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Which parts of the brain are affected by dopamine?

Which parts of the brain are affected by dopamine?



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Does dopamine spread and interact across the whole brain? If not, which areas are affected most and which least?


Quoting my thesis:

CNS Dopamine/DA projections primarily emerge from two subcortical basal ganglia nuclei in the brain stem, travelling along three major pathways (Purves et al., 2004).

The nigrostriatal pathway, connecting the substantia nigra and the striatum, is mainly implicated in higher motor control. The mesolimbic pathway contains DA projections from the Ventral Tegmental Area/VTA and the pars compacta of the Substantia Nigra (SNc) to limbic systems including hip- pocampus, amgydala and thalamus, and is critical in learning and memory in a mechanism that is well-investigated (Lisman & Grace, 2005). The mesocortical pathway connects the VTA and SNc to the cortex. In contrast to the extensive noradrenergic innervation of the cortex, DA therefore reaches only selected areas (Foote & Morrison, 1987). DA density is extensive in prefrontal and anterior cingulate areas, and falls off rapidly across an rostro-caudal gradient. The temporal lobe is only weakly innvervated (including the enthorinal cortex), and little to no innervation reaches parietal and especially occipital lobes, though DA fibers in monkey area 7 have been reported (Foote & Morrison, 1987).

So basically, subcortical innervation is rich, but cortical innervation is focused on frontal areas. DA is often depicted as having zero cortical presence outside of frontal areas, but this is false; while DA innervation density falls off sharply outside of the frontal lobes, at least in humans and other apes, there is some DA reaching at least as far back as the temporal lobes.

Of course, this is only the direct effect of DA. In principle, all of the brain is strongly affected by the effects of DA, because frontal cortices, who are strongly influenced by DA, in turn strongly influence the rest of the bain.

Sources (obviously): Foote, S. L., & Morrison, J. H. (1987). Extrathalamic modulation of cortical function. Annual review of neuroscience, 10, 67-95.


  1. Parts of the brain affected by dopamine Dopamine exerts different effects in different regions and pathways throughout the brain. In the mesolimbic pathway, dopamine is believed to be involved in motivation and addiction due to the feelings of reward and pleasure associated with dopamine release here. In the mesocortical pathway, dopamine is linked to emotional and motivational activities. In the nigrostriatal pathway dopamine is responsible for regulating and initiating motor activity. In the tuberoinfundibular pathway, dopamine regulates the release of hormones from the pituitary gland.
  2. Interaction with the brain and where (already answered by @shayankabiri)

No, unlike norepinephrine and serotonin, dopamine's pathway is limited.actually it affects two part of cognition, reward and motor functions. As part of the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral tegmental area (VTA) and is released in the nucleus accumbens and the prefrontal cortex. The motor functions of dopamine are linked to a separate pathway, with cell bodies in the substantia nigra that manufacture and release dopamine into the striatum.


How Dopamine Works

Chances are that you've heard of the neurotransmitter dopamine, which seems to get as much sensational media coverage as many Hollywood celebrities. In scores of articles on the internet, dopamine is depicted as the secret sauce for human misbehavior — the thing that supposedly causes us to crave everything from sex to chocolate to betting money we can't afford to lose in blackjack. If you believe the hype, it's also what makes us check Facebook every 20 minutes and sit on the couch for hours killing zombies in a video game. Dopamine is often linked with addiction, alcoholism, sexual lust, compulsive behavior and dangerous risk-taking.

As the British science journalist Vaughn Bell once complained, the mere mention of dopamine tends to make something sound like a scientifically proven vice."If you disagree with something, just say it releases dopamine and imply it must be dangerously addictive," he wrote, calling dopamine the Kim Kardashian of neurotransmitters, for its "instant appeal to listless reporting."

In truth, though, dopamine is simply a chemical that enables signals to pass through synapses, the spaces between neurons. By doing that, it enables networks composed of vast numbers of neurons to do their jobs [source: Brookshire]. All of this is actually much more complicated, which we'll get into later.

So why does dopamine have such a scandalous reputation? It's because dopamine signaling is a key player in the brain's reward system, which influences us to do things that feel pleasurable, and to do them over and over. But that's only one of the numerous functions that dopamine performs in our bodies. It's also vital for important processes such as motor control, learning and memory. Malfunctions in the wiring that uses dopamine seems to play a role in numerous disorders, including Parkinson's and schizophrenia [source: Jiang].

In this article we'll explain what dopamine is and how it works in our brains and bodies. We'll also explain what dopamine isn't, and try to dispel some of the myths that have arisen around the chemical.

As we previously explained, dopamine is one of more than 100 chemicals known as neurotransmitters, which enable neurons in the brain to communicate with one another and manage everything that happens in our body [source: Purves et al.].

Like all neurotransmitters, dopamine goes through a cycle, which begins with it being synthesized by a neuron (called the presynaptic cell). That cell releases the dopamine and it floats out into the synapse, the gap between neurons, and then makes contact and binds with structures called receptors on the other neuron, which then transmit the signal to the second neuron. After the dopamine accomplishes its mission, it's rapidly removed and degrades. The effects of dopamine on your brain depend a lot on which neurons are involved and which receptors are binding the dopamine [sources: Brookshire, Purves et al.].

As molecules go, dopamine is fairly compact, consisting of just 22 atoms. Only a tiny portion of the brain's 100 billion or so neurons — as few as 20,000 — generate dopamine, most of them in midbrain structures such as the substantia nigra, which helps control movement, and the prefrontal cortex [sources: Angier, Deans].

Those specialized neurons make dopamine by taking an amino aside called tyrosine and combining it with an enzyme, tyrosine hydroxylase. Add another step to the chemical reaction and you would get a different neurotransmitter, norepinephrine [source: Deans].

In terms of evolutionary history, dopamine has been around for a long time, and it's found in animals from lizards to humans. But people have a lot of dopamine and over time, we seem to have evolved to produce more and more of it, possibly because it helps enable us to be aggressive and competitive. As evolutionary psychiatrist Emily Deans wrote in 2011, "dopamine is what made humans so successful." Researchers have found that humans have about three times as many dopamine-producing neurons as other primates [source: Parkin].

Massachusetts Institute of Technology researchers have developed tiny probes — just 10 microns in diameter — that can be implanted in animal brains to track dopamine. Because they're so small, they don't cause scar tissue to form, and can function for more than a year [source: Trafton].

How Does Dopamine Work in the Human Body?

Dopamine's function at the most basic level is to enable signals to pass through synapses from one neuron to another. But that's the high-level view. Up closer, the networks that use dopamine are composed of vast numbers of neurons, and the effects of releasing dopamine can vary, depending upon what types of neurons are involved and which of the five different types of receptors are using the dopamine to connect the neurons. The particular role the neurons are playing can also be a factor [source: Brookshire].

Dopamine's effects depend upon which of the four pathways is used in the brain and body where it's working to facilitate communication. The first is the nigrostriatal tract, which has to do with motor control in the body. When neurons in that system stop working, it can lead to disorders such as Parkinson's.

Another is the mesocortical pathway, which runs from the ventral tegmental area to the dorsolateral frontal cortex in the brain. It's the pathway associated with planning, prioritizing, responsibility and other executive function activities.

There's also the tuberinfundibular pathway, which connects the hypothalamus and the pituitary gland, and blocks the secretion of milk in the female breast. Blocking this pathway of dopamine enables breastfeeding.

Finally, there's the mesolimbic pathway, which is connected to the brain's limbic system, which controls reward and emotion, and includes the hippocampus and the medial frontal cortex. That's the pathway that gets the most attention, since it's connected with problems such as addiction[source: Deans].

Dopamine plays a role in kidney and heart function, nausea and even psychosis. Many treatments for schizophrenia target dopamine [source: Brookshire].

Until recently, not much was known about the precise mechanisms by which neurons use dopamine. It was thought that it mostly took place through something called volume transmission, in which dopamine spread slowly and nonspecifically across large areas of the brain, and in the process happened to make the right contacts with the certain neurons. But in 2018, Harvard University medical researchers published a paper revealing that specialized sites on those cells release dopamine in an extremely fast —think milliseconds — and precise manner to target sites [source: Jiang].

But all that probably seems ho-hum to you, so in the next section, let's get back to the role of dopamine in the brain's reward system and in pleasure.

How is Dopamine Related to Pleasure?

The earliest experiments involving dopamine function were performed back in the 1950s and 1960s by a researcher named James Olds, who discovered that when rats' brains received a jolt of electrical stimulation in a certain area, they'd keep performing an action such a yanking a lever over and over [source: Chen].

Because dopamine played a role in transmitting the signals, scientists initially suspected that it had something to do with pleasure. People with clinical depression tend to have low levels of dopamine in their brains, which led researchers to hypothesize that low levels of dopamine caused a person to experience less pleasure.

That idea keeps bouncing around in the popular media, because it seems to make good sense. But by the late 1980s, it had been disproven by research. In experiments, animals whose dopamine cells were killed off by drugs still seemed to enjoy the taste of sugar when it was squirted into their mouths, as evidenced by their facial expressions. But they wouldn't seek out additional tastes of the sugar [source: Chen].

While dopamine doesn't cause pleasure, it does influence how pleasure affects the brain. But there are different views of how it accomplishes that. One school of thought is that dopamine's biggest influence is reinforcing the pleasure, so that the brain develops an expectation of experiencing that outcome from the action [source: Chen]. Research on gamblers, for example, have shown that their brains experience as much dopamine activity when they come close to winning as when they actually win. It's almost as if the chemical is urging them on, telling them that they'll win the next time (even if they didn't last time) [source: Chase and Clark].

Another view is that dopamine simply helps the brain to feel more motivated to do something so that the body feels energetic enough to pull that lever again and again [sources: Chen, Salamone and Correa].

Does Dopamine Play a Role in Addiction?

Dopamine doesn't force someone to stick a needle into his or her arm, smoke meth or take a hit from a crack pipe, nor does it create the pleasure that a drug user experiences from getting high. But dopamine does play a role in drug abuse and addiction, by reinforcing the effects of using those drugs.

When a person gets high, it causes a surge in production of dopamine in the neurons in the striatum, including the nucleus accumbens, structures that are part of the brain's reward network. That increase in the chemical enables neurons to make more connections, and plays an important role in programming the brain to connect drugs with pleasure, so that it develops an expectation of a reward and motivation to take them again [source: Volkow, Fowler and Wang, et al.].

"Large surges of dopamine teach the brain to seek drugs at the expense of other, healthier goals and activities," warns an article on the National Institute on Drug Abuse's website.

But while dopamine increases when someone uses certain drugs, not everybody who experiences that surge necessarily becomes an addict. Instead, scientists believe, dopamine acts in combination with a range of other genetic, developmental and/or environmental influences to program some people's brains to develop a compulsion to take those drugs. Imaging studies, for example, have found that people who turn into addicts may already have differences in their dopamine circuitry that make them more vulnerable to getting hooked [source: Volkow, Fowler and Wang, et al.].

The dopamine produced from using drugs is much more intense and long-lasting than the dopamine response from something like eating or another normal activity. Also unlike eating, the dopamine response from drugs doesn't stop when the act is over. The overflow of dopamine is what produces the high.

When an addict uses drugs repeatedly, his or her brain changes in response. It tries to compensate for the surge in dopamine production by shutting down some of its dopamine receptors. But that only exacerbates the situation. The brain is still programmed to want the pleasure that the drugs created, so an addict has to use more and more of the drug to replicate the effect. Additionally, shutting down dopamine receptors reduces the amount of pleasure that an addict gets from any activity, not just taking drugs — a condition called anhedonia. That also may drive a person to shoot up more heroin or smoke more and more meth, because nothing else feels good anymore.

Finally, having fewer dopamine receptors is associated with an increase in impulsivity, which may lead an addict to engage in increasingly reckless behavior in pursuit of a high [source: Butler Center].

In a 2017 New York Times essay, two psychology professors noted that while pleasurable activities stimulate dopamine production, the amount released varies tremendously according to the activity. Playing a video game, they said, releases as much dopamine as eating a slice of pizza, while using a drug such as meth causes 10 times as much to be released. They cited a study published in American Journal of Psychiatry, which found that at most, 1 percent of video game players could exhibit characteristics of addiction [source: Ferguson and Markey].


Here's How Colours Really Affect Our Brain And Body, According to Science

Red makes the heart beat faster. You will frequently find this and other claims made for the effects of different colours on the human mind and body.

But is there any scientific evidence and data to support such claims?

The physiological mechanisms that underpin human colour vision have been understood for the best part of a century, but it is only in the last couple of decades that we have discovered and begun to understand a separate pathway for the non-visual effects of colour.

Like the ear, which also provides us with our sense of balance, we now know that the eye performs two functions.

Light sensitive cells known as cones in the retina at the back of the eye send electrochemical signals primarily to an area of the brain known as the visual cortex, where the visual images we see are formed.

However, we now know that some retinal ganglion cells respond to light by sending signals mainly to a central brain region called the hypothalamus which plays no part in forming visual images.

Light but not vision

The hypothalamus is a key part of the brain responsible for the secretion of a number of hormones which control many aspects of the body's self-regulation, including temperature, sleep, hunger and circadian rhythms.

