APPETIZERS
A passage from George Orwell’s iconic novel 1984 reads: “Who controls the past…controls the future; who controls the present controls the past.” And yet the past, though of its nature alterable, never had been altered. Whatever was true now was true from everlasting to everlasting. It was quite simple. All that was needed was an unending series of victories over your own memory. “Reality control,” they called it: in Newspeak, “doublethink.”
“Doublethink is essentially a form of cognitive dissonance in which one holds contradictory ideas in their mind, and accepts both as reality. Doublethink is everywhere. Every human being compartmentalizes to some extent.”
— Rob Knowles
https://constitution.com/author/rob-knowles
(downloaded 5-16-16)
People in volatile economies do not invest, because it is better to spend now than have their earnings lose value tomorrow.
The development of a future orientation requires stability and consistency in the present, or people cannot make reasonable estimates of the future consequences of their actions.
THE LESS PEOPLE CAN RELY ON THE PROMISES OF GOVERNMENT, INSTITUTIONS, AND FAMILIES, THE MORE THEY ESCHEW THE FUTURE AND FOCUS ON THE PRESENT, CREATING A WORLD OF YES AND NO, BLACK AND WHITE, IS AND IS NOT, RATHER THAN ONE FILLED WITH MAYBES, CONTINGENCIES, AND PROBABILITIES. (Emphasis added.)
— Philip Zimbardo and John Boyd, The Time Paradox, Free Press, 2008
THE MOST APPETIZING APPETIZER IN THIS ISSUE:
WONDERFUEL
® C-8 MCT OIL IN AN EASY HOMEMADE MAYONNAISE
Most commercial mayonnaise contains oils composed largely of long chain omega-6 polyunsaturated fats, such as soybean oil, though there are now some brands of mayonnaise available that contain monounsaturates, such as canola oil or, at a premium price, olive oil. You might prefer a mayonnaise that contains medium chain saturated fats (MCTs), but you won’t find it at your local supermarket or even at a specialty food store. We made up our own from our WonderFuel C-8 MCT OIL (comprised of about 90% C-8 MCTs (an 8 carbon fatty acid called caprylic acid)) and it turned out great. It was very easy using a hand blender, the immersion type. Here’s the recipe we used (but of course there are many recipes available and you can add anything you like to suit your taste). In upcoming issues of this newsletter, we’ll be including more recipes that we found particularly enjoyable and fun.
For one cup of mayonnaise, you’ll need:
An immersion blender
INGREDIENTS
1 large egg yolk
1 tablespoon water
1 tablespoon lemon juice (from 1⁄2 a lemon)
3 teaspoons Dijon mustard
1 cup WonderFuel C-8 MCT OIL
INSTRUCTIONS
Place egg yolk, water, lemon juice, and mustard in the bottom of a small bowl that can easily hold your immersion blender. Pour oil on top and allow to settle for 15 seconds. Place head of immersion blender at bottom of bowl and switch it on. As mayonnaise thickens, slowly lift the head of the immersion blender up and down until all the oil is emulsified. Takes about a minute. Season mayonnaise to taste with salt, if desired. Store in a sealed container in the refrigerator for up to two weeks.
ENJOY!
SOCIAL BEHAVIOR: AGGRESSIVE OR PLAYFUL GRAY MATTER MAY MAKE A DIFFERENCE
Aggression is a character trait that is more commonly expressed by males. Not surprisingly, then, it is males that have always been the instigators and perpetrators of war. Sex, on the other hand, can also involve aggression (the extreme end of it being rape, which is also nearly exclusively carried out by men).
Sex, however, can take the place of violent combat by hijacking the aggressive behavior, a form of displacement activity. This is seen when you compare the sexual behavior in bonobos and chimpanzees. A recent paper (Rilling, 2012) studied the differences in the neural systems of bonobos and chimpanzees, trying to find what sophisticated brain imaging could reveal about why bonobos showed little aggressive behavior between males and females (who engaged in sex instead—the same is true for female-female interactions as well), while chimpanzees were inclined to engage in violent interactions, even including the killing of members of other chimp groups.
This is a very desirable type of research. We need to know how the energy of aggressive behavior can be used for peaceful activity, such as sex, and diverted from destructive ends. In the chimp-bonobo study, the results showed that “bonobos have more gray matter in brain regions involved in perceiving distress in both oneself and others, including the right dorsal amygdala and right anterior insula. Bonobos also have a larger pathway linking the amygdala with the ventral anterior cingulate cortex, a pathway implicated in both top-down control of aggressive impulses as well as bottom-up biases against harming others.” (Rilling, 2012) The authors suggest that this can help explain the relative non-violence of bonobos compared to chimpanzees, but “also behaviors like sex and play that serve to dissipate tension, thereby limiting distress and anxiety to levels conducive with prosocial behavior.”
The involvement of the amygdala, a brain area intimately involved in the sensing and regulation of fear and aggression, suggests that the switch to sexual behavior takes place in the case of bonobos with the active participation of this brain area. It would be very useful indeed to find out more about this “switch.”
