How to Cultivate Your Creativity


Fascinating! Read it please! I’m not summarizing it, it’s too long, but it is informational and fascinating reading! And Dopamine is intimately involved, really, it is.

Being Open

  • Openness to new experiences is the strongest and most consistent personality trait that predicts creative achievement in the arts and sciences.
  • Higher dopamine levels drive our motivation to explore and boost creativity but are also associated with an increased risk of mental illness.
  • New experiences can shift our perspective and inspire creative leaps.
  • Around the time that his cult-classic, drug-culture novel Naked Lunchwas released, author William S. Burroughs was experimenting with a writing strategy that he called the cut-up technique. Burroughs would chop up random lines of text from a page and rearrange them to form new sentences, with the aim of freeing his mind and the minds of his readers from conventional, linear ways of thinking.

    Beat Generation writers such as Burroughs sought to dismantle old belief systems and to encourage alternative ways of looking at the world. They celebrated intellectual exploration, engagement in art and music, unconventionality and deep spiritual questioning. Perhaps no artist captured this spirit more than Jack Kerouac, whose novels have become manifestos for adventure and nonconformity.

  • The revelations and methods of Burroughs, Kerouac and other Beat writers illuminated an important truth about creativity, which is now backed by scientific research: we need new and unusual experiences to think differently. In fact, cultivating a mind-set that is open and explorative might be the best thing we can do for our creative work. As Kerouac famously wrote, “The best teacher is experience.”

    For not only artists but innovators of all stripes, novel experiences provide the crucial tissue of real-world material that can be spun into original work. Openness to experience—the drive for cognitive exploration of one’s inner and outer worlds—is the single strongest and most consistent personality trait that predicts creative achievement.

    Among the “big five” personality traits (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism), openness to experience is absolutely essential to creativity. Those who are high in openness tend to be imaginative, curious, perceptive, creative, artistic, thoughtful and intellectual. They are driven to explore their own inner worlds of ideas, emotions, sensations, and fantasies and, outwardly, to constantly seek out and attempt to make meaning of new information in their environment.

    Seeking truth and beauty
    Openness as a personality trait hinges on engagement and exploration, but it is also more complex and multifaceted than that. Openness to experience comes in many forms, from a love of solving complex problems in math, science and technology, to a voracious love of learning, to an inclination to ask the big questions and seek a deeper meaning in life, to exhibiting intense emotional reactions to music and art. Visionary tech entrepreneurs, world travelers, spiritual seekers and original thinkers of all types tend to have highly open personalities.

    Research conducted by one of us (Kaufman) for his doctoral dissertation suggests that there are at least three major forms of cognitive engagement making up the core of openness. Intellectual engagement is characterized by a searching for truth, a love of problem solving and a drive to engage with ideas, whereas affective engagementhas to do with exploration of the full depths of human emotion and is associated with a preference for using gut feeling, emotions, empathy and compassion to make decisions. Finally, those who are high inaesthetic engagement exhibit a drive toward exploring fantasy and art and tend to experience emotional absorption in beauty. Kaufman found intellectual engagement to be associated with creative achievement in the sciences and affective engagement and aesthetic engagement to be linked with artistic creativity.

  • Kaufman’s research led him and his colleagues to another fascinating observation about “open” personalities. The desire to learn and discover seemed to have significantly more bearing on creative accomplishments than cognitive ability did. He found that people with high levels of cognitive engagement with imagination, emotions and beauty were more likely to make significant artistic creative achievements than people who were only high in IQ or divergent thinking ability (the ability to explore many possible solutions to a problem). Intellectual engagement was sometimes even a better predictor of scientific creative achievement than IQ was.

    Looking at creativity across the arts and sciences, Kaufman and his colleagues found that openness to experience was more highly correlated with total creative achievement than other factors that had been traditionally associated with creativity, such as IQ, divergent thinking and other personality traits. Together these findings suggest the drive for exploration, in its many forms, may be the single most important personal factor predicting creative achievement.

