilhelm Nietzsche (German Philosopher, 1844-1900)

“The moment we find the reason behind an emotion … the wall is breached, and the positive memories it has kept from us return too. That's why it pays to ask those painful questions. The answers can set you free.”
--Gloria Steinem (American Feminist, Political Activist and Editor, 1934-)

A New Treatment for Alcohol Dependence?

Several news outlets have today picked up on an apparently odd report: topiramate, a medicine used for migraine and seizures, may also help some people who are alcohol dependent.

A 14-week multicenter clinical trial was orchestrated by researchers at the University of Virginia, and published today in the Journal of the American Medical Association.

371 male and female alcoholics, all of whom were drinking heavily at the time of entering the trial, were randomly selected to take topiramate (up to 300 mg/day) or placebo. All of them had a weekly 15-minute intervention with a trained nurse to enhance adherence to the medication and treatment regimen.

Trials of people with substance abuse are always complicated by high non-compliance rates. Some studies skew their results by making the questionable assumption that if someone doesn’t show up, then they must be cured! This study was structured more realistically: dropouts were assumed to have relapsed to their baseline drinking level.

Even when the dropouts were included, topiramate lowered the percentage of heavy drinking days (the number of days in which men consumed ≥5 drinks/day and women drank ≥4 drinks/day, divided by the number of study days) by a mean of 8.44% more than placebo. The topiramate group showed a reduction from 82% to a mean of 44% heavy drinking days during the 14 weeks, while the placebo group had a reduction from 82% to a mean of 52% heavy drinking days.

In a second analysis that tested the study hypothesis for all randomized participants who took at least one study medication dose and had at least one double-blind site visit, topiramate was much more efficacious than placebo, lowering the percentage of heavy drinking days by a mean of 16.19% more than placebo.

Topiramate was more efficacious than placebo, on measures of self-reported drinking and the liver enzyme gamma-glutamyltransferase, which is a sensitive marker of alcohol consumption.

There are some good reasons why topiramate may be helpful: it acts on gamma-aminobutyric acid receptors in the brain, which have been implicated in some addictive behaviors, including over-eating.

A few years ago topiramate was being examined as a possible weight loss agent, since it has effects on feeding and on metabolism.

The trials have been suspended in  North America, primarily because of one of the main side effects of topiramate: it may cause cognitive dulling and word finding difficulties in some people. Those side effects sometimes take a few weeks to develop.

A second point is that when it is used for weight management, some people quickly develop tolerance to its effects.

This new study is interesting and may turn out to be very important. We shall have to see whether the effect on alcoholics is robust and sustained over time.

“All excess is ill, but drunkenness is of the worst sort. It spoils health, dismounts the mind, and unmans men. It reveals secrets, is quarrelsome, lascivious, impudent, dangerous and bad.”
--William Penn (English Quaker, Colonizer in America and Founder of Pennsylvania, 1644-1718)

“One reason I don’t drink is that I want to know when I am having a good time.”
--Nancy Lady Astor (American-born British Politician, 1879-1964)

“Hide our ignorance as we will, an evening of wine soon reveals it.”
--Heraclitus (Greek Philosopher, c.540-480 B.C.E.)

“Where the drink goes in, there the wit goes out.”
--George Herbert (English Religious Poet, 1593-1633)

More Clues to the Biology of Alzheimer’s Disease

Alzheimer’s disease remains a puzzle.

Although there are plenty of people who claim that “The Cause” of Alzheimer’s is… and here you can take your pick of three-dozen theories.

The truth of the matter is that simple explanations - Aluminum, lead, stress, pollution, mycoplasma infections and the rest – fail to explain many of the established observations about the causes of the disease.

From what we know about the genes in the brain, it is highly likely that “Alzheimer’s disease” represents a group of disorders that follow an interaction of sets of genetic and environmental factors.

This notion is supported by a report from investigators at Washington University School of Medicine, St. Louis and several other prominent research centers. The study is published in today’s issue of the journal Neuron and indicates that there a biological link between a protein mutation that causes early-onset Alzheimer's disease (AD) and a gene variant linked to late-onset AD.

The investigators tried to link the function of two known causative factors in AD. Mutations in amyloid precursor protein (APP) cause early-onset Alzheimer's disease (AD), but the only genetic risk factor for late-onset AD is the ɛ4 allele of apolipoprotein E (apoE), a major carrier of cholesterol in the circulation and in cell membranes.

Previous research has shown that mutations in APP can cause early-onset AD when the protein is “cleaved” or split, producing a short toxic protein that builds up in the brain and kills neurons. 

In their experiments with mice and cultured mouse cells, the researchers linked APP to the regulation of apoE and its cholesterol transport function. They found that the normal cleavage of APP in the cell gives rise to a nontoxic fragment (called AICD) that suppresses the gene that produces the cell receptor for apoE, known as LRP1. Crouching in nerve cell membranes, this receptor enables the apoE protein to transport its cholesterol cargo into the cell.

The researchers speculated that the loss of LRP1 function in AD might cause a loss of cholesterol that causes malfunction of neurons.

These observations may turn out to be extremely important. If we can restore the activity of the receptor gene, we might have a new treatment strategy for AD.

Protecting Yourself Against Alzheimer’s Disease

I have a keen interest in healthy aging, and we have talked before about some of the strategies that can help protect you against developing cognitive decline.

New research now shows for the first time that, of all lifelong activities, only a high level of mental or cognitive activity protects against the devastating memory loss of Alzheimer's disease. High levels of social or physical activity are not enough.

Researchers from the Byrd Alzheimer's Institute bred mice that are genetically predisposed to developing the pathological changes of Alzheimer’s diseases in their brains.

They then kept the mice in one of four housing environments -- high social activity, high physical activity, high cognitive activity, or a single housing control environment and watched them from young adulthood through old age.

When the researchers tested the mice in a battery of memory tasks in old age, only the mice given a lifelong high level of cognitive activity were protected against memory impairment. In fact, these "high cognitive activity" mice performed as well as normal mice that do not develop Alzheimer's disease. However the Alzheimer's mice raised in one of the other three environments performed poorly in multiple memory tasks.

Not only was memory protected in Alzheimer's mice by a high level of cognitive activity, but also brain levels of the abnormal protein beta-amyloid were substantially reduced. This protein, thought to be key for Alzheimer's development, remained at soaring levels in the brains of Alzheimer's mice raised in social or physical activity environments. Moreover, the researchers found that only the Alzheimer's mice raised with high cognitive activity had an increase in connections between brain cells. Alzheimer's mice raised in one of the other three housing environments had much fewer connections between their brain cells.

The new study is published in the Neurobiology of Learning and Memory Journal.

The lead researcher is Gary Arendash, and he had this to say:

“Our results call into question the earlier human studies suggesting social or physical activity provides protection against Alzheimer's. Alzheimer's begins in the brain several decades before any symptoms´ show up. That means adults in their forties and fifties need to make lifestyle choices now to decrease their risk of getting Alzheimer's disease later."

This is all correct, but there is still an important question: can we really extrapolate from mice to humans? Mice are social creatures, but not to the same extent as humans beings. The lion’s share of the human brain is dedicated to social activities, so you would expect that social activities will be particularly important in the maintenance of the human brain.

An Antibiotic to Treat Stroke

It is fascinating to see a medicine or a therapy that is used for one thing being applied in a completely different area. A good example is thalidomide, a drug that was introduced in 1957 to treat morning sickness. It was pulled from the market because it could cause terrible fetal malformations. Years later it was discovered that it could be very helpful in the treatment of multiple myeloma, leprosy and Behcet’s disease.

Now a new study has shown that people treated with the antibiotic minocycline within six to 24 hours after a stroke (cerebrovascular accident) had significantly fewer disabilities.

In the study 152 men and women received either an oral dose of minocycline or placebo for five days following stroke. People who received minocycline were treated on average within 13 hours of the onset of the stroke compared to 12 hours for the placebo group. Patients were followed up for three months.

People treated with minocycline had significantly better outcomes than those treated with placebo. By three months, the minocycline group performed four times better than the placebo group on the National Institutes of Health Stroke Scale, which measures vision, facial palsy, movement, and speaking ability.

Minocycline appears to be neuroprotective and to prevent programmed cell death or apoptosis.

This could turn out to be very important because current stroke treatments only work during the first few hours after the onset of symptoms, and many people do not get to the hospital in time to be treated.

Alzheimer’s Disease: Diabetes of the Third Kind?

Insulin may have some extremely important roles in the mind as well as the body.

Though best known for its role in promoting glucose uptake into cells, insulin has at least five hundred known functions in the human body. For many years nobody was sure whether insulin was important to the brain: neurons in the brain are unusual in that they do not need insulin to enter them. But then we discovered that insulin acts on other important metabolic processes in neurons. In the brain it also does duty as a chemical messenger and as a growth factor, and brain insulin signaling is crucial for the creation of memory. Over the years a number of theorists have suggested that some neurological and psychiatric illnesses could be a result of disturbances in insulin-related processes in the brain.

It is now beginning to look as if they may have been correct.

Some recent evidence has suggested that Alzheimer’s disease and diabetes mellitus share a number of common pathways and Alzheimer’s disease is associated with peripheral insulin resistance.

New research has been published by investigators from Northwestern University in the FASEB Journal - the journal of the Federation of American Societies for Experimental Biology –  that may finally nail down the reason why insulin signaling may stop working in Alzheimer’s disease.

The research team used mature cultures of neurons from the hippocampus of the brain to study synapses – the connection between neurons - that have been implicated in learning and memory mechanisms. They wanted to examine the effect of a toxic protein, known to attack memory-forming synapses, that is called  “ADDL” for "amyloid ß-derived diffusible ligand." ADDLS are small, soluble aggregated proteins that accumulate in the earliest stages of Alzheimer’s disease. The researchers had previously found that ADDLs bind very specifically at synapses, which in turn initiates deterioration of their function, shape and composition. They now went on and studied the synapses and their insulin receptors before and after ADDLs were introduced. Regions of the nerve with normal numbers of insulin receptors have no ADDL binding, but when the ADDLs are added they remove insulin receptors from nerve cells, effectively making them insulin resistant.

And an insulin resistant neuron cannot participate in the formation of memories.

This finding implies that there is a fundamental connection between diabetes and Alzheimer's disease, and this may in turn help us to see whether existing diabetes treatments might protect neurons from ADDLs and improve insulin signaling in people with Alzheimer's disease.

The first type of diabetes is Type 1, a.k.a. insulin-dependent or juvenile onset. The second is Type 2, a.k.a. non-insulin-dependent diabetes. So is Alzheimer's Type 3?

It has also been known for some time that physical exercise is one of the factors that may help reduce the chance of developing Alzheimer’s disease, and we may now have a mechanism by which it can help.

This is an extraordinarily interesting and important discovery that should lead to a whole new research angle, perhaps with medicines that are already available.

The Neuronal Shield

Sometimes Nature does our experiments for us, and nobody - especially any animals - need to get hurt at all.

