Dr. Mark D'Esposito: How to Optimize Cognitive Function & Brain Health

Dr. Mark D’Esposito (00:00:00)

• Dr. Mark D’Esposito is a neurologist and a professor of neuroscience and psychology at the University of California, Berkeley.
• He is a world expert in the brain mechanisms controlling executive function and memory.
• Executive function is the way in which we are able to designate and carry out specific cognitive strategies.
• It is fundamental to every aspect of our daily lives.
• There's really no separation between executive function and memory.
• Dr. D’Esposito explains the neural circuits controlling executive function and memory and how they interact.
• The key role of dopamine in executive function and something called working memory.
• Dr. D’Esposito teaches ways to optimize executive function and memory, which is how to optimize cognitive function.
• The discussion centers around how to restore cognitive function in disease or injury conditions that deplete executive function and memory, such as:
  • Traumatic brain injury
  • Concussion
  • Alzheimer's
  • Parkinson's
  • Attention deficit disorders
• Dr. D’Esposito shares research findings about behavioral and pharmacologic strategies to enhance executive function and memory.

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• Introduction
  • Dr. Mark D'Esposito is a professor of neuroscience at the University of California, Berkeley, and the director of the Berkeley Center for Long-Term Health.
  • His research focuses on the neural mechanisms of cognitive function and brain health.
• The Importance of Cognitive Function
  • Cognitive function refers to the mental processes involved in acquiring knowledge and understanding.
  • It includes attention, memory, language, problem-solving, and decision-making.
  • Cognitive function is essential for everyday activities and overall well-being.
• Factors that Affect Cognitive Function
  • Age: Cognitive function naturally declines with age, but the rate of decline can vary.
  • Genetics: Some people are more likely to experience cognitive decline than others due to their genes.
  • Lifestyle factors: Certain lifestyle factors, such as lack of exercise, poor diet, smoking, and excessive alcohol consumption, can contribute to cognitive decline.
  • Medical conditions: Some medical conditions, such as Alzheimer's disease, Parkinson's disease, and stroke, can also affect cognitive function.
• Strategies to Optimize Cognitive Function
  • Physical exercise: Regular physical exercise has been shown to improve cognitive function and reduce the risk of cognitive decline.
  • Healthy diet: Eating a healthy diet, rich in fruits, vegetables, whole grains, and lean protein, can help maintain cognitive function.
  • Mental stimulation: Engaging in mentally stimulating activities, such as reading, doing puzzles, and learning new things, can help improve cognitive function.
  • Social engagement: Social interaction and engagement with others can help maintain cognitive function.
  • Sleep: Getting enough sleep is essential for cognitive function.
  • Stress management: Managing stress can help improve cognitive function.
• Conclusion
  • Cognitive function is essential for everyday activities and overall well-being.
  • Several factors can affect cognitive function, including age, genetics, lifestyle factors, and medical conditions.
  • There are several strategies that can be used to optimize cognitive function, including physical exercise, healthy diet, mental stimulation, social engagement, sleep, and stress management.

Brain & Frontal Lobes, Prefrontal Cortex, Executive Function (00:06:23)

• The frontal lobes take up about a third of the cortex and are involved in higher-level cognitive abilities.
• The prefrontal cortex is the highest level of cortex in the brain and is responsible for executive function.
• Executive function includes planning, organizing, and controlling thoughts and actions.
• The frontal lobes are like the CEO of the brain, controlling the rest of the brain.
• Lack of executive function can show up in various ways, including:
  • Difficulty setting priorities.
  • Difficulty achieving goals.
  • Getting distracted easily.
  • Inability to adapt and be flexible.
• Frontal lobe damage can be caused by neurodegenerative diseases, physical injury, sleep deprivation, stress, and normal aging.

Frontal Lobe Development, Children (00:10:31)

• Frontal lobe circuitry becomes functional gradually, with full functionality reached in early 20s.
• Slow development allows for exploration, novel problem-solving, and taking in the world.
• Difficulty focusing, listening, or sitting still in children may indicate slightly lagging frontal lobe function and maturity.
• Frontal lobe has various sub-regions, including the lateral portion involved in executive functions and the orbital frontal cortex involved in social and emotional behavior.
• Different frontal lobe systems may develop at different rates.