    Indeed, openness to experience speaks to our desire and motivation to engage with ideas and emotions—to seek truth and beauty, newness and novelty—and the act of exploring often provides the raw material for great artistic and scientific innovations.

    The dopamine drive
    This engagement starts at the neurological level, with the way the brain reacts to unfamiliar situations and new information. What unites each individual form of openness to experience is an intense desire and motivation to seek new information that is rooted in the individual’s neurophysiology and forms the very core of his or her personality.

    The drive for exploration hinges on the functioning of dopamine, which is probably the most well known of all the brain’s neurotransmitters. As you may know, dopamine plays a strong role in learning and motivation. Unfortunately, there are many misconceptions about dopamine, which is commonly seen as the “sex, drugs and rock ‘n’ roll” neurotransmitter. Despite many popular descriptions, dopamine is not necessarily associated with pleasure and satisfaction.

    Instead dopamine’s primary role is to make us want things. We get a huge surge of dopamine coursing through our brain at the possibility of a big payoff, but there is no guarantee that we will actually like or enjoy what we obtain. Psychologist Colin DeYoung of the University of Minnesota has explained that “the release of dopamine … increases motivation to explore and facilitates cognitive and behavioral processes useful in exploration.” DeYoung has called dopamine the “neuromodulator of exploration.”

    At the broadest level, dopamine facilitates psychological plasticity, a tendency to explore and engage flexibly with new things, in both behavior and thinking. Plasticity leads us to engage with uncertainty—whether it is pondering a new app to meet a consumer demand or questioning the next step in our own life path—exploring the unknown and finding reward in seeking its positive potential. With plasticity comes enhanced cognitive and behavioral engagement and exploration and, frequently, a commitment to personal growth. Of course, there is no guarantee that our open engagement will yield a positive outcome. For most creative people, however, the engagement itself is enough if it provides fodder for innovation. Indeed, research shows that psychological plasticity is associated with high levels of idea generation, engagement with everyday creative activities and publicly recognized creative achievement.

    Plasticity consists of a blend of both extraversion and openness to experience, and dopamine is a source of exploratory motivation. It is easy to see why this might be the case evolutionarily; the drive to explore, the ability to adapt to new environments and the ability to thrive in the face of uncertainty all provide important survival advantages.

    Nevertheless, there are crucial differences between extraversion and openness to experience. Extraversion, the personality trait that is most strongly associated with high sensitivity to environmental rewards, manifests in qualities such as talkativeness, sociability, positive emotionality, assertiveness and excitement seeking. Extraverts tend to be more likely to explore and pursue more primal “appetitive” rewards such as chocolate, social attention, social status, sexual partners or drugs like cocaine. But dopamine, which is indeed important to extraversion, also has projections in the brain that are strongly linked to numerous other aspects of cognition. Individuals who are particularly open to experience get energized not merely through the possibility of appetitive rewards but through the possibility of discovering new information. It is the thrill of the knowledge chase that most excites them.

    This motivation for cognitive exploration engages and energizes us while influencing our drive for creative expression. We see the quality play out again and again in different realms of the arts and sciences. After all, it is difficult to imagine any great creative achievement that wasn’t sparked by the drive to explore some aspect of the human experience.

    “Leaky” filters and messy minds
    It is hardly a stretch to say that dopamine is the mother of invention. In addition to facilitating cognitive exploration, the neurotransmitter is associated with a number of processes that facilitate creativity, including dreaming. We know that both daydreaming and dreaming at night are invaluable tools to help us access deeper realms of creativity. People who are high in openness to experience report dreaming more often and having more vivid dreams than those who are less open, possibly because of their higher dopamine production.

    One intriguing possibility is that dopamine surges into the right hemisphere of the brain support both openness to experience and dreaming. Dreaming inspires creative insights, and those who have more creative insights show more activation in the brain’s right hemisphere. Among people who are high in openness, the brain’s dopamine systems are working day and night to inspire creative insights.

