A biological system requires constant goal seeking to maintain life. If a person reached a state of total satisfaction after achieving a single goal, such as finding a partner or eating, they would lose the drive to continue living. The brain must reset and identify a new objective as soon as one is reached.

If any goal that you achieved, whatever it is, taking a drug, eating a food, getting a partner or whatnot, if that was enough for you, right then you wouldn't keep living. You want that system to keep tracking, and once it gets to one place, you want it to have another place to which it could go. Otherwise you wouldn't live.

Read explains that this tracking mechanism is essential. It ensures that the individual always has a new destination to move toward. This process prevents the cessation of the behaviors necessary for survival.

Dopamine was long thought to be the primary driver of pleasure. The simple explanation was that when dopamine levels rose, a person felt good, and when they dropped, they felt less good. However, research from fields like artificial intelligence has shifted this perspective. It is now understood that dopamine is primarily a learning signal. Fluctuations in its levels, both high and low, serve to control how the nervous system learns from experiences.

Dopamine fluctuations high and low, control learning. It is also playing multiple roles. It plays a role in motivation, and it may also play a role in the way you feel.

Read points out that while dopamine is involved in motivation and feeling, the mechanical connection between these chemical shifts and a person's emotional state is not yet fully understood. It is possible to experience a positive feeling state that does not directly correlate with dopamine being the cause. This suggests that the relationship between brain chemistry and subjective experience is more nuanced than previously believed.

Dopamine plays a fundamental role in how humans and animals learn. While people often associate dopamine with simple reward, it is actually a central player in the algorithms the brain uses to navigate the world. Computational neuroscientists have found a deep connection between dopamine fluctuations and reinforcement learning. This type of learning is found in every mobile creature on the planet. It allows a rodent to learn how to run through a maze or turn left when a light appears. These signals are not just global bursts; they are specific signals found in different parts of the brain that help the organ run its internal procedures.

Dopamine seems to code the difference between expectations before you ever get to the terminal return. It is a fluctuating quantity that tracks your progress toward a goal.

A key concept in this process is the temporal difference error. Read explains this using a weather prediction. If you predict two inches of rain on Saturday, but then update that prediction to ten inches on Thursday, no rain has actually fallen yet. However, your brain experiences a difference between those two expectations. Dopamine encodes these successive shifts in prediction. This is why an animal foraging for food can still learn while wandering, even if it has not found a meal yet. The brain is constantly comparing its current state to its next prediction, allowing it to learn from sequences of events rather than just the final outcome.

The common understanding of reward prediction error often focuses on the difference between what we expect and what we actually receive. This concept suggests that learning happens when there is a mismatch between expectation and reality. However, this model does not reflect reality well because life often involves long stretches of time where nothing happens and no feedback is given. A more accurate way to understand learning is through the difference between successive predictions. This is known as a temporal difference reward prediction error.

The reward prediction error that people talk about dopamine representing is the prediction error that you get for every single step. It is not just expectation and outcome, it is expectation, next expectation, current outcome. And that is what rolls through and that is what we see installed.

This learning algorithm is not unique to humans. Read notes that it is found across the animal kingdom, from the tiny brains of honeybees and sea slugs to the complex systems of the human brain. While dopamine is often the focus in humans, honeybees likely use a different neuromodulator called octopamine to perform similar functions. This mechanism allows a system to learn continuously by updating expectations as it moves through the world, rather than waiting for a final outcome. This same principle was used by researchers at DeepMind to create systems that could master complex games like Go by updating and learning from hundreds of board position changes before the game ended.

Dopamine is often simplified into a model of expectation versus reward. But it is much more interesting than that. It actually updates expectations before a final answer arrives. This process is like foraging. In a real-world scenario like dating, a person collects data over time. They might start with high excitement, then slowly realize a partner is not a good fit. This shifting expectation creates a trajectory that dopamine tracks.

The reality is embedded in this little simple continuous learning update rule. It is called temporal difference reinforcement learning. Expectations are going through their own trajectory and that is what dopamine is coding for.

Read explains that any learning rule should account for a surprising outcome. However, older psychological models did not explain how animals or people chain events together. For example, if a sound predicts a light and a light predicts a reward, humans learn to associate the sound with that reward. This is known as Pavlovian learning. Traditional rules failed to capture this because they did not account for the way expectations evolve.

It won't account for the way animals learn. It won't let you chain events. If I show a light and train on a reward, and I use that expectation outcome learning rule, it won't chain back to something that predicts the light. Suppose a sound predicts the light. People learn they will associate the sound with the outcome.

This insight came from combining theoretical math with biology. Researchers like Sutton and Bartow had written about these rules in the eighties. Read and his colleagues realized that dopamine signaling in the brain matched these mathematical predictions in the early 1990s at the Salk Institute.

