Neural Circuit Taxonomy

Neural network circuits

Brain stuff -- interesting to find out what might go on in that grey matter.

"Precision psychiatry: a neural circuit taxonomy for depression and anxiety"

By Dr. Leanne M Williams, PhD

Summary

"Although there have been tremendous advances in the understanding of human dysfunctions in the brain circuitry for self-reflection, emotion, and cognitive control, a brain-based taxonomy for mental disease is still lacking. 

As a result, these advances have not been translated into actionable clinical tools, and the language of brain circuits has not been incorporated into training programs. 

To address this gap, I present this synthesis of published work, with a focus on functional imaging of circuit dysfunctions across the spectrum of mood and anxiety disorders. 

This synthesis provides the foundation for a taxonomy of putative types of dysfunction, which cuts across traditional diagnostic boundaries for depression and anxiety and includes instead distinct types of neural circuit dysfunction that together reflect the heterogeneity of depression and anxiety. 

This taxonomy is suited to specifying symptoms in terms of underlying neural dysfunction at the individual level and is intended as the foundation for building mechanistic research and ultimately guiding clinical practice."

And from Wikipedia:

"Dysfunction in the salience network have been observed in various psychiatric disorders, including anxiety disorders, post-traumatic stress disorder, schizophrenia, frontotemporal dementia, and Alzheimer's disease. 

The AI node of the salience network has been observed to be hyperactive in anxiety disorders, which is thought to reflect predictions of aversive bodily states leading to worrisome thoughts and anxious behaviors. 

In schizophrenia, both structural and functional abnormalities have been observed, thought to reflect excessive salience being ascribed to internally generated stimuli.

In individuals with autism, the relative salience of social stimuli, such as face, eyes, and gaze, may be diminished, leading to poor social skills."

Currently Reading: Nassim Nicholas Taleb's "Antifragile - Things That Gain From Disorder"

Aside from businessmen and investors, anyone who is uneasy with uncertainty, like anxiety disorder and OCD sufferers, can benefit from the profound insights of this book. You can learn to face uncertainty, It follows Nassim Nicholas Taleb's other great books, Fooled by Randomness and The Black Swan. I highly recommend it.

Nassim Nicholas Taleb

Antifragile is a standalone book in Nassim Nicholas Taleb's landmark Incerto series, an investigation of opacity, luck, uncertainty, probability, human error, risk, and decision-making in a world we don't understand. 

The other books in the series are Fooled by Randomness, The Black Swan, and The Bed of Procrustes. Nassim Nicholas Taleb, the bestselling author of The Black Swan and one of the foremost thinkers of our time, reveals how to thrive in an uncertain world. 

Just as human bones get stronger when subjected to stress and tension, and rumors or riots intensify when someone tries to repress them, many things in life benefit from stress, disorder, volatility, and turmoil. What Taleb has identified and calls "antifragile" is that category of things that not only gain from chaos but need it in order to survive and flourish. 

In The Black Swan, Taleb showed us that highly improbable and unpredictable events underlie almost everything about our world. In Antifragile,  Taleb stands uncertainty on its head, making it desirable, even necessary, and proposes that things be built in an antifragile manner. The antifragile is beyond the resilient or robust. The resilient resists shocks and stays the same; the antifragile gets better and better. Furthermore, the antifragile is immune to prediction errors and protected from adverse events. Why is the city-state better than the nation-state, why is debt bad for you, and why is what we call "efficient" not efficient at all? Why do government responses and social policies protect the strong and hurt the weak? Why should you write your resignation letter before even starting on the job? How did the sinking of the "Titanic" save lives? 

The book spans innovation by trial and error, life decisions, politics, urban planning, war, personal finance, economic systems, and medicine. And throughout, in addition to the street wisdom of Fat Tony of Brooklyn, the voices and recipes of ancient wisdom, from Roman, Greek, Semitic, and medieval sources, are loud and clear. 

Antifragile is a blueprint for living in a Black Swan world. Erudite, witty, and iconoclastic, Taleb's message is revolutionary: The antifragile, and only the antifragile, will make it. 