Exposure to light in the morning, and blue/green light in particular, prompts the release of the hormone cortisol which stimulates and wakes us, and inhibits the release of melatonin. In the late evening as the amount of blue light in sunlight is reduced, melatonin is released into the bloodstream and we become drowsy.

The retinal cells that form the non-image-forming visual pathway between eye and hypothalamus are selectively sensitive to the short wavelengths (blue and green) of the visible spectrum.

What this means is that there is clearly an established physiological mechanism through which colour and light can affect mood, heart rate, alertness, and impulsivity, to name but a few.

For example, this non-image-forming visual pathway to the hypothalmus is believed to be involved in seasonal affective disorder, a mood disorder that affects some people during the darker winter months that can be successfully treated by exposure to light in the morning.

Similarly, there is published data that show that exposure to bright, short-wavelength light a couple of hours prior to normal bedtime can increase alertness and subsequently affect sleep quality.

Poor quality sleep is becoming increasingly prevalent in modern society and is linked with increased risk factors for obesity, diabetes and heart disease.

There is some concern that the excessive use of smartphones and tablets in the late evening can affect sleep quality, because they emit substantial amounts of blue/green light at the wavelengths that inhibit the release of melatonin, and so prevent us from becoming drowsy.

That's one effect of blue/green light, but there is much more research to be done in order to back the many claims made for other colours.

Experiencing colour

I lead the Experience Design research group at the University of Leeds where we have a lighting laboratory especially designed to evaluate the effect of light on human behaviour and psychology.

The lighting system is unique in the UK in that it can flood a room with coloured light of any specific wavelengths (other coloured lighting usually uses a crude mixture of red, green and blue light).

Stephen Westland

Recent research by the group has found a small effect of coloured light on heart rate and blood pressure: red light does seem to raise heart rate, while blue light lowers it. The effect is small but has been corroborated in a 2015 paper by a group in Australia.

In 2009 blue lights were installed at the end of platforms on Tokyo's Yamanote railway line to reduce the incidence of suicide.

As a result of the success of these lights (suicides fell by 74 percent at stations where the blue lights were installed), similar coloured lighting has been installed at Gatwick Airport train platforms.

These steps were taken based on the claim that blue light could make people less impulsive and more calm, but there is little scientific evidence yet to support these claims: a three-year study (forthcoming) by Nicholas Ciccone, a PhD researcher in our group, found inconclusive evidence for the effect of coloured lighting on impulsivity.

Similar studies are underway in our laboratories to explore the effect of colour on creativity, student learning in the classroom, and sleep quality.

It is clear that light, and colour specifically, can affect us in ways that go far beyond regular colour vision.

The discovery of the non-image-forming visual pathway has given a new impetus to research that explores how we respond, both physiologically and psychologically, to colour around us.

The increasing availability and use of coloured lighting that has resulted from advances in LED technology has added to the need to carry out rigorous research in this field, but it is becoming increasingly difficult to separate claims for the effects of colour that are supported by data, from those that are based on intuition or tradition.

Stephen Westland, Professor, Chair of Colour Science and Technology, University of Leeds.

This article was originally published on The Conversation. Read the original article.


How to Increase Dopamine

There are a wide variety of activities that boost dopamine levels in the brain, but not all of them contribute to long-term health. Taking part in behaviors that increase dopamine while improving your health can contribute to the formation of good habits and boost your mood. Some ways to get a natural increase in dopamine include:

  • Consume probiotics: Whether taken in supplement form or by eating probiotic rich foods such as yogurt and fermented foods, probiotics have been shown to support dopamine production.
  • Sleep: Getting enough sleep each night is one of the best ways to keep your dopamine at a healthy level. One night without sleep has actually been shown to increase dopamine in the short-term. However, the increase in dopamine caused by long-term sleep deprivation could cause dopamine receptors to become less sensitive to dopamine, making it difficult for a person to feel awake.
  • Spend time in the sun: Sunlight facilitates the body’s production of vitamin D. Vitamin D, in turn, can help increase dopamine production.
  • Exercise: In addition to endorphins, exercise can increase dopamine levels, contributing to the mood improvement that often comes with physical activity.
  • Listen to music: Multiple studies have shown that listening to music you like causes dopamine to be released in the brain.
  • Avoid sugary foods and junk food: Eating foods that release large amounts of dopamine (which are often high in sugar and fat) can have a desensitizing effect over time. Sticking to whole foods ensures the body’s dopamine receptors don’t become overpowered, thereby creating the need for foods that stimulate the release of more dopamine.

How music affects our psychology and well being

One of the most crucial issues in the psychological effects of music is how music affects the emotional experience. Music can evoke powerful emotions such as chills and thrills amongst the listeners.

Positive emotions are what one feels when listening to music. The reward transmitter dopamine is released when one listens to pleasurable music. The easiest way to alleviate mood or relieve stress is to listen to music. People use music in their everyday lives to regulate, enhance, and diminish undesirable emotional states (e.g., stress, fatigue). How does music listening produce emotions and pleasure in listeners?

#1. Music evokes pleasure

Music enjoyment evokes the same pleasure in our brains as other forms of pleasure such as food, sex and drugs. Listening to music cab be reinforcing and addictive. Music is an aesthetic stimulus which can naturally target the dopamine system of the brain.

#2. Anticipation

Music is pleasurable. It may fulfil or violate expectations but is still considered pleasurable. The more unexpected the events in music, the more surprising is the musical experience. We appreciate music that is less predictable and slightly more complex.

#3. Refined emotions

Appreciation of music also involves an intellectual component. The dopamine systems do not work in isolation, and their influence will be largely dependent on their interaction with other regions of the brain. That is, our ability to enjoy music can be seen as the outcome of our human emotional brain and its more recently evolved neocortex. Evidence shows that people who consistently respond emotionally to aesthetic musical stimuli possess stronger white matter connectivity between their auditory cortex and the areas associated with emotional processing, which means the two areas communicate more efficiently.

#4. Memories

Memories are one of the most vital ways in which musical events evoke emotions. According to a late physician, Oliver Sacks musical emotions and musical memory can survive long after other forms of memory have disappeared. Part of the reason for the durable power of music appears to be that listening to music engages many parts of the brain, triggering connections and creating associations.

#5. Tendency towards action

Music often creates strong action tendencies to move in coordination with the music (e.g., dancing, foot-tapping). Our internal rhythms (e.g., heart rate) speed up or slow down to become one with the music. We float and move with the music.

#6. Mimicry of emotions

Music doesn’t only evoke emotions at the individual level, but also at the interpersonal and intergroup level. Listeners mirror their reactions to what the music expresses, such as sadness from sad music, or cheer from happy music. Similarly, ambient music affects shoppers’ and diners’ moods.

#7. Influence on consumer behaviour

Background music has a surprisingly strong influence on consumer behaviour. For example, one study exposed customers in a supermarket drinks section to either French music or German music. The results showed that French wine outsold German wine when French music was played, whereas German wine outsold French wine when German music was played.

#8. Regulation of mood

People crave ‘escapism’ during uncertain times to avoid their woes and troubles. Music offers a resource for emotional regulation People use music to achieve various goals, such as to energize, maintain focus on a task, and reduce boredom. For instance, sad music enables the listener to disengage from the distressing situations (breakup, death, etc.), and focus instead on the beauty of the music. Further, lyrics that resonate with the listener’s personal experience can give voice to feelings or experiences that one might not be able to express oneself.

#9. Perception of time

Music is a powerful emotional stimulus that changes our relationship with time. Time does indeed seem to fly when listening to pleasant music. Music is therefore used in waiting rooms to reduce the subjective duration of time spent waiting and in supermarkets to encourage people to stay for longer and buy more. Hearing pleasant music seems to divert attention away from time processing. Moreover, this attention-related shortening effect appears to be greater in the case of calm music with a slow tempo.

#10. Development of identity

Music can be a powerful tool for identity development. Young people derive a sense of identity from music.

Listening to music can be entertaining, and some research suggests that it might even make you healthier. Music can be a source of pleasure and contentment, but there are many other psychological benefits as well. Music can relax the mind, energize the body, and even help people better manage pain.

The notion that music can influence your thoughts, feelings, and behaviours probably does not come as much of a surprise. If you’ve ever felt pumped up while listening to your favourite fast-paced rock anthem or been moved to tears by a tender live performance, then you easily understand the power of music to impact moods and even inspire action. The psychological effects of music can be powerful and wide-ranging.


Dopamine – The Happy Brain Chemical

Unfortunately, too many who have read the research on the teenage brain come to quick conclusions about adolescents often fueling misperceptions of teenagers as irrational loose cannons who can’t be trusted with anything. It turns out though that young people are making choices influenced by a very different set of chemical influences than their adult counterparts. For starters, the teenage brain appears to be more sensitive to the effects of a neurotransmitter called dopamine. I like to think of neurotransmitters as “molecules of emotion” because their levels in our brain have a lot to do with our mood. Dopamine is the “happy” neurotransmitter. The more dopamine is circulating in our brains the happier we feel. The growth of more dopamine receptors during adolescence as well as an enhanced dopamine supply provides a rush that adults just don’t feel when engaged in the same activity. There is even some evidence that baseline levels of dopamine are lower during this time but the release is more intense, which could cause craving of dopamine-inducing experiences—like skateboarding behind a moving vehicle.

This hopped up reward system can drown out warning signals about risk. This doesn’t mean that young people don’t stop to think about the consequences or that they “don’t know any better.” Most of the time adolescents know exactly what might happen. It is just that there are times when the reward seems well worth it. So before we write off young people as “irrational,” we would be wise to acknowledge the strategic choices that adolescents often make as they choose between safer or more thrilling adventures. Teenage decisions are not always defined by impulsivity because of lack of brakes, but because of planned and enjoyable pressure to the accelerator.

Skate boarding behind cars isn’t the only thing that activates the reward system in the teenage brain. There are lots of sources of dopamine. Some are negative like alcohol, drugs, and nicotine. Others present a double-edged sword, like peers. Research about risky driving shines a light on the powerful role that peers play in teens decision-making when they are behind the wheel. Evidence is clear that when peers are in the car with a teen driver, they are more likely to get into an accident. The conventional thinking has been that passengers in the car must distract the driver or exert peer pressure for reckless driving, egging their friends through red lights and asking them to gun it on straightaways. Those dynamics might be present at times, of course, but it turns out though that teens drive more recklessly even if their friends do nothing at all. Simply the presence of peers activates young people’s reward systems, amplifying the surge of dopamine they get as their foot hits the car’s accelerator.


Cognition is central to drug addiction

Recent research shows that drug abuse alters cognitive activities such as decision-making and inhibition, likely setting the stage for addiction and relapse.

Most substance abuse researchers once believed that drug abuse and addiction are best explained by drugs' reinforcing effects. Pharmacological studies have long supported that view, showing that drugs of abuse powerfully affect the brain's dopamine system, which regulates emotional responses and plays a part in abuse by providing an emotional "reward" for continued use.

Increasingly, however, scientists are learning that the story is more complicated. Brain-imaging studies in humans and neuropsychological studies in nonhuman animals have shown that repeated drug use causes disruptions in the brain's highly evolved frontal cortex, which regulates cognitive activities such as decision-making, response inhibition, planning and memory.

"We now know that many of the drugs of abuse target not just those aspects of the brain that alter things like emotion, but also areas that affect our ability to control cognitive operations," says Herb Weingartner, PhD, of the Division of Neuroscience and Behavioral Research at the National Institute on Drug Abuse (NIDA).

The new findings hold promise for better understanding why only some drug users become addicted, why drug abusers so easily relapse even after long periods of drug abstinence and, ultimately, how prevention and treatment efforts can be tailored to people's individual vulnerabilities.

"In the past few years, people have begun to recognize that drug abuse is not a pharmacological disease--it's a pharmacological and behavioral disease," says Elliot A. Stein, PhD, a neuroscientist at the Medical College of Wisconsin. "The cognitive functions that sit in the frontal lobes play a role in drug abuse."

For treatment, he believes, that may suggest that it will be difficult to find a "magic bullet" to attack both the pharmacological and the behavioral parts of addiction.

Shifting tide

Since the 1980s, scientists have observed that many people who were addicted to drugs such as cocaine and marijuana appeared to have frontal cortex abnormalities. Such abnormalities, however, were long thought to be incidental side effects of drug abuse, explains Steven Grant, PhD, a program officer in NIDA's Division of Treatment Research and Development.

"We typically haven't thought of the influence of those processes on substance abuse and addiction," he says, "because we have been so focused on the role of reinforcement and the hedonic effects of drugs as being the driving force in drug abuse. That has been the dominant paradigm for the last two decades."

In the past five years, however, the tide has begun to turn. At a 1992 scientific conference, University of Iowa neuroscientist Antoine Bechara, PhD, described research showing that patients with frontal cortex damage had impaired decision-making abilities, reflected in their performance on a laboratory gambling task.

Grant saw Bechara's presentation and made the connection to drug abuse, hypothesizing that disruptions in the frontal cortex might be responsible for impaired decision-making and behavioral inhibition in drug abusers--and that that could help explain the compulsive drug-seeking that is a hallmark of addiction.

