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Authors: Michio Kaku

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BRAIN REGION AFFECTED

Orbitofrontal cortex/caudate nucleus/cingulate cortex

According to the space-time theory of consciousness, many forms of mental illness are typified by the disruption of the checks and balances of opposing feedback loops in the brain that simulate the future. Brain scans are gradually identifying which regions these are. A more complete understanding of mental illness will undoubtedly reveal the involvement of many more regions of the brain. This is only a preliminary sketch.

DEEP BRAIN STIMULATION

Although the space-time theory of consciousness may give us insight into the origin of mental illness, it doesn’t tell us how to create new therapies and remedies.

How will science deal with mental illness in the future? This is hard to predict, since we now realize that mental illness is not just one category, but an entire range of illnesses that can afflict the mind in a bewildering number of ways. Furthermore, the science behind mental illness is still in its infancy, with huge areas totally unexplored and unexplained.

But a new method is being tried today to treat the unending agony of people suffering from one of the most common yet stubbornly persistent forms of mental disorder, depression, which afflicts twenty million people
in the United States.
Ten percent of them, in turn, suffer from an incurable form of depression that has resisted all medical advances. One direct way of treating them, which holds much promise, is to place probes deep inside certain regions of the brain.

An important clue to this disorder was discovered by Dr. Helen Mayberg and colleagues, then doing research at Washington University Medical School. Using brain scans, they identified an area of the brain, called Brodmann area 25 (also called the subcallosal cingulate region), in the cerebral cortex that is consistently hyperactive in depressed individuals for whom all other forms of treatment have been unsuccessful.

These scientists used deep brain stimulation (DBS) in this area, inserting a small probe into the brain and applying an electrical shock, much like a pacemaker. The success of DBS has been astonishing in the treatment of various disorders. In the past decade, DBS has been used on forty thousand patients for motor-related diseases, such as Parkinson’s and epilepsy, which cause uncontrolled movements of the body. Between 60 and 100 percent of patients report significant improvement in controlling their shaking hands. More than 250 hospitals in the United States alone now perform DBS treatments.

But then Dr. Mayberg had the idea of applying DBS directly to Brodmann area 25 to treat depression as well. Her team took twelve patients who were clinically depressed and had shown no improvement after exhaustive use of drugs, psychotherapy, and electroshock therapy.

They found that eight of these chronically depressed individuals immediately showed progress. Their success was so astonishing, in fact, that other groups raced to duplicate these results and apply DBS to other mental disorders. At present, DBS is being applied to thirty-five patients at Emory University, and thirty at other institutions.

Dr. Mayberg says, “
Depression 1.0 was psychotherapy—people arguing about whose fault it was. Depression 2.0 was the idea that it’s a chemical imbalance. This is Depression 3.0. What has captured everyone’s imagination is that, by dissecting a complex behavior disorder into its component systems, you have a new way of thinking about it.”

Although the success of DBS in treating depressed individuals is remarkable, much more research needs to be done. First, it is not clear why DBS works. It is thought that DBS destroys or impairs overactive areas of the brain (as in Parkinson’s and Brodmann area 25) and is hence effective only
against ailments caused by such overactivity. Second, the precision of this tool needs to be improved. Although this treatment has been used to treat a variety of brain diseases, such as phantom limb pain (when a person feels pain from a limb that has been amputated), Tourette’s syndrome, and obsessive-compulsive disorder, the electrode inserted into the brain is not precise, thus affecting perhaps several million neurons rather than just the handful that are the source of distress.

Time will only improve the effectiveness of this therapy. Using MEM technology, one can create microscopic electrodes able to stimulate only a few neurons at a time. Nanotechnology may also make possible neural nanoprobes that are one molecule thick, as in carbon nanotubes. And as MRI sensitivity increases, our capability to guide these electrodes to more specific areas of the brain should grow more precise.

WAKING UP FROM A COMA

Deep brain stimulation has branched into several different avenues of research, including a beneficial side effect: increasing the number of memory cells within the hippocampus. Yet another application is to revive some individuals in a coma.

Comas represent perhaps one of the most controversial forms of consciousness, and often results in national headlines. The case of Terri Schiavo, for example, riveted the public. Due to a heart attack, she suffered a lack of oxygen, which caused massive brain injury. As a result, Schiavo went into a coma in 1990. Her husband, with the approval of doctors, wanted to allow her the dignity of dying peacefully. But her family said this was cruelly pulling the plug on someone who still had some responses to stimuli and might one day be miraculously revived. They pointed out that there had been sensational cases in the past when coma patients suddenly regained consciousness after many years in a vegetative state.

Brain scans were used to settle the question. In 2003, most neurologists, examining the CAT scans, concluded that the damage to Schiavo’s brain was so extensive that she could never be revived, and that she was in a permanent vegetative state (PVS). After she died in 2005, an autopsy confirmed these results—there was no chance of revival.

In some other cases involving coma patients, however, brain scans show
that the damage is not so severe, so there is a slim chance of recovery. In the summer of 2007, a man in Cleveland woke up and greeted his mother after undergoing deep brain stimulation. The man had suffered extensive brain damage eight years earlier and fell into a deep coma known as a minimally conscious state.

Dr. Ali Rezai led the team of surgeons who performed the operation. They inserted a pair of wires into the patient’s brain until they reached the thalamus, which, as we have seen, is the gateway where sensory information is first processed. By sending a low-voltage current through these wires, the doctors were able to stimulate the thalamus, which in turn woke the man up from his deep coma. (Usually, sending electricity into the brain causes that part of the brain to shut down, but under certain circumstances it can act to jolt neurons into action.)