Praise for Antifragile:

"Ambitious and thought-provoking . . . highly entertaining."-- The Economist. "A bold book explaining how and why we should embrace uncertainty, randomness, and error . . . It may just change our lives."--Newsweek.  "Revelatory . . . Taleb pulls the reader along with the logic of a Socrates."--Chicago Tribune. "Startling . . . richly crammed with insights, stories, fine phrases and intriguing asides . . . I will have to read it again. And again." -- Matt Ridley, The Wall Street Journal. "Trenchant and persuasive . . . Taleb's insatiable polymathic curiosity knows no bounds. . .  You finish the book feeling braver and uplifted."--New Statesman. "Antifragility isn't just sound economic and political doctrine. It's also the key to a good life."-- Fortune. "At once thought-provoking and brilliant."-- Los Angeles Times.

Nassim Nicholas Taleb

"Changed my view of how the world works." -- Daniel Kahneman, Nobel laureate "[This] is the lesson of Taleb . . . and also the lesson of our volatile times. There is more courage and heroism in defying the human impulse, in taking the purposeful and painful steps to prepare for the unimaginable." -- Malcolm Gladwell, author of The Tipping Point "[Taleb writes] in a style that owes as much to Stephen Colbert as it does to Michel de Montaigne."--- The Wall Street Journal "The most prophetic voice of all . . . [Taleb is] a genuinely significant philosopher . . . someone who is able to change the way we view the structure of the world through the strength, originality and veracity of his ideas alone." --GQ.

Nassim Nicholas Taleb

Nassim Nicholas Taleb

Dr. Cynthia Thaik: Don't Be Paralyzed by Fear

At some point or another, we've all experienced fear -- that feeling when your heart is racing out of control, your palms are sweating, you're short of breath and your digestive track goes into spasms.

Fear has very real effects on the body, and these effects are meant to protect us from danger.

In day to day life, a small amount of fear or insecurity can be beneficial, in that it keeps you on your toes and motivated.

However, when fear and insecurity eclipse common sense, these unhealthy thought processes can cloud your judgement and prevent you from realizing your goals.

Moreover, constant anxiety, self-doubt and irrational fear can cause a myriad of health problems, including digestive ailments, headaches, depression, high blood pressure and even cardiovascular issues.

It is important to be aware of your own fears and insecurities, and to recognize if and when they are preventing you from living the life that you truly deserve.

How to Let go of Fear and Insecurity

1. Identify your fears and insecurities. Make a list of all your fears. The first step to eliminating fear is recognizing exactly what it is that makes you afraid. Is it a fear of failure? Rejection? Looking foolish? Once you pinpoint your fears, think about why you are afraid of those things. Are your fears rooted in logic or are they a product of your own emotions?

2. Stop overthinking everything. Sure, it is good to think a situation through before you make a major decision, but too much thinking prevents you from actually doing anything. And if you never act on anything, you'll never get ahead. So stop over-analyzing every single little thing, don't talk yourself out of making decisions and instead, just act.

3. Find your strengths and play those up. When you remind yourself of what you are good at and what you like about yourself, you gain more confidence and start to let go of your fear. The next time you feel that sinking feeling in the pit of your stomach, try to think about at least three strengths that you have that make you unique.

4. Exercise and eat well. We all know that exercise and a healthy diet are good for our bodies, but a healthy lifestyle can also improve your mood and make you feel more relaxed, balanced and confident. This in turn, is a surefire way to vanquish anxiety and insecurity.

5. Set goals. Without a plan it is very easy to get lost and feel as though you have no purpose in life. Goal setting can give you some direction and force you to rise above your fears to achieve the things you want in life. In addition, every for milestone or goal that you reach, you will gain that extra boost of confidence that will help you to get over your insecurities.

When it comes down to it, fear is very much a product of the mind and more of an internal struggle than anything to do with the reality of the outside world.

If you look within yourself, trust your decisions and learn to love yourself, you will find that your fears will dissipate and you can get on with enjoying everything that life has to offer.

Harvey Horror Hoarder: Chamber of Chills #20 Warren Kremer Art

This offbeat Harvey Comics horror yarn must have been partially inspired by the infamous hoarders, the Collier brothers. Scans courtesy of art collector Dave O'Dell.