    Another important cognitive process associated with creativity is latent inhibition—a mechanism in the brain that “filters out” objects in our environment that we have seen many times before and therefore consider irrelevant to our current goals and needs. In 2003 psychologist Shelley Carson of Harvard University and her colleagues discovered that the university’s eminent creative achievers were seven times more likely to have a reduced latent inhibition—meaning that they had a harder time filtering out seemingly irrelevant information and continued to notice familiar things.

    But here’s the thing: the information did turn out to be relevant! In related research, Kaufman found that those with a reduced latent inhibition had a greater faith in their intuitions, and their intuitions were, in fact, correct. Reduced latent inhibition speaks directly to the concept of a “messy mind,” often associated with creativity, because it reflects the tendency to tune in to greater amounts of information from our surroundings rather than automatically filtering and compartmentalizing.

    The downside of this quality is that it might make creative people more prone to distraction than others. Researcher Darya Zabelina of Northwestern University found that people with a “leaky” sensory filter—meaning that their brain does not efficiently filter out irrelevant information from the environment—tend to be more creative than those with stronger sensory gating. Zabelina also observed that highly creative people are more sensitive tonoises in their environment—a clock ticking, a conversation in the distance—than less creative people. “Sensory information is leaking in,” Zabelina has explained. “The brain is processing more information than it is in a typical person.”

    This brain quirk was a known characteristic of many eminent creators, including Charles Darwin, Franz Kafka and Marcel Proust, who each expressed a hypersensitivity to sound. Proust kept his blinds drawn and lined his bedroom with cork to filter out unwanted light and noise and wore earplugs while he wrote, whereas Kafka said that he needed the solitude not of a hermit but of a “dead man” to write.

    And although it may sometimes be a hindrance to creative work, this distractibility also seems to be distinctly beneficial to creative thinking. Sensory hypersensitivity most likely contributes to creativity bywidening the brain’s scope of attention and allowing individuals to take note of more subtleties in their environment. Taking in a greater volume of information increases your chances of making new and unusual connections between distantly related pieces of information.

    Genius or madness?
    These findings have deep implications for the long-standing mental illness–creativity debate. Research has linked dopamine production with not only reduced latent inhibition and creativity but also mental illness. To be clear: mental illness is neither necessary nor sufficient for creativity. Nevertheless, there does seem to be a nuanced link between the two because having an extremely open mind makes flights of fancy more likely. In support of this idea, there appear to be variations in the expression of dopamine receptors in certain areas of the brain among both creative individuals and those with psychotic symptoms.

    In 2010 neuroscientist Fredrik Ullén of the Karolinska Institute in Stockholm and his colleagues found that dopamine systems in healthy, highly creative adults are similar in certain ways to those found in the brains of people with schizophrenia. In both cases, they observed alower density of dopamine D2 receptors in the thalamus—a brain area associated with sensory perception and motor function that also plays an important role in creative thought, suggesting one possible link between creativity and psychopathology.

  • Having fewer D2 receptors in the thalamus probably means that the brain is filtering less incoming stimuli, leading to a higher flow of information being transmitted from the thalamus to other parts of the brain. In individuals who are not also suffering from the damaging symptoms of mental illness, this flow can lead to an increase in creative thinking and may very well underlie several cognitive processes that determine creative achievement. “Thinking outside the box might be facilitated by having a somewhat less intact box,” Ullén and his colleagues said in the study.

    An excess of dopamine may cause an influx of emotions, sensations and fantasy, so much so that it causes substantial disruption to functions also important for creativity, such as working memory, critical thinking and reflection. Too little dopamine, however, and there may be less motivation and inspiration to create.

