The Disordered Mind…, Eric R. Kandel

The Disordered Mind: What Unusual Brains Tell us about Ourselves, Eric R. Kandel, 2018.

Kandel is an eminent neuroscientist, known for his work on the low-level mechanisms of learning and memory as demonstrated in Aplysia. He’s won a host of prizes, including the Nobel for this work. Interestingly, as an undergraduate he majored in humanities, and afterwards became a psychiatrist, before migrating into neuroscience. Now in his 90’s, he is writing about larger themes, and addressing himself to more general audiences.

This is his most recent book in this vein; it is preceded by In Search of Memory: The Emergence of a New Science of Mind (2007); The Age of Insight: The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present (2012); and Reductionism in Art and Science: Bridging the Two Cultures (2016).

Contents

What Brain Disorders Can Tell Us About Ourselves
Our Intensely Social Nature: The Autism Spectrum Emotions
The Integrity of the Self: Depression and Bipolar Disorder
The Ability to Think and to Make and Carry Out Decisions: Schizophrenia
Memory, the Storehouse of the Self: Dementia
Our Innate Creativity: Brain Disorders and Art
Movement: Parkinson’s and Huntington’s Diseases
The Interplay of Conscious and Unconscious Emotion: Anxiety, Post-Traumatic Stress and Faulty Decision Making
The Pleasure Principle and Freedom of Choice: Addictions
Sexual Differentiation of the Brain and Gender Identity
Consciousness: The Great Remaining Mystery of the Brain
Conclusion: Coming Full Circle

My Thoughts on the Book — TBD

TBD after reading.

Notes on the Text

Introduction

Here he sets the scene, offering an extremely abbrieviated account of the development of the current view of the brain/mind from Darwin (Expression of Emotions in Man and Animals, which suggests that mental processes have evolved in the same way as morphology, etc.), to the emergence of cognitive science and its synthesis of philosophy, psychology and neurophysiology.

He mentions two concepts in the introduction that I hope to come away with a good understanding of. One is “neural circuits,” and I am curious about what these are, how they function, and whether “circuit” is more of a model or a metaphor. The second, at the end of the introduction, he suggests that we now know that consciousness is not unitary:

Modern studies of consciousness and its disorders suggest that consciousness is not a single uniform function of the brain: instead, is different states of mind in different contexts.

This too I would like to understand better.

C1: What Brain Disorders Can Tell Us About Ourselves

A short recap of the history of psychiatry and neurology

1790. Phillipe Pinel founds psychiatry, making the claim that mental disorders are medical rather than failures of character. He releases patients in the hospital he runs from chains and introduces humane approaches that treat disorders as a product of life stresses and inherited dispositions.
Early 20th C: Emil Kraepelin founds modern scientific psychiatry. Unlike Freud, who believed disorders stem from a person’s experience, K believed that all disorders have a biological (and genetic) origin. Kraepelins views were based on the work of Broca (1860) and Wernicke (1875) who showed that the aphasias named after them were associated with damage to particular areas of the brain.
Differences between neurological and psychiatric disorders.
- Nature of disorder. Neurological disorders tend to produced unusual behavior or fragmented behavior; psychiatric disorders tend to produce exaggerations of everyday behavior.
- Damage: Neurological disorders are often due to gross damage to the brain that is visible in autopsies or structural scans; psychiatric disorders are more difficult to observe: they may involve increased or decreased activity in particular areas of the brain, or alterations in neural circuitry.
Claim: there are no profound differences between neurological and psychiatric disorders.

… Reading Break …

C2: Our Intensely Social Nature: The Autism Spectrum Emotions and the Integrity of the Self: Depression and Bipolar Disorder

Characteristics of autism ( xx%; genetics: 90%)

Autism disorders involve difficulty in socially connecting – verbally or non-verbally – with others.
One way to think of autism is in terms of the theory of mind. Normally, we attribute mental states — beliefs, intentions, opinions — to others, and those attributions assist us in predicting their behavior (or how they might be in response to particular incidents, events or circumstances). The ability to make such predictions accurately is crucial to prospering in a social group.
Autistic children do not appear to behave in this way, according to both behavioral experiments and brain imaging studies.
The superior temporal sulcus, an area of the brain that responds more strongly to ‘biological motion’ (e.g., a person walking) does not show enhanced activity when autistic children are shown such motion. Thus autistic people have difficult reading biological motion, which makes inferring intention more difficult.
Autistic people also have difficulty reading faces. Eye scanning studies show that they tend to focus on the mouth, rather than the eyes (as non-autists do).