Wray Herbert Blog: Feeling Anxious? Think Again

by Wray Herbert. author of 'On Second Thought: Outsmarting Your Mind's Hard-Wired Habits'

The number one fear is public speaking, hands down. Pollsters have reported time and again that the average person dreads public speaking more than disease or even death. These polls merely confirm what our sweaty palms and elevated heart beat make undeniable: Standing up and addressing an audience brings out our worst fears about performance and failure and the judgment of others.

We all experience some measure of social anxiety, but some people suffer much more than others, and not just with public speaking. Dates, job interviews, even idle cocktail chatter -- any kind of social encounter can be a source of unbearable dread for people with a social anxiety disorder, or SAD.

Millions are debilitated by the emotional and physical arousal associated with this most common of mental disorders.

Despite the prevalence of SAD, however, a lot remains unknown about the disorder. While the negative emotions are a hallmark of clinical anxiety disorder, there is conflicting evidence about the physiological symptoms. Do sufferers really have maladaptive bodily responses to social stress, or do they just perceive it that way? An answer to this basic question would be helpful in guiding clinical intervention.

A team of psychological scientists has been exploring the interplay of thinking, attention and physiology in SAD. Jeremy Jamieson of the University of Rochester, Matthew Nock of Harvard and Wendy Berry Mendes of UC -- San Francisco designed two studies to sort out these aspects of the disorder and, beyond that, to test a simple intervention that might diminish the unpleasant symptoms of social anxiety.

Here's the background that sparked the scientists' inquiry. It's a popular belief that stressful arousal -- heightened blood pressure, heart rate and so forth -- accumulates over time, leading to poor health and disease down the road. But this is not entirely true. Stress can indeed be deleterious to people's health, but only if they see the stressful situation as a threat -- something they lack the inner resources to cope with. By contrast, if people see a stressful situation as a challenge to meet, their physiological response is different -- and not as harmful to the body.

In the first study, the scientists wanted to see if they could clarify the psychological and physiological aspects of SAD. They recruited volunteers, some of whom met the clinical definition of SAD, and deliberately confronted them with their worst fear -- speaking in front of judgmental strangers. They used a well-established social stress test, in which volunteers are required to prepare a short speech about their personal strengths and weaknesses, deliver it to an audience of two judges, and then recover from the experience. The judges were trained to give subtle but negative non-verbal feedback during the speech; they didn't smile or nod or otherwise indicate any kind of affirmation of the speaker's performance. Half of the volunteers -- both with SAD and without -- went through this stressful experience, while the remaining volunteers, the controls, gave their speech in private, without a judgmental audience.

During this experiment, all the volunteers were hooked up to monitors, which recorded their physiological reactivity. The scientists also measured the volunteers' vigilance for signs of threat, their negative feelings, and their appraisal of their own stress -- whether they saw it as a challenge or a threat.

Then they crunched all the data together.

The most surprising finding was that there was no significant difference between SAD sufferers and healthy controls on measures of arousal. That is, when required to speak before a judgmental audience, both showed high vigilance and the harmful kind physical arousal, compared to those who did not have to speak in public. Those with SAD reported more subjective anxiety and negative feelings, but on objective measures they were no worse off than healthy people in a highly stressful social situation.

Since this finding was unexpected, the scientists wanted to double-check it, but they also wanted to capitalize on it. If SAD sufferers' biological arousal is indeed disconnected from subjective feelings of anxiety, would it be possible to ameliorate the disorder simply by thinking about physical symptoms constructively? Perhaps they could be thought of as a resource that enhances performance, rather than a liability. This is what the scientists explored in a second experiment.

It was basically the same experiment, except that this time some of the volunteers were urged to reappraise their symptoms in a more positive way. Specifically, they were told this just prior to the speaking task: "In stressful situations, like public speaking, our bodies react in very specific ways. The increase in arousal you may feel during stress is not harmful. Instead, these responses evolved to help our ancestors survive by delivering oxygen to where it is needed in the body." They were explicitly encouraged to reinterpret their arousal as an adaptive response. The idea was that changing perceptions of arousal might mitigate anxiety.