Using Bechara's gambling task, Grant and his colleagues tested drug abusers' decision-making abilities. Last year, they reported in the journal Neuropsychologia (Vol. 38, No. 8) that drug abusers indeed made poorer decisions on the gambling task than did participants in a control group.

More recently, Bechara and his colleagues uncovered three subgroups of drug abusers. About one-third, they found, showed no decision-making impairment on the gambling task. About 25 percent, in contrast, responded exactly as patients with frontal lobe damage have been shown to do, almost invariably choosing a higher immediate reward even knowing that their strategy would be unprofitable in the long run. Finally, about 40 percent of Bechara's study participants appeared to be hypersensitive to potential rewards--no matter whether they were immediate or long-term.

Bechara suggests that these differences in decision-making impairment reflect different vulnerabilities to drug addiction. If so, he argues, they may help shed light on treatment strategies. Drug users who show no decision-making impairment may be at least risk for becoming addicted and may be able to stop if they want to, he suggests. In contrast, he says, for those with severe decision-making impairments, "There's probably nothing you can do. You can put them in jail, but in my opinion, they're unlikely to respond."

Finally, Bechara argues, for drug users who are sensitive to both the short- and long-term consequences of drug use, heightening awareness of the negative long-term consequences of abuse may be sufficient to tip the scales and help people quit using drugs.

In other studies, researchers have used two imaging techniques, positron emission tomography and functional magnetic resonance imaging, to measure drug abusers' brain activity during craving.

In 1996, Grant and NIDA colleagues David B. Newlin, PhD, Edythe D. London, PhD, and others reported in the Proceedings of the National Academy of Sciences (Vol. 93) that cocaine craving was linked to heightened activity in areas of the frontal cortex that regulate decision-making and motivation, but not in the brain's dopamine control centers. Those findings have since been replicated and extended in other laboratories.

"Classically, people thought that drug addiction was a disease that involved the centers of pleasure--that people are taking the drug because it's pleasurable," concludes Nora D. Volkow, MD, a research scientist at the U.S. Department of Energy's Brookhaven National Laboratory. "But that's not the case--in fact, addicted people don't have as strong a pleasure response as people who aren't addicted. Recent data are showing us that addiction entails a basic disruption of motivational circuits."

Seeking clues for treatment

Evidence that craving and drug cues can trigger abnormal activity in the frontal cortex--even in the absence of drugs--has led many researchers to believe that this brain area may be especially important in relapse. Grant suggests it may be in the frontal cortex that the residual effects of drugs manifest themselves, long after dopamine effects have disappeared.

"Without a properly functioning frontal cortex," he says, "one may be unable to look beyond drugs' immediate reinforcing or hedonic aspects and consider the long-term consequences of drug use."

Bechara adds, "I think there are two mechanisms playing in addiction. One is the pharmacological reward process that we've been studying for years. But the other is the behavioral process of controlling your behavior in the face of punishment."

The growing body of research on the roles that the frontal cortex and cognitive processes such as decision making and behavioral inhibition play in addiction raises many questions about treatment:

What is the difference, in the brain, between drug use and addictive drug use?

Do some people have pre-existing, subtle abnormalities in the frontal cortex that make them more vulnerable to drug use? If so, how can such dysfunction be identified and used for early interventions?

What are the long-term brain consequences of drug use? Are they reversible?

How can the recent findings of frontal cortex activation during drug craving be exploited to develop better ways to evaluate treatment effectiveness?

"Right now, the best tool for measuring success of drug treatment is recidivism--does the person show up in the hospital again?" comments Stein. "Compare that with a field like cardiology, where a physician would never release a heart attack patient without a stress test. In drug addiction, we send people out on the street without certainty that the treatment worked."

He hopes that someday, he'll be able to put people in a craving situation and measure their brain responses. "That," he says, "will help us know if the intervention blunted the craving response."


Dopamine and desire

Knockout mice showcase the neurotransmitter's role in motivation.

Neuroscientists are beginning to understand the motivational workings of dopamine--the common neurotransmitter whose absence lowers drive and hurts motor control. Some of the most recent findings come from a team at Seattle's Howard Hughes Medical Institute, whose research suggests that, at least in mice, reward learning is quite possible without dopamine. Such insights may one day help everyone from teachers motivating their students to doctors treating patients with Parkinson's disease to counselors treating drug addiction: Dopamine's reach is that broad.

To reach their finding, the Seattle team used genetically altered knockout mice to tease out the impact of dopamine on subtly different aspects of the motivational system: wanting, liking and learning. By using technology to, in effect, turn off dopamine production and see what happened, they discovered that mice don't need dopamine to connect behavior with rewards or to find the rewards satisfying. The research appears in February's Behavioral Neuroscience (Vol. 119, No. 1).

Neuroscientist Kent Berridge, PhD, of the University of Michigan, says it appears that "dopamine is only needed to use already learned information to generate successful motivated performance." Translation: Dopamine promotes what we think of as "wanting."

By comparing the behavior of mice bred with mutations that inhibit dopamine production with the behavior of normal mice, the Seattle team may have helped clarify dopamine's historically ambiguous role. Especially for diseases linked to dopamine deficiencies, such as Parkinson's and schizophrenia, knowing how and whether one can motivate patients could mean a lot for clinical care.

In addition, "Separating motivation components is a popular and important approach to understanding motivation in the context of addiction," says Mark Kristal, PhD, a behavioral neuroscientist at the University at Buffalo of the State University of New York. In that case, psychologists want to know how to suppress the drug motivation of the addicted.

'What's my motivation?'

From the outside, it's hard to tell what most motivates an animal to seek a reward: the pleasure of the reward itself (roughly, liking), the satisfaction of getting it (wanting), or the acquired association between behavior and reward (learning).

"Wanting and liking are what some philosophers of mind have called 'folk psychological' terms about how the mind is organized," explains Jon Horvitz, PhD, a neuroscientist at Boston College. Although he doubts real brains have clearly demarked scripts for "wanting" or "liking," he says it helps to draw some rough distinctions to enable research into dopamine's behavioral pathway.

The Seattle researchers--graduate student Siobhan Robinson, undergraduate Suzanne Sandstrom, psychologist Victor Denenberg, PhD, and biochemist Richard Palmiter, PhD--chose a knockout approach to get a fair comparison between behavior with and without dopamine. Then, they threw caffeine into the mix to compensate for the motor lethargy but not the cognitive deficits caused by low dopamine.

Dopamine appears to be involved both in goal-directed and motor behavior. On the inside, dopamine-producing neurons extend into neighboring motivational and motor parts of the brain. And on the outside, when scientists block dopamine release, rewards such as food, sex and cocaine stop reinforcing behavior. But what does this mean: Do we stop liking them? Wanting them? Or learning that they're good? Once scientists know, they might be able to devise better therapeutic manipulations using dopamine or to design interventions that bypass the dopamine system.

Genetic engineering, says Berridge, author of a same-issue commentary on the study, "gives a completely independent way of asking the question" because experimenters can control--in a clean, noninvasive way--the relevant aspect of a subject's physiology. In knockout breeding, scientists remove or "knock out" a specific gene in an embryonic stem cell before it divides into many new different types of cells. When the resulting animal breeds, it passes down altered genes. Rodents breed so quickly that in short order, scientists can use genetically altered animals to show what a gene does by virtue of what does or doesn't happen in its absence.

Dopamine-deficient (DD) mice lack the enzyme needed to convert the amino acid tyrosine into levodopa, or L-dopa. Once L-dopa is formed, another enzyme they still have converts L-dopa into dopamine. A shot of L-dopa "rescues" DD mice, which will otherwise perish from starvation. Thus, Robinson explains, "The real beauty of the DD mouse is that the experimenter can control whether dopamine is present in the body by simply giving a shot of L-dopa."

The team's first experiment compared normal mice with lethargic DD mice whose L-dopa shots were converted into dopamine, which got them moving. The scientists trained the mice to run a T-maze with mouse chow at the end of the left or right arm of the upper bar. They compared how eight L-dopa-treated DD mice and nine control mice behaved, reasoning that liking is signaled by how much mice eat, whereas "wanting" is signaled by them chomping down sooner. The learning part comes through efficient running of the maze.

Treated with L-dopa, the knockout mice learned to run the T-maze just like normal mice and ate about as much about as quickly. With dopamine restored, they appeared to like and want the rewards as much as control mice. When the researchers established that DD mice with dopamine perform the task as well as control mice, they had set the stage for the next, more critical experiment. In that, they tested whether mice like, learn about and yearn for rewards without any dopamine in the brain. Would the lab equivalent of a cup of coffee get them going?

The researchers injected 25 DD mice with saline solution, L-dopa or caffeine, the latter of which stimulates locomotor activity through a nondopamine system. Then they measured how fast the mice in each group learned the T-maze. Then the researchers gave all the mice L-dopa and rechecked their learning.

At first the caffeinated DD mice didn't appear to learn much, but in the study's second phase they learned the task much quicker than would typical first-timers. Predictably, the saline-treated DD mice didn't do much of anything in the first phase and had novice learning times in the second one, and the L-dopa treated DD mice maxed out in their learning the first time around.

Thus it appeared that the caffeinated DD mice learned something during the first phase--and they learned it without dopamine. The authors thus conclude that normal reward learning does not depend on dopamine. This finding, coupled with previous findings that wanting does depend on dopamine, creates a fuller picture of motivation.

Still, Kristal cautions, "The mechanism for locomotor and motivational activation with caffeine may be separate from that for dopamine, and caffeine may alter the rate of dopamine metabolism--thereby confounding the results." Berridge agrees that the use of caffeine in DD mice "may muddy the picture a bit."

The plot thickens

New technologies raise new questions. For example, says Berridge, "It's always possible that [in the DD knockout mice], brain development produced some compensation. Maybe these mice have brains that can learn without dopamine." That's why, he says, neuroscientists, including those at the University of Washington lab, are trying to develop "inducible knockouts" in which the mouse could develop normally and then scientists could knock out a gene in later tests. For now, he says the study demonstrates that "brains without dopamine can still learn normally about rewards--at least, if they have caffeine activating them via a separate nondopamine biochemical pathway."

As another example, Kristal notes that the researchers didn't know whether the control mice--littermates with one of the two alleles (gene variations) needed for a functioning gene--behaved the same as normal mice from normal litters. If they behaved differently, that could confound the results and undermine the study's validity.

"Sometimes it almost seems that the correct answer to 'what does dopamine do?' might mostly be 'to confuse neuroscientists,'" says Berridge.

Horvitz adds, "The functional organization of the brain may or may not correspond well to categories such as liking and wanting. I think [the Seattle researchers] mean that dopamine is a player in neural circuitry that serves to vigorously mobilize behavior toward a particular goal object, which in humans, at least, is often accompanied by what we describe as 'wanting.'

"However," he continues, "it's unlikely that a particular neurotransmitter will correspond perfectly to a specific psychological construct such as wanting--or liking for that matter."

Palmiter agrees, saying, "It is very difficult to extrapolate from our studies with mice to humans, especially because our DD mice have much less dopamine than people with even severe Parkinson's disease." However, lead author Siobhan Robinson suggests that, "Perhaps caffeine can be used as a substitute for L-dopa during behavioral therapy with Parkinson's patients. To avoid the motor abnormalities induced by L-dopa during training, patients might learn new tasks without it that they'd be able to perform when on their daily L-dopa regimen."

Palmiter adds that it's also hard to immediately transfer the findings to everyday motivation, because "if dopamine levels were so low that motivation was affected, there would be many other Parkinson's-like symptoms." It is clear that research is needed to more fully understand these results and to begin to think about implications for relapsing drug addition, which is thought to result from over- (not under-) activity of the dopamine system, observe researchers in the area.

Still, Robinson likes to speculate about crafty real-world manipulation of natural dopamine mechanisms. One idea she has: "Designing classroom activities that may increase dopamine signaling, such as unexpected rewards along the way, may enhance the desire to perform well during and after learning. This could lead to better performance of learned tasks."


Novelty and the Brain: Why New Things Make Us Feel So Good

We all like shiny new things, whether it's a new gadget, new city, or new job. In fact, our brains are made to be attracted to novelty—and it turns out that it could actually improve our memory and learning capacity. The team at social sharing app Buffer explains how.

Having just moved to a new country, I’m currently surrounded by novel sights, sounds, and experiences. It’s an overload of new for my brain. However, after only being here a week, I’m surprised how ordinary my house and my street seem. After walking the same route to the train station three or four times, it quickly became boring. How quickly novelty can disappear as we become familiar with the things around us, and yet how completely stimulated we become when we find yet another brand new experience to have or sight to see.

It turns out, this isn’t just because I’m part of a generation of compulsive email checkers or internet addicts, or because I don’t appreciate life enough. It’s actually hardwired into my brain —and yours—to appreciate and seek out novelty.

How We Find Novelty

Anything that’s new, different or unusual is bound to catch our eye. A new phone, a new working environment, a new friend. Changing our hair color, wearing new clothes, visiting a new place. In fact, we can even be drawn to novelty without being conscious of it. Of course, this makes a lot of sense—we wouldn’t get much done if ordinary things captivated us constantly.