Improvements in DBS technology should increase the number of success stories in different fields. Today a DBS electrode is about 1.5 millimeters in diameter, but it touches up to a million neurons when inserted into the brain, which can cause bleeding and damage to blood vessels.
One to three percent of DBS patients in fact have bleeding that can progress to a stroke. The electric charge carried by DBS probes is also still very crude, pulsing at a constant rate. Eventually, surgeons will be able to adjust the electrical charge carried by the electrodes so that each probe is made for a specific person and a specific ailment. The next generation of DBS probes is bound to be safer and more precise.

THE GENETICS OF MENTAL ILLNESS

Another attempt to understand and eventually treat mental illness involves tracing its genetic roots. Many attempts have been made in this area, with disappointing, mixed results. There is considerable evidence that schizophrenia and bipolar disorder run in families, but attempts to find the genes common to all these individuals have not been conclusive. Occasionally scientists have followed the family trees of certain individuals afflicted by mental illness and found a gene that is prevalent. But attempts to generalize this result to other families have often failed. At best, scientists have concluded that environmental factors as well as a combination of several genes are necessary to trigger mental illness. However, it has generally been accepted that each disorder has its own genetic basis.

In 2012, however, one of the most comprehensive studies ever done showed that there could in fact be a common genetic factor to mental illness after all. Scientists from the Harvard Medical School and Massachusetts General Hospital analyzed sixty thousand people worldwide and found that there was a genetic link between five major mental illnesses: schizophrenia, bipolar disorder, autism, major depression, and attention deficit hyperactivity disorder (ADHD). Together they represent a significant fraction of all mentally ill patients.

After an exhaustive analysis of the subjects’ DNA, scientists found that four genes increased the risk of mental illness. Two of them involved the regulation of calcium channels in neurons. (Calcium is an essential chemical involved in the processing of neural signals.) Dr. Jordan Smoller of the Harvard Medical School says, “
The calcium channels findings suggest that perhaps—and that is a big if—treatments to affect calcium channeling functioning might have effects across a range of disorders.” Already, calcium channel blockers are being used to treat people with bipolar disorder. In the future, these blockers may be used to treat other mental illnesses as well.

This new result could help explain the curious fact that when mental illness runs in a family, members may manifest different forms of disorders. For example, if one twin has schizophrenia, then the other twin might have a totally different disorder, such as bipolar disorder.

The point here is that although each mental illness has its own triggers and genes, there could be a common thread running through them as well. Isolating the common factors among these diseases could give us a clue to which drugs might be most effective against them.


What we have identified here is probably just the tip of the iceberg,” says Dr. Smoller. “As these studies grow, we expect to find additional genes that might overlap.” If more genes are found among these five disorders, it could open up an entirely new approach to mental illness.

If more common genes are found, it could mean that gene therapy might be able to repair the damage caused by defective genes. Or it might give rise to new drugs that could treat the illness at the neural level.

FUTURE AVENUES

So at present, there is no cure for patients with mental illness. Historically, doctors were helpless in treating them. But modern medicine has given us a
variety of new possibilities and therapies to tackle this ancient problem. Just a few of them include:

1. Finding new neurotransmitters and new drugs that regulate the signaling of neurons.

2. Locating the genes linked to various mental illnesses, and perhaps using gene therapy.

3. Using deep brain stimulation to dampen or increase neural activity in certain areas.

4. Using EEG, MRI, MEG, and TES to understand precisely how the brain malfunctions.

5. And in the chapter on reverse engineering the brain, we will explore yet another promising avenue, imaging the entire brain and all its neural pathways. This may finally unravel the mystery of mental illnesses.

But to make sense of the wide variety of mental illnesses, some scientists believe that mental illnesses can be grouped into at least two major groups, each one requiring a different approach:

1. Mental disorders involving injury to the brain

2. Mental disorders triggered by incorrect wiring within the brain

The first type includes Parkinson’s, epilepsy, Alzheimer’s, and a wide variety of disorders caused by strokes and tumors, in which brain tissue is actually injured or malfunctioning. In the case of Parkinson’s and epilepsy, there are neurons in a precise area of the brain that are overactive. In Alzheimer’s, a buildup of amyloid plaque destroys brain tissue, including the hippocampus. In strokes and tumors, certain parts of the brain are silenced, causing numerous behavioral problems. Each of these disorders has to be treated differently, since each injury is different. Parkinson’s and epilepsy may require probes to silence the overactive areas, while damage from Alzheimer’s, strokes, and tumors is often incurable.

In the future, there will be advances in methods to deal with these injured parts of the brain besides deep brain stimulation and magnetic fields. One day stem cells may replace brain tissue that has been damaged. Or perhaps
artificial replacements can be found to compensate for these injured areas using computers. In this case, the injured tissue is removed or replaced, either organically or electronically.

The second category involves disorders caused by a miswiring of the brain. Disorders like schizophrenia, OCD, depression, and bipolar disorder might fall into this category. Each region of the brain may be relatively healthy and intact, but one or more of them may be miswired, causing messages to be processed incorrectly. This category is difficult to treat, since the wiring of the brain is not well understood. So far, the main way to deal with these disorders is through drugs that influence neurotransmitters, but there is still a lot of hit or miss involved here.

But there is another altered state of consciousness that has given us new insights into the working mind. It has also provided new perspectives on how the brain works and what might happen if there is a disorder. This is the field of AI, artificial intelligence. Although it is still in its infancy, it has opened profound insights into the thinking process and has even deepened our understanding of human consciousness. So the questions are: Can silicon consciousness be achieved? If so, how might it differ from human consciousness? And will it try one day to control us?

No, I’m not interested in developing a powerful brain. All I’m after is just a mediocre brain, something like the President of the American Telephone and Telegraph Company.

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