The central core of reinforcement learning has stood the test of time. In the 1990s, critics argued that while the models matched biological data, they were not useful for actual learning. Modern technology has proven those critics wrong. The same algorithm describing how dopamine neurons fire is what allowed DeepMind to create AlphaGo Zero. This program was trained from scratch without expert advice and has never been beaten.

That same algorithm is installed in your head. It is installed in the head of a songbird. There are these little gremlins in your brain stem that run that algorithm. They have now been externalized and put into a computer program that now does things that supersede us.

This represents a unique convergence in history. Humans discovered a biological learning rule and wrote it into computer code. We have now created systems that can outperform our own biological minds using our own rules. While dopamine is a major player in this process, it does not work alone. Andrew and Read emphasize that other chemicals like serotonin, acetylcholine, and norepinephrine also contribute to how the brain functions and learns.

The fact that we took biological learning rules and gave them to a computer, and the computer then can beat our own use of the biological learning rules, is pretty spectacular.

Dopamine is far more than a simple reward at the end of a task. It acts as a signal for prediction errors, helping the brain decide how much motivation to apply based on changing information. When we interact with someone new, every detail we learn updates our expectations. These shifts are encoded by positive and negative fluctuations in dopamine, which determine whether we feel more optimistic or pessimistic about the interaction.

Those prediction errors are perfect signals for deciding how motivated you should be, how much should you want a thing by measuring across those kinds of signals.

Modern environments like social media or financial markets are built to keep us in a constant foraging mode. Because the nervous system is designed to keep pushing us forward, these systems ensure there is never a final outcome. If a single meal or a single social interaction were enough to satisfy us forever, we would stop living. Instead, our brains are wired to constantly look for the next thing.

Read explains that dopamine operates on different timescales. There are small, quick fluctuations and slower changing tonic levels. A great experience, such as a spectacular show, can raise the baseline level of dopamine. This higher baseline changes how future events are processed. Conversely, a disappointment can lower these levels. This suggests that dopamine is both a learning tool that updates our internal maps and a driver of our overall motivation.

Dopamine fluctuations are encoding the learning rule. It lets you update and learn, and it codes for the kind of motivation you should have.

Parkinson's disease is a condition where a person typically loses 70 to 75 percent of their dopamine neurons in the brainstem before symptoms even appear. These neurons are the primary source of dopamine for the entire brain. When these neurons degenerate, the remaining system becomes very noisy. This makes it difficult for the brain to generate a clear signal for movement or decision-making.

Parkinson's disease is a condition where by the time you show up with symptoms in the doctor's office, you've lost 70 to 75 percent of your dopamine neurons in your brain stem. Those are the only source of dopamine in your brain.

Read suggests that dopamine is essential for computing the value of different actions. In a state like Parkinson's, the noise level is so high that the brain cannot see the difference in value between staying still and moving. This leads to what Read calls an active freezing disease. The nervous system decides to stay put because it takes energy to transition to a new state, and it cannot perceive anything more valuable than its current position.

I've always thought about Parkinson's as an active freezing disease. The nervous system is doing exactly what it would do because it takes energy to transition from where you are to doing the next thing. Why do that if there's nothing more valuable there?

Andrew proposes replacing the word motivation with the term urgency. He defines urgency as a persistent and resilient need to move the body or thoughts in a particular direction. Read agrees with this framing, noting that dopamine and other neuromodulators are responsible for stabilizing and sustaining brain states. These chemical systems allow a person to hold onto a thought before moving to the next one, essentially sequencing the movement of the mind just like the movement of the body.

Andrew asks if increasing dopamine makes the world more mentally sticky. He wonders if it forces someone into a narrow trench of focus rather than allowing them to forage randomly. Read agrees that it likely stabilizes brain states and prevents them from diverting. This behavior mirrors how bees operate in a hive. When a forager bee finds nectar, it performs a waggle dance to tell others where to go. While some bees follow this language perfectly, others act like they have ADHD. These bees feel the dance and start toward the nectar but soon get distracted.

There are the ADD bees and the concentration bees. The ADD bees feel the waggle dance and start running for the nectar, but then they get distracted. By being distracted, they explore more. The ones on the far end fly right to the nectar source. You need both. One is exploiting where the nectar source is, and the ADD guys are the explorers looking for new information.

The brain constantly balances these two modes. One part of the mind acts as the explorer, seeking new information and lateral connections. This is highly valuable for finding new opportunities. The other part acts as the exploiter, following the best course of action to get a result. This distribution of abilities exists within every person, though it varies from one individual to the next. Society needs both the lateral thinkers who wander and the people who can stay on course to follow a specific chain of instructions.

Everyone possesses both an ADHD-like mode and a highly focused mode within them. While these states exist in everyone, individuals differ in which one they favor. Those who operate primarily in a focused mode are very linear and task-oriented. They can form a specific task in their mind and hold it there for a long time without losing track of their objective.