The cool thing about this is how intricately novelty seems to be associated with learning , which means we can use this knowledge to our advantage for learning new things and improving our memory.

How the Brain Handles Novelty

There’s a region in our midbrain called the substantia nigra/ventral segmental area or SN/VTA. This is essentially the major “novelty center” of the brain, which responds to novel stimuli. The SN/VTA is closely linked to areas of the brain called the hippocampus and the amygdala, both of which play large roles in learning and memory. The hippocampus compares stimuli against existing memories, while the amygdala responds to emotional stimuli and strengthens associated long-term memories.

It’s been thought before that novelty was a reward in itself, but, like dopamine, it seems to be more related to motivation. Researchers Bunzeck and Düzel tested people with an “oddball” experiment that used fMRI imaging to see how their brains reacted to novelty. They showed the subjects images such as indoor and outdoor scenes and faces with occasional novel images (oddballs) thrown in.

The experiment found that the SN/VTA was activated by novel images—that is, brand new images that hadn’t been seen before. Images that only slightly deviated from more familiar ones didn’t have the same effect, and neither did images with strongly negative emotional context such as car crashes or angry faces. The Dopamine pathways, which are activated when we are exposed to novelty, look something like this (highlighted in blue):

A second part of the experiment was designed to test whether relative novelty or absolute novelty was required for the SN/VTA to activate. Images that were slightly more novel to the subject than others (relative novelty) were tested, as were images that were completely novel compared to others (absolute novelty).

The SN/VTA only activated when shown absolutely novel stimuli —images that had never been seen before. Other related areas of the brain still reacted to the images, but the reactions decreased slightly with each showing as they became more familiar. Dr Düzel explained it like this:

“We thought that less familiar information would stand out as being significant when mixed with well-learnt, very familiar information and so activate the midbrain region just as strongly as absolutely new information. That was not the case. Only completely new things cause strong activity in the midbrain area.”

This is similar to what might happen during repetition of flash cards or educational material. Only the completely new information stands out among a group of overly familiar objects or images.

How Novelty Motivates Us

You’ve probably heard about dopamine before, and its effects on the brain. It’s often touted as a "reward chemical" or part of the brain’s "reward center," but more recent research has shown that, like novelty, it’s actually more closely related to our motivation to seek rewards rather than being a reward itself. Animal studies around the brain’s reaction to novelty have suggested increased dopamine levels in the context of novelty. So the brain reacts to novelty by releasing dopamine which makes us want to go exploring in search of a reward.

You might remember how a new level or world to explore in a video game motivates you to play for longer, in the hopes of the reward of unlocking an achievement or gaining more points. Each new stimuli gives you a little rush of motivation to explore, because it makes you anticipate a reward. Here's a graph that shows activity in your brain on this:

Dr Düzel said this about how novelty motivates us:

“When we see something new, we see it has a potential for rewarding us in some way. This potential that lies in new things motivates us to explore our environment for rewards. The brain learns that the stimulus, once familiar, has no reward associated with it and so it loses its potential. For this reason, only completely new objects activate the midbrain area and increase our levels of dopamine.”

What This Means for Learning

This is pretty interesting stuff, but it’s only useful if we can take something away from it to apply to our own lives. Unfortunately the human studies on this subject, such as the one mentioned above, are few and far between at this stage. More studies have been completed on animals, but the research is still in early stages. This doesn’t mean we can’t learn from it though. Here’s what it means for those of us who want to improve our learning and knowledge retention.

Remember how I said the hippocampus is closely tied to the SN/VTA? Well these animal studies also showed that the plasticity of the hippocampus (the ability to create new connections between neurons) was increased by the influence of novelty—both during the process of exploring a novel environment or stimuli and for 15–30 minutes afterwards.

As well as increasing our brain’s plasticity—and therefore potential for learning new concepts and facts—novelty has been shown to improve the memory of test subjects :

"Separate behavioural experiments were also conducted without the use of a scanner to test the subjects’ memory. Their memory of the novel, familiar and very familiar images they had studied was tested after 20 minutes and then a day later. Subjects performed best in these tests when new information was combined with familiar information during learning. After a 20 minute delay, subjects’ memory for slightly familiar information was boosted by 19 per cent if it had been mixed with new facts during learning sessions."

This information could help boost students’ performance both during classes and in exams, as well as helping those who suffer from memory loss. Dr Düzel pointed out the possible medical benefits that could come from this research:

We hope that these findings will have an impact on behavioural treatments for patients with poor memory. Current practice by behavioural psychologists aims to improve memory through repeatedly exposing a person to information – just as we do when we revise for an exam. This study shows that revising is more effective if you mix new facts in with the old. You actually learn better, even though your brain is also tied up with new information."

How You Can Learn More and Improve Memory

If you want to start putting these findings to work, you can improve your knowledge retention and make new ideas and concepts stick by introducing novelty into your learning process. Here are some ideas to get you started:

Add Something New

Each time you review information or facts that you’ve learned before, add in a small number of new ones. This will make your brain notice and recognize slightly-familiar information more easily because it’s offset by brand new concepts.

Change Your Environment

Your environment can offer a huge amount of novel stimuli for your brain. Try offsetting the familiarity of learning material by reviewing it in new settings. On top of this, changing temperature or lighting in the room you are already in can make a big difference.

Learn After Doing Something New

Use your brain’s increased plasticity wisely by setting aside time to learn right after taking in novel stimuli. If you meet someone new for coffee or explore a new place, your brain will be more open to making new connections during and right after this time, so you might as well take advantage.

Belle Beth Cooper has spent the past four years as a freelance writer and social media consultant. She's written for The Next Web, Desktop Magazine, and Social Media Examiner. She now spends her days wielding a pencil as Attendly's head of content.

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DISCUSSION

"You might remember how a new level or world to explore in a video game motivates you to play for longer, in the hopes of the reward of unlocking an achievement or gaining more points."

As a gamer, that was my first thought when I started reading the article. In addition to what you pointed out, this search for novelty has also got me playing more new games rather than playing the same ole over and over. I used to be obsessed with multiplayer, but exploring new worlds and seeing how developers design their gameplay and write their stories have been appealing to me more and more.

One other thing I would point out is those of us who are more driven towards novelty can find certain things at work/school to be, um, challenging. Your tip to "add something new" perfectly describes how I approach things. Luckily my environment and the people around me allow me to do that 95% of the time. There are though some instances where sticking with the same ole is expected, and that's where I sometimes "waste" time because I try new techniques or add new data points even though they may not be necessary (they help me to learn for sure, but they don't really benefit the end users so that's why I think that time is "wasted").


COVID-19 can affect the brain. New clues hint at how

COVID-19 can come with brain-related problems, but just how the virus exerts its effects isn’t clear.

Roxana Wegner/Moment/Getty Images

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For more than a year now, scientists have been racing to understand how the mysterious new virus that causes COVID-19 damages not only our bodies, but also our brains.

Early in the pandemic, some infected people noticed a curious symptom: the loss of smell. Reports of other brain-related symptoms followed: headaches, confusion, hallucinations and delirium. Some infections were accompanied by depression, anxiety and sleep problems.

Recent studies suggest that leaky blood vessels and inflammation are somehow involved in these symptoms. But many basic questions remain unanswered about the virus, which has infected more than 145 million people worldwide. Researchers are still trying to figure out how many people experience these psychiatric or neurological problems, who is most at risk, and how long such symptoms might last. And details remain unclear about how the pandemic-causing virus, called SARS-CoV-2, exerts its effects.

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“We still haven’t established what this virus does in the brain,” says Elyse Singer, a neurologist at the University of California, Los Angeles. There are probably many answers, she says. “It’s going to take us years to tease this apart.”

Getting the numbers

For now, some scientists are focusing on the basics, including how many people experience these sorts of brain-related problems after COVID-19.

A recent study of electronic health records reported an alarming answer: In the six months after an infection, one in three people had experienced a psychiatric or neurological diagnosis. That result, published April 6 in Lancet Psychiatry, came from the health records of more than 236,000 COVID-19 survivors. Researchers counted diagnoses of 14 disorders, ranging from mental illnesses such as anxiety or depression to neurological events such as strokes or brain bleeds, in the six months after COVID-19 infection.

“We didn’t expect it to be such a high number,” says study coauthor Maxime Taquet of the University of Oxford in England. One in three “might sound scary,” he says. But it’s not clear whether the virus itself causes these disorders directly.

The vast majority of those diagnoses were depression and anxiety, “disorders that are extremely common in the general population already,” points out Jonathan Rogers, a psychiatrist at University College London. What’s more, depression and anxiety are on the rise among everyone during the pandemic, not just people infected with the virus.

Mental health disorders are “extremely important things to address,” says Allison Navis, a neurologist at the post-COVID clinic at Icahn School of Medicine at Mount Sinai in New York City. “But they’re very different than a stroke or dementia,” she says.

About 1 in 50 people with COVID-19 had a stroke, Taquet and colleagues found. Among people with severe infections that came with delirium or other altered mental states, though, the incidence was much higher — 1 in 11 had strokes.

Serious neurological damage, such as these strokes caused by blocked blood vessels, turn up in people with COVID-19. K. Thakur et al/Brain 2021

Taquet’s study comes with caveats. It was a look back at diagnosis codes, often entered by hurried clinicians. Those aren’t always reliable. And the study finds a relationship, but can’t conclude that COVID-19 caused any of the diagnoses. Still, the results hint at how COVID-19 affects the brain.

Blood vessels scrutinized

Early on in the pandemic, the loss of smell suggested that the virus might be able to attack nerve cells directly. Perhaps SARS-CoV-2 could breach the skull by climbing along the olfactory nerve, which carries smells from the nose directly to the brain, some researchers thought.

That frightening scenario doesn’t seem to happen much. Most studies so far have failed to turn up much virus in the brain, if any, says Avindra Nath, a neurologist who studies central nervous system infections at the National Institutes of Health in Bethesda, Md. Nath and his colleagues expected to see signs of the virus in brains of people with COVID-19 but didn’t find it. “I kept telling our folks, ‘Let’s go look again,’” Nath says.

That absence suggests that the virus is affecting the brain in other ways, possibly involving blood vessels. So Nath and his team scanned blood vessels in post-mortem brains of people who had been infected with the virus with an MRI machine so powerful that it’s not approved for clinical use in living people. “We were able to look at the blood vessels in a way that nobody could,” he says.

Damage abounded, the team reported February 4 in the New England Journal of Medicine. Small clots sat in blood vessels. The walls of some vessels were unusually thick and inflamed. And blood was leaking out of the vessels into the surrounding brain tissue. “You can see all three things happening at the same time,” Nath says.

Those results suggest that clots, inflamed linings and leaks in the barriers that normally keep blood and other harmful substances out of the brain may all contribute to COVID-related brain damage.

Signs of damage in the brains of people with COVID-19 involve inflammation, including these immune cells around a blood vessel (left), and changes in cells (right) that might have resulted from low oxygen. J. Lou et al/Free Neuropathology 2021

But several unknowns prevent any definite conclusions about how these damaged blood vessels relate to people’s symptoms or outcomes. There’s not much clinical information available about the people in Nath’s study. Some likely died from causes other than COVID-19, and no one knows how the virus would have affected them had they not died.

Inflamed body and brain

Inflammation in the body can cause trouble in the brain, too, says Maura Boldrini, a psychiatrist at Columbia University in New York. Inflammatory signals released after injury can change the way the brain makes and uses chemical signaling molecules, called neurotransmitters, that help nerve cells communicate. Key communication molecules such as serotonin, norepinephrine and dopamine can get scrambled when there’s lots of inflammation.

Neural messages can get interrupted in people who suffer traumatic brain injuries, for example researchers have found a relationship between inflammation and mental illness in football players and others who experienced hits to the head.

Similar evidence comes from people with depression, says Emily Troyer, a psychiatrist at the University of California, San Diego. Some people with depression have high levels of inflammation, studies have found. “We don’t actually know that that’s going on in COVID,” she cautions. “We just know that COVID causes inflammation, and inflammation has the potential to disrupt neurotransmission, particularly in the case of depression.”

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Among the cells that release inflammatory proteins in the brain are microglia, the brain’s version of the body’s disease-fighting immune system. Microglia may also be involved in the brain’s response to COVID-19. Microglia primed for action were found in about 43 percent of 184 COVID-19 patients, Singer and others reported in a review published February 4 in Free Neuropathology. Similar results come from a series of autopsies of COVID-19 patients’ brains 34 of 41 brains contained activated microglia, researchers from Columbia University Irving Medical Center and New York Presbyterian Hospital reported April 15 in Brain.

With these findings, it’s not clear that SARS-CoV-2 affects people’s brains differently from other viruses, says Navis. In her post–COVID-19 clinic at Mount Sinai, she sees patients with fatigue, headaches, numbness and dizziness — symptoms that are known to follow other viral infections, too. “I’m hesitant to say this is unique to COVID,” Navis says. “We’re just not used to seeing so many people getting one specific infection, or knowing what the viral infection is.”

Teasing apart all the ways the brain can suffer amid this pandemic, and how that affects any given person, is impossible. Depression and anxiety are on the rise, surveys suggest. That rise might be especially sharp in people who endured stressful diagnoses, illnesses and isolation.