    Dopamine aside, research has suggested similarities in brain activations between highly creative thinkers and people who are prone to psychosis. In 2014 neuropsychologist Andreas Fink of the University of Graz in Austria and his colleagues found that people scoring high in schizotypy—a personality continuum ranging from normal levels of openness to experience and imagination to extreme manifestations of magical thinking, apophenia (perceiving patterns that do not really exist) and psychosis—showed similar difficulty deactivating or suppressing activity in the precuneus region of the brain, an area associated with self-consciousness, a sense of self and the retrieval of deeply personal memories.

    In reality, all of us lie somewhere on the schizotypy spectrum, and the existence of schizotypal characteristics does not necessarily indicate schizophrenia. Psychologically healthy biological relatives of people with full-blown schizophrenia tend to have unusually creative jobs and hobbies, compared with the general population, according to a 2001 study by Saybrook University psychologist Ruth Richards and her colleagues. Similarly, Simon Kyaga and his co-workers at the Karolinska Institute reported in 2013 that among more than 1.2 million Swedes, the siblings of patients with autism and the first-degree relatives of patients with schizophrenia were significantly overrepresented in scientific and artistic occupations.

    It is possible that relatives of people with mental illness inherit creativity-boosting traits while avoiding the aspects of the mental illness that are more debilitating. In support of this observation, researchers have found that schizotypal characteristics—particularly the “positive” ones, such as unusual perceptual experiences and impulsive nonconformity—are related to creative personal qualities—individualistic, insightful, eclectic, reflective, resourceful and unconventional—as well as everyday creative achievements.

    Go with the flow
    Schizotypy is related to so-called flow states of consciousness and absorption. Flow is the mental state of being completely present and fully absorbed in a task. When in a flow state, the creator and his or her world become one—outside distractions recede from consciousness, and the mind is fully open and attuned to the act of creating. This happens, for instance, when a playwright sits up all night crafting a new scene without realizing that the sun is rising or when a filmmaker spends hours in front of a computer editing a rough cut.

    Flow is essential to the artist’s experience. In a study of 100 artists in music, visual arts, theater and literature, researchers Barnaby Nelson and David Rawlings, both at the University of Melbourne in Australia, found that those who said they experienced more flow during the creative process were also higher in schizotypy and openness to experience. Nelson and Rawlings linked their findings to latent inhibition, arguing that a leaky sensory filter is a common thread running through schizotypy and openness to experience—and, perhaps surprisingly, flow and absorption. The failure to precategorize incoming information as irrelevant, which is experienced by individuals with reduced latent inhibition, can, the researchers wrote, result in “immediate experience not being as shaped or determined by preceding events.”

    In other words, an exceptionally large amount of information, far more than for those with higher levels of latent inhibition, enters their field of awareness and is explored by their mind. As Nelson and Rawlings explained, “it is precisely this newness of appreciation and the associated sense of exploration and discovery, that stimulates the deep immersion in the creative process, which itself may trigger a shift in quality of experience, generally in terms of an intensification or heightening of experience.”

    So what determines whether schizotypy goes the way of intense absorption and creative achievement or tips over into mental illness? This is where a number of other factors come into play. If mental illness is defined as extreme difficulty functioning effectively in the real world, then the complete inability to distinguish imagination from reality is surely going to increase the likelihood of mental illness. If, however, one has an overactive imagination but also has the ability to distinguish reality from imagination and can harness these capacities to flourish in daily life (with the help of things such as motivation, post-traumatic growth, resilience and a supportive environment), then that is far from mental illness.

    Mental processes on the schizotypy spectrum may interact with protective mental qualities such as greater intellectual curiosity, improved working memory and cognitive flexibility. Indeed, in 2011 neuroscientist Hikaru Takeuchi of Tohoku University in Japan and his colleagues studied people with no history of neurological or psychiatric illness and found that the most creative thinkers among them were those who were able to simultaneously engage their executive attention in an effortful memory task and keep the imagination network in the brain active.

    You never know—some of the most seemingly irrelevant or “crazy” ideas at one point may be just the ingredients for a brilliant insight or connection in a different context. It bears repeating: creativity is all about making new connections.