Rules, Context & Impulse Control; Learning & Goals (00:14:12)

• The frontal lobes control goal-directed behavior, intentions, and cognitive control, acting as the executive center of the brain.
• The frontal lobes use contextual knowledge to generate appropriate algorithms for different situations.
• Damage to the frontal lobes can lead to socially inappropriate behavior due to an inability to apply learned rules correctly.
• The frontal lobes store rules hierarchically, with different levels for various situations.
• The prefrontal cortex is responsible for applying learned rules to achieve complex actions.
• The two-marshmallow experiment is a frontal lobe task that involves delaying gratification for a greater reward.
• Children and adults can train their prefrontal cortical abilities through experience-dependent neuroplasticity to strategize and defer gratification.
• Maintaining long-term goals and applying them to actions is a crucial function of the prefrontal cortex and is predictive of success.

Focus, Improving Executive Function (00:21:45)

• The prefrontal cortex can learn and generalize rules and algorithms.
• Studying with self-imposed constraints, such as setting a timer and avoiding distractions, can help build prefrontal ability to refocus.
• The sensation of mental friction, or the discomfort of staying focused on a task despite distractions, may be a key factor in generalization.
• Cognitive therapy has shown limited success in improving memory and executive function, as improvements often don't generalize to real-life situations.
• Goal Management Training, developed by Brian Levine and colleagues, has been successful in teaching patients to improve executive function and translate it to real-world scenarios.
• The therapy involves learning through individual projects, such as planning a meal or a podcast, and developing strategies to stay focused, avoid distractions, and manage anxiety and procrastination.
• Over time, patients report improvements in their ability to do things better in general, not just in the specific tasks they were trained on.
• The term "lyic friction" is used to describe the interactions of the frontal cortex with other circuitry involved in attention and focus.

Connections & Top-Down Signals (00:26:04)

• The prefrontal cortex connects to every part of the brain and the subcortex, making it anatomically important.
• It controls heart rate and respiration, not just brain functions.
• The prefrontal cortex sends top-down signals to other brain areas, directing attention to relevant information and ignoring irrelevant information.
• It allows switching between tasks by directing attention to different relevant information.

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Frontal Lobe Injury; Emotional Regulation (00:30:29)

• The prefrontal cortex (PFC) is responsible for high-level executive functions, social and emotional behavior, and the ability to take thoughts and move them towards action.
• Damage to the PFC can result in inappropriate behavior, changes in personality, and social or emotional impairments.
• Routines and scripts can help individuals overcome reflexes and live life based on their intentions, goals, and desires, but the frontal cortex's unique ability lies in its flexibility and adaptability to unexpected situations.
• Emotion and context influence our executive function, leading to poor decision-making in stressful situations.

Smartphones, Social Media (00:37:26)

• Smartphones have become an integral part of our lives, assisting in various domains such as medicine and communication, but they also introduce new task-switching demands and expose users to a constant stream of emotionally charged content, which may have implications for cognitive function and brain health.
• The algorithms learned through smartphone use, such as rapid thumb movement and constant engagement, may not generalize to other cognitive tasks or enhance overall brain function.
• Unlike traditional activities like reading or playing sports, smartphone use does not provide clear rules or strategies that can be applied to improve cognitive abilities.
• While smartphones offer quick access to information, they do not directly contribute to better decision-making or enhance frontal lobe function.
• Excessive reliance on technology, such as GPS navigation, may lead to a decline in problem-solving skills and spatial awareness.

Working Memory, Dopamine (00:44:37)

• Working memory involves holding, manipulating, and operating on information that is no longer accessible.
• It is essential for cognitive functions like reading comprehension, planning, and organization.
• Dopamine acts as an accelerator for working memory, enhancing its efficiency.
• The prefrontal cortex circuit is the dopamine circuit relevant to working memory.
• Working memory and long-term memory are separate systems with distinct brain regions, with the frontal lobes being crucial for working memory.
• Dopamine sustains persistent neural activity in the frontal lobes, enhancing working memory.
• Acetylcholine plays a more significant role in long-term memory due to its projections to the hippocampus.