These goals have to be reconstituted and pursued. If you wanted to go play in the NBA and then all of a sudden six months into that you decided you want to go do ice hockey, well that's a problem. That's a person who can't focus.

Andrew points out that athletes are a prime example of this linear focus. They set goals that may take years to achieve and commit to a difficult path to reach them. Success in these areas requires a person to wake up every morning and pursue the same goal repeatedly. Shifting interests too quickly prevents a person from reaching a high level of achievement in any single field.

Rapid consumption of short-form video might strengthen the brain circuits used for quick updates while weakening the circuits needed to reach long-term goals. This creates a sort of ADHD muscle. While it is unlikely that social media actually causes ADHD, repeatedly engaging with fast-paced stimuli can shift the brain toward seeking constant novelty. In artificial intelligence, developers must carefully balance these two modes. If a system is over-trained to chase every new signal, it loses the ability to pursue a single objective. Human brains face a similar challenge in finding a balance between foraging for new information and staying on task.

I don't know the answer to that in people, but I do know about training artificial systems to do it. And you have to be very careful to control the mix so that it doesn't over train on one of these two possibilities: chase a goal, or chase everything that flies along.

There are specific settings where a high-speed, scanning state of mind is necessary. In combat or for fighter pilots, rapid decision-making and situational awareness are vital. However, these professionals do not rely on raw instinct alone. They undergo intense mental training and practice being surprised or stressed so they can function effectively. This suggests that the ability to navigate choppy terrain and enter a focused state is a skill that can be developed. For many people with ADHD, focus is not impossible. They often display intense concentration on things they find genuinely interesting, such as a favorite video game.

Read views the battle over screen time as a common struggle for parents. Short-form clips often provide mind-numbing entertainment without offering long-term value. Real learning is defined by whether information is reflected upon later. While a book often provides several points worth revisiting, short videos rarely stick in the mind. Andrew notes that most impactful insights require a deliberative, intentional action, such as reading. He recalls a rare instance where a social media clip stuck with him, suggesting the purpose of life is to learn to enjoy the passage of time.

One of the things that I define learning by as useful learning is: did I reflect on it again at a point later in time?

Activities that require high effort usually move at a slower pace. Andrew wonders if this effort is what strengthens neural circuits compared to the effortless scrolling of social media, where very little learning occurs. Read suggests the benefit might not be the effort itself, but rather the fact that it forces a person to slow down. While animal models like rodents are often used in neuroscience, they are poor substitutes for studying the complex mental states and social pressures humans face with modern technology.

I don't know whether effort is itself the cause or whether the fact that effort is slow and so it slows it down. We could design an experiment to see.

The rapid speed of social media creates a unique challenge for the current generation. Read describes the spread of these technologies as a tsunami that is nearly impossible to hold back. Even for parents who see the downsides, the social cost of exclusion is high. For example, Read explains that his daughter felt left out of discussions because she was the last in her class to get a phone. Collective action to limit these devices is difficult because humans rarely act in perfect unison.

To manage the cognitive load of these devices, Andrew uses a physical lockbox for his social media phone. He was motivated by research showing that even having a phone in the same room lowers cognitive performance. The device constantly pulls on mental resources even if it is face down or tucked away in a bag. Physical distance from the device seems to be the only way to restore full cognitive ability.

If your phone is upside down on a table or in your bag in the same room, it lowers cognitive performance. Even if you're not aware of the phone, it's pulling resources.

The dopamine system can learn to find pleasure in resistance just as it does in indulgence. While this can manifest pathologically in conditions like anorexia, where resisting food becomes its own reward, it also has healthy applications. Athletes often find a sense of satisfaction in doing what others will not, such as training in difficult conditions or choosing rest over social activities to get stronger.

I relished the whole I'm running this tennis court hill while all those other soft guys are asleep and I'm throwing up on top of the hill. That was a thing. And it meant when you got in a tough spot. I was a wrestler all through high school. You have to put up with things that are really demanding on you. The main thing you do when your air is cut off is don't panic. You have to learn how to do that.

Read explains that wrestling taught him the vital skill of staying calm and thinking clearly under physical pressure. This same discipline applies to academic pursuits. People who study intensely often find motivation in the idea of achieving a goal that is difficult for others. The healthiest version of this mindset is purely internal. It involves living by a personal set of standards without needing external validation or comparing oneself to others.

This type of self-regulation is being encouraged in educational settings through collective action. For example, some schools have implemented total phone bans during the day to help students stay present. As these institutions manage distractions, they are also beginning to address how students should interface with AI systems that are increasingly sophisticated.

Dopamine and serotonin work together as an opponent system. While dopamine tracks positive events and rewards, serotonin often manages negative outcomes and active waiting. This means that when dopamine rises in anticipation of a reward, serotonin levels usually fall. This type of relationship is common throughout the nervous system. It is similar to how the eyes process light and dark. Read and his team have been able to measure these fluctuations in humans during brain surgeries to see how these chemicals interact during social tasks.