THE SWITCH
The switch from aggressive behavior to sexual playfulness may be related to the following phenomenon. In studies of animals, such as rodents and non-human primates, the response to a threat involves a release of dopamine. You may be surprised at this, as dopamine is usually thought of as a response to a reward or the expectation of a reward. However, there is a subset of dopamine neurons that specifically respond to stress perceived as a threat. When an animal is exposed to a threat, its brain releases reduced amounts of dopamine in the nucleus accumbens in response to danger, but when the animal perceives that the danger is CONTROLLABLE, more dopamine (rather than less) is released in that area. “…whether an increase or decrease in [nucleus] accumbens dopamine levels is observed in response to stress depends on whether the stressor is appraised as controllable (increase) or not (decrease).” (Lloyd, 2016)
One hypothesis is that when a threat is perceived as controllable, it switches from representing a danger to a signal for possible safety and this makes all the difference to the dopamine releasing neurons in the nucleus accumbens. “Thus, provided the animal has the expectation that the situation is controllable, observation of the aversive stimulus should predict this future appetitive [rewarding] outcome…” (Lloyd, 2016)
References
Rilling et al. Differences between chimpanzees and bonobos in neural systems supporting social cognition. Soc Cogn Affect Neurosci. 7:369-79 (2012).
Lloyd and Dayan. Safety out of control: dopamine and defence. Behav Brain Funct.12(1):15. doi: 10.1186/s12993-016-0099-7. (2016).
WORDS OF WISDOM FROM A GHOST ON WAR AND PEACE
The following is from a satirical comic fantasy entitled “Conjuring the Ghost of Richelieu” written by David Goldman and published in his Affluent Investor on May 26, 2016 (affluentinvestor.com) with the main character being the ghost of Cardinal Richelieu (Armand Jean du Plesses, Cardinal-Duc de Richelieu):
“Do you know,” the ghastly Cardinal continued, “why really interesting wars last for 30 years? That has been true from the Peloponnesian War to my own century. First you kill the fathers, then you kill their sons. There aren’t usually enough men left for a third iteration.”
Later in the same fantasy, the Cardinal explains the problem with majority rule: “It is a matter of calculation—what today you would call game theory. If you compose a state from antagonistic elements to begin with, the rulers must come from one of the minorities. All the minorities will then feel safe, and the majority knows that there is a limit to how badly a minority can oppress a majority…” “The moment you introduce majority rule in the tribal world,” the Cardinal replied, “you destroy the natural equilibrium of oppression.”
THE MISSING MAJORITY
Thus the rise of diversity means that, although our political systems are theoretically founded on majority rule, it may be impossible to form a majority even on issues crucial to survival. In turn, this collapse of consensus means that more and more governments are MINORITY governments, based on shifting and uncertain coalitions.” “The missing majority makes a mockery of standard democratic rhetoric. It forces us to question whether, under the convergence of speed and diversity, any constituency can ever be “represented.”
—Alvin Toffler, The Third Wave
William Morrow & Co., 1980, pg. 426
COULD YOU BE ADDICTED TO SUGAR?
YOU COULD BE—AND HERE’S WHY
An exceptionally informative paper (Avena, 2008) describes the authors’ experiments in rats as well as reviews papers providing a convincing body of evidence that sugar can produce neurochemical effects in the brain that mimic those of addiction to drugs such as cocaine and heroin. In its detailed overview of these effects, the paper provides a description of how sugar can be addicting, using a model developed using rats that depicted the four stages of the addictive process as (1) binging, (2) withdrawal, (3) craving, and (4) sensitization. In addition, the paper elaborates the sequential alterations in brain neurochemistry that take place during each of these stages, offering very useful guidance to many places where intervention may be helpful. “Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin [part of the opioid system] mRNA expression and dopamine and acetylcholine release in the nucleus accumbens.” (Avena, 2008) (The usual limitation applies—that the evidence presented was what was known as of the date of publication, but to our knowledge, their understanding is still the accepted view of addiction.)
Many people feel compelled to eat sweet foods. These feelings are beyond their usual self-control, and are often likened to an “addiction.” But, as the evidence shows, sugar craving is not a metaphor for an addiction, but is a true addiction. The paper presents the authors’ hypothesis that “intermittent, excessive intake of sugar can have dopaminergic, cholinergic and opioid effects that are similar to psychostimulants and opiates, albeit smaller in magnitude.” (Avena, 2008)
Another paper (Morris, 2010) explains that glucose is released from the liver in response to circulating adrenaline (aka epinephrine), a neurotransmitter of the adrenergic nervous system, which is involved in feeding and glucose regulation, as discussed below.
References
Avena et al. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 32(1):20-39 (2008)
Morris et al. Age-related memory impairments due to reduced blood glucose responses to epinephrine. Neurobiol Aging. 31:2136-45 (2010). (In this paper, the authors found that in a study of rats, adrenaline and glucose were about equally effective in improving memory in young rats, but that in old rats, glucose was more effective in doing so.)
COULD YOU BE ADDICTED TO SUGAR?
