So the left hemisphere, which is analytical and controls language, tends to become manic if left to itself. The right hemisphere, on the contrary, is holistic and tends to check this mania. Dr. V. S. Ramachandran writes, “If left unchecked, the left hemisphere would likely render a person delusional or manic.… So it seems reasonable to postulate a ‘devil’s advocate’ in the right hemisphere that allows ‘you’ to adopt a detached, objective (allocentric) view of yourself.”
If human consciousness involves simulating the future, it has to compute the outcomes of future events with certain probabilities. It needs, therefore, a delicate balance between optimism and pessimism to estimate the chances of success or failures for certain courses of action.
But in some sense, depression is the price we pay for being able to simulate the future. Our consciousness has the ability to conjure up all sorts of horrific outcomes for the future, and is therefore aware of all the bad things that could happen, even if they are not realistic.
It is hard to verify many of these theories, since brain scans of people who are clinically depressed indicate that many brain areas are affected. It is difficult to pinpoint the source of the problem, but among the clinically depressed, activity in the parietal and temporal lobes seems to be suppressed, perhaps indicating that the person is withdrawn from the outside world and living in their own internal world. In particular, the ventromedial cortex seems to play an important role. This area apparently creates the feeling that there is a sense of meaning and wholeness to the world, so that everything seems to have a purpose. Overactivity in this area can cause mania, in which people think they are omnipotent. Underactivity in this area is associated with depression and the feeling that life is pointless. So it is possible that a defect in this area may be responsible for some mood swings.
A THEORY OF CONSCIOUSNESS AND MENTAL ILLNESS
So how does the space-time theory of consciousness apply to mental illness? Can it give us a deeper insight into this disorder? As we mentioned before, we define human consciousness as the process of creating a model of our world in space and time (especially the future) by evaluating many feedback loops in various parameters in order to achieve a goal.
We have proposed that the key function of human consciousness is to simulate the future, but this is not a trivial task. The brain accomplishes it by having these feedback loops check and balance one another. For example, a skillful CEO at a board meeting tries to draw out the disagreement among staff members and to sharpen competing points of view in order to sift through the various arguments and then make a final decision. In the same way, various regions of the brain make diverging assessments of the future, which are given to the dorsolateral prefrontal cortex, the CEO of the brain. These competing assessments are then evaluated and weighed until a balanced final decision is made.
We can now apply the space-time theory of consciousness to give us a definition of most forms of mental illness:
Mental illness is largely caused by the disruption of the delicate checks and balances between competing feedback loops that simulate the future (usually because one region of the brain is overactive or underactive).
Because the CEO of the mind (the dorsolateral prefrontal cortex) no longer has a balanced assessment of the facts, due to this disruption in feedback loops, it begins to make strange conclusions and act in bizarre ways. The advantage of this theory is that it is testable. One has to perform MRI scans of the brain of someone who is mentally ill as it exhibits dysfunctional behavior, evaluating how its feedback loops are performing, and compare it to the MRI scans of normal people. If this theory is correct, the dysfunctional behavior (for example, hearing voices or becoming obsessed) can be traced back to a malfunctioning of the checks and balances between feedback loops. The theory can be disproven if this dysfunctional behavior is totally independent of the interplay between these regions of the brain.
Given this new theory of mental illness, we can now apply it to various forms of mental disorders, summarizing the previous discussion in this new light.
We saw earlier that the obsessive behavior of people suffering from OCD might arise when the checks and balances between several feedback loops are thrown out of balance: one registering something as amiss, another carrying out corrective action, and another one signaling that the matter has been taken care of. The failure of the checks and balances within this loop can cause the brain to be locked into a vicious cycle, so the mind never believes that the problem has been resolved.
The voices heard by schizophrenics might arise when several feedback loops are no longer balancing one another. One feedback loop generates spurious voices in the temporal cortex (i.e., the brain is talking to itself). Auditory and visual hallucinations are often checked by the anterior cingulate cortex, so a normal person can differentiate between real and fictitious voices. But if this region of the brain is not working properly, the brain is flooded with disembodied voices that it believes are real. This can cause schizophrenic behavior.
Similarly, the manic-depressive swings of someone with bipolar disorder might be traced to an imbalance between the left and right hemispheres. The necessary interplay between optimistic and pessimistic assessments is thrown off balance, and the person oscillates wildly between these two diverging moods.
Paranoia may also be viewed in this light. It results from an imbalance between the amygdala (which registers fear and exaggerates threats) and the prefrontal cortex, which evaluates these threats and puts them into perspective.
We should also stress that evolution has given us these feedback loops for a reason: to protect us. They keep us clean, healthy, and socially connected. The problem occurs when the dynamic between opposing feedback loops is disrupted.
This theory can be roughly summarized as follows:
MENTAL ILLNESS
Paranoia
FEEDBACK LOOP #1
Perceiving a threat
FEEDBACK LOOP #2
Discounting threats
BRAIN REGION AFFECTED
Amygdala/prefrontal lobe
MENTAL ILLNESS
Schizophrenia
FEEDBACK LOOP #1
Creating voices
FEEDBACK LOOP #2
Discounting voices
BRAIN REGION AFFECTED
Left temporal lobe/anterior cingulate cortex
MENTAL ILLNESS
Bipolar disorder
FEEDBACK LOOP #1
Optimism
FEEDBACK LOOP #2
Pessimism
BRAIN REGION AFFECTED
Left/right hemisphere
MENTAL ILLNESS
OCD
FEEDBACK LOOP #1
Anxiety
FEEDBACK LOOP #2
Satisfaction
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 examp
le, 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.