Can the Bacteria in Your Gut Explain Your Mood?

Pretty amazing article and developments. There are about 100 trillion bacteria in our gut, and can weigh as much as six pounds! These bacteria make neurochemicals, such as dopamine, serotonin and γ amino butyric acid (GABA), molecules that affect and regulate our moods.These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety. Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients. The human genome has about 23,000 genes, while the microbiome (the genetic material of the bacteria in our gut) add up to 2 million unique bacterial genes! Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. And psychobiotics and fecal transplants may be the wave of the future! So much amazing information in this article, read on, my friends!

Eighteen vials were rocking back and forth on a squeaky mechanical device the shape of a butcher scale, and Mark Lyte was beside himself with excitement. ‘‘We actually got some fresh yesterday — freshly frozen,’’ Lyte said to a lab technician. Each vial contained a tiny nugget of monkey feces that were collected at the Harlow primate lab near Madison, Wis., the day before and shipped to Lyte’s lab on the Texas Tech University Health Sciences Center campus in Abilene, Tex.

Lyte’s interest was not in the feces per se but in the hidden form of life they harbor. The digestive tube of a monkey, like that of all vertebrates, contains vast quantities of what biologists call gut microbiota. The genetic material of these trillions of microbes, as well as others living elsewhere in and on the body, is collectively known as the microbiome. Taken together, these bacteria can weigh as much as six pounds, and they make up a sort of organ whose functions have only begun to reveal themselves to science. Lyte has spent his career trying to prove that gut microbes communicate with the nervous system using some of the same neurochemicals that relay messages in the brain.

Inside a closet-size room at his lab that afternoon, Lyte hunched over to inspect the vials, whose samples had been spun down in a centrifuge to a radiant, golden broth. Lyte, 60, spoke fast and emphatically. ‘‘You wouldn’t believe what we’re extracting out of poop,’’ he told me. ‘‘We found that the guys here in the gut make neurochemicals. We didn’t know that. Now, if they make this stuff here, does it have an influence there? Guess what? We make the same stuff. Maybe all this communication has an influence on our behavior.’’

Since 2007, when scientists announced plans for a Human Microbiome Project to catalog the micro-organisms living in our body, the profound appreciation for the influence of such organisms has grown rapidly with each passing year. Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. Biologists now believe that much of what makes us human depends on microbial activity. The two million unique bacterial genes found in each human microbiome can make the 23,000 genes in our cells seem paltry, almost negligible, by comparison. ‘‘It has enormous implications for the sense of self,’’ Tom Insel, the director of the National Institute of Mental Health, told me. ‘‘We are, at least from the standpoint of DNA, more microbial than human. That’s a phenomenal insight and one that we have to take seriously when we think about human development.’’

 Given the extent to which bacteria are now understood to influence human physiology, it is hardly surprising that scientists have turned their attention to how bacteria might affect the brain. Micro-organisms in our gut secrete a profound number of chemicals, and researchers like Lyte have found that among those chemicals are the same substances used by our neurons to communicate and regulate mood, like dopamine, serotonin and gamma-aminobutyric acid (GABA). These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety. Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients.

At the time of my visit to Lyte’s lab, he was nearly six months into an experiment that he hoped would better establish how certain gut microbes influenced the brain, functioning, in effect, as psychiatric drugs. He was currently compiling a list of the psychoactive compounds found in the feces of infant monkeys. Once that was established, he planned to transfer the microbes found in one newborn monkey’s feces into another’s intestine, so that the recipient would end up with a completely new set of microbes — and, if all went as predicted, change their neurodevelopment. The experiment reflected an intriguing hypothesis. Anxiety, depression and several pediatric disorders, including autism and hyperactivity, have been linked with gastrointestinal abnormalities. Microbial transplants were not invasive brain surgery, and that was the point: Changing a patient’s bacteria might be difficult but it still seemed more straightforward than altering his genes.