YOU COULD BE—AND HERE’S WHY
An exceptionally informative paper (Avena, 2008) describes the authors’ experiments in rats as well as reviews papers providing a convincing body of evidence that sugar can produce neurochemical effects in the brain that mimic those of addiction to drugs such as cocaine and heroin. In its detailed overview of these effects, the paper provides a description of how sugar can be addicting, using a model developed using rats that depicted the four stages of the addictive process as (1) binging, (2) withdrawal, (3) craving, and (4) sensitization. In addition, the paper elaborates the sequential alterations in brain neurochemistry that take place during each of these stages, offering very useful guidance to many places where intervention may be helpful. “Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin [part of the opioid system] mRNA expression and dopamine and acetylcholine release in the nucleus accumbens.” (Avena, 2008) (The usual limitation applies—that the evidence presented was what was known as of the date of publication, but to our knowledge, their understanding is still the accepted view of addiction.)
Many people feel compelled to eat sweet foods. These feelings are beyond their usual self-control, and are often likened to an “addiction.” But, as the evidence shows, sugar craving is not a metaphor for an addiction, but is a true addiction. The paper presents the authors’ hypothesis that “intermittent, excessive intake of sugar can have dopaminergic, cholinergic and opioid effects that are similar to psychostimulants and opiates, albeit smaller in magnitude.” (Avena, 2008)
Another paper (Morris, 2010) explains that glucose is released from the liver in response to circulating adrenaline (aka epinephrine), a neurotransmitter of the adrenergic nervous system, which is involved in feeding and glucose regulation, as discussed below.
References
Avena et al. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 32(1):20-39 (2008)
Morris et al. Age-related memory impairments due to reduced blood glucose responses to epinephrine. Neurobiol Aging. 31:2136-45 (2010). (In this paper, the authors found that in a study of rats, adrenaline and glucose were about equally effective in improving memory in young rats, but that in old rats, glucose was more effective in doing so.)
WHEN DOPAMINE IS RELEASED IN RESPONSE TO AN AVERSIVE STIMULUS, RATHER THAN A REWARDING ONE
While dopamine is known as a signal for reward (or the anticipation of a reward), some neurons that express dopamine release dopamine in response to an AVERSIVE stimulus. The authors of a very recent paper (Lloyd, 2016) pointed out that an aversive stimulus could, if there is a way to escape it, actually be a rewarding stimulus because safety can be a reward. As they point out, “…relative to this new state of danger, the possible prospect of future safety—a positive outcome—comes into play.” “Thus, provided the animal has the expectation that it will ultimately be able to achieve safety, i.e., that the situation is controllable, observation of the aversive stimulus should predict this future appetitive [rewarding] outcome…” Another paper expressed it this way: “Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance.” (Kim, 2006)
This leads to the interesting economic concept of “opportunity costs,” where there is a cost to NOT doing a thing that might have a large payoff. “… if the subject fails to explore, for instance because it believes the aversive stimulus to be insufficiently controllable, then it would never discover that it actually might be removed.” The researchers then go on to explain that an inadequate response by the dopamine (D2) receptor could lead to a failure to consider the possibility of achieving safety.
References
Lloyd and Dayan. Safety out of control: dopamine and defence. Behav Brain Funct.12:15 (2016).
Kim et al. Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain. PLoS Biol. 4(8):e233 (2006).
FOOD ADDICTION, A TRUE ADDICTION
The basis for addiction is REWARD. All addictive substances are rewarding. The frantic bar pressing of a rat is a good example of how important reward can be in focusing the attention of an animal. In the case of food, unlike addictive drugs, the pleasure of its consumption is important for survival. From an evolutionary perspective, it would have been highly adaptive for the consumption of food to be rewarding, especially in the case of foods rich in fat and sugar, since they can be rapidly converted into energy.
Interestingly, in the case of cocaine addiction, a decreased number of D2 receptors are available to provide the motivation to obtain and use cocaine. The form of the D2 receptor known as the TaqA1 variant that is associated with a lower release of dopamine in humans is a fairly common version of the D2 receptor in Caucasians. (Reuter, 2013) Possessing it causes individuals to be susceptible to risky behavior, including the use of addictive drugs, but also for less extreme sorts of risky activity, such as auto racing, skydiving, mountain climbing, gambling, promiscuous sexuality, and even risky trading at the stock market. Activating the D2 receptors at medium spiny neurons that express the dopamine D2 receptors has been shown in mice to suppress cocaine self-administration. (Bock, 2013) The way this works is that the D2 receptor signals reward (or the prediction of reward) and when the numbers of these receptors are reduced, dopamine release is lower, and this induces behavior to increase dopaminergic release. One way people do this is by engaging in “thrill-seeking.”
References
Reuter et al. The influence of dopaminergic gene variants on decision making in the ultimatum game. Front Hum Neurosci. 4;7:242. doi: 10.3389/fnhum.2013.00242. (June 2013).
Bock, Shin, et al. Strengthening the accumbal indirect pathway promotes resilience to compulsive cocaine use. Nat Neurosci. 16(5):632-8 (2013).
HOW IS FOOD INTAKE REGULATED?