In a postmortem brain from a person with COVID-19, a clotting protein called fibrinogen (red) indicates that the blood vessels are damaged and leaky. Avindra Nath

Just being in an intensive care unit can lead to confusion. Delirium affected 606 of 821 people — 74 percent — while patients were in intensive care units for respiratory failure and other serious emergencies, a 2013 study found. Post-traumatic stress disorder afflicted about a third of people who had been seriously sick with COVID-19 (SN: 3/12/21).

More specific aspects of treatment matter too. COVID-19 patients who spent long periods of time on their stomachs might have lingering nerve pain, not because the virus attacked the nerve, but because the prone position compressed the nerves. And people might feel mentally fuzzy, not because of the virus itself, but because a shortage of the anesthetic drug, propofol, meant they received an alternative sedative that can bring more aftereffects, says Rogers, the psychiatrist at University College London.

Lingering questions — what the virus actually does to the brain, who will suffer the most, and for how long — are still unanswered, and probably won’t be for a long time. The varied and damaging effects of lockdowns, the imprecision doctors and patients use for describing symptoms (such as the nonmedical term “brain fog”) and the indirect effects the virus can have on the brain all merge, creating a devilishly complex puzzle.

For now, doctors are busy focusing on ways in which they can help, even amid these mysteries, and designing larger, longer studies to better understand the effects of the virus on the brain. That information will be key to helping people move forward. “This isn’t going to be over soon, unfortunately,” Troyer says.

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Here's How Colours Really Affect Our Brain And Body, According to Science

Red makes the heart beat faster. You will frequently find this and other claims made for the effects of different colours on the human mind and body.

But is there any scientific evidence and data to support such claims?

The physiological mechanisms that underpin human colour vision have been understood for the best part of a century, but it is only in the last couple of decades that we have discovered and begun to understand a separate pathway for the non-visual effects of colour.

Like the ear, which also provides us with our sense of balance, we now know that the eye performs two functions.

Light sensitive cells known as cones in the retina at the back of the eye send electrochemical signals primarily to an area of the brain known as the visual cortex, where the visual images we see are formed.

However, we now know that some retinal ganglion cells respond to light by sending signals mainly to a central brain region called the hypothalamus which plays no part in forming visual images.

Light but not vision

The hypothalamus is a key part of the brain responsible for the secretion of a number of hormones which control many aspects of the body's self-regulation, including temperature, sleep, hunger and circadian rhythms.

Exposure to light in the morning, and blue/green light in particular, prompts the release of the hormone cortisol which stimulates and wakes us, and inhibits the release of melatonin. In the late evening as the amount of blue light in sunlight is reduced, melatonin is released into the bloodstream and we become drowsy.

The retinal cells that form the non-image-forming visual pathway between eye and hypothalamus are selectively sensitive to the short wavelengths (blue and green) of the visible spectrum.

What this means is that there is clearly an established physiological mechanism through which colour and light can affect mood, heart rate, alertness, and impulsivity, to name but a few.

For example, this non-image-forming visual pathway to the hypothalmus is believed to be involved in seasonal affective disorder, a mood disorder that affects some people during the darker winter months that can be successfully treated by exposure to light in the morning.

Similarly, there is published data that show that exposure to bright, short-wavelength light a couple of hours prior to normal bedtime can increase alertness and subsequently affect sleep quality.

Poor quality sleep is becoming increasingly prevalent in modern society and is linked with increased risk factors for obesity, diabetes and heart disease.

There is some concern that the excessive use of smartphones and tablets in the late evening can affect sleep quality, because they emit substantial amounts of blue/green light at the wavelengths that inhibit the release of melatonin, and so prevent us from becoming drowsy.

That's one effect of blue/green light, but there is much more research to be done in order to back the many claims made for other colours.

Experiencing colour

I lead the Experience Design research group at the University of Leeds where we have a lighting laboratory especially designed to evaluate the effect of light on human behaviour and psychology.

The lighting system is unique in the UK in that it can flood a room with coloured light of any specific wavelengths (other coloured lighting usually uses a crude mixture of red, green and blue light).

Stephen Westland

Recent research by the group has found a small effect of coloured light on heart rate and blood pressure: red light does seem to raise heart rate, while blue light lowers it. The effect is small but has been corroborated in a 2015 paper by a group in Australia.

In 2009 blue lights were installed at the end of platforms on Tokyo's Yamanote railway line to reduce the incidence of suicide.

As a result of the success of these lights (suicides fell by 74 percent at stations where the blue lights were installed), similar coloured lighting has been installed at Gatwick Airport train platforms.

These steps were taken based on the claim that blue light could make people less impulsive and more calm, but there is little scientific evidence yet to support these claims: a three-year study (forthcoming) by Nicholas Ciccone, a PhD researcher in our group, found inconclusive evidence for the effect of coloured lighting on impulsivity.

Similar studies are underway in our laboratories to explore the effect of colour on creativity, student learning in the classroom, and sleep quality.

It is clear that light, and colour specifically, can affect us in ways that go far beyond regular colour vision.

The discovery of the non-image-forming visual pathway has given a new impetus to research that explores how we respond, both physiologically and psychologically, to colour around us.

The increasing availability and use of coloured lighting that has resulted from advances in LED technology has added to the need to carry out rigorous research in this field, but it is becoming increasingly difficult to separate claims for the effects of colour that are supported by data, from those that are based on intuition or tradition.

Stephen Westland, Professor, Chair of Colour Science and Technology, University of Leeds.

This article was originally published on The Conversation. Read the original article.


Novelty and the Brain: Why New Things Make Us Feel So Good

We all like shiny new things, whether it's a new gadget, new city, or new job. In fact, our brains are made to be attracted to novelty—and it turns out that it could actually improve our memory and learning capacity. The team at social sharing app Buffer explains how.

Having just moved to a new country, I’m currently surrounded by novel sights, sounds, and experiences. It’s an overload of new for my brain. However, after only being here a week, I’m surprised how ordinary my house and my street seem. After walking the same route to the train station three or four times, it quickly became boring. How quickly novelty can disappear as we become familiar with the things around us, and yet how completely stimulated we become when we find yet another brand new experience to have or sight to see.

It turns out, this isn’t just because I’m part of a generation of compulsive email checkers or internet addicts, or because I don’t appreciate life enough. It’s actually hardwired into my brain —and yours—to appreciate and seek out novelty.

How We Find Novelty

Anything that’s new, different or unusual is bound to catch our eye. A new phone, a new working environment, a new friend. Changing our hair color, wearing new clothes, visiting a new place. In fact, we can even be drawn to novelty without being conscious of it. Of course, this makes a lot of sense—we wouldn’t get much done if ordinary things captivated us constantly.

The cool thing about this is how intricately novelty seems to be associated with learning , which means we can use this knowledge to our advantage for learning new things and improving our memory.

How the Brain Handles Novelty

There’s a region in our midbrain called the substantia nigra/ventral segmental area or SN/VTA. This is essentially the major “novelty center” of the brain, which responds to novel stimuli. The SN/VTA is closely linked to areas of the brain called the hippocampus and the amygdala, both of which play large roles in learning and memory. The hippocampus compares stimuli against existing memories, while the amygdala responds to emotional stimuli and strengthens associated long-term memories.

It’s been thought before that novelty was a reward in itself, but, like dopamine, it seems to be more related to motivation. Researchers Bunzeck and Düzel tested people with an “oddball” experiment that used fMRI imaging to see how their brains reacted to novelty. They showed the subjects images such as indoor and outdoor scenes and faces with occasional novel images (oddballs) thrown in.

The experiment found that the SN/VTA was activated by novel images—that is, brand new images that hadn’t been seen before. Images that only slightly deviated from more familiar ones didn’t have the same effect, and neither did images with strongly negative emotional context such as car crashes or angry faces. The Dopamine pathways, which are activated when we are exposed to novelty, look something like this (highlighted in blue):

A second part of the experiment was designed to test whether relative novelty or absolute novelty was required for the SN/VTA to activate. Images that were slightly more novel to the subject than others (relative novelty) were tested, as were images that were completely novel compared to others (absolute novelty).

The SN/VTA only activated when shown absolutely novel stimuli —images that had never been seen before. Other related areas of the brain still reacted to the images, but the reactions decreased slightly with each showing as they became more familiar. Dr Düzel explained it like this:

“We thought that less familiar information would stand out as being significant when mixed with well-learnt, very familiar information and so activate the midbrain region just as strongly as absolutely new information. That was not the case. Only completely new things cause strong activity in the midbrain area.”

This is similar to what might happen during repetition of flash cards or educational material. Only the completely new information stands out among a group of overly familiar objects or images.

How Novelty Motivates Us

You’ve probably heard about dopamine before, and its effects on the brain. It’s often touted as a "reward chemical" or part of the brain’s "reward center," but more recent research has shown that, like novelty, it’s actually more closely related to our motivation to seek rewards rather than being a reward itself. Animal studies around the brain’s reaction to novelty have suggested increased dopamine levels in the context of novelty. So the brain reacts to novelty by releasing dopamine which makes us want to go exploring in search of a reward.

You might remember how a new level or world to explore in a video game motivates you to play for longer, in the hopes of the reward of unlocking an achievement or gaining more points. Each new stimuli gives you a little rush of motivation to explore, because it makes you anticipate a reward. Here's a graph that shows activity in your brain on this:

Dr Düzel said this about how novelty motivates us:

“When we see something new, we see it has a potential for rewarding us in some way. This potential that lies in new things motivates us to explore our environment for rewards. The brain learns that the stimulus, once familiar, has no reward associated with it and so it loses its potential. For this reason, only completely new objects activate the midbrain area and increase our levels of dopamine.”

What This Means for Learning

This is pretty interesting stuff, but it’s only useful if we can take something away from it to apply to our own lives. Unfortunately the human studies on this subject, such as the one mentioned above, are few and far between at this stage. More studies have been completed on animals, but the research is still in early stages. This doesn’t mean we can’t learn from it though. Here’s what it means for those of us who want to improve our learning and knowledge retention.

Remember how I said the hippocampus is closely tied to the SN/VTA? Well these animal studies also showed that the plasticity of the hippocampus (the ability to create new connections between neurons) was increased by the influence of novelty—both during the process of exploring a novel environment or stimuli and for 15–30 minutes afterwards.

As well as increasing our brain’s plasticity—and therefore potential for learning new concepts and facts—novelty has been shown to improve the memory of test subjects :

"Separate behavioural experiments were also conducted without the use of a scanner to test the subjects’ memory. Their memory of the novel, familiar and very familiar images they had studied was tested after 20 minutes and then a day later. Subjects performed best in these tests when new information was combined with familiar information during learning. After a 20 minute delay, subjects’ memory for slightly familiar information was boosted by 19 per cent if it had been mixed with new facts during learning sessions."

This information could help boost students’ performance both during classes and in exams, as well as helping those who suffer from memory loss. Dr Düzel pointed out the possible medical benefits that could come from this research:

We hope that these findings will have an impact on behavioural treatments for patients with poor memory. Current practice by behavioural psychologists aims to improve memory through repeatedly exposing a person to information – just as we do when we revise for an exam. This study shows that revising is more effective if you mix new facts in with the old. You actually learn better, even though your brain is also tied up with new information."

How You Can Learn More and Improve Memory

If you want to start putting these findings to work, you can improve your knowledge retention and make new ideas and concepts stick by introducing novelty into your learning process. Here are some ideas to get you started:

Add Something New

Each time you review information or facts that you’ve learned before, add in a small number of new ones. This will make your brain notice and recognize slightly-familiar information more easily because it’s offset by brand new concepts.

Change Your Environment

Your environment can offer a huge amount of novel stimuli for your brain. Try offsetting the familiarity of learning material by reviewing it in new settings. On top of this, changing temperature or lighting in the room you are already in can make a big difference.

Learn After Doing Something New

Use your brain’s increased plasticity wisely by setting aside time to learn right after taking in novel stimuli. If you meet someone new for coffee or explore a new place, your brain will be more open to making new connections during and right after this time, so you might as well take advantage.

Belle Beth Cooper has spent the past four years as a freelance writer and social media consultant. She's written for The Next Web, Desktop Magazine, and Social Media Examiner. She now spends her days wielding a pencil as Attendly's head of content.

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DISCUSSION

"You might remember how a new level or world to explore in a video game motivates you to play for longer, in the hopes of the reward of unlocking an achievement or gaining more points."

As a gamer, that was my first thought when I started reading the article. In addition to what you pointed out, this search for novelty has also got me playing more new games rather than playing the same ole over and over. I used to be obsessed with multiplayer, but exploring new worlds and seeing how developers design their gameplay and write their stories have been appealing to me more and more.

One other thing I would point out is those of us who are more driven towards novelty can find certain things at work/school to be, um, challenging. Your tip to "add something new" perfectly describes how I approach things. Luckily my environment and the people around me allow me to do that 95% of the time. There are though some instances where sticking with the same ole is expected, and that's where I sometimes "waste" time because I try new techniques or add new data points even though they may not be necessary (they help me to learn for sure, but they don't really benefit the end users so that's why I think that time is "wasted").


COVID-19 can affect the brain. New clues hint at how

COVID-19 can come with brain-related problems, but just how the virus exerts its effects isn’t clear.