When Lyte began his work on the link between microbes and the brain three decades ago, it was dismissed as a curiosity. By contrast, last September, the National Institute of Mental Health awarded four grants worth up to $1 million each to spur new research on the gut microbiome’s role in mental disorders, affirming the legitimacy of a field that had long struggled to attract serious scientific credibility. Lyte and one of his longtime colleagues, Christopher Coe, at the Harlow primate lab, received one of the four. ‘‘What Mark proposed going back almost 25 years now has come to fruition,’’ Coe told me. ‘‘Now what we’re struggling to do is to figure out the logic of it.’’ It seems plausible, if not yet proved, that we might one day use microbes to diagnose neurodevelopmental disorders, treat mental illnesses and perhaps even fix them in the brain.

In 2011, a team of researchers at University College Cork, in Ireland, and McMaster University, in Ontario, published a study in Proceedings of the National Academy of Science that has become one of the best-known experiments linking bacteria in the gut to the brain. Laboratory mice were dropped into tall, cylindrical columns of water in what is known as a forced-swim test, which measures over six minutes how long the mice swim before they realize that they can neither touch the bottom nor climb out, and instead collapse into a forlorn float. Researchers use the amount of time a mouse floats as a way to measure what they call ‘‘behavioral despair.’’ (Antidepressant drugs, like Zoloft and Prozac, were initially tested using this forced-swim test.)

For several weeks, the team, led by John Cryan, the neuroscientist who designed the study, fed a small group of healthy rodents a broth infused with Lactobacillus rhamnosus, a common bacterium that is found in humans and also used to ferment milk into probiotic yogurt. Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal. Recent studies have shown that mice stressed during pregnancy pass on lowered levels of the bacterium to their pups. This type of bacteria is known to release immense quantities of GABA; as an inhibitory neurotransmitter, GABA calms nervous activity, which explains why the most common anti-anxiety drugs, like Valium and Xanax, work by targeting GABA receptors.

Cryan found that the mice that had been fed the bacteria-laden broth kept swimming longer and spent less time in a state of immobilized woe. ‘‘They behaved as if they were on Prozac,’’ he said. ‘‘They were more chilled out and more relaxed.’’ The results suggested that the bacteria were somehow altering the neural chemistry of mice.

Until he joined his colleagues at Cork 10 years ago, Cryan thought about microbiology in terms of pathology: the neurological damage created by diseases like syphilis or H.I.V. ‘‘There are certain fields that just don’t seem to interact well,’’ he said. ‘‘Microbiology and neuroscience, as whole disciplines, don’t tend to have had much interaction, largely because the brain is somewhat protected.’’ He was referring to the fact that the brain is anatomically isolated, guarded by a blood-brain barrier that allows nutrients in but keeps out pathogens and inflammation, the immune system’s typical response to germs. Cryan’s study added to the growing evidence that signals from beneficial bacteria nonetheless find a way through the barrier. Somehow — though his 2011 paper could not pinpoint exactly how — micro-organisms in the gut tickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety. Soon after that, Cryan and a co-author, Ted Dinan, published a theory paper in Biological Psychiatry calling these potentially mind-altering microbes ‘‘psychobiotics.’’

It has long been known that much of our supply of neurochemicals — an estimated 50 percent of the dopamine, for example, and a vast majority of the serotonin — originate in the intestine, where these chemical signals regulate appetite, feelings of fullness and digestion. But only in recent years has mainstream psychiatric research given serious consideration to the role microbes might play in creating those chemicals. Lyte’s own interest in the question dates back to his time as a postdoctoral fellow at the University of Pittsburgh in 1985, when he found himself immersed in an emerging field with an unwieldy name: psychoneuroimmunology, or PNI, for short. The central theory, quite controversial at the time, suggested that stress worsened disease by suppressing our immune system.