Dopamine and serotonin are opponent to one another. When dopamine goes up, serotonin goes down. When serotonin goes up, dopamine goes down.

SSRIs like Prozac or Lexapro are designed to increase the amount of serotonin in the brain. However, this process can have unexpected effects. When serotonin is not cleared away normally, it can sometimes enter dopamine terminals. This can cause the brain to send negative signals during events that should be positive. This interaction might explain why some individuals experience a loss of interest or pleasure while taking these medications.

If you put the negative juice in the positive terminals, then the cells that control the release of that are going to chatter for positive things. You might start negatively conditioning on things that you should actually pursue.

Dopamine and serotonin work in opposition within the deep structures of the brain. When things go well and we anticipate a positive outcome, dopamine levels rise while serotonin levels fall. Conversely, during periods of loss or uncertainty, serotonin increases and dopamine decreases. These dynamics are not static and change based on an individual's physical state, such as hunger.

Read notes that hunger acts as a form of stress that can fundamentally alter how the brain processes information. In rodent models, extreme hunger shifts the role of dopamine entirely. Instead of tracking rewards, it begins to encode punishment prediction errors. This shift represents an emergency state where the primary goal is no longer seeking rewards but simply staying alive.

In a sense, flipping dopamine's meaning is exactly what you'd want to do. You're in an emergency state, and you want to use this reinforcement system, this expectation system to stay alive. You want to be motivated and pay attention and avoid the negative things.

The impact of hunger on decision making is visible in human settings as well. One study on judges showed that their rulings were significantly influenced by whether they had eaten recently. This suggests that a general state of stress drives the brain to either reinforce positive outcomes or focus heavily on negative ones. If you are starving, it is likely because your past decisions have not worked out. In that state, the brain stops waiting for future rewards and prioritizes immediate survival.

Using negative feedback or punishment is an ineffective way to teach or train others. Severe negative events can cause the nervous system to overgeneralize. For example, if a traumatic event occurs in a specific location, a person might begin to fear any environment that looks similar. This overgeneralization is a rational survival mechanism, but it hinders the ability to learn specific skills. When a teacher uses punishment for mistakes, the brain focuses on the threat rather than the information being taught.

Severe stress can fundamentally alter how the brain processes dopamine. Instead of signaling positive or pleasurable experiences, dopamine shifts toward a survival mechanism aimed at preventing things from getting worse. This explains why certain forms of psychological pressure and torture are effective. When a person is under intense stress, the simple removal of a threat can feel like a significant reward. Read notes that the brain can reach a state where incremental relief from threat becomes the primary driver of behavior.

The odd thing is when you stress someone enough, it is remarkable what becomes rewarding. The incremental removal of threat, given that you've made good on a little promise, could be a lot.

When dopamine levels are pushed too high by substances like cocaine, they create a state of self-obsession where every idea feels uniquely brilliant. Andrew highlights that musicians often find it difficult to collaborate while using cocaine because it acts as a me drug. Beyond drugs, overindulging in food or other high-dopamine activities resets the brain's baseline expectations. This makes it difficult for natural events to provide any sense of satisfaction because they cannot compete with the artificially high levels of dopamine the brain has grown to expect.

Read describes an abused rescue dog whose world was permanently inverted. For that animal, basic safety became the only reward and its default behavior was to bite because it was constantly in an emergency state. This behavioral commitment makes sense when survival is the only goal. People who have experienced trauma or struggle with addiction often find themselves in similar states. They make decisions that lead them back down the same hole because their internal systems have adapted to a landscape of constant hardship.

It is just a lot easier as a behavioral commitment to just start out by biting. Because you are going to have to bite at some point anyway.

Andrew explains that while dopamine typically encodes positive expectations, it is highly adaptive. If an individual is raised in conditions where survival itself is the reward, the dopamine system adjusts its baseline. In these emergency states, the brain needs to anticipate negative events to stay alive. Read notes that the brain will actually give a positive pulse for learning about potential threats.

You need to have positive prediction errors to the prediction of negative events because that is what is going to keep you alive by paying attention to that.

This adaptation explains why someone transitioning from a toxic environment to a healthy one may feel intense anxiety. Andrew recalls a friend who felt like a cat in a room full of rocking chairs after entering a peaceful relationship. It took years for his dopamine system to reset its baseline and begin working for rewards again instead of just scanning for threats. While dopamine's role is becoming clearer, the serotonin system's role in these difficult situations is still being explored. In humans, data suggests serotonin acts as an opponent to dopamine and moves in the opposite direction.

Selective serotonin reuptake inhibitors, or SSRIs, increase serotonin levels by preventing neurons from reabsorbing the chemical. A significant portion of this excess serotonin actually moves into the dopamine system. This crossover can lower the rewarding properties of positive experiences. When serotonin occupies dopamine terminals, it can send signals that interfere with how the brain processes pleasure and reward.