Roxana Wegner/Moment/Getty Images

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For more than a year now, scientists have been racing to understand how the mysterious new virus that causes COVID-19 damages not only our bodies, but also our brains.

Early in the pandemic, some infected people noticed a curious symptom: the loss of smell. Reports of other brain-related symptoms followed: headaches, confusion, hallucinations and delirium. Some infections were accompanied by depression, anxiety and sleep problems.

Recent studies suggest that leaky blood vessels and inflammation are somehow involved in these symptoms. But many basic questions remain unanswered about the virus, which has infected more than 145 million people worldwide. Researchers are still trying to figure out how many people experience these psychiatric or neurological problems, who is most at risk, and how long such symptoms might last. And details remain unclear about how the pandemic-causing virus, called SARS-CoV-2, exerts its effects.

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“We still haven’t established what this virus does in the brain,” says Elyse Singer, a neurologist at the University of California, Los Angeles. There are probably many answers, she says. “It’s going to take us years to tease this apart.”

Getting the numbers

For now, some scientists are focusing on the basics, including how many people experience these sorts of brain-related problems after COVID-19.

A recent study of electronic health records reported an alarming answer: In the six months after an infection, one in three people had experienced a psychiatric or neurological diagnosis. That result, published April 6 in Lancet Psychiatry, came from the health records of more than 236,000 COVID-19 survivors. Researchers counted diagnoses of 14 disorders, ranging from mental illnesses such as anxiety or depression to neurological events such as strokes or brain bleeds, in the six months after COVID-19 infection.

“We didn’t expect it to be such a high number,” says study coauthor Maxime Taquet of the University of Oxford in England. One in three “might sound scary,” he says. But it’s not clear whether the virus itself causes these disorders directly.

The vast majority of those diagnoses were depression and anxiety, “disorders that are extremely common in the general population already,” points out Jonathan Rogers, a psychiatrist at University College London. What’s more, depression and anxiety are on the rise among everyone during the pandemic, not just people infected with the virus.

Mental health disorders are “extremely important things to address,” says Allison Navis, a neurologist at the post-COVID clinic at Icahn School of Medicine at Mount Sinai in New York City. “But they’re very different than a stroke or dementia,” she says.

About 1 in 50 people with COVID-19 had a stroke, Taquet and colleagues found. Among people with severe infections that came with delirium or other altered mental states, though, the incidence was much higher — 1 in 11 had strokes.

Serious neurological damage, such as these strokes caused by blocked blood vessels, turn up in people with COVID-19. K. Thakur et al/Brain 2021

Taquet’s study comes with caveats. It was a look back at diagnosis codes, often entered by hurried clinicians. Those aren’t always reliable. And the study finds a relationship, but can’t conclude that COVID-19 caused any of the diagnoses. Still, the results hint at how COVID-19 affects the brain.

Blood vessels scrutinized

Early on in the pandemic, the loss of smell suggested that the virus might be able to attack nerve cells directly. Perhaps SARS-CoV-2 could breach the skull by climbing along the olfactory nerve, which carries smells from the nose directly to the brain, some researchers thought.

That frightening scenario doesn’t seem to happen much. Most studies so far have failed to turn up much virus in the brain, if any, says Avindra Nath, a neurologist who studies central nervous system infections at the National Institutes of Health in Bethesda, Md. Nath and his colleagues expected to see signs of the virus in brains of people with COVID-19 but didn’t find it. “I kept telling our folks, ‘Let’s go look again,’” Nath says.

That absence suggests that the virus is affecting the brain in other ways, possibly involving blood vessels. So Nath and his team scanned blood vessels in post-mortem brains of people who had been infected with the virus with an MRI machine so powerful that it’s not approved for clinical use in living people. “We were able to look at the blood vessels in a way that nobody could,” he says.

Damage abounded, the team reported February 4 in the New England Journal of Medicine. Small clots sat in blood vessels. The walls of some vessels were unusually thick and inflamed. And blood was leaking out of the vessels into the surrounding brain tissue. “You can see all three things happening at the same time,” Nath says.

Those results suggest that clots, inflamed linings and leaks in the barriers that normally keep blood and other harmful substances out of the brain may all contribute to COVID-related brain damage.

Signs of damage in the brains of people with COVID-19 involve inflammation, including these immune cells around a blood vessel (left), and changes in cells (right) that might have resulted from low oxygen. J. Lou et al/Free Neuropathology 2021

But several unknowns prevent any definite conclusions about how these damaged blood vessels relate to people’s symptoms or outcomes. There’s not much clinical information available about the people in Nath’s study. Some likely died from causes other than COVID-19, and no one knows how the virus would have affected them had they not died.

Inflamed body and brain

Inflammation in the body can cause trouble in the brain, too, says Maura Boldrini, a psychiatrist at Columbia University in New York. Inflammatory signals released after injury can change the way the brain makes and uses chemical signaling molecules, called neurotransmitters, that help nerve cells communicate. Key communication molecules such as serotonin, norepinephrine and dopamine can get scrambled when there’s lots of inflammation.

Neural messages can get interrupted in people who suffer traumatic brain injuries, for example researchers have found a relationship between inflammation and mental illness in football players and others who experienced hits to the head.

Similar evidence comes from people with depression, says Emily Troyer, a psychiatrist at the University of California, San Diego. Some people with depression have high levels of inflammation, studies have found. “We don’t actually know that that’s going on in COVID,” she cautions. “We just know that COVID causes inflammation, and inflammation has the potential to disrupt neurotransmission, particularly in the case of depression.”

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Among the cells that release inflammatory proteins in the brain are microglia, the brain’s version of the body’s disease-fighting immune system. Microglia may also be involved in the brain’s response to COVID-19. Microglia primed for action were found in about 43 percent of 184 COVID-19 patients, Singer and others reported in a review published February 4 in Free Neuropathology. Similar results come from a series of autopsies of COVID-19 patients’ brains 34 of 41 brains contained activated microglia, researchers from Columbia University Irving Medical Center and New York Presbyterian Hospital reported April 15 in Brain.

With these findings, it’s not clear that SARS-CoV-2 affects people’s brains differently from other viruses, says Navis. In her post–COVID-19 clinic at Mount Sinai, she sees patients with fatigue, headaches, numbness and dizziness — symptoms that are known to follow other viral infections, too. “I’m hesitant to say this is unique to COVID,” Navis says. “We’re just not used to seeing so many people getting one specific infection, or knowing what the viral infection is.”

Teasing apart all the ways the brain can suffer amid this pandemic, and how that affects any given person, is impossible. Depression and anxiety are on the rise, surveys suggest. That rise might be especially sharp in people who endured stressful diagnoses, illnesses and isolation.

In a postmortem brain from a person with COVID-19, a clotting protein called fibrinogen (red) indicates that the blood vessels are damaged and leaky. Avindra Nath

Just being in an intensive care unit can lead to confusion. Delirium affected 606 of 821 people — 74 percent — while patients were in intensive care units for respiratory failure and other serious emergencies, a 2013 study found. Post-traumatic stress disorder afflicted about a third of people who had been seriously sick with COVID-19 (SN: 3/12/21).

More specific aspects of treatment matter too. COVID-19 patients who spent long periods of time on their stomachs might have lingering nerve pain, not because the virus attacked the nerve, but because the prone position compressed the nerves. And people might feel mentally fuzzy, not because of the virus itself, but because a shortage of the anesthetic drug, propofol, meant they received an alternative sedative that can bring more aftereffects, says Rogers, the psychiatrist at University College London.

Lingering questions — what the virus actually does to the brain, who will suffer the most, and for how long — are still unanswered, and probably won’t be for a long time. The varied and damaging effects of lockdowns, the imprecision doctors and patients use for describing symptoms (such as the nonmedical term “brain fog”) and the indirect effects the virus can have on the brain all merge, creating a devilishly complex puzzle.

For now, doctors are busy focusing on ways in which they can help, even amid these mysteries, and designing larger, longer studies to better understand the effects of the virus on the brain. That information will be key to helping people move forward. “This isn’t going to be over soon, unfortunately,” Troyer says.

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How Dopamine Works

Chances are that you've heard of the neurotransmitter dopamine, which seems to get as much sensational media coverage as many Hollywood celebrities. In scores of articles on the internet, dopamine is depicted as the secret sauce for human misbehavior — the thing that supposedly causes us to crave everything from sex to chocolate to betting money we can't afford to lose in blackjack. If you believe the hype, it's also what makes us check Facebook every 20 minutes and sit on the couch for hours killing zombies in a video game. Dopamine is often linked with addiction, alcoholism, sexual lust, compulsive behavior and dangerous risk-taking.

As the British science journalist Vaughn Bell once complained, the mere mention of dopamine tends to make something sound like a scientifically proven vice."If you disagree with something, just say it releases dopamine and imply it must be dangerously addictive," he wrote, calling dopamine the Kim Kardashian of neurotransmitters, for its "instant appeal to listless reporting."

In truth, though, dopamine is simply a chemical that enables signals to pass through synapses, the spaces between neurons. By doing that, it enables networks composed of vast numbers of neurons to do their jobs [source: Brookshire]. All of this is actually much more complicated, which we'll get into later.

So why does dopamine have such a scandalous reputation? It's because dopamine signaling is a key player in the brain's reward system, which influences us to do things that feel pleasurable, and to do them over and over. But that's only one of the numerous functions that dopamine performs in our bodies. It's also vital for important processes such as motor control, learning and memory. Malfunctions in the wiring that uses dopamine seems to play a role in numerous disorders, including Parkinson's and schizophrenia [source: Jiang].

In this article we'll explain what dopamine is and how it works in our brains and bodies. We'll also explain what dopamine isn't, and try to dispel some of the myths that have arisen around the chemical.

As we previously explained, dopamine is one of more than 100 chemicals known as neurotransmitters, which enable neurons in the brain to communicate with one another and manage everything that happens in our body [source: Purves et al.].

Like all neurotransmitters, dopamine goes through a cycle, which begins with it being synthesized by a neuron (called the presynaptic cell). That cell releases the dopamine and it floats out into the synapse, the gap between neurons, and then makes contact and binds with structures called receptors on the other neuron, which then transmit the signal to the second neuron. After the dopamine accomplishes its mission, it's rapidly removed and degrades. The effects of dopamine on your brain depend a lot on which neurons are involved and which receptors are binding the dopamine [sources: Brookshire, Purves et al.].

As molecules go, dopamine is fairly compact, consisting of just 22 atoms. Only a tiny portion of the brain's 100 billion or so neurons — as few as 20,000 — generate dopamine, most of them in midbrain structures such as the substantia nigra, which helps control movement, and the prefrontal cortex [sources: Angier, Deans].

Those specialized neurons make dopamine by taking an amino aside called tyrosine and combining it with an enzyme, tyrosine hydroxylase. Add another step to the chemical reaction and you would get a different neurotransmitter, norepinephrine [source: Deans].

In terms of evolutionary history, dopamine has been around for a long time, and it's found in animals from lizards to humans. But people have a lot of dopamine and over time, we seem to have evolved to produce more and more of it, possibly because it helps enable us to be aggressive and competitive. As evolutionary psychiatrist Emily Deans wrote in 2011, "dopamine is what made humans so successful." Researchers have found that humans have about three times as many dopamine-producing neurons as other primates [source: Parkin].

Massachusetts Institute of Technology researchers have developed tiny probes — just 10 microns in diameter — that can be implanted in animal brains to track dopamine. Because they're so small, they don't cause scar tissue to form, and can function for more than a year [source: Trafton].

How Does Dopamine Work in the Human Body?

Dopamine's function at the most basic level is to enable signals to pass through synapses from one neuron to another. But that's the high-level view. Up closer, the networks that use dopamine are composed of vast numbers of neurons, and the effects of releasing dopamine can vary, depending upon what types of neurons are involved and which of the five different types of receptors are using the dopamine to connect the neurons. The particular role the neurons are playing can also be a factor [source: Brookshire].

Dopamine's effects depend upon which of the four pathways is used in the brain and body where it's working to facilitate communication. The first is the nigrostriatal tract, which has to do with motor control in the body. When neurons in that system stop working, it can lead to disorders such as Parkinson's.

Another is the mesocortical pathway, which runs from the ventral tegmental area to the dorsolateral frontal cortex in the brain. It's the pathway associated with planning, prioritizing, responsibility and other executive function activities.

There's also the tuberinfundibular pathway, which connects the hypothalamus and the pituitary gland, and blocks the secretion of milk in the female breast. Blocking this pathway of dopamine enables breastfeeding.

Finally, there's the mesolimbic pathway, which is connected to the brain's limbic system, which controls reward and emotion, and includes the hippocampus and the medial frontal cortex. That's the pathway that gets the most attention, since it's connected with problems such as addiction[source: Deans].

Dopamine plays a role in kidney and heart function, nausea and even psychosis. Many treatments for schizophrenia target dopamine [source: Brookshire].

Until recently, not much was known about the precise mechanisms by which neurons use dopamine. It was thought that it mostly took place through something called volume transmission, in which dopamine spread slowly and nonspecifically across large areas of the brain, and in the process happened to make the right contacts with the certain neurons. But in 2018, Harvard University medical researchers published a paper revealing that specialized sites on those cells release dopamine in an extremely fast —think milliseconds — and precise manner to target sites [source: Jiang].

