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-)

We have all heard about the supposed association between full moon and mental illness, though most of the research has failed to find an association between phases of the moon and mood disorders or psychosis.

But something that we have not heard so much about is the possible association between solar activity and human problems.

Investigators from Chile presented some interesting data (NR308) at the 2007 Annual Meeting of the American Psychiatric Association in San Diego last month.

They used a measure of solar activity called the Wolf number that is based on the number of sunspots. The sunspot cycles are usually between 9.5 and 11 years. They examined the clinical records of 1862 individuals who had been seen at a psychiatric clinic in Santiago over a sixteen-year period, which corresponded to one and a half solar cycles. They found that there was a big rise in admission for severe depression during years with low solar activity and a slight increase in the number of admission for mania during years of high solar activity.

This is not the first time that a connection has been found between the sun and human affairs.

The same authors published a paper in Spanish two years ago in which they also found that depression is more common when there is less solar activity and mania increases when there is more activity. They cannot say whether it is just light that is causing this or some other form of radiation.

Two researchers used the Maine Medicaid database to look at the relationship between solar cycles and human disease, and found that that radiation peaks in solar cycles and particularly in chaotic solar cycles (CSCs) are associated with a higher incidence of mental disorders. The same researchers had previously used the same database to suggest that CSCs produce more ultraviolet radiation and it is this that limits human longevity by causing chromosomal damage.

Interestingly, in 1993 two researchers also suggested a relationship between solar activity and longevity. They looked at the mean longevity of birth cohorts from 1740 to 1900 for United States of America (U.S.) Congressional Representatives exhibited oscillations that coincided with the 9- to 12-year sunspot cycle. They found that the mean longevities of these cohorts were 2-3 years longer during times of low sunspot activity than at peak activity. This phenomenon was confirmed in data from members of the House of Commons of the United Kingdom Parliament and from University of Cambridge alumni.

Researchers in Slovakia have suggested that there may be an association between solar radiation and cerebral strokes, though their data is a little difficult to interpret.

It is clear that the Heavens have more of an impact upon us than many scientists realized, and need to be factored into studies of human mood and behavior.

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.

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.

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…