Diabetes mellitus is one example, in which heart disease, arteriosclerosis and stroke are many times more common than they are in the general population, and give us a perfect place to start looking at some of the causes of arterial diseases in general.

Another, and far more rare, example is a group of brain diseases called lissencephaly, in which whole layers of the cerebral cortex fail to find their homes and develop. The result is a brain that has a fairly smooth surface, rather than being covered in the complex hills and valleys (“gyri” and “sulci”) that cover the surface of the healthy brain. People with lissencephaly usually have quite severe mental retardation, motor problems, muscle spasms and seizures. What normally happens during embryonic development is that the six main layers of the cerebral cortex are generated by neuronal progenitor cells that migrate long distances before they finally find their correct place and settle down. At the beginning of brain development the cells look like an unruly mob trying to find their seats at a concert. Eventually they find their spot, settle down and get to work. The precise spatial organization of these layers of cells is essential to normal cortical functions.

Though lissencephaly is rare, there are other disorders, including some forms of epilepsy and some types of schizophrenia that also result from abnormal migration of nerve cells during the development of the brain.

Researchers from the Mouse Biology Unit of the European Molecular Biology Laboratory (EMBL) in Italy have now discovered that a protein called n-cofilin, that helps organizing the cells' skeleton is crucial for preventing such defects. In the current issue of Genes & Development they report that mice lacking n-coffin show many of the classic signs and symptoms of lissencephaly.

The skeleton of a cell consists of constantly growing and shrinking filaments that function like strings and struts to give the cell shape and stability, and it is largely responsible for the migration of neurons in the developing brain. N-cofilin interacts with actin - one kind of skeletal filaments - and helps to disassemble them into their individual building blocks. Interfering with this filament remodeling impairs the cell's ability to move and that blocks migration of neurons during cortical development.

N-cofilin also controls the fate of neural stem cells that are involved in development of the cortex. If it is absent, stem cells stop moving and re-new themselves instead of differentiating. This imbalance depletes the pool of neuronal progenitors cells so that fewer cells can be made to build a complete and functional cortex. The study provides the first proof that proteins affecting actin filament dynamics are involved in neuronal migration disorders.

It is remarkable that a single gene can be so important in the development of the brain, and it opens up new fascinating possibilities for treatment.

Even Neurons Need Friends

In many neurological diseases, including multiple sclerosis (MS) and some types of neuropathy, myelin - the insulation that covers and surrounds most of the larger nerves - is damaged or deranged.

Scientists at the Weizmann Institute of Science in Rehovot, Israel, working with colleagues in the United States, recently reported finding an important new line of communication between cells in the nervous system that is crucial to the development of myelinated nerves. This new discovery may eventually help us to restore the normal function of the affected nerve fibers.

Nerve cells (neurons) have long, thin extensions called axons. The longest of these axons is in the verves supplying the feet, and they can be over three feet or more in length. The larger axons are covered by myelin, which is formed by a group of specialized cells called glia.

Glial cells move around the axon, laying down the myelin sheath in segments, while leaving small nodes of exposed nerve in between. Myelin provides protection for the delicate axons, and it also allows nerve signals to jump rapidly between the gaps or nodes, increasing the speed and efficiency of the transfer of electrical signals down the axon. When myelin is missing or damaged, the nerve signals cannot skip down the axons, leading to abnormal function of the affected nerve and eventually the now naked nerve may degenerate and die.

In research published in Nature Neuroscience, Elior Peles, Ivo Spiegel and their colleagues in the Molecular Cell Biology Department at the Weizmann Institute and in the United States, provided a new insight into the mechanism by which glial cells recognize and myelinate axons.

They found a pair of proteins that pass messages from axons to glial cells. These proteins, called Necl1 and Necl4, belong to a larger family of cell adhesion molecules. The whole class of cell adhesion molecules does exactly that: they sit on the outer membranes of cells and provide the glue that helps them to stick together. Even when removed from their cells, Necl1, which is normally found on the surface of the axon, and Necl4, that is found on the glial cell membrane, adhere together very tightly. When these molecules are in their natural homes of the axon and glial cell, they not only create physical contact between axon and glial cell, but also serve to transfer signals to the interior of the glial cells, initiating changes needed to undertake myelination.

The scientists found that production of Necl4 in the glial cells rises when they come into close contact with an unmyelinated axon and as the process of myelination begins. If Necl4 is absent from the glial cells, or if they blocked the attachment of Necl4 to Necl1, the axons that were in contact with the glial cells did not myelinate.

This is an exceptionally important discovery. Most of the approaches that we use for treating MS, peripheral neuropathy and other degenerative diseases, can often help with symptoms and may slow but not cure the diseases. But if we can understand the mechanisms that control the process of wrapping the axons by their protective sheath, we may be able to recreate that process in patients.

Depression, Folic Acid and Bread

A remarkable study was published in the July edition of the Journal of Epidemiology and Community Health, by researchers at the University of York and Hull York Medical School.

They reviewed 11 studies involving 15,315 individuals and confirmed that there is a link between depression and low levels of folate, a vitamin that comes primarily from leaf vegetables such as spinachturnip greens, dried beans and peas, fortified cereal products, sunflower seeds and certain other fruits and vegetables are rich sources of folate, as is liver. and

Last month, the British Food Standards Agency  recommended to Health Ministers that they should introduce mandatory fortification of either bread or flour with folic acid to prevent neural tube defects, which can result in miscarriage, neonatal death or lifelong disability. This new study suggests that the measure may also help to reduce the frequency and severity of depression.

Lead author Simon Gilbody said:

"Our study is unique in that for the first time all the relevant evidence in this controversial area has been brought together. Although the research does not prove that low folate causes depression, we can now be sure that the two are linked. Interestingly, there is also some trial evidence that suggests folic acid supplements can benefit people with depression. We recommend that large trials should be carried out to further test this suggestion."

Recent research from the same team published in the American Journal of Epidemiology has also shown that people with depression, bipolar disorder and schizophrenia commonly have a genetic mutation named MTHFR C677T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on chromosome 1. The enzyme that the gene codes for is involved in folate metabolism, and the mutation (polymorphism) means that they process folate less efficiently. Folate is linked to the production of some of the chemicals in the brain, including serotonin, that in some part some the brain elevate mood. The identification of this gene provides a plausible explanation as to why folic acid supplements may help people with depression.

There is also another implication of the finding: it is well known that some diseases are more common in people who have depression, bipolar disorder and schizophrenia, including coronary artery disease ad some forms of cancer.

This same genetic polymorphism has been linked to cancers of the breast and lung, as well as coronary artery disease. It may be that folate is one of the factors involved in both.

Yet another research project!

The Speech Field

If you think about it, our remarkable ability to receive and decode speech is a biological miracle of the first order. The more so because it appears that we have only learned the trick in the last 50-100,000 years.

I have commented before about the importance of looking at entire brain systems rather than individual spots in the brain or individual brain cells. The brain is supposed to operate as a unified whole. If it doesn’t things are going wrong. Another concept, and one that is not widely known outside of neuroscience community, is that instead of thinking about a stimulus causing a set of neurons to fire, it is better to think about stimuli modulating the activity pattern of neural circuits that are already active.

Think of the appearance f a TV screen when the set isn’t tuned to a particular station. You get a fast moving “snow” effect. It is only when a coherent signal arrives that the “snow” gets itself organized.

Now colleagues from the University of Maryland have published some new data which may help explain how we discriminate speech, and why sometimes it can go wrong.

It appears that a particular resonance pattern in the brain's auditory processing region appears to be the key.

Huan Luo and David Poeppel found that the inherent rhythm of neural activity called "theta band" specifically reacts to spoken sentences by changing its phase. The researchers also noted that the natural oscillation of this frequency provides further evidence that the brain samples speech segments about the length of a syllable.

The findings represent the first time that such a broad neural response has been identified as central to perceiving the highly complex dynamics of human speech. Previous research studies have looked at the responses of individual neurons to speech sounds, but not the response of the auditory cortex as a whole.

In their experiments, the researchers asked volunteers to listen to spoken sentences. One example was, “He held his arms close to his sides and made himself as small as possible."

At the same time, the subjects' brains were scanned using magnetoencephalography. In this imaging technique, sensitive detectors are used to measure the magnetic fields produced by electrical activity in brain regions.

The theta band oscillates between four and eight cycles per second, and it changes its phase pattern with unique sensitivity and specificity in response to the spoken sentences. As a second experiment, when the experimenters degraded the intelligibility of the sentences, the theta band pattern lost its tracking resonance with the speech.

The researchers said their findings suggest that the brain discriminates speech by modulating the phase of the continuously generated theta wave in response to the incoming speech signal.

Second, looking at the time-dependent characteristics of this theta wave suggest that the brain samples the incoming speech in "chunks" that are about the length of a syllable from any given language.

When you hear something, it goes from your ears to your brain where fields begin to sample what you are hearing. From that you decode the message and turn into something that you can understand, and you make the decision on whether or not you need to act.

It’s remarkable what’s going on under the hood!

The Ancient Core of the Modern Brain

Here is a question for biology students everywhere: “Which part of the brain is closest to the surface of the body?”

The answer is the retina of the eye.

We have known for two centuries that some parts of the brain are involved in primary perception.

But some extraordinarily interesting new research suggests that the brain may have started out as a sensory organ.

Hormones are usually divided into three major groups:
Endocrine
Paracrine
Autocrine

They are important in the control of growth, metabolism, reproduction and many other important biological processes.

In human beings, as in all other known vertebrates, the hormonal control signals are generated by specialized centers in the brain such as the hypothalamus. The signals generate a cascade of effects in different endocrine organs throughout the body. Over the years the list of endocrine organs has been growing, now including the heart and intestines. There is a long list of illnesses that can occur if organs escape from these control signals, or do the adolescent trick of ignoring what they are told.

Over the last decade we have been learning that many of our hormones have been around with little structural change for hundreds of millions of years, though they may have different roles in mammals, fish and birds.

It was interesting to learn that researchers from the European Molecular Biology Laboratory (EMBL) have shown that the hypothalamus and its hormones are not purely vertebrate inventions, but have their evolutionary roots in marine, worm-like ancestors.

Writing in the journal Cell they report that hormone-secreting brain centers are much older than expected and likely evolved from multifunctional cells of the last common ancestor of vertebrates, flies and worms.

For the most part hormones mostly have slow, long-lasting effects that complement the faster activity of the nervous system. Insects and nematode worms have simple but effective nervous system and rely more on the secretion of hormones to transmit information, within and between individuals.

Kristin Tessmar-Raible from Detlev Arendt's laboratory at EMBL compared two types of hormone-secreting nerve cells in zebra fish, a vertebrate, and the annelid worm Platynereis dumerilii. The researchers found some astonishing similarities. Not only were both cell types located at the same positions in the developing brains of the two species, but they also looked similar and shared the same molecular composition.

One of the cell types secretes vasotocin, a hormone controlling reproduction and water balance, while the other secretes a hormone called RF-amide.

