Projections: A Story of Human Emotions Deisseroth, Karl (20%)

But in psychiatric illness, the organ itself is not damaged in a way we can see, as we can visualize a fractured leg or a weakly pumping heart. It is not the brain’s blood supply but rather its hidden communication process, its internal voice, that struggles.
In contrast, most animal neurons normally do not respond to light—there would be no reason to, as it is quite dark inside the skull. With our optogenetic approach (using genetic tricks to produce these exotic microbial proteins only in specific subsets of neurons in the brain, but not others), those brain cells newly endowed with microbial proteins become much different from their neighbors. At this point the modified neurons are the only cells in the brain able to respond to a pulse of light delivered by a scientist—and the result is called optogenetics.
hydrogel-tissue chemistry
This physical transformation helps turn an intact structure like the brain (normally dense and opaque) into a state that allows light to pass freely, which in turn allows high-resolution visualization of component cells and their embedded biomolecules.
We do this to take advantage of a distinct alchemy that this different class of microbes developed—turning not oxygen, but rather light, into energy and information—via specialized genes (called microbial opsins) that allow conversion of light into ionic current flowing through the surface membrane of a cell.
Feeling bad seems gratuitous—and more than that, a vast and unnecessary source of suffering. Much of the clinical disability in psychiatry, after all, arises from the subjective negativity of states like anxiety and depression. One reason may be that life requires making choices between utterly distinct categories that cannot be compared directly. Subjectivity—feeling good or bad, for example—may be a sort of universal monetary instrument for the inner economy of the brain, allowing positivity or negativity from diverse pursuits, from food to sleep to sex to life itself, to be converted into a single common currency. This arrangement would allow difficult category-crossing decisions to be made and actions chosen—quickly and in a way best suited to the survival needs of the particular animal and its species. Otherwise, in a complex and fast-paced world, wrong calls will be made: freeze when a turn is called for; turn when a stop is needed.
Pure emotional tears, as we experience the phenomenon, are not clearly present elsewhere even among our close relatives in the great ape family; the reason, if any, is a mystery. Tears are powerful for driving emotional connection;
Tears come when we feel hope and frailty together, as one. I managed to keep myself from writing this in the chart—or writing that Mateo had no hope left to cry for.
This time, I had thought I could do something—not much, but something. And that matters—realizing at a place and moment you have been called to be whatever it is that humanity can be for a person. That is not nothing.
The computational energy required in the brain, in order to constantly run these unconscious predictive models, would be vast. Perhaps this expendable element is the neural circuit-level resource exhausted quickly in the introvert, or in people—most people—who tire from prolonged social interaction.
Was social avoidance in autism not resulting from exhaustion of some computational or energetic resource, but rather arising from a fear of uncertainty or other people? Or perhaps there was something more subtle and hard to put into words at work here. For me, this latter possibility underscored the magnitude of the challenge of autism: how will patients already limited in linguistic expression tell us what is going on inside, if even we can’t put it into words—and worse, if the words don’t quite exist anyway?
“What does it feel like when you do briefly make eye contact? Does it make you feel anxious or fearful?” “No,” he said. “I’m not afraid.” “Is it overwhelming?” I asked. “Yes,” Charles said, with no hesitation. “Tell me about that, Charles, if you can.” “Well, when I’m looking at you and talking, if your face changes then I have to think about what that means, and how I should react to that, and change what I’m saying.” “And what then?” I gently pressed. “What exactly makes you look away?” “Well,” Charles said, “and then that overloads. It overloads the rest of me.” “So it’s like too much information, and that feels bad?” “Yes,” he said right away, “and if I’m looking away, it’s easier.”
Thinking of the rate of all information as the challenge in this way, rather than just social information, could also usefully explain unpredictability as a key problem in autism. Only unpredictable data is really information; if a person understands a system to the point of predicting everything about it accurately, then it is impossible to inform the person further about the system. The challenge with autism, then, seemed to be about the rate of information itself.
The mode of dealing with a dynamic, unpredictable system (exemplified by social interaction) may be incompatible, or at least dwell in tension, with another mode that we need at other times. This second state would be one that allows us to quietly evaluate an unchanging system—a simple tool, a page of code, an algorithm, a calendar, a timetable, a proof—anything static and predictable, for which the best strategy toward understanding is to take the time to look at the system from different angles, with confidence that it will remain unchanged between one inspection and another.