A host of molecules are involved in the process of addiction. It is because an overpowering desire to consume opiates and an obvious withdrawal syndrome is easier to distinguish than an overpowering desire to eat certain kinds of food followed by its own form of the withdrawal syndrome that the label “addiction” is easy to apply to opiate addiction but is less readily recognized in the eating of food. The molecules regulating the processes tell the story.
A mechanism has been identified to explain in part how these molecules foster addiction: they activate the vitally important reward system in which the cholinergic and dopaminergic nervous systems interact. In fact, a study (Joshua, 2008) reports that midbrain dopaminergic neurons and striatal cholinergic interneurons distinguish between rewarding and aversive stimuli. Importantly, the interaction between the dopaminergic and cholinergic nervous systems links these neurotransmitters to experimental findings that show that eating is initiated by a cholinergic signal and is terminated by a dopaminergic signal. (Rada, 2000) (Other studies have reported initiation by a dopaminergic signal and termination by a cholinergic signal; thus, the evidence is inconsistent.) This hub in which the neurotransmitter systems interact is a target for the complex process of food and perhaps other addictions.
References
Joshua et al. Midbrain dopaminergic neurons and striated cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J Neurosci. 28(45):11673-84 (2008).
Rada et al. Acetylcholine release in ventral tegmental area by hypothalamic self-stimulation, eating, and drinking. Pharmacol Biochem Behav. 65(3):375-39 (2000).
DOPAMINE IS RELEASED IN RESPONSE TO HIGHLY PALATABLE FOOD
WHY IS THIS RELEASE ATTENUATED FOLLOWING REPEATED SERVINGS?
Many papers (see, for example, Avena, 2011) report that the release of dopamine that normally accompanies the consumption of a tasty meal becomes attenuated as the meal progresses, suggesting (according to some papers) that this is due to a loss of “novelty” of the food. We wonder whether this is the reason for decreasing pleasure in a meal and suggest that it might be due, instead, to a downregulation of the dopaminergic receptors or transient exhaustion of the dopamine supply.
Reference
Avena et al. Overlaps in the nosology of substance abuse and overeating: the translational implications of ‘food addiction’. CURRENT DRUG ABUSE REVIEWS 4:133-139 (2011)
SHORT CHAIN FATTY ACIDS AND KETONES DIRECTLY REGULATE THE SYMPATHETIC (ADRENERGIC) NERVOUS SYSTEM
Another neurotransmitter system importantly involved in eating and glucose regulation is the sympathetic (adrenergic) nervous system, in which adrenaline (also called epinephrine) and noradrenaline (also called norepinephrine) are the neurotransmitters.
“To balance energy intake, dietary excess and fasting triggers an increase or a decrease in energy expenditure, respectively, by regulating activity of the sympathetic nervous system, and its dysregulation leads to metabolic disorders such as obesity and diabetes. In feeding, excessive energy is consumed by the enhancement of sympathetic function, resulting in increases in heart rate and diet-induced thermogenesis, whereas in fasting, energy use is saved by the suppression of the sympathetic function as a survival mechanism, resulting in the reduction in heart rate and activity.” “In the present study, we show that SCFAs [short chain fatty acids] and ketone bodies, major energy sources in the body, directly regulate sympathetic activity via GPR41 [an SCFA receptor].” (Kimura, 2011) Perhaps the enhancement of sympathetic function resulting from eating a fatty meal at bedtime can cause insomnia.
Reference
Kimura et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A.108(19):8030-5 (2011).
THE BRAIN REQUIRES GLUCOSE FOR SELF-CONTROL
A 2007 paper reports on the advantages that having good self-control gives a person. As the paper (Gailliot, 2007) explains, prior evidence has amply shown that good self-control leads to such desirable outcomes as “healthier interpersonal relationships, greater popularity, better mental health, more effective coping skills, reduced aggression, and superior academic performance…” Other benefits they mention include reduced susceptibility to addictive drugs and to eating disorders.
The authors explained that in order for the brain to exert self-control, it requires the expenditure of energy, a lot of energy, in the form of glucose (the brain’s major source of energy). In fact, they report that a SINGLE act of self-control reduces the ability of an individual to perform a subsequent act of self-control. They describe a study in which participants had to resist eating freshly baked cookies and later, it found, those subjects who did resist were less able to persist in a task which also required self-control. The paper (Gailliot, 2007) also provided references to several other studies of limits to self-control after another act of self-control, that included control of prejudicial behavior, coping with fears of death, controlling spending, controlling one’s temper, and limiting alcohol intake.
The researchers (Gailliot, 2007) then showed that a deficiency of glucose was the cause of the reduced self-control that followed a prior act of self-control by treating some of the participants with a glucose drink after their initial task of self-control. “Even though nearly all of the brain’s activities consume some glucose, most cognitive processes are relatively unaffected by subtle or minor fluctuations in glucose levels within the normal or healthy range. Controlled, effortful processes that rely on executive function, however, are unlike most other cognitive processes in that they seem highly susceptible to normal fluctuations in glucose.” An example of such an effortful process relying on higher cognitive areas that use a lot of energy is the struggle for self-control that addicts engage in when they try to resist the urge to take drugs. It is interesting to note that a dose of sugar can temporarily overcome that urge. It is, in fact, a common anecdotal suggestion for those trying to “kick the habit” (whether for cigarettes or something else) to consume sugar for temporary relief.