When you put an SSRI on the serotonin that is released, it is not going back into serotonin terminals. It goes into the dopamine system. There is all this serotonin sitting there in these terminals. You would have a hard time learning about positive things. You might also register negative events as being rewarding and you would learn yourself into a kind of depression that way.

A 2005 paper by John Danny demonstrated this effect. He showed a 40 percent difference when dopamine reuptake was blocked. Read explains that this physical interaction between neurotransmitter systems changes how neurons communicate positive and negative information. Andrew notes that important scientific findings like these require advocates to help them reach the public and change clinical understanding.

Measuring dopamine levels in the human brain often requires very specific clinical conditions. This typically occurs during deep brain stimulation surgery for patients with Parkinson's disease or essential tremors. During these procedures, doctors place tiny electrodes deep into the brain. Read and his team use a specialized neural network model to interpret the electrical signals from these electrodes. This allows them to measure dopamine, serotonin, and other chemicals in real time without affecting the patient's treatment.

We put an electrode in equipped with a neural network model that knows how to interpret electrical signals on the electrode as dopamine, serotonin, norepinephrine, ph and peroxide fluctuations.

A more recent and flexible approach involves the olfactory system. By working with Christina Zelano, the team discovered they could place electrodes against the olfactory epithelium by snaking them through the nose. This tissue sits high up in the nasal cavity near the eyes. The major advantage of this technique is that it can be used with healthy volunteers rather than only surgical patients. Researchers can now observe how dopamine and serotonin fluctuate while people eat, meditate, or perform simple decision making tasks.

Why is that important? Other than being weird, you can consent healthy people into doing this. You can snake this thing up there and clip it to their nostril and then you can do all kinds of stuff, including letting them eat, letting them do mindfulness meditation, breathing exercises, letting them do decision making tasks.

Nasal probes used in clinical settings allow researchers to monitor how dopamine and serotonin fluctuate in the brain. These measurements align closely with the activity of neurons in the midbrain. Dopamine levels typically increase when a person has a positive expectation. Conversely, serotonin increases when there is a negative expectation. This provides a clear picture of how these neurotransmitters reflect positive and negative effects in real time.

Dopamine increases when there is a positive expectation. Serotonin increases when there is a negative expectation. And you are recording that from the nose, essentially non invasively.

Individual needs for sleep and focus vary significantly between people. Read shares that he has naturally required less sleep than average since childhood. He often wakes up as early as three or four in the morning. He finds that the absolute silence of the early morning is essential for his scientific thinking. This quiet allows for a type of deep work that is impossible to achieve around other people.

The way I do science is I have to get quiet. That part I cannot do with other people. I have to do it in dead quiet.

Andrew observes that this sleep pattern may be more efficient than it appears. The first phase of sleep often captures the deep sleep necessary for physical repair and growth hormone release. The second phase likely provides enough REM sleep for emotional stability. While society often dictates a specific amount of sleep, Read emphasizes the importance of trusting your own baseline. He realized early in life that he could decide how he felt based on his own experience rather than comparing himself to others.

Nobody gets through life without making mistakes. Personal growth often comes from difficult experiences that leave metaphorical scars. These challenges help build the character needed for a demanding career. Science is a contact sport at the leading edge. When a researcher does something significant, they are often met with intense criticism from peers. This environment requires scientists to look inside themselves and decide if their work is truly important. The role of a scientist is to push the boundaries of what is known rather than staying safe to avoid errors.

The reason we are paid tax money to discover stuff is our job is to push the edge of what we know, not sit there just getting money to twiddle our thumbs. If you are on the edge, you are going to make mistakes or you are going to be wrong or you are going to be attacked or not popular. That never ends.

Read explains that a career in science is like having two jobs wrapped into one. A researcher must work exceedingly hard just to get the resources and funding to do the work. Only then can they actually perform the research itself. This reality is often a shock to newcomers who joined the field through an apprenticeship model. In that model, students mostly focus on absorbing the intuition and techniques of their mentors without seeing the harsh administrative side of the profession.

The American grant system is particularly competitive compared to other regions. Andrew notes that review panels are often forced to eliminate seventy percent of the grant applications they read. This scarcity of funding creates a culture where experts must find reasons to dislike projects to narrow the field. While this process is punishing, it builds a specific kind of fortitude. Success in science requires a high tolerance for hard work and a thick skin for constant peer review.

I sat on study section review panels for a lot of years. You go in there knowing you are going to have to eliminate 70% of the grants that you read. You advocate for the ones that you really like, but you have to come up with reasons why you dislike things. That is an unfortunate consequence of not enough funding.