We suppress the visual stream of information on the phone, or simplify the entire social data stream using emails and posts and texts; each of these methods for reducing data-per-interaction confers a kind of insulation and enables a higher rate of individual social events, if desired
The trend toward increased social partners and contacts, with fewer bits of data transmitted at each contact, may have already reached a practical limit,
People with autism (at least on the high end of the spectrum) can seem more socially adept if the interaction is moved out of real time—to low bit rates, as with text. Though any interaction style still risks errors and misunderstandings, communication can seem improved if given the grace of time.
recipient—over minutes, hours, or days—to be evaluated from different angles. Possible replies may be considered, and scenarios run forward like a chess match for two or twenty moves, off the clock—until a reply may come, a tap or two when ready: Morse for the late-modern human.
We can put off pleasure at any moment, but we cannot as readily ignore pain. Perhaps, then, pain would be an even more powerful force for guiding behavior. Reduction of, or distraction from, inner pain might work as a motivation for just getting up in the morning, or for socializing with friends, or for protecting children—though the mannerisms might look odd to us, as we are constructed now.
For example, depending on the specific circuits targeted, we can cause animals to become more or less aggressive, defensive, social, sexual, hungry, thirsty, sleepy, or energetic—by writing in neural activity with optogenetics (in other words, dictating that just a few spikes of activity occur in a handful of defined cells or connections). As the subject’s behavior changes instantaneously, shifting to the favor of one pursuit over another, and thus seemingly switching from one system of values to another,
It has been discovered that early-life stress and helplessness can increase habenula activity, and borderline patients may be locked in constant uncontrolled negativity from their habenula-to-dopamine neuronal connection—or
“Similarly, you could feel that your actions are not your own, but reflect control from outside. It could just be that in schizophrenia, one part of your brain has no idea what another part wants or is trying to implement, and so an action of the body gets interpreted as a sign of meddling from the outside. The brain—casting around for explanations, which it always does—finds only unlikely ideas, like control by radio transmissions or satellites.”
It could have been a cosmic ray, a long-range particle traveling from the sun, or a gamma ray from another galaxy even, traveling through space for billions of years, and hitting one chemical bond in one gene in one cell of one young girl in Wisconsin. This was happening all the time to everyone, but in Winnie’s cell there was already another problem, an altered gene from birth. A disruption came atop another; it was a double tap, too much, and the system tipped over into the uncontrolled growth of cancer.
since the hypothalamus holds, within its seemingly chaotic mix, not just neurons involved in sleep but also cells for sex, aggression, and body temperature, as well as hunger and thirst, and virtually every primal survival drive.
The conundrum of agency (does free will meaningfully exist or not?), while not answered, is particularly well framed here. That a few spikes of electrical activity in a few cells control choices and actions of the individual—this now cannot be denied.
what our brains seem so well evolved for: solving problems, in a general and abstract way, to address needs that could never have been anticipated by evolution. And perhaps if we were not such versatile problem solvers, we would never have developed the ability to suffer this class of disease.
In major depressive disorder, loss of pleasure is a classical symptom, and a classical-sounding name is given: anhedonia, the absence of beauty and joy from life.
Natural selection provides one potential answer for the meaning of joy, which is that there is none. Meaning is an elusive, even absurd quantity in evolution;
Learned behaviors can be rapidly tuned by modulating the strength of connections in the brain,
It is possible that instead, for at least some stages of white-matter damage like multi-infarct dementia, memories remain intact—but lie isolated from input or output projections, with only their connectivity lost.
Can deeper scientific understanding of the biology save us? Little is known about the biology of antisocial personality. There is a heritable component (accounting for as much as 50 percent) revealed by studies of twins, and some evidence for reduced volume of cells in the prefrontal cortex,
Meeting this complexity head-on may eventually allow us to understand and treat (and feel empathy for) the antisocial, who may have as much free will and personal responsibility as any other person but who can often be cruel to themselves, to their own selves, as well—perhaps through a biologically definable form of detachment, or dissociation, from the feelings of both self and others.

ciwchris / books

Projections: A Story of Human Emotions Deisseroth, Karl (20%) #5