In conclusion, the authors note that “…despite our manipulations, we do not intend to advocate consuming large quantities of sugar as an ideal strategy for improving self-control.” We wouldn’t either, but see next paragraph for a different approach.
We wonder how these experiments would have worked out if the subjects had been given C-8 MCT OIL as an alternative energy source, rather than glucose. It seems to us that this would make a meaningful experiment and we do think that prior evidence supports the idea that the C-8 MCT OIL could similarly support the energy requirements for self-control without promoting an insulin surge that would lower subsequent blood glucose levels.
Reference
Gailliot, Baumeister, et al. Self-control relies on glucose as a limited energy source: Willpower is more than a metaphor. J Pers Soc Psychol. 92(2):325-36 (2007).
LACK OF SELF-CONTROL (IMPULSIVITY) PREDICTS LIKELIHOOD OF CRIMINAL ACTIVITY
A very recent paper (Akerlund, 2016) followed 13,606 children for 18 years in a study of time discounting, that is, how much the children valued a sum of money now (about $140 in U.S. dollars) as compared to a larger sum of money (about $1,400 in U.S. dollars) 5 years later.
“Our results show that individuals with short time horizons have a significantly higher risk of criminal involvement later in life.” (Akerlund, 2016) They suggest as the reason that individuals may perceive that the relative costs and benefits of criminal activity involve rewards that “are savored immediately and its potential costs in terms of apprehension and punishment [ ] are borne in the future.”
The study’s authors use the expression “self-control” to describe an individual’s ability to resist impulsively choosing an immediate reward as compared to waiting for a later, larger reward. “… the ability to exercise self-control in the face of opportunity is hypothesized to explain a large portion of criminal behavior.” The researchers found that there is an association between intelligence and crime (being more prevalent in those with low intelligence and especially strongly associated with men of low intelligence) and that “patience [that is, non-impulsivity] among adults is significantly associated with higher cognitive ability.”
They further refer to the famous “marshmallow” experiments where 4-year old children were offered an extra marshmallow if they could delay for fifteen minutes the gratification of immediately eating a marshmallow. Those who waited were later found to have better outcomes in many aspects of their young adult lives, including SAT scores, educational achievement, income, less likelihood of using addictive drugs, and other things. The authors note that similar experiments in adults have found that time preferences (immediate vs. delayed gratification) “are significantly correlated with field outcomes such as occupational choice, credit card borrowing, and smoking.” (Akerlund, 2016)
The experimenters did not report in their paper a link (should there be one) between glucose and engagement in criminal activity and, again, we believe that this would have added to their results by providing a physiological reason for the differences between the impulsive and non-impulsive children. Because the brain requires glucose for self-control (see above), it is plausible that a relative glucose insufficiency in the brain may be a causative factor in the tendency to engage in criminal activity. (A “relative glucose insufficiency” does not necessarily mean that an individual does not consume enough glucose, but that he or she uses glucose inefficiently, as would be the case for insulin resistance.)
Reference
Akerlund, Golsteyn, et al. Time discounting and criminal behavior. Proc Natl Acad Sci U S A. Early edition. 13(22):6160-5. doi: 10.1073/pnas.1522445113. (2016).
THE ADRENERGIC NERVOUS SYSTEM AND PREJUDICE
A recent paper (Terbeck, 2012) showed that, in a randomized, double-blind, placebo controlled study of 36 white university students (a typical source for participants in these sorts of studies!) were given a single dose of 40 mg. of propranolol, a beta-adrenoceptor antagonist (beta blocker) and their racial bias determined by the IAT (implicit association task). The IAT assesses implicit racial prejudice (the physical expression of prejudice) by an “item sorting task” to distinguish that from explicit racial prejudice, which is limited to what the subject thinks. Explicit racial prejudice was assessed by subjects indicating how “warm” they felt toward various racial groups.
Propranolol is a widely used medication in hypertension and other conditions in which an overactive sympathetic (adrenergic) nervous system is involved.
The results showed that, compared to placebo, “propranolol significantly lowered heart rate and abolished implicit racial bias, without affecting the measure of explicit racial prejudice.” (Terbeck, 2012)
In another fairly recent paper (Kimura, 2011), scientists generated mice without a GPR41 receptor that regulates sympathetic (adrenergic) nervous system activity via the interaction of short chain fatty acids and ketone bodies with the receptor. “…a ketone body, beta-hydroxybutyrate, produced during starvation or diabetes, suppressed SNS [sympathetic nervous system] activity by antagonizing GPR41.”
References
Kimura et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A.108(19):8030-5 (2011).
Terbeck et al. Propranolol reduces implicit negative racial bias. Psychopharmacology (Berl). Aug;222(3):419-24 (2012).
