Eric Kandel tells us what unusual Brains tell us about ourselves in his new book.

Prof. Kandel

Eric Kandel wrote the standard textbook of Neural Science (in which he was a pioneer) and just published a book titled The Disordered Mind – What Unusual Brains Tell Us About Ourselves.. I will just select a few interesting points from the book about the pre-frontal cortex, since that is a part of the brain that gives us all sorts of desirable characteristics, such as will-power, concentration, decision making, judgment, and planning for the future. The pre-frontal cortex has neurons that are key to working memory too. Plus it is important in what we call the moral emotions–indignation, compassion, shame, and embarrassment.

If you are under a lot of stress, your adrenal gland releases cortisol, which heightens vigilance. Unfortunately, over time it destroys synaptic connections in your prefrontal cortex. The mental disease of depression also causes a flood of Cortisol, and interestingly, various drugs that treat depression, such as Imipramine and Iproniazid and Ketamine, increase the number of synapses in the prefrontal cortex.
Ketamine works faster than traditional antidepressants, so it is prescribed for the first two weeks, until the other antidepressants take effect. The idea is to prevent suicide in those two weeks. It would be used for more than two weeks, but the problem is it has side effects. Ketamine works faster because it latches onto receptors on the target cell and keeps an excitatory neurotransmitter (Glutamate) from occupying that receptor and over-exciting the neuron. This is a direct effect. Other drugs usually target Serotonin, whose effects are indirect, they somehow fine tune the action of other neurotransmitters, whether excitatory or inhibitory. And the effects are slower.
(Ketamine is not always used wisely, in fact, drug dealers sell it and their customers often use it along with other drugs such as Ecstasy or cocaine or sprinkle it on marijuana blunts.  You can’t save people from themselves.   But I digress.)
A really interesting fact is that children have many more synapses than adults. Beginning about puberty, synaptic pruning removes the dendritic spines that the brain isn’t using, including spines that are not actually helping working memory. (Each incoming neural dendrite has spines on it, and those spines are where other neurons connect.) In Schizophrenia, synaptic pruning appears to go haywire during adolescence, snipping off far too many dendritic spines. So if you are a parent who has Schizophrenia in the family tree, you can’t breathe easy about the risk to your children until they get past adolescence.
There is actually a gene named C4 that produces a protein involved in tagging synapses for removal, and a variant of it named C4-A facilitates over-aggressive pruning.

Kandel’s subtitle for the book indicates that he is interested on what the various abnormalities he describes in the book, including Autism, Alzheimer’s, Gender behavior that doesn’t match external appearance, reveal about those of us without brain disorders.

One question raised in my mind was sparked by the section on Bipolar disorder. Bipolar disorder is characterized by extreme changes in mood, thought, and energy. Manic episodes include racing thoughts and decreased need for sleep. These episodes can be associated with high-risk behaviors such as excessive spending. Patients may get in trouble with the law. Later, a depressive episode will occur.
Kandel writes: “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.”
The question that occurred to me is – are the rest of us feeling the appropriate mood for our situation?. Are we too much into optimism and risk taking? Are we too depressed and pessimistic? What is the right balance?

As you get old, you may develop Frontotemporal Dementia, which begins in the frontal lobe. Your moral reasoning degenerates, and you may end up being arrested for acts such as shoplifting. You may spend yourself into bankruptcy, or regularly overeat. So lets not be too judgmental on old people who start acting in an anti-social way.

In psychopaths, there is more gray matter (cell bodies) in and around the limbic system (which is involved in emotion), but the neural circuitry that connects the emotional areas to the frontal lobes is disrupted. I don’t know what this really means, but maybe we should not be too judgmental about psychopaths either!
More than 3 million Americans have bipolar disorder. About 20 million Americans suffer from major depression. Much suffering is caused by disorders of the brain. There is hope for  these disorders (if they are not caused by early miswiring in development, as Schizophrenia often is). Scientists are already finding genes involved in these diseases, and relevant proteins that are either overactive, or under-active, or malformed in some way. Perhaps as well some day researchers will find a way to make neurons divide and fill wounded areas.

Kandel’s book gives you a different way at looking at human behavior – and is worth reading.

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