Each cell type has a unique combination of regulatory genes that are active in a cell and give it its identity. The similarities between the fingerprints of vasotocin and RF-amide-secreting cells in zebra fish and Platynereis indicate a common evolutionary origin of the cells.

Another point in common is that in both species the cells are multifunctional: they secrete hormones and at the same time have sensory properties. The vasotocin-secreting cells contain a light-sensitive pigment, while RF-amide appears to be secreted in response to certain chemicals.

What this tells us is that we are probably looking at the most ancient types of neuron. Most likely their role was to link sensory cues from the marine environment to changes in the animal's body. Over time these autonomous cells might have clustered together and become more specialized, eventually forming complex brain centers like the vertebrate hypothalamus.

If this were just a clever bit of molecular biology and a trip down the memory lane of evolution it would be interesting but nothing more.

Instead these findings force us to think about the development of the brain in a totally new way.

It looks as if the brain did not start out like a little computer for integrating and interpreting incoming sensory information. It began life as a sensory organ and we will likely find that it is not just the retina that has a sensory function.

Rethinking the brain as an organ for sensation and association instead of a computer for analyzing and processing may help explain a number of puzzles about the brain and how we use it.

Rhythms in the Brain

It is often a bit frustrating to read articles about the brain in which the writer says things like: “research has shown that the insula does this…” or “the amygdala does that…”

This idea that it is possible to reduce brain functions to regions of the brain is not correct. Some years ago I used the term “Neo-phrenology,” to describe this fallacy, though I am sure that I was not the first. (Phrenology was the old and discredited theory that you tell things about people by examining the bumps on their heads.)

So why is it a fallacy? The idea that certain functions can be “localized” to a bit of the brain is called “naïve localizationism.” The vast majority of the psychological functions of the brain are performed by distributed networks, not a single lump of tissue. One of the remarkable things about the human brain is that it can recruit new circuits as they are need. If we do not have enough brainpower to solve a problem, other systems are taken off line so that they do not distract and may be able to help. You have probably had the experience of working on something so intensely that you lose track of time, and fail to hear things going on around you.

Yes, there are regions that have jobs to do. For instance the auditory cortex is responsible for processing sound. But after that initial processing the rest of the brain becomes involved in deciding what to do with the information. The key to understanding the brain is how different regions of the brain communicate. As I recently mentioned in a different context, there are good reasons for believing that a number of problems, from the schizophrenias to the attention deficit disorders, may all be a result of poor communication between different regions of the brain.

Part of the problem is working out how regions communicate has been technical: we have not had the computers or hardware to do the measurements. But that is beginning to change.

Earl Miller, a professor of neuroscience at Massachusetts Institute of Technology's Picower Institute for Learning and Memory, recently said that today's faster computers and more advanced electronics might provide scientists with the tools they need to unlock the brain's mysteries.

"Multiple electrode recording techniques, offer a whole new level of brain interactions that can't be seen using the [current] piecemeal approach."

Two studies published recently in th journal Science support this idea.

In the first Thilo Womelsdorf and a group of neuroscientists at the F. C. Donders Center for Cognitive Neuroimaging at Radboud University Nijmegen in the Netherlands, looked at the electrical activities of groups of neurons in the brains of cats and monkeys wile they were engaged in an array of different tasks. They found that two groups of neurons could only communicate efficiently with each other when their rhythms are coordinated, or synchronized.  If the rhythms are not coordinated, then one group sends information while the other is not ready to take it on and vice versa.

The researchers found that when the rhythms of electrical activity are synchronized between neurons in distinct brain areas, memories are made and tasks are completed more efficiently.

The other study, by scientists at the University of Melbourne in Australia, also revealed communication between the cerebral cortex and the deep medial temporal region.

They flashed two images at a group of macaque monkeys for less than a second. The monkeys had to decide whether the spatial orientation of a stack of bars in two images were the same or different. While the animals worked, researchers monitored the electrical fields in the posterior parietal cortex, which is one part of the system involved in directing spatial attention. At the same time they looked at the medial temporal area, a region deep in the midbrain that handles movement perception. The researchers had hypothesized that these two areas need to communicate with one another to enable reasoning.

The researchers observed activity first in the parietal cortex, followed by synchronous action there and in the medial temporal area. The delay illustrates "a top-down" feedback from the cortex, which then signals the lower area.

One of the authors, Trichur Vidyasagar, said,

“The parietal neurons seem to code for what is salient or relevant in the world and allocate attentional resources accordingly. The medial temporal neurons are sensory ones that process the visual signals, but due to the influence of the parietal cortex the activity across the medial temporal area is varied."

The studies were accompanied by an editorial in which Robert Knight, a cognitive neuroscientist at the University of California, Berkeley, praised the findings - and their potential significance.

This research is important for two reasons:
First it confirms that the key to understanding the brain is the interaction of networks.

Second, there are a number of periodic disorders, such as depression, seasonal affective disorder, mania and even some rare types of episodic psychosis that are episodic and are not associated with any clearly defined neuroanatomical disruption. It may well be that some of the periodic symptoms are caused by intermittent network dysfunction, as a result of disturbed oscillatory dynamics.

“In all things there is a law of cycles.”
--Publius Cornelius Tacitus (Roman Historian, Writer, Orator and Public Official, A.D.56-c.120)

“Human beings, vegetables or cosmic dust, we all dance to the same mysterious tune, intoned in the distance by an invisible player.”
--Albert Einstein (German-born American Physicist and, in 1921, Winner of the Nobel Prize in Physics, 1879-1955)

“It has been said that a complete understanding of the Law of Cycles would bring man to a high degree of initiation. This Law of Periodicity underlies all the processes of nature and its study would lead a man out of the world of objective effects into that of subjective causes.”
--Alice A. Bailey (English Writer, Spiritual Teacher and Founder of the Arcane School, 1880-1949)

“At the heart of each of us, whatever our imperfections, there exists a silent pulse of perfect rhythm, a complex of wave forms and resonances, which is absolutely individual and unique, and yet connects us to everything in the universe. The act of getting in touch with this pulse can transform our personal experience and in some way alter the world around us.”
--George Leonard (American Aikidoist and Writer, 1923-)

Your Brain's Inertial Navigation System

There are many mysteries about the human brain. One is the role of the cerebellum that lies at the back of your head right underneath the cerebral hemispheres. Most students believe that it is only involved in balance and motor coordination, but that does not make much sense: relative to the rest of the brain, humans have the largest cerebellum of any species apart form the dolphin. And there are good reasons for believing that it is involved in the coordination of emotional and social processes, as well as language.

We now learn that it may have yet another function. Colleagues from Washington University School of Medicine in St. Louis report that there is a sophisticated neural computer that is buried deep in the cerebellum, that performs inertial navigation calculations to calculate our precise movement through space.

These calculations are incredibly complex and involve the vestibular system in the inner ear that provides the primary source of input to the brain about the body's movement and orientation in space. However, the vestibular sensors in the inner ear only give us information about the position of our head position. In addition the vestibular system's detection of head acceleration cannot distinguish between the effect of movement and that of gravitational force.

Dora Angelaki and her team based their brain studies on the predictions of a theoretical mathematical model. The model proposed that the brain could calculate inertial motion by combining two things:
1. Rotational signals from the semicircular canal in the inner ear with
2. Gravity

Based on previous research, they concentrated their search for the brain's inertial navigation system on particular types of neurons called Purkinje cells, in a region of the cerebellum known to receive signals from the vestibular system. This region is known as the posterior cerebellar vermis, a narrow, worm-like structure between the brain's hemispheres. It has been known for two centuries that damage to the cerebellar vermis can produce bizarre neurological problems.

In their experiments, the researchers measured the electrical activity of these Purkinje cells in monkeys as the animals' heads were maneuvered through a precise series of rotations and accelerations. After analyzing the electrical signals measured from the Purkinje cells during these movements, the researchers concluded that the specialized Purkinje cells were, as predicted, computing earth-referenced motion from head-centered vestibular information.

This is a remarkable finding: the cells are able to make complex deductions based on very little information.

Cells in the brain, particularly cells of the Purkinje type are designed to adapt and learn. So the finding gives yet more credence to the idea that balance, coordination and orientation in space are learnable skills. That will be the topic of another research project.

But for now, the evidence suggests that anything that helps you to practice these skills will likely pay dividends as you get older.

Who’s In Charge of Your Brain?

There has been a lot of discussion in the neuroscience community about the way in which different circuits in the brain are integrated. We know that the right and left sides of the brain normally operate together, and that most of the time the three major systems of the brain: reptilian, limbic and neocortical regions work together. However, we have also speculated that one of the causes for some neurological, psychological and psychiatric illnesses might be a result of “disconnections” between different regions of the brain. The idea that some brain regions may be uncoordinated goes back more than a hundred years, but was resurrected and developed quite brilliantly in the 1960s by one of my mentors, the late Norman Geschwind, who was one of the three smartest people that I ever met.

Now there is some new research that may have important implications for neurology and psychology.

Colleagues from Washington University School of Medicine in St. Louis have found strong evidence that there is not one but two complementary commanders in charge of the brain. It is rather like having two captains in charge of the same ship.

The two captains are networks of brain regions that do not consult each other but still work toward a common purpose: the control of voluntary, goal-oriented behavior. These behaviors include a vast range of activities from walking and talking, reading and deciding on a course of action. There are yet other systems that control behaviors that are usually involuntary such as control of the pulse rate or digestion.

Last year the researchers found that there are 39 brain regions that consistently became active before the brain goes to work on a task. They did this through functional magnetic resonance imaging (fMRI) scans that follow the oxygenation of the blood. As a region of the brain is activated, blood flow increases and we can work out which brain regions are contributing to a mental task. One of the keys to our mental capacity is the ability to recruit different parts of the brain as we need them. The previous research suggested that these brain regions create task sets: plans for using the specialized talents of various brain regions to achieve a goal. Let me give you an example.

Read the word: CAT

You can do many things with that word: make a mental image of a cat, read it aloud, make rhymes or lists of words and so on. And each of those activities involves a different set of circuits in the brain. The person with good powers of attention and concentration is able to mobilize and coordinate more of his or her mental resources than the person who is less focused on a task.

In this new study the researchers used a different brain scanning technique called “resting state functional connectivity MRI.” Volunteers were asked to relax while their brains are scanned instead of working on a task.

They then used graph theory, a branch of mathematics that visually graphs relationships between pairs of objects to work out how different brain regions are coordinated. This mathematical technique is rather like the party game Six Degrees of Kevin Bacon, in which you use paired connections to go from one actor or actress to another until you've identified a chain of connections linking Kevin Bacon and another actor, actress or movie that wasn't immediately obvious.

They were able to identify pairs of brain regions where blood oxygen levels rose and fell roughly in synch with each other, implying that the regions most likely work together. What they found was two separate systems. Each system had multiple connections to other regions in its own team, but they never connected to regions on the opposite team.