By 1990, at a lab in Mankato, Minn., Lyte distilled the theory into three words, which he wrote on a chalkboard in his office: Stress->Immune->Disease. In the course of several experiments, he homed in on a paradox. When he dropped an intruder mouse in the cage of an animal that lived alone, the intruder ramped up its immune system — a boost, he suspected, intended to fight off germ-ridden bites or scratches. Surprisingly, though, this did not stop infections. It instead had the opposite effect: Stressed animals got sick. Lyte walked up to the board and scratched a line through the word ‘‘Immune.’’ Stress, he suspected, directly affected the bacterial bugs that caused infections.

To test how micro-organisms reacted to stress, he filled petri plates with a bovine-serum-based medium and laced the dishes with a strain of bacterium. In some, he dropped norepinephrine, a neurochemical that mammals produce when stressed. The next day, he snapped a Polaroid. The results were visible and obvious: The control plates were nearly barren, but those with the norepinephrine bloomed with bacteria that filigreed in frostlike patterns. Bacteria clearly responded to stress.

Then, to see if bacteria could induce stress, Lyte fed white mice a liquid solution of Campylobacter jejuni, a bacterium that can cause food poisoning in humans but generally doesn’t prompt an immune response in mice. To the trained eye, his treated mice were as healthy as the controls. But when he ran them through a plexiglass maze raised several feet above the lab floor, the bacteria-fed mice were less likely to venture out on the high, unprotected ledges of the maze. In human terms, they seemed anxious. Without the bacteria, they walked the narrow, elevated planks.

Each of these results was fascinating, but Lyte had a difficult time finding microbiology journals that would publish either. ‘‘It was so anathema to them,’’ he told me. When the mouse study finally appeared in the journal Physiology & Behavior in 1998, it garnered little attention. And yet as Stephen Collins, a gastroenterologist at McMaster University, told me, those first papers contained the seeds of an entire new field of research. ‘‘Mark showed, quite clearly, in elegant studies that are not often cited, that introducing a pathological bacterium into the gut will cause a change in behavior.’’

Lyte went on to show how stressful conditions for newborn cattle worsened deadly E. coli infections. In another experiment, he fed mice lean ground hamburger that appeared to improve memory and learning — a conceptual proof that by changing diet, he could change gut microbes and change behavior. After accumulating nearly a decade’s worth of evidence, in July 2008, he flew to Washington to present his research. He was a finalist for the National Institutes of Health’s Pioneer Award, a $2.5 million grant for so-called blue-sky biomedical research. Finally, it seemed, his time had come. When he got up to speak, Lyte described a dialogue between the bacterial organ and our central nervous system. At the two-minute mark, a prominent scientist in the audience did a spit take.

‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.

But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.

Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.

Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student and now a neuroscientist at Caltech, and others, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.

The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’

Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.

The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’

Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added, ‘‘We really need a lot more research done before we actually have people trying therapies out.’’

If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’

Disruption of Communication Between Two Regions of the Brain Contributes to Symptoms of Psychiatric Illnesses

Basically, when the synaptic transmission between the hippocampus and the prefrontal cortex is disrupted, symptoms of mental illnesses such as schizophrenia are seen. This has been known for a long time. What wasn’t known was how is this communication between the hippocampus and prefrontal cortex disrupted? That is, what are the mechanisms responsible for the disruption of communication between these two regions of the brain? Well, in this paper below, they show over activation of the D2-like Dopamine receptors leads to a decrease in another type of receptor called the NMDA receptor. This leads to a marked disruption of synaptic transmission between the two brain regions. This newly discovered relationship between the Dopamine and NMDA receptors may lead to treatment options for people with mental illnesses like schizophrenia.

“Synaptic transmission between the hippocampus and prefrontal cortex is required for many executive cognitive functions. It is believed that disruption of this communication contributes to symptoms observed in psychiatric disorders including schizophrenia. Hyperdopaminergic tone and hypofunction of NMDA receptor-mediated glutamate transmission are distinctive elements of schizophrenia. Here we demonstrate that activation of low-affinity D2-like dopamine receptors leads to a lasting depression of NMDA receptors at the hippocampal– prefrontal projection of juvenile rats, leading to a marked disruption of synaptic transmission. These data demonstrate a link between dopamine and hypofunction of NMDA receptormediated transmission with potential implications for psychiatric disease.”