And that's just what they found, and detail in a forthcoming article in the journal Clinical Psychological Science. Both socially anxious and healthy volunteers, when encouraged to see their bodily arousal as functional, improved on a number of measures. They still saw public speaking as stressful and personally demanding, but they saw themselves as more resourceful -- better able to cope with the social stress of speaking. What's more, their physiological response actually improved as well; it came to resemble the more adaptive, healthier kind of arousal. Finally, they were not so preoccupied with threatening cues in the world. This shift in attention, away from negativity, could be protective, diminishing the likelihood of reacting to new social threats in the future.

Wray Herbert's blogs -- "Full Frontal Psychology" and "We're Only Human" -- appear regularly in The Huffington Post.

Anxiety: Face Your Fears: Extinction through CBT

Some of the best ways to treat anxiety disorders are through the processes of desensitization, exposure response prevention (ERP), and fear extinction. It seems that those with high levels of anxiety may suffer a super-sensitive "fear circuit," that stores and recalls emotionally-charged learned memories much more quickly and strongly than neurotypicals.

Cognitive Behavioral Therapy (or CBT) retrains the arousal system and "overwrites" the phobias or triggers until at last the mind relents, and accepts that the feared situations are not so threatening. The mind is basically sending out a "Chicken Little"-styled false alarm. However, although desensitized, the fearful memories remain encoded in the brain, and under stress and certain conditions, a person may experience a relapse or resurgance. Then it's time to pick yourself up, dust yourself off, and go back to the same technique.

Avoidance is the worst response, because the fears can grow, and become debilitating.


From yee Wiki:

Extinction is the conditioning phenomenon in which a previously learned response to a cue is eliminated when the cue is presented in the absence of the previously paired aversive (unpleasant) or appetitive (pleasant) stimulus.

Fear conditioning

Extinction is typically studied within the Pavlovian fear conditioning framework in which extinction refers to the reduction in a conditioned response (CR; e.g., fear response/freezing) when a conditioned stimulus (CS; e.g., neutral stimulus/light or tone) is repeatedly presented in the absence of the unconditioned stimulus (US; e.g., foot shock/loud noise) with which it has been previously paired.

The simplest explanation of extinction is that as the CS is presented without the aversive US, the animal gradually "unlearns" the CS–US association which is known as the associative loss theory. However, this explanation is complicated by observations where there is some fear restoration, such as reinstatement (restoration of CR in the context where extinction training occurred but not a different context after aversive US is presented again), renewal (restoration of CR in context A but not in B when learning occurred in context A and extinction in context B), and spontaneous recovery (restoration of CR when the retention test occurs after a long but not a short delay after extinction training) and alternative explanations have been offered.

Research on fear extinction in animal models (typically rats) has clinical implications such as exposure-based therapies for the treatment of phobias and anxiety conditions.


Theories

The dominant account of extinction involves associative models. However, there is debate over whether extinction involves simply "unlearning" the US–CS association (e.g., the Rescorla–Wagner account) or, alternatively, a "new learning" of an inhibitory association that masks the original excitatory association (e.g., Konorski, Pearce and Hall account). A third account concerns non-associative mechanisms such as habituation, modulation and response fatigue. Myers and Davis laboratory work with fear extinction in rodents has suggested that multiple mechanisms may be at work depending on the timing and circumstances in which the extinction occurs.

Given the ompeting views and difficult observations for the various accounts researchers have turned to investigations at the cellular level (most often in rodents) to tease apart the specific brain mechanisms of extinction, in particular the role of the brain structures (amygdala, hippocampus, the prefontal cortex), and specific neurotransmitter systems (e.g., GABA, NMDA). A recent study in rodents by Amano, Unal and Paré published in Nature Neuroscience found that extinction is correlated with synaptic inhibition in the fear output neurons of the central amygdala that project to the periaqueductal gray that controls freezing behavior. They infer that inhibition derives from the prefrontal cortex and suggest promising targets at the cellular level for new treatments of anxiety.