KETONES ARE FUEL FOR THE EYE’S PHOTORECEPTORS
POSSIBLY PROTECTIVE AGAINST MACULAR DEGENERATION
Other tissues, besides those of the brain, use ketones as a source of energy when glucose is in short supply. The retina, for example, is highly energetic, requires (like the rest of the brain) a continuously available energy source and can also use ketones as a replacement when there is an inadequate supply of glucose. “… the retina uses not only glucose, but also fatty acids, as an energy source, and [ ] the beta-oxidation of fatty acids has an important role in meeting the demands of photoreceptors. Thus defective fatty acid metabolism could contribute to the development of AMD [age-related macular degeneration].” (Rajala, 2016)
References
Rajala and Gardner. Burning fat fuels photoreceptors. Nat Med. 6;22(4):342-3. doi: 10.1038/nm.4080. (2015); Joyal et al. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar 1. Nat Med. 22(4):439-45 (2016).
THE SPEED OF THOUGHT
Speeding through the universe,
Thinking is the best way to travel.
—from The Best Way To Travel by The Moody Blues
A paper has reported an attempt to compare the “speed of thought” for brains to that of digital computers. (Nagarajan, 2008) The comparative data are as of 2008, so may be considerably different now. Computers are certainly much faster and even some brains may be faster, depending upon such things as increasing the brain’s myelin content, which speeds the transmission of information in the brain (for more on this, see next section below).
While the brain’s basic unit is the neuron, that of the computer is the transistor. At the time this paper was published, “modern very large scale integrated (VLSI) microprocessor circuits” were said to “have about a million transistors per square millimeter of chip area.” In the brain, on the other hand, the smallest computing element that processes information is the neuronal synapse. The “grey matter of most brain regions contains about 10 to the fifth synapses per microliter, a value not so different from the volume density of transistors.” (Nagarajan, 2008)
After supposing that “each neuron carries out an instruction each time it produces a nerve impulse” and that the neocortex contains about 10 to the tenth neurons, the resulting calculation indicates that the modern microprocessor would provide 100 fold less instructions per second than the brain. So, the computer (at that time) was calculated to be 100 times slower than the brain, even though it had a much faster processor speed because the brain contains so many synapses.
Reference
Nagarajan and Stevens. How does the speed of thought compare for brains and digital computers? Curr Biol. 18(17):R756-8 (2008).
THE BRAIN’S PROCESSING SPEED DEPENDS UPON MYELIN
The myelin coat that sheaths neuronal tracts in the brain (white matter or gray matter) is what enables the brain to transmit information rapidly from one area to another. As we have written before, myelin is used by the brain as a source of fats for conversion to ketones when the brain’s supply of glucose—its primary fuel for energy—is depleted. This occurs in many circumstances, including fasting, ischemia, aging, stroke, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, to name just a few. That is why we have written so extensively about C-8 MCT OIL, which the brain can use as a source of fat for conversion to ketones, an alternative to glucose for fuel, thus sparing its valuable and limited supply of myelin.
THINKING ABOUT THE FUTURE
Mental Time Travel
One of Sandy’s books on memory (The Memory Process, MIT Press, 2011) covers a lot more than just memory. It roams far and wide, with fascinating material on such things as imagination, the language of music, consciousness, romantic fiction, dreams, and a lot of other stuff, just what you might expect from a well-done book coming out of the Massachusetts Institute of Technology (note: MIT’s publications on politically “sensitive” subjects are not necessarily so well done).
In this heavily referenced book, there is a discussion on how thinking about the future uses virtually the same neural pathways as does remembering the past, being appropriately called “Mental Time Travel.” It is also called “episodic future thinking” by Alan Richardson, author of Ch. 13 of The Memory Process, pg. 280, who concludes that thinking of the future and past share common neurological mechanisms.
A very informative description of how memory works is given on pg. 290: “Episodic memories … tend to reflect personal experience rather than general knowledge or implicit skills…” These memories are depicted as being “fragmentary and fragile” and are used to “reconstruct” memories from bits and pieces put together in a creative process rather than storing “exact replicas of past experience.” The beauty of this system is that it enables the bits and pieces to be reused in new, original combinations, both for recreating the past and for imagining the future.
A 2007 published study is described in the book (pg. 279) in which researchers found that amnesic patients with damage to the hippocampus had a diminished capacity to imagine hypothetical future scenarios, something that is also seen in normal aging. It is easy to see how an inability to see what might lie ahead, particularly if it involves any rewarding events, could lead to apathy concerning whether you live or die. The “will to live” is a vital factor in remaining alive and has been shown to be important in the length of time patients with terminal diseases survive.
PERSONALITY AND THE COMT GENE
Personality generally “refers to the ‘characteristic patterns of behavior, thoughts and feelings’ of a person over time.” (Montag, 2015)
One cannot really understand human personalities without knowledge of dopamine and COMT (catechol-O-methyltransferase), the latter being one of the enzymes that catabolizes and inactivates dopamine. Dopamine is a neurotransmitter importantly involved in the brain’s reward circuitry. Its regulation is responsible for much of the personality differences exhibited by individuals. People who have certain variants of specific dopamine receptors show very different patterns of behavior. The DRD2 and DRD4 dopamine receptor genes are associated with, for instance, impulsivity, novelty-seeking, and risk-seeking (tending to engage in more risky types of behavior) and linked to lower levels of dopamine release.