Having established the existence of two control networks, the next task was to work out their roles. One network - the “cinguloopercular network" - was linked to a "sustain" signal. It turns on when you start doing a task and stays constant while you do it. When you are finished it switches off.

The second is the frontoparietal network that is consistently active at the start of mental tasks and during the correction of errors.

In some senses this is not too much of a surprise. Many systems of the body have multiple control systems. I have often talked about the scores of systems involved in the control of body weight, which means that a dietetic approach directed at only one system is doomed to failure. If the body thinks that it is starving other systems jump in to slow your metabolism, reduce your activity level and make you crave certain foods.

Another good example is body temperature. Your temperature is regulated by several independent factors including your sweat glands, metabolism and activity level. If one of them goes wrong, other systems will try and compensate. When one controlling factor goes awry, others can try to compensate. The controls of your weight and body temperature are known as complex adaptive systems, and they are found not only in biology, but also in ecology, economics and atmospheric dynamics. We study them using an approach called network dynamics.

The findings may help our efforts to understand the effects of brain injury and develop new strategies to treat such injuries.

They may also help us understand problems like goal-directed behavior and human motivation.

If only one of the two systems has agreed that you need to go out and exercise, it may help us design new strategies to help you and explain why some approaches to, say, diet and exercise, are more effective than others.

Groundbreaking stuff!

Brain Training and the Paradox of Aging

For centuries, people in cultures throughout the world have believed that increasing age is associated with increasing wisdom. Not just knowledge and experience, but wisdom. Is this an old wives' tale, or is there something to it?

There is growing evidence that as we age our brains actually become stronger. Everyone missed it, because the emphasis was on memory, concentration and thinking speed, and those may all deteriorate with age. What changes is that as we age we become more efficient at making associations rather than thinking linearly. we also recruit regions of the brain that may have lain dormant for years. At the same time, different types of mental training, including meditation, can improve many aspects of our cognitive abilities, and may also enrich and even grow appropriate regions of the brain.

Some new data from a study being conducted at Wake Forest University Baptist Medical Center in North Carolina suggests that it is possible to use a fitness program for your brain that can improve thinking skills, attention and concentration as reliably as lifting weights can increase muscle strength.

Preliminary findings from the study, which used functional magnetic resonance imaging (fMRI) to record brain activity, were presented last week at the Organization for Human Brain Mapping conference in Chicago.

As we age, we do experience changes in how we perceive the information that our senses gather from the environment. As I mentioned older adults combine information from the different senses more readily than do younger adults. This is known as sensory integration, and the down side is that it can lead to difficulties in blocking out distracting sights and sounds while still maintaining focus on important information. You are probably familiar with the "Cocktail Party Phenomenon." You are in a loud room, but because someone is saying something interesting, you are able to block out uninteresting information. This technical term for this is cortricofugal inhibition. As we get older it gets more difficult to do the inhibiting.

The Brain Fitness in Older Adults (B-fit) study has been designed to establish whether eight hours of brain exercise can improve the ability of healthy older adults, ages 65 to 75 years, to filter out unwanted sights and sounds.

The B-fit study uses fMRI to visualize blood flow and brain activity to determine how attention training affects brain function. The training involves either a structured one-on-one mental work-out program or a group brain exercise program. During the one-on-one sessions, the volunteers were asked to ignore distracting information and tasks get harder as the eight-week training progresses. For the group sessions, participants learn new information relevant to healthy aging and are then tested on their ability to apply the new information.

All participants had an fMRI scan during a distraction task. They had to look for target words or numbers while ignoring distracting sounds. The scans showed brain activity in areas related to both sight and sound. Follow-up fMRIs showed that in the group receiving the one-on-one training, activity related to sight was increased, while activity related to sound was decreased. In addition, performance on the task was improved.

So the data do indeed suggest that attention training is a way to reduce older adults' susceptibility to distracting stimuli and therefore help improve concentration.

And what about wisdom?

I have written in Healing, Meaning and Purpose that "Wisdom is the integration of understanding:" making more new associations and drawing conclusions based on a new perspective is a gift of aging. The training enables us to make sense of and communicate our conclusions.

When it comes to the brain, use it or lose!

A New Treatment for Parkinson’s Disease?

It is remarkable how often we find that a treatment for one problem may turn out to help something completely different.

Parkinson’s disease is caused by a loss of dopamine neurons in specific circuits in the brain. Dopamine has a great many actions, but I these particular circuits it is involved in the control of movement. Once it starts, the process usually continues on inexorably. The mystery has been why the neurons die in the first place.

There is a very promising article that was published online today in the journal Nature.

Investigators from the Department of Physiology in the Feinberg School of Medicine at Northwestern University in Chicago and the Department of Cellular and Molecular Pharmacology at the Chicago Medical School, Rosalind Franklin University of Medicine and Science have looked at a medicine that is usually used for treating hypertension, and found that it may protect dopaminergic neurons.

Their studies have suggested that the dopaminergic neurons involved are unusually reliant on a type of calcium channel that maintains their rhythmic activity. If the pacemaker is damaged, the neurons become more vulnerable to stressors such as neurotoxins. As we age, calcium ions begin to enter the neurons and change their behavior. They showed that mice that had been engineered to develop a progressive Parkinson's-type disease did not become ill when their condition was treated with the calcium channel blocker  israpidine. Their dopamine neurons appeared to revert back to their original, youthful form.

It is much to early to think about using isradipine for treatment. We do not, for example, know whether it works in humans and we have any idea how much of the drug would be needed. But this research does suggest a whole new line of research and possibilities for treatment.

That is exciting, though when I read about research like this I always wish that researchers did not use animals in their experiments. But since the animals have made the sacrifice to help us, we need to acknowledge their help.

Negative Ions to Help Treat Mania

Last year I talked about some of the nasty problems that can be caused by the hot dry winds that blow in many parts of the planet.

I have just seen that a paper that I was asked to look at a few months ago has just appeared in print, though according to the journal it came out in February!

The investigators used a negative ionizer to augment the treatment of 20 acutely manic people. It was a standard double-blind crossover study with raters who did not know who had received what treatment.

The negative ions did indeed produce a significant improvement in manic symptoms. We already know that atmospheric ions can have an impact on serotonin levels in some parts of the brain, and that could be the mechanism of action.

It is surprising that there has been so little research into such a simple intervention, though it is important to note that the patients were also receiving medications. But it would be valuable to see if such a simple environmental change could modulate serious mood problems before they get to the level of needing hospitalization.

Neurological Complications of Gastric Bypass Surgery

Our bodies are highly complex systems. They are not just bags of randomly assorted organs. So tinkering with one part of the system can have an impact in an entirely different part of the body. Many of us have worried for some time about the long-term consequences of gastric bypass surgery for weight loss. We know that some people who have had the surgery develop “substitution addictions.” If they had a real addiction to food before the surgery, after it they may begin to develop an addiction to something else, such as drugs or alcohol.

Now neurologists at the University of Arkansas for Medical Sciences (UAMS) in Little Rock have reported the results of a ten-year study found a link between gastric bypass surgery and several serious neurological conditions.

The study was published online May 22 in the medical journal Neurology and concludes that patients who undergo gastric bypass surgery, also known as bariatric surgery, are at risk for long-term vitamin and mineral deficiencies and as a result may develop a variety of neurological symptoms.

We know that ever more of these operations are being done every year, and so long as people are motivated they are usually successful in reducing weight. But they are not without risk, and we always have to balance that risk against the risk of being morbidly obese. This work is important because it suggests that there is an extra risk about which we previously knew very little.  Many of the complications that patients experience affect the nervous system, and they are often disabling and irreversible.

More than 150 patients who came to the UAMS Neurology Clinic following gastric bypass were included in the report. In 26 of these patients a link between the surgery and their neurological condition was found.

All of the patients involved in the study had previously undergone what is known as the Roux-en-Y gastric bypass procedure in which a small stomach pouch is created by stapling part of the stomach together and bypassing part of the small bowel, resulting in reduced food intake and a decreased ability to absorb the nutrients in food. The interval between surgery and onset of neurological symptoms ranged from 4 weeks to 18 years.

The neurological problems involved many different parts of the nervous system, and the symptoms included confusion, auditory hallucinations, optic neuropathy, weakness and loss of sensation in the legs, and pain in the feet, among other conditions. None of the patients had prior neurological symptoms.

Many of the patients also experienced multiple nutritional abnormalities, especially low serum copper, vitamin B12, vitamin D, iron and calcium.

This study underlines something very important. Many heavy people are actually malnourished, because they eat the wrong things and an excess of fat in the diet can create problems in the absorption of some vitamins and minerals. In addition, surgery like this can cause a form of malabsorption.

It is therefore essential to make sure that people who have this kind of surgery have an adequate long-term intake of vitamin and mineral supplements to prevent these neurological complications. It is important for everyone to know about these potential problems and to be on the lookout for neurological symptoms.

Meditation and Learning to Pay Attention

I have talked before about the increasing difficulties that we all have with paying attention.

Over the years we have tried all sorts of things to help people to become better at focusing and controlling their attention, from games, to biofeedback devices to meditation. It is the last of those that seems to be the most effective.

We know from personal experience that paying close attention to one thing can keep us from noticing something else. If we are shown two visual signals half a second apart, we usually miss the second because we are still focused on the first one. We are consciously unaware of the second flash. It is rather like missing something when we blink our eyes, and indeed psychologists call it “attentional blink.” Many psychologists have assumed that attention is something fixed: we can only give a certain amount of attention to one thing at a time before we have to move onto something else or get a kind of brain freeze.

But we have known for some time now that sometimes people do notice the second flash of light, and with practice they can notice it all the time, suggesting that the limitation on seeing the two flashes is not entirely physical, but that it may be possible to bring it under mental control. The first style of meditation that I ever learned was Vipassana, and I well remember being astonished at how quickly my attention and focus began to improve, even when I was not meditating.

Now there is an important new study from the University of Wisconsin-Madison that suggests that attention does not have a fixed capacity, and that it can be improved by directed mental training such as meditation.

The work was done in Richard Davidson’s lab at the University of Wisconsin-Madison School of Medicine and Public Health and the Waisman Center for Brain Imaging and Behavior and published online in the journal PLoS Biology. (This is one of the growing number of open access journals, and for people not yet convinced of the value of open journals have a look at this paper, in which everything is available to you for free.)

The investigators recruited people who were interested in meditation to study whether conscious mental training can affect attention.

They examined the effects of three months of intensive training in Vipassana meditation, which focuses on reducing mental distraction and improving sensory awareness.

Volunteers were asked to look for target numbers that were mixed into a series of distracting letters and quickly flashed on a screen. As subjects performed the task, their brain activity was recorded with electrodes placed on the scalp. In some cases, two target numbers appeared in the series less than one-half second apart - close enough to fall within the typical attentional blink window.

The researchers found that the three months of rigorous training in Vipassana meditation improved people's ability to detect a second target within the half-second time window. In addition, though the ability to see the first target did not change, the mental training reduced the amount of brain activity associated with seeing the first target.