Training in a science lab or pursuing a PhD teaches a person how to set up a reward expectation and motivation loop based on long term goals. It is important to register small daily wins, like a good cup of coffee, while also being able to handle failures. This training helps people navigate life without expecting massive rewards every day. In science, the biggest rewards often come years apart through publishing papers. This creates a template for sustaining losses and finding the motivation to continue.

I go through life now not expecting great things to happen every day or even every week because I was trained in a system where the big rewards came every couple of years in terms of publishing papers. But you have to register your wins in order to continue to have motivation. You also need to register your losses in order to not make the same mistakes.

Read encourages his children to participate in sports to understand the relationship between effort and reward. Sports teach children how to lose even when they have performed their absolute best. This is a vital life lesson that parents cannot easily teach through words alone. In a science lab, students go through a similar evolution. They start with little knowledge and eventually transition into the most valuable members of the team before they eventually move on to their own careers.

Beyond the physical benefits, sports remove the distraction of phones and teach emotional regulation. Wrestling is a particularly strong example because it forces an individual to manage a rising sense of panic. This type of stress management is difficult to find in other modern settings. In the professional world, a boss might be difficult, but they are not physically choking you. Sports provide a socially acceptable environment to learn how to think clearly under intense pressure.

The main thing you learn when you are a wrestler is how to manage your rising sense of panic. Don't panic. Think about where you are. You are not good at that at first. Losing is such an amazing lesson, especially when you do not want to lose and you did the absolute best thing.

Modern civilization requires humans to manage stress in ways the brain was not originally designed for. In the past, humans lived in small groups where they had to defend themselves physically. Today, those same instincts remain, but there are fewer healthy outlets for them. Sports serve as a necessary test that prepares the mind for the challenges of the modern world.

Andrew reflects on how his background in skateboarding provided a valuable foundation for scientific research. The sport required a constant cycle of pain and failure before achieving success. This resilience transferred to working alone in a lab, where long hours and failed experiments mirrored the discomfort of learning a new trick. Andrew notes that while science is difficult, it is often less punishing than falling on concrete.

Skateboarding was great because as hard as this is, it is not as hard as falling on concrete. When I tried to learn to snowboard, everyone said it was tough. I thought, it is snow. Concrete hurts. Snow is soft.

Read connects these physical experiences to the concept of cognitive control. He explains that individuals can intentionally inhibit their natural instincts to avoid pain or quit when things get hard. By sustaining efforts through aversion signals, people train their brains to update expectations about whether an investment is worth the cost. This training is a key reason why sports are so valuable for children. Read mentions a school with a no-cut policy that allows all students to experience the cycle of expectation and recovery through competition.

I cannot teach a kid a lesson that good. It is training these same systems. It is expectations, disappointment, elation, recovery, and doing it again. It is all built in.

Neurotransmitter fluctuations such as dopamine and norepinephrine follow the natural cycle of breathing. In freeform breathing, the brain tracks the inhale and exhale cycles like a metronome. This synchronization is visible in deep brain structures like the amygdala and the hippocampus. When breathing is structured or instructed, such as following a specific count, the brain must engage cognitive control. This extra effort causes the neurotransmitter signals to wobble as the brain struggles to maintain the rhythm.

The amplitude of the neurotransmitter fluctuations follows the inhale, exhale cycles. It is like a metronome. The easy breathing is registered cleanly, but with instructed breathing, you have to engage cognitive control and the transmitters wiggle and wobble.

Research using nasal probes shows that breathing also registers with mitochondrial function. During economic tasks like the ultimatum game, breathing tracks when the brain needs oxygen to produce energy for learning or updating social models. This suggests that the body prepares for the metabolic cost of making decisions. Read explains that dopamine serves as the brain's internal currency. Just as money allows us to compare the value of different objects, dopamine provides a common scale to weigh various goals and actions against one another.

Andrew notes that this currency is also relevant in human social dynamics. People often attempt to rob others of their motivation or impact through unfair criticism. This is essentially a struggle over dopamine. Those who are winning often have more energy to continue succeeding, while those who are losing may try to take that currency away from others to balance the social scale.

Dopamine serves as a universal currency for social and political dynamics. It is part of a coordinated system that provides life and energy. Read explains that dopamine actually turns on mitochondria. It binds to the outside of the mitochondria to increase electron transport and make ATP available. This creates a direct connection between neural signals and the body's energy production.

Dopamine turns on mitochondria. It binds to the outside of mitochondria to monoamine oxidase, and it gins up electron transport. It is a signal to make ATP available. That is a really direct connection.

There is a massive gap between biological and mechanical computing efficiency. Modern computer servers generate so much heat that they would burst into flames without constant cooling. In contrast, the human brain runs on only 23 watts of power. Scientists do not yet fully understand the link between the algorithms of the brain and this incredible energy efficiency.

Sleep and meditation provide essential rejuvenative properties by allowing the brain to perform an algorithmic cleaning. Andrew notes that going without sleep for even two days fundamentally changes a person. This leads to a drop in motivation and significant shifts in dopamine dynamics. Read explains that the brain functions like a computational device that requires downtime to manage information. During sleep, the brain decides which data to save through consolidation and which to erase.