The COMT Val158Met polymorphism (version) of the COMT gene is a high activity version of COMT, that is, it breaks down more dopamine than the Met/Met COMT polymorphism. “Carriers of the Met/Met variant [of COMT] catabolize three to four times less dopamine than carriers of the homozygous Val/Val variant.” (Montag, 2015) By catabolizing less dopamine, this means that there is more dopamine available to activate dopamine receptors. COMT Val158Met, on the other hand, causes there to be LESS dopamine available to activate dopamine receptors.
Met stands for methionine, Val for valine; the gene can either specify a valine (Val) or a methionine (Met) at position 158 and this importantly defines how strongly the COMT enzyme degrades dopamine. The variant most commonly found has a Met and a Val at that position and is called the Val158Met polymorphism. That variant is associated with a very interesting personality type that in its most productive form is found in people such as entrepreneurs, inventors, and similar types who also share personality characteristics such as being risk takers and novelty seekers. At the extreme end of the spectrum of those who have this variant may be found people who have a tendency to engage in impulsively reckless activity or thrill-seeking, and may even, in some cases, use addictive drugs.
The authors of Montag, 2015 explained that they searched the PubMed.gov literature for papers on COMT Val158Met and found that, at the time, there were nearly 400 papers on the subject. They then narrowed the search by using the keywords “COMT Val158Met” and “personality” as search terms and received back 56 papers. (They also searched “Google Scholar” using these keywords.) Ultimately, they focused on papers dealing with “COMT in the context of [ ] [certain] biologically oriented personality theories…” The literature on COMT continues to rapidly increase.
INHIBITING COMT TO DECREASE DOPAMINE
DEGRADATION IN THE BRAIN GREATER REWARDS™
We developed a formulation called GREATER REWARDS that we take regularly to inhibit COMT to reduce the degradation of dopamine, thereby increasing the reward signaling of dopamine. One of its ingredients is EGCG, epigallocatechin-3-O-gallate, the major catechin found in green or white tea. EGCG is a high-potency inhibitor of COMT (catechol-O-methyltransferase). (Zhu, 2008)
Another ingredient in our GREATER REWARDS is taurine. Taurine increases dopamine levels in the dopamine reward system. The rat dopamine reward system is organized like that of humans, with the mesolimbic dopamine neurons projecting from the ventral tegmental area to the nucleus accumbens. Researchers looking for receptors involved in the regulation of dopamine in this pathway reported that local perfusion of taurine (by microdialysis) increased dopamine levels in the nucleus accumbens reward center and that this involved taurine acting as an agonist at (activating) glycine receptors. (Ericson, 2006)
Another constituent of GREATER REWARDS is quercetin, a flavonoid found in many plants. It has been shown to possibly inhibit COMT. (Singh, 2003; Nagai, 2004)
We’ve also added lithium. In the low concentrations found in drinking water and in some mineral waters, lithium has a protective effect against suicide and reduces the number of arrests for robbery, burglary, and theft, suggesting that it can help decrease impulsivity. “…the antisuicidal effects of lithium may work at lower levels than so-called therapeutic levels and not only in patients with mood disorders but also in the general population.” (Schrauzer, 1990; Terao, 2009)
We’ve also added hesperidin, a flavonoid widely found in fruits and vegetables for its ability to promote neurogenesis by enhancing the survival of neural progenitors that are developing into mature neurons. (Nones, 2012)
References
Montag et al. The role of the catechol-O-methyltransferase (COMT) gene in personality and related psychopathological disorders. CNS Neurol Disord Drug Targets. 11(3):236-50 (2012).
Zhu et al. Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (-)-epigallocatechin-3-O-gallate. Xenobiotica.38(2):130-46 (2008).
Ericson et al. Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Eur J Neurosci. 23:3225-9 (2006).
Singh et al. Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. Pharmacology. 68:81-8 (2003).
Nagai et al. Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 32(5):497-504 (2004).
Nones et al. Effect of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. Int J Dev Neurosci. 30:303-13 (2012).
Schrauzer and Shrestha. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res. 25:105-113 (1990).
Terao et al. Even very low but sustained lithium intake can prevent suicide in the general population? Med Hypotheses. 73:811-2 (2009).
PERSONALITY AND THE 2 GENE
“REWARD DEFICIENCY SYNDROME”
by Sandy Shaw
Reward deficiency syndrome is the actual name of a psychiatric disorder, in which people do not have as much dopaminergic activity in the brain’s reward circuitry as most other people do. A reduced number of DRD2 dopamine receptors is a way that this can happen.
Some of those who appear to suffer from “reward deficiency syndrome” could be classed as “losers.” Yet, some “losers” are in fact quite successful in material terms, but are simply unable to FEEL good about their material or other successes. A good example could be Ray Charles, who surely must have earned an immense amount of money in his life, yet sung (and possibly wrote) many songs with the theme of being a loser; his “BORN TO LOSE” is a particularly apt example.