Because the subjects were not meditating during the test, their improvement suggests that prior training can cause lasting changes in how people allocate their mental resources.

As Richard Davidson says,

“Their previous practice of meditation is influencing their performance on this task. The conventional view is that attentional resources are limited. This shows that attention capabilities can be enhanced through learning.”

The finding that attention is a flexible skill opens up many possibilities. It provides further evidence that attention training is worth examining for attentional problems such as attention deficit hyperactivity disorder.

“When we raise ourselves through meditation to what unites us with the spirit, we quicken something within us that is eternal and unlimited by birth and death. Once we have experienced this eternal part in us, we can no longer doubt its existence. Meditation is thus the way to knowing and beholding the eternal, indestructible, essential center of our being.”
--Rudolf Steiner (Croatian-born Austrian Mystic, Occultist, Social Philosopher, Architect and Founder of Anthroposophy, 1861-1925)

“The moment one gives close attention to anything, even a blade of grass, it becomes a mysterious, awesome, indescribably magnificent world in itself.”
--Henry Miller (American Writer, 1891-1980)

“The path of spiritual attention is not easy, although anyone can make a beginning by trying to understand.”
-- Sri Raghavan Iyer (Indian-born Prodigy, Rhodes Scholar, Academic, Philosopher, Theosophist, and, from 1965-1986, Professor of Political Science at the University of California, Santa Barbara, and Father of Pico Iyer, 1930-1995)

Vyvanse

There is no doubt that we need more options for the treatment of attention-deficit/hyperactivity disorder (ADHD), and though it would be nice to be able to treat everyone with a diet or some other approach, for many it is just not feasible.

Of the current medicines, most do not last quite long enough, and occasionally may need to be taken more than once a day. The trouble is that taking these medicines intermittently, or only having it in the circulation for a short time, plays havoc with the dopamine receptors in the brain.

One of the big problems with the current group of stimulant medicines is that they are amphetamines, and have enormous abuse potential. They are sold and re-sold and taken by mouth, inhaled, smoked and injected. In some parts of the United States abuse of ADHD medicines is the number one form of substance abuse.

So it would be a huge advantage to have long-lasting medicines with a much-reduced risk of abuse.

Vyvanse is an extremely interesting new treatment for ADHD that has just been approved by the FDA and should be available in the United States in the very near future. It is manufactured by Shire Pharmaceuticals that is getting a reputation as the company with the biggest interest in ADHD.

During development, Vyvanse was known as NRP104. Its main ingredient is lisdexamfetamine dimesylate. Vyvanse is unique in another way too: it is a prodrug or 'conditionally bioreversible derivative' of amphetamine, the main ingredient in Adderall and Adderall XR. This is a key point: unlike other stimulants it is conjugated to an amino acid, and has to go through the stomach and be digested before it can become active. Therefore there is a much reduced risk that it will be abused, since it cannot be snorted or injected like other ADHD medicines.

There was a great deal of new data presented at the In research presented this week at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. The bottom line seems to be that the medicine is both effect and well tolerated. It is going to be a genuinely useful addition to the treatments that we can offer people with ADHD.

Brain-Derived Growth Factors and Bipolar Disorder

As we are learning more about the plasticity of the brain, and the way in which new neurons can continue to grow throughout life, there is a great deal of interest in factors that stimulate the growth or development of neurons. This is particularly important in condition like schizophrenia and bipolar in which cognitive decline may occur.

Researchers from Portugal presented some interesting new data (NR68) on Monday at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF), one of the most common neurotrophic factors in the brain, may be associated with the pathophysiology of bipolar disorder. The data has been a bit of a mixed bag: previous studies have suggested that BDNF may be associated with either a worse or better neurocognitive outcome in tests of frontal lobe function.

The researchers examined 28 people with bipolar disorder whose mood was currently normal: i.e. they were euthymic,  and they compared them with 25 healthy volunteers. They measured BDNF levels and performed a battery of neuropsychological tests.

The people with bipolar disorder had clear evidence of problems with attention and executive function even when their mood was normal. However it does not seem to have much to do with BDNF: the levels were the same in both patients and healthy volunteers. There was an association between BDNF levels and memory in people with bipolar disorder. This makes sense: BDNF has been implicated in the formation of memory traces in the brain.

What this means is that problems of attention and executive function are likely to be trait-markers of bipolar disorder, while BDNF levels may be a state-related biological marker.

It is interesting how the wheel keeps turning: the person who first differentiated dementia praecox (schizophrenia) from manic depression (bipolar disorder) was Emil Kraepelin. He originally said that people with dementia praecox became worse over time, because of progressive cognitive decline, while people with manic depression did not. When he passed away in 1926 he was working on a whole re-visioning of mental illness, saying that the two could not be so clearly differentiated, because cognitive decline could occur in either illness.

Many pharmaceutical companies are looking into the possibility of improving cognition in major mental illnesses, but there are also a great many non-pharmacological interventions  that can be done to help cognition in people with major mental illness.

Musical Hallucinations

A paper on auditory hallucinations of music was presented this afternoon at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California.

The researcher looked at 22 people diagnosed with schizophrenia and 23 with schizoaffective disorder at Maimonides Medical Center in Brooklyn, New York. The question was whether it would be possible to use the presence of musical hallucinations to distinguish between schizophrenia and schizoaffective disorder. The conclusions from the study were that these auditory hallucinations of music were more common in people with schizoaffective disorder and that voices with a religious or superstitious content were more common in people with schizophrenia.

Though it is good to see someone examine the content of hallucinations, this was a very puzzling study.

First, there is always a lot of debate around the “schizoaffective” diagnosis. Although there are clear criteria for it in the DSM-IV, many experts believe that most people who have been labeled “schizoaffective” actually have a form of bipolar disorder. But in any case, bipolar disorder and schizophrenia probably lie on a spectrum. People’s diagnoses often change over time. Not because of disagreement or inaccuracy, but because people change over time. The term “phenomenological drift” has been used to describe this observation. What that means is that we always need to be sure of the diagnosis at the time of the study, rather than what was written in the chart in the dim and distant past.

The other point is that genuine musical hallucinations are very rare. The world literature contains under a hundred papers in European languages, and the classic paper, published by German Berrios in 1991 was an analysis of just 46 cases. Berrios is regarded by many as one of the finest phenomenologists in Europe, so it is surprising that the investigator in New York found so many cases.

It will be good to see if the author or someone else can replicate the work. The classic teaching about musical hallucinations has been that they:

• Are more common in women
• Are more common in people who have hearing problems or are deaf
• Are more likely to occur in people with neurological diseases, including Alzheimer’s disease
• If they occur in people with neurological disease, it is more likely that the damage will be in the right or non-dominant hemisphere of the brain. (In men, language tends to be in the dominant hemispheres and music in the non-dominant. The pattern is a bit more complicated in women, but they also usually sing and recognize music with the right or non-dominant hemisphere)

A recent report from Japan reported that an elderly man with musical hallucinations was helped with the cholinesterase inhibitor donepezil (Aricept), suggesting that cholinergic neurons are somehow involved in generating musical hallucinations.

Many of us have music or tunes giong round in our heads, but that is quite different from hallucinating music.

And let me repeat: hearing things is common, and does not mean that someone is mentally ill.

 

Non-pharmacological and Lifestyle Approaches to Attention-Deficit/Hyperactivity Disorder: 6. Biofeedback

It seems odd that hyperkinetic children and adults with attentional problems should be able to stop long enough to try yoga, meditation of biofeedback. Yet there is good evidence that they can and they do, and that all three modalities can be helpful.

Today we are going to look at the use of a specific form of biofeedback.

Neurofeedback is a form of behavioral training that is aimed at developing skills to help people self-regulate the activity of their brains.

The first attempts to use biofeedback in children with behavioral problems took place in the early 1980s, following some interesting work on using it to control epilepsy, headaches and an array of other problems. Several good quality neurofeedback studies have been published over the last ten years.

In neurofeedback training, people are taught to control specific aspects of electrical brain activity. They are hooked up to machine that records electric impulses from the brain – a form of electroencephalograph (EEG) and they are given immediate feedback and positive reinforcement, usually using a visual display.

In frequency training, people are asked to increase or decrease the activity of different EEG frequency bands. To learn to regulate their level of cortical excitability they are trained to generate and regulate slow cortical potentials (SCPs). Slow cortical potentials are slow event-related direct-current shifts of the EEG.

With a little practice, almost anyone can learn the basic techniques, and as they do, they constantly improve their ability to regulate their attention, thoughts, moods and reactions. Many young people with attention-deficit hyperactivity disorder (ADHD) look at it like a game, and quickly become engaged with it.

Studies of neurofeedback have shown some specific effects on attention and memory processes. The key point is that the improvements in performance are maintained once the person is engaged in real-life activities. The techniques can be used to help healthy people perform better as well as helping people with problems.

Several studies have shown that children with ADHD had improvements in behavioral and cognitive variables after both frequency (e.g., theta/beta) training and SCP training. Some of the improvements have been sustained for six months. It has also been possible to show improvements in some neurophysiological measurements. Most studies have been done in children with ADHD, and in most other things were done as well. For instance the children were kept on medications, or children were given other types of exercises to reinforce what they were learning.

There has been some good brain imaging research that has shown that neurofeedback in children with ADHD normalizes the functioning of the anterior cingulate cortex, the key neural substrate of selective attention

There is also another type of feedback training. There is evidence that the level of activity in a classroom containing hyperactive boys can be reduced using feedback about the level of activity together with positive reinforcement. Some recent research has produced preliminary data in which investigators used a device that combines a beeper and actigraphy technology for measuring, monitoring, and modifying motor excess in children. The feedback reduced the activity level of seven out of nine hyperactive boys.

There remain a lot of unanswered questions about biofeedback in the treatment of ADHD. In an excellent review article, John Gruzelier and Tobias Egner from London pointed out that neurofeedback had grown and been widely adopted with little in the way of research to back it up. However their own work has shown that the technique can help improve cognition, and they provided the first evidence of conscious control over the ratio of alpha and theta waves in the brain. They also showed that the technique could lead to remarkable improvements in artistic aspects of music performance, which were equivalent to two class grades in conservatory students.

The evidence for biofeedback is growing, and since it is non-invasive ad may be associated with a number of other improvements in mood and cognition, it will likely bean important option for some people with ADHD.

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.

Risk-taking in Teenagers

The study of adolescence is in an intersting state of flux.

The expectation that teenagers are rebellious by nature is probably not correct. After all, it is nly recently that adolescence, which more or less corresponds to the teen years, has been recognized at all. As recently as the early 1960, most young people went straight from school to employment, and wore the same clothes as everyone else at work. And of course that is still the pattern in many parts of the world, with the exception of school, which is sadly unavailable to so many. In most cultures teenage rebellion is not recognized at all.