Operant conditioning

In the operant conditioning paradigm, extinction refers to the decline of an operant response when it is no longer reinforced in the presence of its discriminative stimulus. Extinction is observed after withholding of reinforcement for a previously reinforced behavior which decreases the future probability of that behavior. For example, a child who climbs under his desk, a response which has been reinforced by attention, is subsequently ignored until the attention-seeking behavior no longer occurs. In his autobiography, B.F. Skinner noted how he accidentally discovered the extinction of an operant response due to the malfunction of his laboratory equipment:

My first extinction curve showed up by accident. A rat was pressing the lever in an experiment on satiation when the pellet dispenser jammed. I was not there at the time, and when I returned I found a beautiful curve. The rat had gone on pressing although no pellets were received. ... The change was more orderly than the extinction of a salivary reflex in Pavlov's setting, and I was terribly excited. It was a Friday afternoon and there was no one in the laboratory who I could tell. All that weekend I crossed streets with particular care and avoided all unnecessary risks to protect my discovery from loss through my accidental death.
When the extinction of a response has occurred, the discriminative stimulus is then known as an extinction stimulus (SΔ or S-delta). When an S-delta is present, the reinforcing consequence which characteristically follows a behavior does not occur. This is the opposite of a discriminative stimulus which is a signal that reinforcement will occur. For instance, in an operant chamber, if food pellets are only delivered when a response is emitted in the presence of a green light, the green light is a discriminative stimulus. If when a red light is present food will not be delivered, then the red light is an extinction stimulus (food here is used as an example of a reinforcer).

Successful extinction procedures

In order for extinction to work effectively, it must be done consistently. Extinction is considered successful when responding in the presence of an extinction stimulus (a red light or a teacher not giving a bad student attention, for instance) is zero. When a behavior reappears again after it has gone through extinction, it is called resurgence.

Extinction burst

While extinction, when implemented consistently over time, results in the eventual decrease of the undesired behavior, in the short-term the subject might exhibit what is called an extinction burst. An extinction burst will often occur when the extinction procedure has just begun. This consists of a sudden and temporary increase in the response's frequency, followed by the eventual decline and extinction of the behavior targeted for elimination.

Take, as an example, a pigeon that has been reinforced to peck an electronic button. During its training history, every time the pigeon pecked the button, it will have received a small amount of bird seed as a reinforcer. So, whenever the bird is hungry, it will peck the button to receive food. However, if the button were to be turned off, the hungry pigeon will first try pecking the button just as it has in the past. When no food is forthcoming, the bird will likely try again ... and again, and again. After a period of frantic activity, in which their pecking behavior yields no result, the pigeon's pecking will decrease in frequency.

Although not explained by reinforcement theory, the extinction burst can be understood using control theory. In perceptual control theory, the degree of output involved in any action is proportional to the discrepancy between the reference value (desired rate of reward in the operant paradigm) and the current input. Thus, when reward is removed, the discrepancy increases, and the output is increased. In the long term, 'reorganisation', the learning algorithm of control theory, would adapt the control system such that output is reduced.

The evolutionary advantage of this extinction burst is clear. In a natural environment, an animal that persists in a learned behavior, despite not resulting in immediate reinforcement, might still have a chance of producing reinforcing consequences if the animal tries again. This animal would be at an advantage over another animal that gives up too easily.

Despite the name, however, not every explosive reaction to adverse stimuli subsides to extinction. Indeed a small minority of individuals persist in their reaction indefinitely.

Extinction-induced variability

Extinction-induced variability serves an adaptive role similar to the extinction burst. When extinction begins, subjects can exhibit variations in response topography (the movements involved in the response). Response topography is always somewhat variable due to differences in environment or idiosyncratic causes but normally a subject's history of reinforcement keeps slight variations stable by maintaining successful variations over less successful variations. Extinction can increase these variations significantly as the subject attempts to acquire the reinforcement that previous behaviors produced. If a person attempts to open a door by turning the knob, but is unsuccessful, they may next try jiggling the knob, pushing on the frame, knocking on the door or other behaviors to get the door to open. Extinction-induced variability can be used in shaping to reduce problematic behaviors by reinforcing desirable behaviors produced by extinction-induced variability.

D-Cycloserine

D-Cycloserine (DCS) is being trialed as an adjuvant to conventional exposure-based treatments for anxiety disorders. The psychotropic responses are related to D-Cycloserine's action as a partial agonist of the neuronal NMDA receptor for glutamate and have been examined in implications with sensory-related fear extinction in the amygdala.

Here's a video link on exposure therapy, that Dr. R. shared with me when I started my CBT with him:

http://www.medicanalife.com/Treatment-of-Snake-Phobia-Part-1-of-3_v5606