It's a combination of physiological responses and the algorithmic cleaning up. It's a computational device. You need a time off. You can't have information streams processing through when you need to be going, I'm not going to save all that or I'm going to consolidate that. A lot of it's about erasure and homeostasis and recovery.

This process of erasure and homeostasis is vital for physical recovery. It involves recycling neurotransmitters and rebuilding the systems that allow for high levels of motivation. This need for sleep is universal among animals. Even the echidna, which scientists once believed was an exception, has been shown to experience REM sleep. This discovery highlights how fundamental these periods of recovery are for all biological life.

Learning involves understanding what happens, where it happens, and when it happens. This process relies heavily on dopamine signals and internal timing. While scientists once thought the suprachiasmatic nucleus was the primary source of biological clocks, it is now understood that every cell in the body contains multiple clocks. These systems allow us to register the timing of events and learn from them.

Read notes that dopamine is central to what is called interval timing. This involves an animal or human anticipating something at a specific point in the near future. While people often look for a simple rule about whether more dopamine makes time move faster or slower, the reality is more complex. There is no simple statement to be made because time perception involves multiple systems that are not always conscious.

One of the things that is latent in any description of what dopamine is doing, either from a point of view of psychology or algorithms that I focus on, is timing. To learn something is to learn what is going to happen when and how much, what, where, when, and how. You have to have a lot of clocks in there.

Different substances affect this perception in unique ways. For example, people using cannabis often feel as though a long period of time has passed when only a few minutes have gone by. Conversely, individuals taking Ritalin often report losing track of time. This is likely because they are concentrating intensely for long periods. These experiences suggest that time perception is a sophisticated calculation used in reinforcement learning.

Read struggles with tracking time throughout the day and has a poor sense of direction. He is also stereo blind, a condition affecting about five percent of the population where the brain cannot properly perceive depth through stereoscopic vision. He discovered this during a lecture when he was unable to see the visual patterns intended to demonstrate depth perception.

He was showing all these pictures and he says, 'Can anyone in here not see the thing?' I couldn't see anything. He says, 'Oh, you're stereo blind.' I was a hurdler in high school and college and then throwing balls and I also pole vaulted.

Despite this lack of stereoscopic vision, Read was a successful athlete in sports like baseball and pole vaulting. He likely compensated for his lack of depth perception by using motion parallax. This involves moving the head or body to create movement that helps the brain calculate distance. Additionally, Read was naturally left handed until age eight, when his mother forced him to switch to his right hand. Andrew notes that this forced change likely resulted in significant brain plasticity during his development.

Andrew notices that very driven or obsessive people often struggle to track time. They tend to immerse themselves so deeply in their work that they discard the rest of the world. This trait might be changing in younger generations who grow up with constant digital noise. Constant bombardment from social media and smartphones may make it harder for people to envision long term goals or perceive the arc of their lives. Read remembers a much calmer childhood where he wandered through forests for hours without parental monitoring. This allowed for a sense of peace that is rarely found in the modern, information-heavy environment children inhabit today.

The conversation shifts to the incredible capabilities of modern AI. Read uses Claude to compare and contrast scientific literatures, a task that traditional databases like PubMed cannot perform. He once asked the AI to explain the link between the subjunctive mood in language and complex numbers in quantum mechanics. The AI explained that both involve counterfactuals or possibilities that influence reality.

I don't really care whether it maps onto some notion of consciousness or smart. I don't know any person that could do that. And it's a better writer than I am. I'm just blown away by it.

Significant breakthroughs like AlphaFold have solved the decades old problem of protein folding. This success comes from treating complex biological problems like a game using reinforcement learning. Read points out that these same algorithms are actually installed in our own heads. Biology discovered that reinforcement learning is the most effective way to handle reality and stay alive. As our understanding grows, we may eventually learn how to engineer these systems within ourselves.

Future technology may allow individuals to track their own neurochemicals like dopamine and serotonin using a smartphone. Read describes a project aimed at commercializing a device that measures these signals through the nose. This would allow people to observe their brain reactions in real time during daily activities or mental exercises.

You could hack your own serotonin onto your cell phone. You could put it up there and you could go do a thing and you could watch it on your cell phone. And we've never had anything like that before.

For example, a person could use the device while solving a puzzle or reflecting on their dating life. They could see how their reward expectations and dopamine signals are functioning. Current research involves tracking word-by-word valence changes as people listen to sentences or engage in social games. The goal is to move these measurements from a research setting into a commercial space where anyone can use them for personal insight.

New technology might soon help people learn to concentrate better. Read explains that devices could measure neurotransmitters like dopamine and serotonin in real-time. This would allow a person to see how their brain responds while reading or performing a task. Neural networks could then analyze this data to help train the brain. This approach is becoming a dominant force in neurobiology.