Two years ago Professor Philip Graham, author of an excellent book published by Oxford University Press called 'The End of Adolescence' and a leading child and adolescent psychiatrist, challenged the myth that teenagers are trouble. He believes that the social attitudes towards the 'adolescent stereotype' that prevail in Western society have significant negative effects on the mental health of young people.

This stereotyping can cause some real problems:

• Low expectations of behaviour are often shared by teenagers themselves, leading to low self-esteem
• at least some of the frustration shown by young people in secondary schools can be attributed to the fact that they are 'disempowered' in relation to their intellectual and emotional competence
• The legal position of young people, for instance in relation to the age of criminal responsibility, voting age and the consumption of drugs and alcohol, is wildly inconsistent, and results both in injustice and in inadequate preparation for adult life
• The organisation of mental health services often fails to take into account the need to recognise the 'young adult' status of this age group.

The other side of this research is the risky behavior of many young people.

There is an excellent review in this month's issue of Current Directions in Psychological Science by Laurence Steinberg, Distinguished University Professor and the Laura H. Carnell Professor of Psychology at Temple University in Philadelphia. He is also the Director of the John D. and Catherine T. MacArthur Foundation Research Network on Adolescent Development and Juvenile Justice.

The review points out that over the past 10 years there has been a great deal of new research on adolescent brain development that sheds light on why yonug peple engage in risky and dangerous behavior. And also answer the question about why the educational programs or interventions that have been developed have not been especially effective. According to Steinberg, heightened risk taking in adolescence is the result of competition between two very different brain systems, the "socioemotional" and cognitive-control networks. Both are undergoing maturation during adolescence, but along very different timetables. During the adolescence, the socioemotional system becomes more assertive during puberty, while the cognitive-control system gains strength only gradually and over a longer period of time.

The "socioemotional" system processes social and emotional information, and it becomes very active during puberty, allowing adolescents to become more easily aroused and experience more intense emotion. They also become more sensitive to social influence.

On the other side, the cognitive-control system is the part of the brain that regulates behavior and makes the ultimate decisions, but it is still maturing during adolescence and into a person's mid-20s and perhaps beyond.

The socioemotional system is not always going full bore. When the system is not highly activated, for example, when individuals are not emotionally excited or they are alone, the cognitive-control network is strong enough to impose regulatory control over impulsive and risky behavior, even in early adolescence.

In the presence of peers, or in situations where emotions run high, the socioemotional network becomes sufficiently activated to diminish the regulatory effectiveness of the cognitive-control network.

Steinberg cites a study in which the presence of peers more than doubled the number of risks teenagers took in a video driving game.

As he says,

"In adolescence, not only is more merrier -- it is also riskier."

"There is a window of vulnerability in teens between puberty and mid-to-late adolescence in which kids have already started to experience the increased arousal of the socioemotional system, but they don't yet have a fully mature cognitive control system," he says. "Because their cognitive-control system is still not fully mature, it is more easily disrupted, especially when the socioemotional system is quite excited. And it gets excited by the presence of other people."

"I don't want people to think that education should not continue, I just think that it alone is not going to make much of a difference in deterring risky behavior. Some things just take time to develop, and, like it or not, mature judgment is probably one of them."

Steinberg advocates stricter laws and policies that would limit opportunities for immature judgment that often have harmful consequences. For example, strategies such as raising the price of cigarettes, more vigilantly enforcing laws governing the sale of alcohol, expanding adolescents' access to mental-health and contraceptive services, or raising the driving age would likely be more effective than education in limiting adolescent smoking, substance abuse, pregnancy, and automobile fatalities.

This is controversial stuff, but is also an illustration of a way in which science can help us make better decisions about how best to help young people to avoid auto-destruction.

Neurologically, teenagers are not just small adults, they are still large children. The problem is heightened because so many young people are constantly multi-tasking and children are being exposed to risky behaviors at ever younger ages, when their brains are least able to handle complex decisions about things that may have long-term consequences for them.

Linking Depression, Diabetes and Alzheimer’s Disease

It has been known for many years that Alzheimer's disease and depression are associated with type 2 diabetes. Good control of blood glucose may reduce the risk of developing Alzheimer’s disease and depression, while treating depression may improve metabolic control.

Decreased levels of brain-derived neurotrophic factor (BDNF) have also been implicated in the pathogenesis of Alzheimer's disease and depression, and animal models have suggested that BDNF may play a role in insulin resistance.

So a group of scientists at The Centre of Inflammation and Metabolism, Department of Infectious Diseases at the University of Copenhagen in Denmark, decided to see whether BDNF plays a role in human glucose metabolism.

In the first study they looked at 233 people and found that BDNF was inversely associated with fasting plasma glucose, but not with insulin. In a second smaller study they did what are known as hyperglycemic and a hyperinsulinemic-euglycemic clamp studies, that allowed them to look at the relationships between BDNF, glucose and insulin. What they found was that output of BDNF from the brain was inhibited when blood glucose levels were elevated.

So it seems that low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a factor involved not only in dementia and depression, but also in type 2 diabetes, and it may be the missing link that explains the way in which the three conditions cluster together in epidemiological studies

This link between a chemical produced in the brain and diabetes is not altogether unexpected. The French physiologist Claude Bernard demonstrated that stimulation of the fourth ventricle of the brain caused glucose to rise, and it was later found that opiates put into this region of the brain could do the same thing.

This study reinforced the close links between metabolism and the brain, and gives us another reason for recommending that as we get older we must ensure that out glucose remains stable and that we do not become depressed.

Insulin Resistance in the Brain and What It Means for Dieters

Most people have been taught that increasing weight is the cause of insulin resistance, which in turn may cause an array of different health problems. That is only half true: insulin resistance may contribute to the development of obesity, and once we start gaining abdominal fat then that may indeed contribute to insulin resistance. So a vicious circle is established in which insulin resistance helps cause obesity, which in turn causes more insulin resistance.

Another thing that we have been taught for half a century that the brain is an insulin-insensitive tissue. What that means is that the uptake and use of glucose by the brain is not affected by circulating levels of glucose and insulin. That has always seemed a bit strange, because insulin is very important in cognition. Some experts believe that disturbances of insulin and closely related hormone – insulin like growth factor 1 (IGF-1) are involved in the pathogenesis of Alzheimer’s disease. 

When someone is insulin resistant, they have high circulating levels of insulin, and an obvious question is whether these high insulin levels may interfere with the normal functions of the brain. This is not a new idea. It has been known for many years that high levels of triglycerides, that may be a marker for insulin resistance, may be associated with cognitive impairment in people with type 2 diabetes.

Now colleagues in London have found that people who have peripheral insulin resistance also have brain insulin resistance especially in two brain regions  - the ventral striatum and prefrontal cortex – that are involved in appetite and reward.

It looks as if one of the reasons why people with insulin resistance become obese is that the normal link between the control of food intake and energy balance is broken.

This is yet more evidence that a simple diet will not work in the long term. If the problem is metabolic and involves damage to the mechanisms that control eating, the only way to help is to use a combined approach that deals not only with the composition of the diet, but the precise time when people should eat, and the psychological and social barriers that are left over from millions of years of evolution. I outline a comprehensive and highly successful weight management technique in Healing, Meaning and Purpose. Over the last few months I have had an enormous number of requests to expand that material into another book, and in between writing this blog, I am hard at work on completing a full account of exactly what we do to help people manage their weight.

Lithium and Brain Growth

There’s an interesting story about the way that lithium was found to be helpful to some people with bipolar disorder. It was thought that there was a link between bipolar disorder and gout, and gout is caused by an accumulation of uric acid in some joints. It just so happens that lithium is very good at getting guinea pigs to pass any excess uric acid in their urine. So in 1949 a medical scientist in Australia called John Cade tried lithium in bipolar disorder. It worked, but not because of any effect on uric acid: the lithium/uric acid connection only works in guinea pigs. But now, all these years later, it turns out that there may actually be a link between bipolar disorder and uric acid after all: uric acid levels often rise in people who are insulin resistant, and insulin resistance is a common feature of bipolar disorder.

The last few years have seen the growth of an impressive body of evidence about the effects of lithium on the brain.  Lithium modulates the way in which many neurotransmitters act in the brain. That raised interesting questions, because many of the chemical transmitters do not only send messages between neurons, they may also stimulate the growth of cell processes and perhaps neurons themselves. Then it was discovered that lithium protects neurons by increasing the levels of a neuroprotective protein called Bcl-2. Then it was found to help stimulate the production of new neurons (neurogenesis) in the hippocampus.

A major breakthrough came in 2000, with the demonstration that lithium increases the amount of gray matter in the human brain, probably by stimulating the production of a growth promoter called brain-derived neurotrophic factor. Gray matter is composed primarily of neurons, so this suggested that lithium was either stimulating the growth of new neurons, or causing the migration of neural stem cells, or alternatively somehow preventing the death of neurons.

Within less than two years it was confirmed that treatment with lithium increased the amount of gray matter in the brains of people with bipolar disorder.

The findings remained controversial for two reasons: first was the seeming impossibility of stimulating the production of new gray matter. That is no longer such a problem: there is more and more evidence that the adult brain can indeed produce new neurons. The second problem was technology: the measurements were open to different interpretations.

Now neuroscientists at UCLA, using brain scans collected by collaborators at the University of Pittsburgh School of Medicine have shown that lithium does indeed increase the amount of gray matter in the brains of patients with bipolar disorder. But what is far more important is that the effects are seen in precise regions of the brain that are thought to be implicated in bipolar disorder.

The research is published in the July issue of the journal Biological Psychiatry.

Carrie Bearden, a clinical neuropsychologist and assistant professor of psychiatry at UCLA, and Paul Thompson, who is associate professor of neurology at the UCLA Laboratory of NeuroImaging, used a novel method of three-dimensional magnetic resonance imaging (MRI) to map the entire surface of the brain in people diagnosed with bipolar disorder. Everyone interested in the brain has been amazed by the quality of the images coming from the UCLA lab over the last six or seven years. (Graphics from the study, including the one above, are available online here.)

When the researchers compared the brains of bipolar patients on lithium with those of people without the disorder and those of bipolar patients not on lithium, they found that the volume of gray matter in the brains of those on lithium was as much as 15 percent higher in the cingulate and paralimbic regions of the brain, that are critical for attention, motivation and emotional control. There was no change in the amount of white matter, telling us that these effects are unlikely to be either artifacts or swelling of the brain.

These are extraordinary findings that may help explain how lithium works. If lithium increases the amount of gray matter in specific regions of the brain, this may suggest that existing gray matter in these regions may be underused or dysfunctional in people with bipolar disorder.

Conventional MRI studies in bipolar disorder measured the total volume of the brain, but these new imaging techniques employ high-resolution MRI and cortical pattern-matching methods to map gray matter differences that are so precise that they can pick up subtle differences in brain structure and this is the first time that researchers have been able to look at specific regions of the brain in people with bipolar disorder, and examine the effects of treatment.

