The Disordered Mind: What Unusual Brains Tell Us About Ourselves

by Eric R. Kandel

Even more compelling, he found that an identical twin of a person with schizophrenia or bipolar disorder is much more likely than a fraternal twin to have the same disorder. Because identical twins share all the same genes and fraternal twins share only half their genes, this finding clearly implicated the identical twins’ genes, rather than their shared environment, in the higher incidence of these mental disorders.

In 2008 Kevin Pelphrey of Yale University, then at Carnegie Mellon University, discovered that autistic children have difficulty distinguishing biological motion.

Relation to the Uncanny Valley?

Thomas Insel, formerly the director of the National Institute of Mental Health, argues that the contrast between autism and Williams syndrome suggests that our brain uses specific networks for specific types of functions, such as social interaction.

The fact that this single segment, containing about twenty-five of the twenty-one thousand or so genes in our genome, could have such a profound influence on complex social behavior is astonishing. This kind of discovery gives scientists something very specific to pursue and should open important new avenues in developing treatments.

So why haven't we figured it out yet?

Excessive concentrations of cortisol destroy synaptic connections between neurons in the hippocampus, the region of the brain that is important in memory storage, and neurons in the prefrontal cortex, which regulates a person’s will to live and influences a person’s decision making and memory storage. The breakdown of synaptic connections in these regions leads to the flattening of emotion and to the impaired memory and concentration that accompany major depression and chronic stress.

The scientists reasoned that inhibiting the action of the enzyme that removes the monoaminergic transmitter from the synapse leaves more noradrenaline and serotonin in the synapses, thereby relieving the symptoms of depression. Thus, the idea of monoamine oxidase inhibitors as a treatment for depression was born. Later, researchers found that iproniazid and imipramine also lead to an increase in the size and number of synapses in the hippocampus and the prefrontal cortex, the brain regions in which synaptic connections are damaged by stress and depression. Understanding how these two antidepressants work led to the development of the monoamine hypothesis, which holds that depression results from partial depletion of noradrenaline or serotonin, or both.

Because ketamine acts on the excitatory neurotransmitter glutamate, which directly affects the target cell, the drug reduces depression more quickly than drugs that act on the modulatory transmitter serotonin.

Mayberg was familiar with these advances and thought that slowing the firing rate of neurons in area 25 might relieve the symptoms of depression. She used deep-brain stimulation in the anterior insula region to treat twenty-five people whose depression was resistant to treatment. She collaborated with a team of neurosurgeons, first at the University of Toronto and then at Emory, who implanted the electrodes. When she turned on the electricity in the operating room, she saw almost immediate changes in the patients’ mood. The patients no longer felt the unending psychic pain characteristic of depression. Moreover, the other symptoms of depression gradually lifted as well. People recovered and were stabilized for the long term.15

Once the first manic episode is initiated—usually at the age of seventeen or eighteen—the brain is changed in ways we do not yet understand, such that even minor events can trigger a later manic episode. After the third or fourth manic episode, a trigger may not be required.

Useful fact for finding a root cause

In schizophrenia, synaptic pruning appears to go haywire during adolescence, snipping off far too many dendritic spines (fig. 4.4). Consequently, the pyramidal neurons are left with too few synaptic connections in the prefrontal cortex to form the robust neural circuits we need for an adequate working memory and other complex cognitive functions. This excessive-pruning hypothesis for schizophrenia, first proposed by Irwin Feinberg, now at the University of California, Davis,2 has been documented by David Lewis and Jill Glausier at the University of Pittsburgh.

As we saw in chapter 3, those disorders result from a functional defect, in which properly built neural circuits fail to work correctly. Such defects can often be reversed. Schizophrenia, like autism spectrum disorders, involves an anatomical defect, in which certain neural circuits fail to develop correctly. To remedy these anatomical defects in schizophrenia, scientists will have to think of some way to either intervene in synaptic pruning during development or create compounds that stimulate the growth of new spines later on.

Pavlov’s work had an extraordinary impact on psychology: it marked a decisive shift toward a behavioral concept of learning. To Pavlov, learning involved not only an association between ideas but also an association between a stimulus and behavior. This made learning amenable to experimental analysis: responses to stimuli could be measured objectively, and the parameters of a response could be specified or even modified.

Nearly one-third of all Americans will experience symptoms of an anxiety disorder at least once during their lifetime, making these disorders the most common psychiatric illnesses by far. Moreover, anxiety disorders can affect children as well as adults.

Post-traumatic stress disorder is a perfect example of this interaction. Not everyone who is exposed to a traumatic stress will develop PTSD. In fact, if one hundred people were exposed to the same traumatic event, about four men and ten women would develop the disorder. (Scientists don’t know why men who experience traumatic stress are so much less likely to develop PTSD.)

Notably, early trauma can cause epigenetic changes, that is, molecular changes in reaction to the environment that do not alter the DNA of a gene but do affect the expression of that gene. Some of these epigenetic changes are initiated in childhood and persist into adulthood. One such change is known to occur in a gene that regulates our response to stress; this change heightens the risk of developing PTSD in response to traumatic stress in adulthood.

People in the treatment group were given propranolol, a drug that blocks the action of noradrenaline, a neurotransmitter released in response to stress that triggers our fight, flight, or freeze response.

58% Why We Sleep. Same nonadernalie effect as prazosin in helping REM. Weird that this is both at 58% in each book.

They would press the lever over and over and over again to produce the desired stimulus. In fact, the pleasure from the electrode was so intense that the animals soon lost interest in everything else. They stopped eating and drinking. They stopped all courtship behavior. They just crouched in the corner of their cage, transfixed by their bliss. Within days, many of the rats died of thirst.

What happens when humans can be controlled this reliably?

Normally, when dopamine binds to receptors on target cells it is taken up and removed from the synapse within a short period of time. However, brain imaging reveals that cocaine, a highly addictive drug, interferes with the removal of dopamine from the synapse. As a result, dopamine lingers there and continues to produce pleasurable feelings that persist beyond those produced by ordinary physiological stimuli. In this way cocaine hijacks the brain’s reward system.

Washington University in St. Louis, involves Vietnam veterans who had become hooked on very high quality heroin while overseas. Amazingly, most of them were able to conquer their addiction when they returned to the United States because none of the cues that had encouraged them to use heroin in Vietnam were present at home.

A solution technique?

First, the neural circuits that control the gender-specific behavior of each sex are present in both sexes.

A female mouse with a mutant pheromone-detection gene behaves like a male mouse, seeking out female partners, and a male mouse with a mutant pheromone-detection gene behaves like a female mouse, caring for infant mice rather than killing them, as a male normally would.

These findings suggest that the sex hormones released in our body before birth influence our gender-specific behavior independently of our chromosomal and anatomical sex.

Gender identity, as we have seen, begins to be apparent early in childhood and is not based on anatomical sex. That is why even as a child, a person can feel that he or she is trapped in the wrong body, expected to behave one way but feeling and wanting to behave differently.

The proximity of the regions concerned with sexuality and aggression, and the zone of overlap, help explain why these two instinctual drives can be so readily fused, as they are, for example, in sexual rage, the extra pleasure some couples derive from sexual experiences that follow an argument.

The basic finding from brain imaging is the same. Conscious activity is restricted in what it can focus on: it selects only a single item at a time and broadcasts it widely across the brain. Unconscious processing of information, in contrast, can take place in many different areas of the cortex simultaneously,

UI thread vs background thread

Instead, you are best off when you allow yourself to gather as much information as possible about the decision and then let it percolate unconsciously.