But all that probably seems ho-hum to you, so in the next section, let's get back to the role of dopamine in the brain's reward system and in pleasure.

How is Dopamine Related to Pleasure?

The earliest experiments involving dopamine function were performed back in the 1950s and 1960s by a researcher named James Olds, who discovered that when rats' brains received a jolt of electrical stimulation in a certain area, they'd keep performing an action such a yanking a lever over and over [source: Chen].

Because dopamine played a role in transmitting the signals, scientists initially suspected that it had something to do with pleasure. People with clinical depression tend to have low levels of dopamine in their brains, which led researchers to hypothesize that low levels of dopamine caused a person to experience less pleasure.

That idea keeps bouncing around in the popular media, because it seems to make good sense. But by the late 1980s, it had been disproven by research. In experiments, animals whose dopamine cells were killed off by drugs still seemed to enjoy the taste of sugar when it was squirted into their mouths, as evidenced by their facial expressions. But they wouldn't seek out additional tastes of the sugar [source: Chen].

While dopamine doesn't cause pleasure, it does influence how pleasure affects the brain. But there are different views of how it accomplishes that. One school of thought is that dopamine's biggest influence is reinforcing the pleasure, so that the brain develops an expectation of experiencing that outcome from the action [source: Chen]. Research on gamblers, for example, have shown that their brains experience as much dopamine activity when they come close to winning as when they actually win. It's almost as if the chemical is urging them on, telling them that they'll win the next time (even if they didn't last time) [source: Chase and Clark].

Another view is that dopamine simply helps the brain to feel more motivated to do something so that the body feels energetic enough to pull that lever again and again [sources: Chen, Salamone and Correa].

Does Dopamine Play a Role in Addiction?

Dopamine doesn't force someone to stick a needle into his or her arm, smoke meth or take a hit from a crack pipe, nor does it create the pleasure that a drug user experiences from getting high. But dopamine does play a role in drug abuse and addiction, by reinforcing the effects of using those drugs.

When a person gets high, it causes a surge in production of dopamine in the neurons in the striatum, including the nucleus accumbens, structures that are part of the brain's reward network. That increase in the chemical enables neurons to make more connections, and plays an important role in programming the brain to connect drugs with pleasure, so that it develops an expectation of a reward and motivation to take them again [source: Volkow, Fowler and Wang, et al.].

"Large surges of dopamine teach the brain to seek drugs at the expense of other, healthier goals and activities," warns an article on the National Institute on Drug Abuse's website.

But while dopamine increases when someone uses certain drugs, not everybody who experiences that surge necessarily becomes an addict. Instead, scientists believe, dopamine acts in combination with a range of other genetic, developmental and/or environmental influences to program some people's brains to develop a compulsion to take those drugs. Imaging studies, for example, have found that people who turn into addicts may already have differences in their dopamine circuitry that make them more vulnerable to getting hooked [source: Volkow, Fowler and Wang, et al.].

The dopamine produced from using drugs is much more intense and long-lasting than the dopamine response from something like eating or another normal activity. Also unlike eating, the dopamine response from drugs doesn't stop when the act is over. The overflow of dopamine is what produces the high.

When an addict uses drugs repeatedly, his or her brain changes in response. It tries to compensate for the surge in dopamine production by shutting down some of its dopamine receptors. But that only exacerbates the situation. The brain is still programmed to want the pleasure that the drugs created, so an addict has to use more and more of the drug to replicate the effect. Additionally, shutting down dopamine receptors reduces the amount of pleasure that an addict gets from any activity, not just taking drugs — a condition called anhedonia. That also may drive a person to shoot up more heroin or smoke more and more meth, because nothing else feels good anymore.

Finally, having fewer dopamine receptors is associated with an increase in impulsivity, which may lead an addict to engage in increasingly reckless behavior in pursuit of a high [source: Butler Center].

In a 2017 New York Times essay, two psychology professors noted that while pleasurable activities stimulate dopamine production, the amount released varies tremendously according to the activity. Playing a video game, they said, releases as much dopamine as eating a slice of pizza, while using a drug such as meth causes 10 times as much to be released. They cited a study published in American Journal of Psychiatry, which found that at most, 1 percent of video game players could exhibit characteristics of addiction [source: Ferguson and Markey].


Cognition is central to drug addiction

Recent research shows that drug abuse alters cognitive activities such as decision-making and inhibition, likely setting the stage for addiction and relapse.

Most substance abuse researchers once believed that drug abuse and addiction are best explained by drugs' reinforcing effects. Pharmacological studies have long supported that view, showing that drugs of abuse powerfully affect the brain's dopamine system, which regulates emotional responses and plays a part in abuse by providing an emotional "reward" for continued use.

Increasingly, however, scientists are learning that the story is more complicated. Brain-imaging studies in humans and neuropsychological studies in nonhuman animals have shown that repeated drug use causes disruptions in the brain's highly evolved frontal cortex, which regulates cognitive activities such as decision-making, response inhibition, planning and memory.

"We now know that many of the drugs of abuse target not just those aspects of the brain that alter things like emotion, but also areas that affect our ability to control cognitive operations," says Herb Weingartner, PhD, of the Division of Neuroscience and Behavioral Research at the National Institute on Drug Abuse (NIDA).

The new findings hold promise for better understanding why only some drug users become addicted, why drug abusers so easily relapse even after long periods of drug abstinence and, ultimately, how prevention and treatment efforts can be tailored to people's individual vulnerabilities.

"In the past few years, people have begun to recognize that drug abuse is not a pharmacological disease--it's a pharmacological and behavioral disease," says Elliot A. Stein, PhD, a neuroscientist at the Medical College of Wisconsin. "The cognitive functions that sit in the frontal lobes play a role in drug abuse."

For treatment, he believes, that may suggest that it will be difficult to find a "magic bullet" to attack both the pharmacological and the behavioral parts of addiction.

Shifting tide

Since the 1980s, scientists have observed that many people who were addicted to drugs such as cocaine and marijuana appeared to have frontal cortex abnormalities. Such abnormalities, however, were long thought to be incidental side effects of drug abuse, explains Steven Grant, PhD, a program officer in NIDA's Division of Treatment Research and Development.

"We typically haven't thought of the influence of those processes on substance abuse and addiction," he says, "because we have been so focused on the role of reinforcement and the hedonic effects of drugs as being the driving force in drug abuse. That has been the dominant paradigm for the last two decades."

In the past five years, however, the tide has begun to turn. At a 1992 scientific conference, University of Iowa neuroscientist Antoine Bechara, PhD, described research showing that patients with frontal cortex damage had impaired decision-making abilities, reflected in their performance on a laboratory gambling task.

Grant saw Bechara's presentation and made the connection to drug abuse, hypothesizing that disruptions in the frontal cortex might be responsible for impaired decision-making and behavioral inhibition in drug abusers--and that that could help explain the compulsive drug-seeking that is a hallmark of addiction.

Using Bechara's gambling task, Grant and his colleagues tested drug abusers' decision-making abilities. Last year, they reported in the journal Neuropsychologia (Vol. 38, No. 8) that drug abusers indeed made poorer decisions on the gambling task than did participants in a control group.

More recently, Bechara and his colleagues uncovered three subgroups of drug abusers. About one-third, they found, showed no decision-making impairment on the gambling task. About 25 percent, in contrast, responded exactly as patients with frontal lobe damage have been shown to do, almost invariably choosing a higher immediate reward even knowing that their strategy would be unprofitable in the long run. Finally, about 40 percent of Bechara's study participants appeared to be hypersensitive to potential rewards--no matter whether they were immediate or long-term.

Bechara suggests that these differences in decision-making impairment reflect different vulnerabilities to drug addiction. If so, he argues, they may help shed light on treatment strategies. Drug users who show no decision-making impairment may be at least risk for becoming addicted and may be able to stop if they want to, he suggests. In contrast, he says, for those with severe decision-making impairments, "There's probably nothing you can do. You can put them in jail, but in my opinion, they're unlikely to respond."

Finally, Bechara argues, for drug users who are sensitive to both the short- and long-term consequences of drug use, heightening awareness of the negative long-term consequences of abuse may be sufficient to tip the scales and help people quit using drugs.

In other studies, researchers have used two imaging techniques, positron emission tomography and functional magnetic resonance imaging, to measure drug abusers' brain activity during craving.

In 1996, Grant and NIDA colleagues David B. Newlin, PhD, Edythe D. London, PhD, and others reported in the Proceedings of the National Academy of Sciences (Vol. 93) that cocaine craving was linked to heightened activity in areas of the frontal cortex that regulate decision-making and motivation, but not in the brain's dopamine control centers. Those findings have since been replicated and extended in other laboratories.

"Classically, people thought that drug addiction was a disease that involved the centers of pleasure--that people are taking the drug because it's pleasurable," concludes Nora D. Volkow, MD, a research scientist at the U.S. Department of Energy's Brookhaven National Laboratory. "But that's not the case--in fact, addicted people don't have as strong a pleasure response as people who aren't addicted. Recent data are showing us that addiction entails a basic disruption of motivational circuits."

Seeking clues for treatment

Evidence that craving and drug cues can trigger abnormal activity in the frontal cortex--even in the absence of drugs--has led many researchers to believe that this brain area may be especially important in relapse. Grant suggests it may be in the frontal cortex that the residual effects of drugs manifest themselves, long after dopamine effects have disappeared.

"Without a properly functioning frontal cortex," he says, "one may be unable to look beyond drugs' immediate reinforcing or hedonic aspects and consider the long-term consequences of drug use."

Bechara adds, "I think there are two mechanisms playing in addiction. One is the pharmacological reward process that we've been studying for years. But the other is the behavioral process of controlling your behavior in the face of punishment."

The growing body of research on the roles that the frontal cortex and cognitive processes such as decision making and behavioral inhibition play in addiction raises many questions about treatment:

What is the difference, in the brain, between drug use and addictive drug use?

Do some people have pre-existing, subtle abnormalities in the frontal cortex that make them more vulnerable to drug use? If so, how can such dysfunction be identified and used for early interventions?

What are the long-term brain consequences of drug use? Are they reversible?

How can the recent findings of frontal cortex activation during drug craving be exploited to develop better ways to evaluate treatment effectiveness?

"Right now, the best tool for measuring success of drug treatment is recidivism--does the person show up in the hospital again?" comments Stein. "Compare that with a field like cardiology, where a physician would never release a heart attack patient without a stress test. In drug addiction, we send people out on the street without certainty that the treatment worked."

He hopes that someday, he'll be able to put people in a craving situation and measure their brain responses. "That," he says, "will help us know if the intervention blunted the craving response."


Dopamine – The Happy Brain Chemical

Unfortunately, too many who have read the research on the teenage brain come to quick conclusions about adolescents often fueling misperceptions of teenagers as irrational loose cannons who can’t be trusted with anything. It turns out though that young people are making choices influenced by a very different set of chemical influences than their adult counterparts. For starters, the teenage brain appears to be more sensitive to the effects of a neurotransmitter called dopamine. I like to think of neurotransmitters as “molecules of emotion” because their levels in our brain have a lot to do with our mood. Dopamine is the “happy” neurotransmitter. The more dopamine is circulating in our brains the happier we feel. The growth of more dopamine receptors during adolescence as well as an enhanced dopamine supply provides a rush that adults just don’t feel when engaged in the same activity. There is even some evidence that baseline levels of dopamine are lower during this time but the release is more intense, which could cause craving of dopamine-inducing experiences—like skateboarding behind a moving vehicle.

This hopped up reward system can drown out warning signals about risk. This doesn’t mean that young people don’t stop to think about the consequences or that they “don’t know any better.” Most of the time adolescents know exactly what might happen. It is just that there are times when the reward seems well worth it. So before we write off young people as “irrational,” we would be wise to acknowledge the strategic choices that adolescents often make as they choose between safer or more thrilling adventures. Teenage decisions are not always defined by impulsivity because of lack of brakes, but because of planned and enjoyable pressure to the accelerator.

Skate boarding behind cars isn’t the only thing that activates the reward system in the teenage brain. There are lots of sources of dopamine. Some are negative like alcohol, drugs, and nicotine. Others present a double-edged sword, like peers. Research about risky driving shines a light on the powerful role that peers play in teens decision-making when they are behind the wheel. Evidence is clear that when peers are in the car with a teen driver, they are more likely to get into an accident. The conventional thinking has been that passengers in the car must distract the driver or exert peer pressure for reckless driving, egging their friends through red lights and asking them to gun it on straightaways. Those dynamics might be present at times, of course, but it turns out though that teens drive more recklessly even if their friends do nothing at all. Simply the presence of peers activates young people’s reward systems, amplifying the surge of dopamine they get as their foot hits the car’s accelerator.


How music affects our psychology and well being

One of the most crucial issues in the psychological effects of music is how music affects the emotional experience. Music can evoke powerful emotions such as chills and thrills amongst the listeners.