The researchers at UCLA analyzed MRI scans of 28 adults with bipolar disorder, 20 of whom were lithium-treated, and 28 healthy control subjects collected by collaborators at the University of Pittsburgh. The analysis involved detailed spatial analyses of the distribution of gray matter by measuring local volumes of gray matter at thousands of locations in the brain.

This is superb research, and one of the signs of good research is that it raises yet more questions:

• We do not know whether these effects on gray matter persist once the medicine is stopped.
• Neither do we know whether the same effect might occur in other illnesses in which there is loss of gray matter. It may just be that lithium corrects an abnormality that is specific to bipolar disorder. That being said, there is recent evidence that lithium may be neuroprotective in a mouse model of Alzheimer’s disease.
• We also do not know if these brain changes correlate with clinical improvement.
• Lithium can have a lot of side effects, so we shall also need to factor that into the equation.
• We also need to know whether other medicines - or any other kind of therapy - might produce similar effects: there are already several medicines that have been shown to do something similar in some animals.

It's still a bit too early to suggest putting lithium in the water supply...

Dying of a Broken Heart

Some colleagues in London have discovered how intense stress may cause severe irregularities (arrhythmias) of the heart that could be fatal.

It has been known for some time that emotional trauma and psychological stress can precipitate cardiac arrhythmia and sudden death through over-activity of the sympathetic nervous system, the system usually associated with "Fight or flight." It has also been known that people with preexisting heart disease are particularly at risk. This is one stereotype that is true: if someone with heart disease gets a bad shock, they may indeed die. It has been known for centuries that suffering a sudden unexpected bereavement can be a fatal stressor.

It is extremely important to understand how stress can affect the heart, and researchers at the Wellcome Trust Centre for Neuroimaging at University College London and the Brighton and Sussex Medical School have made  an important breakthrough that has just been published in the Proceedings of the National Academy of Sciences. Measuring the electrical activity of the brain and heart at the same time, they discovered at the regions of the brain responsible for learning, memory and emotion can destabilise the cardiac muscle of someone who already has heart disease. These areas of the brain can participate in a "vicious cycle" with the heart.

The patients performed the task of counting backwards in sevens, which is for most people mildly stressful.

The researchers discovered that activity in "higher level" regions of the brain such as the cerebral cortex, not only reflected the responses of the heart to stress, but also became involved in a "feedback loop", often worsening the situation by making the heart muscle less stable.

The regions of the brain responsible for regulating heart function can be unbalanced by stress, and it can be fatal.

It is further evidence that there is a constant "conversation" between the heart and the brain.

It is also the best evidence to date that comprehensive care of people with heart disease must include stress management.

And why wait until it's too late?

Now is the time to start building your resilience to stress!

Stem Cell Treatment for Cerebral Palsy?

Medical News Today is carrying a interesting article entitled, "Dramatic Improvement For 19-Year-Old Hungarian Cerebral Palsy Sufferer After Stem Cell Treatment."

According to the report a 19-year-old from Hungary named Gabor Bocskai had stem cells injected into the fluid around his spinal cord.

It goes on to say,

"The successful procedure, performed at China's top stem cell facility, makes Mr. Bocskai the first teenage European CP patient to   see rapid improvement through stem cell therapy. Unedited   videos taken before and after Mr. Bocskai's injections dramatically demonstrate the profound improvement in his 19-year battle to walk, write, focus his eyes, concentrate, and overcome the many other detrimental effects resulting from the CP he acquired at birth. More details and the videos have been published on China's leading Stem Cell News site at http://www.stemcellschina.com.

    Some of Mr. Bocskai's most noticeable and immediate physical   improvements after the eight-week stem cell therapy program   include improved vision, increased eye focus and better   concentration on one subject. He also reported clearer writing, enhanced muscle tone, the ability to sit up unsupported, and a new capability to walk and swim in an unassisted manner. As a lifelong quadriplegic with paralysis in his lower limbs, Mr. Bocskai was never able to walk independently, using a wheelchair for transportation. Within four months of the initial treatment, he stated that he was able to walk with the help of a walker and no other support, and at a rate three times faster than ever before with increased maneuverability in his legs and torso. Even his   speech became clearer and faster.

    In Mr. Bocskai's most recent blog entry dated March 11, 2007, he excitedly stated, "My ability to concentrate has increased up to 6 hours a day as a result of stem cell treatment, so studying is much easer than before. I no longer get tired from learning." (Gabor's CP Blog is at   http://www.stemcellschina.com/blogs/Gabor%20cp/)The   Hospital announced that Mr. Bocskai has since returned to   Hungary from China and has reported continued daily   improvement. It also cautioned that not every teenage CP   patient treated with stem cell therapy should expect the   same impressive results."

There is very little information on the procedure, and I could not find any information about where the stem cells came from. I do see that he also had "certain medications" as well as hyperbaric oxygen.

The article is so enthusiastic that it reads like an advertisement!

I do very much hope that Gabor gets some real help from all of these treatments, but we need to be very cautious until we have a great deal more information not just about the science, but also the ethics of the treatment that he has had. For example, where did the stem cells come from? Do we know that they were stem cells?

It is always great to hear about success stories, but sad to say, we then need to do the boring bit: the checking, the testing and the replicating that go into sustainable medical progress.

I have done an extensive literature search and cannot find any published scientific reports, but I only covered the languages that I can read. So there could be something in Chinese that I missed.

I shall let you know immediately if we find out any more about the use of stem cell treatments in humans.

Blood Pressure and the Brain

We have known for almost a century that regions of the brain are involved in the control of blood pressure.

Yet over the last three decades most of the emphasis in research into hypertension (high blood pressure) has focused on blood vessels, the heart and kidneys.

Now research from Bristol University in England has been published in this month’s issue of the journal Hypertension, and it may put the brain back into the center of research into the causes and treatment of high blood pressure.

Working with rats, the researchers isolated a protein called JAM-1 (junctional adhesion molecule-1), that is located in the walls of blood vessels in the brain. It appears to trap white blood cells causing obstruction of blood flow in some of the smallest blood vessels. This can cause inflammation and result in poor oxygen supply to the brain, which may in turn trigger events that raise blood pressure.

Though this work is in its early stages, this is exciting stuff: if confirmed, it might be possible to treat hypertension with drugs that reduce blood vessel inflammation and increase blood flow within the brain.

It also ties in with other recent research from Imperial College, London and Oxford University, in which a team of neurosurgeons and physiologists discovered changes in blood pressure while fitting brain electrodes to 15 patients for pain control.

Deep brain stimulation involves placing very thin electrodes on very exact locations in the brain and is already used to relieve pain and to help Parkinson's disease patients with their movement.

The researchers found that they could make patients' blood pressure increase or decrease by stimulating very specific regions of the brain with the electrodes. Regions that have been associated with blood pressure control in the past. If they stimulated an area deep down in the midbrain called the ventral periventricular/periaqueductal gray matter, blood pressure went down, and if they stimulated the dorsal periventricular/periaqueductal gray matter it went up.

Nobody is suggesting that we should start sticking electrodes in peoples’ brain, but this chance observation may have profound implications, particularly for people who drop their blood pressure too far when they are treated with standard medicines.

These two pieces of research may also help explain why a balanced inflammation–reducing diet and relaxation may both reduce blood pressure.

Schizophrenia, Psychosis and Psychopathy

Ever since the tragedy in Virginia earlier this week, everyone has been trying to second guess what happened. As I said, to the trained eye there is a lot to suggest that he had a psychotic condition, but whether it was schizophrenia, bipolar disorder or psychotic depression is guess work.

One of the things that has been worrying in all the media coverage has not only been the sensationalism that we have seen in some quarters, but the mistakes that reporters - and even some of the "experts" - have made in talking about mental illness. I have heard people constantly mixing up schizophrenia and psychopathy, which is more accurately called antisocial personality disorder. I have even heard an old mistake that I had thought died years ago: that schizophrenia is a "split personality." I think that mistake probably goes back to a misunderstanding of the roots of the term "schizophrenia," and it was perpetuated by Alfred Hitchcock's movie Psycho in 1960.

Let me just repeat: schizophrenia is NOT a split personality. Neither is it multiple personality disorder. There is even a lot of discussion whether multiple personality disorder, now known as "Dissociative identity disorder" really exists: a discussion for another day.

Because there has been so much confusion, I thought that it would be good to clarify what each of these disorders is.

You can get some of the information from Wikipedia. What has worried me a bit is that some websites have slightly questionable infrmation. Many people know that I do a great deal of advocacy work for the mentally ill, so these notes are from my own lectures.

For reliable back up information, I recommend using Healia.com to search, and you can check out at Wikipedia, Schizophrenia.com, the National Institute of Mental Health website, Medline Plus and the National Alliance for the  Mentally Ill.


Psychosis
Psychosis is simply a generic term for a mental illness in which people have a "loss of contact with reality." There are often other symptoms, such as hallucinations, delusional beliefs, disorganized thinking and a lack of insight into the unusual or bizarre nature of his or her behavior. Almost anything that stresses the nervous system enough may lead to psychosis. I have often told students that it is possible to induce psychosis in just about anyone. It is a symptom and not a disease. We sometimes call it the "fever of the nervous system."


Schizophrenia
This is a group of illnesses that describe a mental disorder characterized by impairments in people's perception or expression of reality and by significant social or occupational dysfunction. The point is that other people don't share their view of reality and it is causing suffering. There is always some smart Alec student who says, "But isn't religion a delusion?" The answer is no, of course it isn't. Millions of people share the same beliefs. The second piece is also important: is it causing suffering, distress or disability? Many people have ideas that are "different." That does not mean that they are mentally ill. Professionals should not get involved unless the beliefs are causing a problem.

A person experiencing schizophrenia typically has disorganized thinking, and may experience delusions or hallucinations. In Western cultures these are most commonly auditory hallucinations. Simply having hallucinations does NOT mean that someone is mentally ill. I seem to be one of the few psychiatrists that supports the aims of the Hearing Voices Network. The Network tries to help people who are experiencing hallucinations and to educate the public and professionals that there are many possible reasons for hearing voices and many have nothing to do with mental illness.

One of the most disabling things about the schizophrenic group of illnesses is that they primarily affect  cognition, and that is one of the things that can lead to chronic problems with behavior and emotion. For a long time there was a worry that the cognitive problems were a result of being on some of the older medications. But these cognitive problems were identified decades before the introduction of these medicines. Hence the old name of schizophreia: dementia praecox.

The diagnosis is based on self-report and observation. We do not have a laboratory test for these illnesses, but we are finding reproducible changes in the brain and in many genes. The main evidence for the illnesses is still based on their response to treatment.

There has been a lot of discussion about whether we should abandon the term "schizophrenias," since the current diagnostic approach is flawed: many people have psychotic experiences without becoming dsitressed or disabled. Neither can they - or should they - be diagnosed. This gets back to the categorical and dimensional argument that I have talked about before. The second point is that the label "schizophrenia" can be so stigmatizing.