The reward deficiency syndrome is characterized by behavior that you can see in many people around you and which now seems to have spread throughout the population of young adults, particularly among men. The most notable features of reward deficiency syndrome can include risk-seeking, novelty seeking, a high risk for addictive, impulsive, and compulsive behavioral propensities such as compulsive shopping, pathological gambling, sexual infidelity and promiscuity, as well as drug addiction, smoking, and often suffering from attention-deficit hyperactivity disorder. (See, for example, Blum, 2008)
The key mechanism behind the reward deficiency syndrome is explained: In individuals possessing an abnormality in the DRD2 dopamine receptor gene, the brain lacks sufficient numbers of dopamine receptor sites to use the normal amount of dopamine in reward centers. (Blum, 2008) What this means is that individuals with this form of the DRD2 gene (and it is far from uncommon, judging from the features of the reward deficiency syndrome as noted in the paragraph above) are driven to “engage in activities that will increase brain dopamine function…” because it is “…the DRD2 gene that makes it difficult for neurons to respond to dopamine, the neurotransmitter that is involved in feelings of pleasure and the regulation of attention.” (Blum, 2008)
Obese individuals have fewer D2 dopamine receptors than lean individuals do. Eating causes a release of dopamine in the dorsal striatum and the amount of dopamine released is correlated with the pleasure of eating. “It has therefore been postulated that obese individuals have hypofunctioning reward circuitry, which leads them to overeat to compensate for a hypofunctioning dopamine reward system.” (Stice, 2008) In order to study striatal dopamine activity, the authors (Stice, 2008) used blood oxygen level-dependent (BOLD) fMRI to identify the areas of the brain activated when the subjects ate either a chocolate milk shake or a “tasteless solution” placebo (water). The results were consistent with the hypothesis that “the dorsal striatum is less responsive to food reward in obese, relative to lean, individuals, potentially because the former have reduced D2 receptor density and compromised dopamine signaling, which may prompt them to overeat in an effort to compensate for this reward deficit.” (Stice, 2008)
References
Stice et al. Relation between obesity and blunted striatal response to food is moderated by Taq1A allele. Science. 322:449-52 (2008).
Blum et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat. 4(5):893-917 (2008).
REWARD DEFICIENCY SYNDROME AND MULTIPLE ADDICTIONS
A recent paper (Blum, 2011) provides a very extensive overview of the “Reward Deficiency Syndrome” as well as describing the results of a study of the incidence of dopaminergic genes in two families with multiple addictions. A certain variation of the DRD2 gene (Taq1, also called TaqA1) was found in these families, an incidence of 100% in “Family A” (with N=32) and 47.8% in “Family B” (with N=23). As the authors explain, “[t]he DRD2 gene, and especially the Taq1 allele, has been associated with neuropsychiatric disorders in general, including alcoholism, other addictions (e.g. carbohydrate), and it also may be involved in co-morbid antisocial personality disorder symptoms…” and other conditions such as “attention deficit hyperactivity disorder (ADHD) or Tourette Syndrome and high novelty-seeking behavior.”
“Utilizing a Bayesian mathematical model, we have found that at least for carriers of the DRD2 A1 allele, the estimated predictive value [of having the reward deficiency syndrome as a result of having the gene] is 74%.” Meanwhile, Table 3 in the study (pg. 4437) shows the correlation of the reward deficiency syndrome and psychiatric disorders with DRD2, disorders* which include novelty or sensation seeking, pathological gambling, post-traumatic stress disorder excessive eating, extraversion and creativity, hypersexuality, and many others. The authors note that there is a “significantly higher frequency for the DRD2 Taq1A polymorphism among addicts (69.9%) compared to control subjects (42.6%)…”
* Though these conditions are called “disorders,” by the authors, some, such as creativity, may be beneficial when they are not associated with pathology.
Reference
Blum et al. Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors. Int J Environ Res Public Health. 8:4425-59 (2011)
THE DRD2 GENE UNEQUIVOCALLY IDENTIFIED AS REGULATING RISKY BEHAVIOR IN RATS
A study of rats published in NATURE (Zalocasky, 2016) provides strong support for the view that DRD2 gene expression in the nucleus accumbens (NAc) is importantly involved in risky behavior such as gambling.
The experiments presented rats with an opportunity to get a sure reward of sugary treats every time or a much larger reward of the same treats (but only 25% of the time) when they pressed a lever. Some of the rats were considered “daredevils” as they kept on going for the big reward even after getting nothing time and time again. Others were cautious and went for the sure reward. Rats with the MOST DRD2 activity were the ones that became very cautious (“chicken”) after a loss (receiving nothing). The daredevil rats had low levels of DRD2 activity and kept on going for the big one.
THRILL SEEKING
People with the syndrome are prone to activities that supply extra stimulation to cause enough dopamine release to provide pleasure, hence, thrill-seeking, the desire to engage in risky, often dangerous activities, such as (for example) skydiving, gambling, using potentially dangerous drugs, and promiscuous unprotected sex. The DRD2 genetic variant has also been associated with aggressive behavior, “which also stimulates the brain’s use of dopamine.” (Blum, 2008)
References
Zalocusky et al. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature. 31;531(7596):642-6. doi: 10.1038/nature17400 (2016 Mar).
Blum et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat. 4(5):893-917 (2008).