[Leslie Brothers] argued that social interaction requires a network of interconnected brain regions that process social information and together give rise to a theory of mind; she coined the term social brain to describe this network. The regions include the inferior temporal cortex (involved in face recognition), the amygdala (emotion), the superior temporal sulcus (biological motion) the mirror neuron system (empathy), and the areas in the temporal parietal junction involved in theory of mind’

ibid., p. 35

People with autism lack coordinated or synchronized activity among these areas of the brain. Some of these brain areas — the frontal lobe and amygdala – may develop out of sequence, which can disturb patterns of growth in other areas of the brain.
Autistic children often fail to exhibit certain infant behaviors including babbling, eye contact, social behaviors like nodding yes or waving bye-bye, and may interact with toys in unusual ways (arranging by color, rather than acting out events or situations). Most autistic children show some improvement as they age.
An autistic person says: “Autism makes my life loud. … Everything is amplified. … A bright light feels brighter. A soft buzzing from a light feels thunderous. Instead of happy I feel overwhelmed. Instead of sad I feel overwhelmed. … Autism makes my life stressful.“

Causes of autism

Autism as a genetic disorder: if one identical twin has autism, the odds are 90% that the other will as well. That is a higher correlation than for any other developmental disorder.
Genetics: Geneticists have recently discovered two new types of genetic mutations: de novo mutations (which are not inherited from parents, but rather occur during replication), and copy number variations which involve sequences and alter the structure of chromosomes.
Copy number variations involve either deletion or duplication, and can increase or decrease the number of genes in a chromosome by up to 30. There is a region in gene 7 where, if it is lost, autism can result, and if it is duplicated, Williams syndrome (hyper social behavior) can be the result.
De novo mutations have been shown to increase with the age of father (since sperm cells continue to divide through the lifespan, whereas a mother is born with all her eggs). De novo mutations play a role in autism, and also in schizophrenia and bipolar disorders.
Synaptic Prunning. Autistic brains have two many synapses; Schizophrenic brains have too few.
Hormones. Oxytocin appears related to bonding between mothers and offspring; likewise vasopressin also appears to contribute to paternal behavior and pair bonding.

C3: The Integrity of the Self: Depression and Bipolar Disorder

Emotion — ephemeral;
mood, an emotion that extends in time – longer lasting;
temperament — tendency or inclination to a mood.
Prefrontal Cortex <=> Amygdala <=> Hypothalmus
- Prefrontal Cortex: executive function & self-esteem and regulates effect of emotion on thought and memory
- Amygdala: coordinates emotion
- Hypothalmus: bodily functions such as heart rate, blood pressure, sleep cycles, etc.
- Note on above: Functions of prefrontal cortex and amygdala seem vague… “coordinates” emotions? what does that mean?
Charles Darwin: Emotions are part of a pre-verbal system of social communication
The text speaks of emotions and feelings — how do they differ?
Emil Kraepelin — the founder of psychiatry — distinguished between disorders of mood (now bipolar), which also are episodic, and disorders of thought (now schizophrenia), which tend to be long-running and grow worse with time

Depression (5%; genetics: ?%)