We haven't had a way to measure that in real humans in settings that are like the real world. You train a neural network who looks at the performance step by step with the transmitters there, and it generates a picture of that.

Scientific trends often shift over time. Decades ago, fields like artificial intelligence and brain-machine interfaces were ignored. Now, they are at the center of neuroscience. Andrew notes that a similar shift is happening in the health space with things like meditation and breathwork. Even if a field is mocked at first, persistence can lead to a major breakthrough.

Whatever people are beating up on now, that is going to be the next big thing. It just going to take a while. And you have to be discerning in how you go about it.

The human brain is also highly adaptable. While many worry about how much time younger generations spend on phones, Andrew points out that they are often finding ways to thrive. They can manage multiple tasks and navigate technology in ways that show the brain capacity for change. This generation is often doing spectacularly well despite the concerns about social media and screen time.

The concept of a dopamine hit is a common way to describe rewarding experiences. While unexpected rewards do cause dopamine to fluctuate, this is only an incomplete part of the story. Andrew notes that modern neuroscience is moving toward a more nuanced understanding as technology allows for real-time recording of neurotransmitters in humans. Read explains that the most obvious feature of schizophrenia is that blocking dopamine receptors can reduce symptoms. This disorder has long been viewed as a state with too much dopamine activity.

The most conspicuous feature of schizophrenia is the fact that blocking dopamine receptors turns the symptoms down a little bit. It was very early on seen as a hyper dopaminergic state. If you block dopamine receptors, you don't hear voices anymore.

This evidence supports the idea that dopamine is linked to specific symptoms like paranoia and hallucinations. If a person without the disorder takes high doses of L-dopa, they can begin to hear voices or feel paranoid. This shows a rational assignment of dopamine to these features. However, many psychiatric terms remain poorly defined. As scientists record neurotransmitters in both healthy and sick people, these categories will likely be refined. Both dopamine and serotonin fluctuate in cases of depression and schizophrenia.

The distinction between grit and the sunk cost fallacy depends on how the brain sets expectations. Dopamine is linked to the drive to persist. However, it does not work alone. The brain is an electrochemical machine. Electrical activity in specific networks sets the expectations for neurotransmitter release. We do not yet understand how these expectations are managed or updated from state to state. Read believes that AI will help map these processes over the next twenty years.

If the brain is only a chemical machine, Grok left off the fact that it's an electrochemical machine and that the electrical activity in the networks set things like expectations which defines when the release is happening or not.

Dopamine does not equal pleasure. This is a common myth. Serotonin treatments for depression are also misunderstood. These drugs can be inconsistent or even toxic over many decades. Much of the success of psychotropic medications comes from the placebo effect. This effect is not fake. It shows that beliefs and expectations can physically change brain activity. We have a poor understanding of how a belief actually marshals these internal resources.

We do not have measurements for dopamine signals during purely internal satisfaction. Activities like meditation or private hobbies lack external rewards. It is hard to track these signals when a person is cut off from the world. Building persistence may require intense self-training. Read describes running up a hill until he vomited just to test his capacity for effort. He did this simply because he could.

Read and Andrew discuss the intense physical toll of high intensity training. Read shares his early experiences following Russian training manuals that focused on plyometrics and box jumps. At the time, Eastern bloc sprinters dominated the Olympics, and Read adopted their grueling routines. He would train with a weight vest until he reached total physical exhaustion, often leading to nausea. This style of training is a solitary pursuit for Read, who prefers to work out alone to maintain his focus.

I copied the Russians. I had books, Russian books. They did a lot of plyometrics and weight box jumps. I would put weight vest on and do it until I just threw up. It is my moment every day. That is why I do not like to work out with anybody.

The conversation highlights the influence of Arthur Jones, the creator of Nautilus, and his advocacy for high intensity training. Read recalls meeting Jones and even training in the same facility as musician Isaac Hayes. Andrew notes that the high intensity work Jones encouraged is one of the most effective ways to stimulate hypertrophy. However, the sheer intensity of these workouts, especially leg days, is famous for causing physical sickness due to the extreme effort required.

SSRIs often lead to side effects such as sexual dysfunction and motivational issues. This occurs because these drugs bind to many different types of serotonin receptors. While there are relatively few dopamine receptors, there are likely around 80 different serotonin receptors. This variety creates a wide range of possibilities for unintended side effects.

There are probably 80 serotonin receptors or something. There is a great number of them. And so there is just a field of dreams of way you can have side effects. Also, just the idea that you are on them is itself an effect. I am on a drug. This is a drug to manipulate my mood state. That has an effect on your mood state and the way you feel.

Read notes that beyond the chemical interactions, the psychological aspect of taking a drug plays a role. Simply knowing that one is taking a medication intended to manipulate their mood state can influence how they feel.