“New research has identified the mechanisms that trigger disruption in the brain’s communication channels linked to symptoms in psychiatric disorders including schizophrenia. The University of Bristol study, published in the Proceedings of National Academy of Sciences, could have important implications for treating symptoms of brain disorders.

Many of our everyday cognitive functions such as learning and memory rely on normal communication between the two regions of the brain – the hippocampus and prefrontal cortex. While previous studies have identified disruption to communication channels in these two areas of the brain contribute to symptoms in psychiatric disorders, the mechanisms that lead to these disturbances have been largely unknown, until now.

In this study, led by Professor Zafar Bashir from Bristol’s School of Physiology and Pharmacology, the researchers studied the neurotransmitters glutamate and dopamine, which work together in controlling normal transmission between these brain regions by communicating chemical information throughout our brain and are disrupted in schizophrenics.

The team found that subtle changes in the interplay of these transmitters completely altered the flow of information from the hippocampus to prefrontal cortex. Over-activation of the D2 class of dopamine receptors led to suppression of the function of NMDA receptors, which are activated by the neurotransmitter glutamate, at the synaptic connection between hippocampus and prefrontal cortex. This in turn leads to a marked disruption of communication between these brain regions.

Dr Paul Banks, one of the researchers, said: “Our findings demonstrate a mechanism for how dopamine neurotransmission can influence NMDA receptor function at a connection in the brain needed for complex mental tasks which are disrupted in schizophrenic patients. It has been known for some time that dopamine and NMDA receptor function are altered in schizophrenic patients – our data mirror the direction of these changes and therefore might give insight into how these changes come about mechanistically.”

Why Don’t Animals Get Schizophrenia (and How Come We Do)? Article in Scientific American


Short answer: Because their brains aren’t as complex as human brains. Unfortunately that’s the price we people with prefrontal cortexes pay. In bipolar disorder, as in schizophrenia, people with these illnesses can become out of touch with reality. This is called psychosis, or being psychotic. Auditory hallucinations happen to 90% of people with schizophrenia, i.e. they hear voices, this also happens up to 80% of people with bipolar d/o. There are also visual hallucinations (seeing things), even olfactory hallucinations, where you may smell something that isn’t there! (Luckily for me, I have never had auditory hallucinations, I am forever grateful for this! Interestingly enough, I have had olfactory hallucinations, I smelled the scent of Camay soap once when it was nowhere to be found.)

Let’s get back to the point of this article from Scientific American. It basically says that schizophrenia 9and I assume bipolar d/o in psychosis) are the price we pay for a much more complex brain. It is a defect of the gamma amino butyric acid (GABA) system. This is an inhibitory neurotransmitter, meaning it inhibits neurons from firing, in part by suppressing dopamine in certain parts of the brain. So when there is a problem with this system, then neurons that wouldn’t normally be firing are firing, and dopamine is also not suppressed, and this is happening in the prefrontal cortex (PFC). This leads to hallucinations. See quote below.

Yes the psychotic brain, whether in schizophrenia or bipolar d/o runs amok. And it can run so crazily amok because it is so complicated. So complicated that when things go wrong, they go wrong in a big way. Hence hallucinations.

“They also found that these culprit genes are involved in various essential human neurological functions within the PFC, including the synaptic transmission of the neurotransmitter GABA. GABA serves as an inhibitor or regulator of neuronal activity, in part by suppressing dopamine in certain parts of the brain, and it’s impaired transmission is thought to be involved in schizophrenia. If GABA malfunctions, dopamine runs wild, contributing to the hallucinations, delusions and disorganized thinking common to psychosis. In other words, the schizophrenic brain lacks restraint.”