Andrew Solomon — a self-phenomenology of depression. Tired, overwhelmed by everyday tasks, lack of pleasure; withdrawal. Then anxiety — manifests as intense, crippling, non-specific fear… what you feel when falling, but it persists.
Both depression and stress appear to activate the body’s hypothalmic-pituitary-adrenal axis causing the adrenal gland to produce cortisol, the body’s primary stress hormone. Over time depression appears to reduce connections between the pre-frontal cortex and the hippocampus (memory). This leads to flattening of emotion and impaired memory and concentration.
Brain imaging can distinguish between patients who can helped by psychiatry and those who need both psychiatry and medication.
Two types of neurotransmitters: modulatory (‘tune’ whole circuits — dopamine and serotonin), and mediating (act on directly on the cell — GABA[-] and glutamate[+])
Two components of the neural circuit of depression are Area 25, subcallosal cingulate nucleus (thought, motor control and motivation) and the right anterior insula (self-awareness and social experience). The right anterior insula connects to the hypothalmus, hippocampus, and prefrontal cortex.
The anterior cingulate gyrus also functions abnormally in people with depression.
Initially depression was treated with SSRIs (selective serrotonin reuptake inhibitors) like prozac, leading to the theory that insufficient serotonin was responsible for depression. But boosting serotonin didn’t help all patients get better, and typically takes about two weeks to affect patients it does help.
Later Ketamine, which prevents glutamate from binding to cells, was found to immediately alleviate depression (although it has side effects which prevents it from being a long term solution).
Almost all anti-depressants stimulate the growth of cells in the prefrontal cortex and the hippocampus.
Aron Beck developed cognitive behavioral therapy in the 1970s which has been shown to work as well or better for mild and medium depression as anti depression medications.
Psychotherapy produces visible, lasting changes in brain activity.
ECT and deep-brain stimulation can also be effective

Bipolar (1%; genetics: 70%)

About 25% of people with depression go on to experience a manic episode.
Once a first manic episode occurs, the brain is changed in ways that make subsequent episodes more likely to occur with very minor stimuli.
Lithium ameliorates mania by passing through sodium channels but it is not pumped out like sodium — so it generally lowers neural sensitivity to internal and external stimuli. But not everyone responds to Lithium, and it has unpleasant side effects.
If one identical twin has bipolar, the chance of the other having it is 70%
It seems like little is known about neural circuits on transmitters. They found one gene associated with bipolarity which is related to the facilitation of neural signaling…

C4: The Ability to Think and to Make and Carry Out Decisions: Schizophrenia (1%; genetics: 50%)

Schizophrenia is a neurodevelopmental disorder; it appears to have its origins early in life, but only manifests in adolescence or early adulthood, perhaps as a result of overactive synaptic pruning. It is due to anatomical defects in neural circuits, and therefore can not be reversed. It is progressive and over time a reduction in gray matter is observed.
Symptoms: Visual or auditory hallucinations; delusions of persecution, control, or grandeur. Also social withdrawal and loss of motivation. Cognitive symptoms include impaired working memory, executive function, and volition.
Eugen Bleuler defined schizophrenia as a disassociation of feelings from cognition and emotion.
Antipsychotic drugs can allieviate positive symptoms for about 80% of patients; but they have unpleasant side effects — many produce Parkinson-like symptoms. Psychotherapy can also help, by assisting schizophrenics in recognizing they have a disorder.
Mesolimbic and nigrostriatal (dopaminergic) pathways are implicated in schizophrenia.There are five types of dopamine receptors, and different drugs have different effects on the various types of receptors. Drugs that effect the receptors that dominate the nigrostriatal pathway tend to have Parkinsonian-like side effects…
If oncoming (prodomal phase) schizophrenia can be identified, cognitive psychotherapy can be helpful as early intervention.
A three year old’s brain has twice as many synapses as an adults; pruning begins at about puberty.

C5: Memory, the Storehouse of the Self: Dementia

C5: Our Innate Creativity: Brain Disorders and ArtC6:

C6: Movement: Parkinson’s and Huntington’s Diseases

C7: The Interplay of Conscious and Unconscious Emotion: Anxiety, Post-Traumatic Stress and Faulty Decision Making

C8: The Pleasure Principle and Freedom of Choice: Addictions

C9: Sexual Differentiation of the Brain and Gender Identity

C10: Consciousness: The Great Remaining Mystery of the Brain Conclusion: Coming Full Circle

Table of Contents