Positive emotions are what one feels when listening to music. The reward transmitter dopamine is released when one listens to pleasurable music. The easiest way to alleviate mood or relieve stress is to listen to music. People use music in their everyday lives to regulate, enhance, and diminish undesirable emotional states (e.g., stress, fatigue). How does music listening produce emotions and pleasure in listeners?

#1. Music evokes pleasure

Music enjoyment evokes the same pleasure in our brains as other forms of pleasure such as food, sex and drugs. Listening to music cab be reinforcing and addictive. Music is an aesthetic stimulus which can naturally target the dopamine system of the brain.

#2. Anticipation

Music is pleasurable. It may fulfil or violate expectations but is still considered pleasurable. The more unexpected the events in music, the more surprising is the musical experience. We appreciate music that is less predictable and slightly more complex.

#3. Refined emotions

Appreciation of music also involves an intellectual component. The dopamine systems do not work in isolation, and their influence will be largely dependent on their interaction with other regions of the brain. That is, our ability to enjoy music can be seen as the outcome of our human emotional brain and its more recently evolved neocortex. Evidence shows that people who consistently respond emotionally to aesthetic musical stimuli possess stronger white matter connectivity between their auditory cortex and the areas associated with emotional processing, which means the two areas communicate more efficiently.

#4. Memories

Memories are one of the most vital ways in which musical events evoke emotions. According to a late physician, Oliver Sacks musical emotions and musical memory can survive long after other forms of memory have disappeared. Part of the reason for the durable power of music appears to be that listening to music engages many parts of the brain, triggering connections and creating associations.

#5. Tendency towards action

Music often creates strong action tendencies to move in coordination with the music (e.g., dancing, foot-tapping). Our internal rhythms (e.g., heart rate) speed up or slow down to become one with the music. We float and move with the music.

#6. Mimicry of emotions

Music doesn’t only evoke emotions at the individual level, but also at the interpersonal and intergroup level. Listeners mirror their reactions to what the music expresses, such as sadness from sad music, or cheer from happy music. Similarly, ambient music affects shoppers’ and diners’ moods.

#7. Influence on consumer behaviour

Background music has a surprisingly strong influence on consumer behaviour. For example, one study exposed customers in a supermarket drinks section to either French music or German music. The results showed that French wine outsold German wine when French music was played, whereas German wine outsold French wine when German music was played.

#8. Regulation of mood

People crave ‘escapism’ during uncertain times to avoid their woes and troubles. Music offers a resource for emotional regulation People use music to achieve various goals, such as to energize, maintain focus on a task, and reduce boredom. For instance, sad music enables the listener to disengage from the distressing situations (breakup, death, etc.), and focus instead on the beauty of the music. Further, lyrics that resonate with the listener’s personal experience can give voice to feelings or experiences that one might not be able to express oneself.

#9. Perception of time

Music is a powerful emotional stimulus that changes our relationship with time. Time does indeed seem to fly when listening to pleasant music. Music is therefore used in waiting rooms to reduce the subjective duration of time spent waiting and in supermarkets to encourage people to stay for longer and buy more. Hearing pleasant music seems to divert attention away from time processing. Moreover, this attention-related shortening effect appears to be greater in the case of calm music with a slow tempo.

#10. Development of identity

Music can be a powerful tool for identity development. Young people derive a sense of identity from music.

Listening to music can be entertaining, and some research suggests that it might even make you healthier. Music can be a source of pleasure and contentment, but there are many other psychological benefits as well. Music can relax the mind, energize the body, and even help people better manage pain.

The notion that music can influence your thoughts, feelings, and behaviours probably does not come as much of a surprise. If you’ve ever felt pumped up while listening to your favourite fast-paced rock anthem or been moved to tears by a tender live performance, then you easily understand the power of music to impact moods and even inspire action. The psychological effects of music can be powerful and wide-ranging.


How to Increase Dopamine

There are a wide variety of activities that boost dopamine levels in the brain, but not all of them contribute to long-term health. Taking part in behaviors that increase dopamine while improving your health can contribute to the formation of good habits and boost your mood. Some ways to get a natural increase in dopamine include:

  • Consume probiotics: Whether taken in supplement form or by eating probiotic rich foods such as yogurt and fermented foods, probiotics have been shown to support dopamine production.
  • Sleep: Getting enough sleep each night is one of the best ways to keep your dopamine at a healthy level. One night without sleep has actually been shown to increase dopamine in the short-term. However, the increase in dopamine caused by long-term sleep deprivation could cause dopamine receptors to become less sensitive to dopamine, making it difficult for a person to feel awake.
  • Spend time in the sun: Sunlight facilitates the body’s production of vitamin D. Vitamin D, in turn, can help increase dopamine production.
  • Exercise: In addition to endorphins, exercise can increase dopamine levels, contributing to the mood improvement that often comes with physical activity.
  • Listen to music: Multiple studies have shown that listening to music you like causes dopamine to be released in the brain.
  • Avoid sugary foods and junk food: Eating foods that release large amounts of dopamine (which are often high in sugar and fat) can have a desensitizing effect over time. Sticking to whole foods ensures the body’s dopamine receptors don’t become overpowered, thereby creating the need for foods that stimulate the release of more dopamine.

Dopamine and desire

Knockout mice showcase the neurotransmitter's role in motivation.

Neuroscientists are beginning to understand the motivational workings of dopamine--the common neurotransmitter whose absence lowers drive and hurts motor control. Some of the most recent findings come from a team at Seattle's Howard Hughes Medical Institute, whose research suggests that, at least in mice, reward learning is quite possible without dopamine. Such insights may one day help everyone from teachers motivating their students to doctors treating patients with Parkinson's disease to counselors treating drug addiction: Dopamine's reach is that broad.

To reach their finding, the Seattle team used genetically altered knockout mice to tease out the impact of dopamine on subtly different aspects of the motivational system: wanting, liking and learning. By using technology to, in effect, turn off dopamine production and see what happened, they discovered that mice don't need dopamine to connect behavior with rewards or to find the rewards satisfying. The research appears in February's Behavioral Neuroscience (Vol. 119, No. 1).

Neuroscientist Kent Berridge, PhD, of the University of Michigan, says it appears that "dopamine is only needed to use already learned information to generate successful motivated performance." Translation: Dopamine promotes what we think of as "wanting."

By comparing the behavior of mice bred with mutations that inhibit dopamine production with the behavior of normal mice, the Seattle team may have helped clarify dopamine's historically ambiguous role. Especially for diseases linked to dopamine deficiencies, such as Parkinson's and schizophrenia, knowing how and whether one can motivate patients could mean a lot for clinical care.

In addition, "Separating motivation components is a popular and important approach to understanding motivation in the context of addiction," says Mark Kristal, PhD, a behavioral neuroscientist at the University at Buffalo of the State University of New York. In that case, psychologists want to know how to suppress the drug motivation of the addicted.

'What's my motivation?'

From the outside, it's hard to tell what most motivates an animal to seek a reward: the pleasure of the reward itself (roughly, liking), the satisfaction of getting it (wanting), or the acquired association between behavior and reward (learning).

"Wanting and liking are what some philosophers of mind have called 'folk psychological' terms about how the mind is organized," explains Jon Horvitz, PhD, a neuroscientist at Boston College. Although he doubts real brains have clearly demarked scripts for "wanting" or "liking," he says it helps to draw some rough distinctions to enable research into dopamine's behavioral pathway.

The Seattle researchers--graduate student Siobhan Robinson, undergraduate Suzanne Sandstrom, psychologist Victor Denenberg, PhD, and biochemist Richard Palmiter, PhD--chose a knockout approach to get a fair comparison between behavior with and without dopamine. Then, they threw caffeine into the mix to compensate for the motor lethargy but not the cognitive deficits caused by low dopamine.

Dopamine appears to be involved both in goal-directed and motor behavior. On the inside, dopamine-producing neurons extend into neighboring motivational and motor parts of the brain. And on the outside, when scientists block dopamine release, rewards such as food, sex and cocaine stop reinforcing behavior. But what does this mean: Do we stop liking them? Wanting them? Or learning that they're good? Once scientists know, they might be able to devise better therapeutic manipulations using dopamine or to design interventions that bypass the dopamine system.

Genetic engineering, says Berridge, author of a same-issue commentary on the study, "gives a completely independent way of asking the question" because experimenters can control--in a clean, noninvasive way--the relevant aspect of a subject's physiology. In knockout breeding, scientists remove or "knock out" a specific gene in an embryonic stem cell before it divides into many new different types of cells. When the resulting animal breeds, it passes down altered genes. Rodents breed so quickly that in short order, scientists can use genetically altered animals to show what a gene does by virtue of what does or doesn't happen in its absence.

Dopamine-deficient (DD) mice lack the enzyme needed to convert the amino acid tyrosine into levodopa, or L-dopa. Once L-dopa is formed, another enzyme they still have converts L-dopa into dopamine. A shot of L-dopa "rescues" DD mice, which will otherwise perish from starvation. Thus, Robinson explains, "The real beauty of the DD mouse is that the experimenter can control whether dopamine is present in the body by simply giving a shot of L-dopa."

The team's first experiment compared normal mice with lethargic DD mice whose L-dopa shots were converted into dopamine, which got them moving. The scientists trained the mice to run a T-maze with mouse chow at the end of the left or right arm of the upper bar. They compared how eight L-dopa-treated DD mice and nine control mice behaved, reasoning that liking is signaled by how much mice eat, whereas "wanting" is signaled by them chomping down sooner. The learning part comes through efficient running of the maze.

Treated with L-dopa, the knockout mice learned to run the T-maze just like normal mice and ate about as much about as quickly. With dopamine restored, they appeared to like and want the rewards as much as control mice. When the researchers established that DD mice with dopamine perform the task as well as control mice, they had set the stage for the next, more critical experiment. In that, they tested whether mice like, learn about and yearn for rewards without any dopamine in the brain. Would the lab equivalent of a cup of coffee get them going?

The researchers injected 25 DD mice with saline solution, L-dopa or caffeine, the latter of which stimulates locomotor activity through a nondopamine system. Then they measured how fast the mice in each group learned the T-maze. Then the researchers gave all the mice L-dopa and rechecked their learning.

At first the caffeinated DD mice didn't appear to learn much, but in the study's second phase they learned the task much quicker than would typical first-timers. Predictably, the saline-treated DD mice didn't do much of anything in the first phase and had novice learning times in the second one, and the L-dopa treated DD mice maxed out in their learning the first time around.

Thus it appeared that the caffeinated DD mice learned something during the first phase--and they learned it without dopamine. The authors thus conclude that normal reward learning does not depend on dopamine. This finding, coupled with previous findings that wanting does depend on dopamine, creates a fuller picture of motivation.

Still, Kristal cautions, "The mechanism for locomotor and motivational activation with caffeine may be separate from that for dopamine, and caffeine may alter the rate of dopamine metabolism--thereby confounding the results." Berridge agrees that the use of caffeine in DD mice "may muddy the picture a bit."

The plot thickens

New technologies raise new questions. For example, says Berridge, "It's always possible that [in the DD knockout mice], brain development produced some compensation. Maybe these mice have brains that can learn without dopamine." That's why, he says, neuroscientists, including those at the University of Washington lab, are trying to develop "inducible knockouts" in which the mouse could develop normally and then scientists could knock out a gene in later tests. For now, he says the study demonstrates that "brains without dopamine can still learn normally about rewards--at least, if they have caffeine activating them via a separate nondopamine biochemical pathway."

As another example, Kristal notes that the researchers didn't know whether the control mice--littermates with one of the two alleles (gene variations) needed for a functioning gene--behaved the same as normal mice from normal litters. If they behaved differently, that could confound the results and undermine the study's validity.

"Sometimes it almost seems that the correct answer to 'what does dopamine do?' might mostly be 'to confuse neuroscientists,'" says Berridge.

Horvitz adds, "The functional organization of the brain may or may not correspond well to categories such as liking and wanting. I think [the Seattle researchers] mean that dopamine is a player in neural circuitry that serves to vigorously mobilize behavior toward a particular goal object, which in humans, at least, is often accompanied by what we describe as 'wanting.'

"However," he continues, "it's unlikely that a particular neurotransmitter will correspond perfectly to a specific psychological construct such as wanting--or liking for that matter."

Palmiter agrees, saying, "It is very difficult to extrapolate from our studies with mice to humans, especially because our DD mice have much less dopamine than people with even severe Parkinson's disease." However, lead author Siobhan Robinson suggests that, "Perhaps caffeine can be used as a substitute for L-dopa during behavioral therapy with Parkinson's patients. To avoid the motor abnormalities induced by L-dopa during training, patients might learn new tasks without it that they'd be able to perform when on their daily L-dopa regimen."

Palmiter adds that it's also hard to immediately transfer the findings to everyday motivation, because "if dopamine levels were so low that motivation was affected, there would be many other Parkinson's-like symptoms." It is clear that research is needed to more fully understand these results and to begin to think about implications for relapsing drug addition, which is thought to result from over- (not under-) activity of the dopamine system, observe researchers in the area.

Still, Robinson likes to speculate about crafty real-world manipulation of natural dopamine mechanisms. One idea she has: "Designing classroom activities that may increase dopamine signaling, such as unexpected rewards along the way, may enhance the desire to perform well during and after learning. This could lead to better performance of learned tasks."