Antisocial Personality Disorder
Antisocial personaity disorder is also referred to as psychopathy, sociopathy or dyssocial personality disorder. It is a condition characterized by lack of empathy or conscience, and poor impulse control or manipulative behaviors. The term originally came from the Greek psyche (meaning soul, breath or mind) and pathos (to suffer). At one time the term was used to describe all mental illness, and that is why there is confusion. It is quite different from psychosis. Psychosis is a chronic or intermittent symptom that comes on at some time in life. Antisocial personality disorder should have been present all the time, even though we cannot formally diagnose it until the age of eighteen. The term "psychopath" is not a good one: it has no precise equivalent in either the DSM-IV-TR or the ICD-10.

Only a minority of diagnosable psychopaths are violent offenders . There has been a lot of discussion about whether the manipulative skills of some of the non-violent psychopaths are valuable in corporate America, the military and academia, because they may bold and often charismatic leaders. The has even been a suggestion that becoming a "psychopath" may be an adaptation to working in a highly competitive environment: it gets results for both the individual and for their corporations or countries.

There is a recent book - Snakes in Suits - that does a good job of exploring these ideas.

In summary:
Psychosis = A symptom
Schizophrenia = A group of acute or chronic illnesses in which psychosis is a central feature
Antisocial Personality Disorder = a.k.a. "Psychopathy:" life long personality trait

   

Genius Genes

I have talked before about the fascinating topic of child prodigies, and the continuing debate about the contributions and interactions of nature and nurture.

There is an important new study published in the journal Behavioral Genetics that should be of interest to anyone interested in thinking, intelligence and optimizing the potential of children.

A team of researchers from Washington University School of Medicine in St. Louis, has gathered the most extensive evidence to date that a gene that activates signaling pathways in the brain influences at least one kind of intelligence. They have confirmed a link between the gene, CHRM2 and performance IQ, that involves a person's ability to organize thoughts or events logically.

The team found that several variations within the CHRM2 gene could be correlated with slight differences in performance IQ scores, which measure a person's visual-motor coordination, logical and sequential reasoning, spatial perception and abstract problem solving skills. When people had more than one positive variation in the gene, the improvements in performance IQ were cumulative.

Typical IQ tests also measure verbal skills and typically include many subtests. For this study, subjects took five verbal subtests and four performance subtests, but the genetic variations influenced only performance IQ scores.

The researchers studied DNA gathered as part of the Collaborative Study on the Genetics of Alcoholism (COGA). In this multi-center study, people who have been treated for alcohol dependence and members of their families provide DNA samples and investigators have isolated DNA regions related to alcohol abuse and dependence as well as a variety of other outcomes.

Some of the participants in the study also took the Wechsler Adult Intelligence Scale-Revised, a traditional IQ test. Members of 200 families, including more than 2,150 individuals, took the Wechsler test, and those results were matched to differences in individuals' DNA.

By comparing individual differences embedded in DNA, the team focused on CHRM2, a muscarinic receptor gene on chromosome 7. The CHRM2 gene activates a multitude of signaling pathways in the brain involved in learning, memory and other higher brain functions. The research team does not yet understand how the gene exerts its effects on intelligence.

Intelligence was one of the first pscyhological factors that attracted the attention of people interested in the interplay of genes and environmental influences. Early studies of adopted children showed that when children grow up away from their biological parents, their IQs are more closely correlated to biological parents, with whom they share genes, than adoptive parents, with whom they share an environment.

But in spite of the association between genes and intelligence, it has been difficult to find specific variations that influence intelligence. The genes identified in the past were those that had profoundly negative effects on intelligence - genes that cause mental retardation, for example. Those that contribute to less dramatic differences have been much harder to isolate.

The St. Louis team is not the first to notice a link between intelligence and the CHRM2 gene. In 2003, a group in Minnesota looked at a single marker in the gene and noted that the variation was related to an increase in IQ. A more recent Dutch study looked at three regions of DNA along the gene and also noticed influences on intelligence. In this new study, however, researchers tested multiple genetic markers.

The lead investigator in St. Louis, Danielle Dick, had this to say,

"This is not a gene FOR intelligence, it's a gene that's involved in some kinds of brain processing, and specific alterations in the gene appear to influence IQ. But this single gene isn't going to be the difference between whether a person is a genius or has below-average intelligence."

"One way to measure performance IQ may be to ask people to order pictures correctly to tell a story. A simple example might be pictures of a child holding a vase, the vase broken to bits on the floor and the child crying. The person taking the test would have to put those pictures into an order that tells the story of how the child dropped the vase and broke it and then cried."

"If we look at a single marker, a DNA variation might influence IQ scores between two and four points, depending on which variant a person carries. We did that all up and down the gene and found that the variations had cumulative effects, so that if one person had all of the 'good' variations and another all of the 'bad' variations, the difference in IQ might be 15 to 20 points. Unfortunately, the numbers of people at those extremes were so small that the finding isn't statistically significant, but the point is we saw fairly substantial differences in our sample when we combined information across multiple regions of the gene."

Most experts believe that there are at least 100 genes that could influence intelligence, but it is unlikely that any one gene is going to be the ONE determinant of how smart someone is. After all, IQ itself has very poor predictive value for anything much in life apart from achievement in high school. The many genes involved probably have small, cumulative effects on increasing or decreasing IQ, and the key will be to understand the interaction between environmental influences and these genes. We already know that childhood nutrition, socio-economic status and emotional and cognitive environments have a profound influence on intelligence and achievement. Altogether too many children have all the mental machinery but do not even realize the possibilities open to them.

It is also clear that early influences will have a lot to do with the repertoire of intelligences that a person has. In the book and CD series Healing, Meaning and Purpose I spend some time discussing Howard Gardner’s important concept of multiple intelligences. Many of us have skills in certain domains and it is a terrible mistake to assume that because a child is not very good at logical or verbal tasks, that they are not smart. After all, how many brilliant musicians, computer scientists and entrepreneurs never finished high school or college?

There is clearly more than a gene deciding our intelligence and success at certain activities. The genes may give us the machinery and the fuel, but there are clearly many other factors. I’ve always been a very keen chess player and I once had a friend who was a nationally ranked contract bridge Master. He would destroy most normal mortals at any card game: including me! Even when we played scratch games of contract bridge he would always try to avoid partnering me: he told me that I sucked too badly! 8-(

He also had a hobby: he built and designed all kinds of board games. He used to get upset that whatever the game, if it was played on a board, I almost always won. But here’s the interesting thing: our IQs were virtually identical. But he was murderously good at card games but not at anything involving a board: another refinement of intelligence. I probably did well with board games because I could plan and visualize in three dimensions. My friend had a phenomenal memory for cards that I simply don’t possess.

As the owners of some establishments in Las Vegas once discovered to their glee....

“Intelligence is quickness to apprehend as distinct from ability, which is capacity to act wisely on the thing apprehended.”
--Alfred North Whitehead (English Mathematician and Philosopher, 1861-1947)

“Intelligence is the ability to find and solve problems and create products of value in one's own culture.”
--Howard Gardner (American Psychologist and Professor at Harvard, 1943-)

“The test of a first-rate intelligence is the ability to hold two opposed ideas at the same time, and still retain the ability to function.”
--F. Scott Fitzgerald (American Writer, 1896-1940)

“To the dull mind all nature is leaden. To the enlightened mind the whole world sparkles and burns.”
--Ralph Waldo Emerson (American Poet and Essayist, 1803-1882)

“It is the sign of a dull mind to dwell upon the cares of the body, to prolong exercise, eating and drinking and other bodily functions. These things are best done by the way; all your attention must be given to the mind.”
--Epictetus (Phrygian-born Greek Stoic Philosopher, c.A.D.55- c.A.D.135)

New Causes for Hope in Psychotic Illnesses

Since many health care providers read this blog, I try to update everyone on promising new treatments that can be used to provide a comprehensive care plan for people.

I have talked before about some new medicines for the treatment of schizophrenic illnesses, and yet more are coming down the road.

There is a short article with quite a number of links here.

"I would like to quote something from the article that is very important for all of us:
It is very interesting that most experts are now focusing on medicines that will make it easier for us to undertake psychosocial rehabilitation, rather than simply relying on a medicine to "cure" the illness.

The most important message from all this research is that the future looks promising for many of our sickest patients."

Medicines designed to help and support, not to sedate or damp down the mind's activity, but to enable a person to take back control of themselves, their thinking and theior emotions.

Teenage Mood Swings

How many of us have been perplexed by the violent mood swings of teenagers? One minute they are out skipping through the countryside and picking wild flowers. The next they seem intent on burning down the forest…

The mood swings and anxiety often make them seem as if they have some kind of "bipolar-lite."

An important new study has revealed that teenage mood swings may be explained by biological changes in the adolescent brain. The research is published in the journal Nature Neuroscience.

Sheryl Smith, a physiologist at the State University of New York, and her colleagues experimented on adolescent female mice and showed that their brains respond to stress in a different way from adults and pre-pubescent individuals.

Anxiety is highly complex and involves a cascade of chemical neurotransmitters and genes. One of its important regulators is the brain’s principal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA counteracts the effect of glutamate, an excitatory neurotransmitter in the limbic system of the brain. There is a kind of Yin/Yang relationship between GABA and glutamate.

The brain is full of what are known as “Neurosteroids:” steroid molecules that interact with  genes and receptors in nerve cells. Neurosteroids generally reduce anxiety, but this research shows that they promote anxiety in female mice around puberty via the selective desensitization of extrasynaptic GABA-A receptors.

Stress causes the release of a steroid known as 3α,5α-Tetrahydroprogesterone also known as Allopregnanolone or THP. In adult and pre-pubescent individuals THP increases the "calming" effect of GABA in the limbic system. However, Smith and her team found that THP had the opposite effect in adolescent mice. In other words the developing adolescent brain simply behaves differently

It would appear that THP has two roles, one in the limbic system where it helps to calm things down, and another in the hippocampus where in adolescents it heats things up. The hippocampus is important in memory and also in the regulation of emotion.

The underlying mechanism appears to be different levels of expression of a type of receptor known as the "alpha-4-beta-2-delta" GABA-A receptor in the hippocampal brain region known as CA1.

In adults and pre-adolescents there are few of these receptors and THP modulates and calms these regions of the brain.

However, in adolescents, the expression of these receptors is high, and the anxiety raising effect of THP in the hippocampus outweighs the calming effect it has in the limbic system.

Smith and her team were able to reverse the puberty effect in the mice by genetically altering the number of receptors.

The result of all this is that the teenage brain amplifies its reactions to stress. So whether the young person reacts by crying or being angry, the emotion will be much more pronounced than it would be in a pre-pubescent person or an adult. To adults it may seem like an overreaction, to the teenager it is his or her only response.

This study is thought to be the first to suggest an underlying physiological, as opposed to a psychological explanation for teenage mood swings.

Apart from raising understanding about what teenagers are going through, the finding raises the possibility of a new approach to more severe mood swings, such as bipolar disorder.