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Dopamine Levels & Working Memory, Cognitive Tasks, Genetics (00:54:22)

• Dopamine plays a crucial role in working memory, with an inverted U-shaped relationship between dopamine levels and working memory performance.
• Measuring dopamine levels directly is challenging, but working memory capacity can serve as a proxy for dopamine levels.
• Genetic studies of the enzyme COMT, which breaks down dopamine in the prefrontal cortex, can provide insights into individual dopamine levels.
• People with an underactive COMT enzyme have higher dopamine levels, while those with an overactive enzyme have lower dopamine levels.
• Genotyping individuals through a saliva test can identify these genetic variations and predict how they will respond to certain interventions, allowing for tailored interventions to increase or decrease dopamine levels based on an individual's genetic makeup.

Bromocriptine & Working Memory, Dopamine (01:00:03)

• Bromocryptine, a dopamine agonist, has been shown to improve working memory in healthy individuals.
• These drugs are safe and well-tolerated in low doses, with no noticeable side effects.
• The benefits of these drugs are not limited to specific diseases but can be applied to general cognitive enhancement.
• Other dopamine agonists and drugs like paroxetine can also enhance working memory.
• Studying the interactions and combinations of different drugs is challenging and requires significant infrastructure, which is why pharmaceutical companies are better equipped to conduct such studies.

Guanfacine, Neurotransmitter Levels, Pupil Dilation & Biomarker Tests (01:06:21)

• Norepinephrine-boosting drugs like guanfacine and Wellbutrin may improve working memory.
• Serotonin-boosting drugs can indirectly help working memory by improving other cognitive processes.
• A personalized combination of drugs tailored to an individual's neurochemistry may be necessary for optimal cognitive function.
• Pupil dilation can serve as a proxy for the noradrenergic system, indicating arousal and alertness.
• The balance of dopamine between the prefrontal cortex and the basal ganglia is crucial for cognitive function.
• Neurologists use various methods to understand neuromodulatory systems and develop biomarkers that provide information about brain function and help improve brain health.

Bromocriptine, Olympics; Pharmacology & Cognitive Function, Adderall (01:12:46)

• Bromocryptine, a dopamine agonist, has been used by athletes to enhance reaction time and performance in sprint races.
• The use of pharmacology for cognitive enhancement is becoming more prevalent, with substances like Adderall and Ritalin being commonly used on college campuses and even in elementary schools.
• Excessive dopamine levels can have negative effects on cognitive performance, so caution is advised when using drugs like Adderall and Ritalin, which should be done under the supervision of a trained psychiatrist.
• Dr. Mark D'Esposito recommends using drugs like bromocryptine and guanosine that can modulate specific neurotransmitters, rather than those that boost multiple neurotransmitters, as they lack precise control over the modulation of the brain system.
• The goal is to optimize cognitive function and brain health, not to reach superhuman potential, but to bring out the best in people's abilities.
• Sleep is the foundation of mental health, physical health, and performance, and without adequate sleep, pharmacological interventions may provide temporary benefits but will eventually lead to negative consequences.
• The effects of drugs like modafinil, which are thought to be true cognitive enhancers, are still not fully understood, and more research is needed to determine their specific mechanisms and effects.

Concussion, Traumatic Brain Injury (TBI) (01:19:27)

• Concussions are more common than previously thought and can result from various incidents, not just sports injuries.
• Persistent post-concussion syndrome affects a significant number of individuals, with symptoms lasting for a year or more after the initial injury.
• During a concussion, the brain's axons, which facilitate communication between brain cells, are damaged, and the severity and duration of symptoms are linked to the extent of this damage.
• Understanding the nature of a concussion and providing patients with information about their condition can be comforting and beneficial.
• The frontal lobes, which control the rest of the brain, are particularly vulnerable to concussion-related damage, leading to mild executive symptoms such as mental fog and difficulty completing tasks.
• Even a slight decline in cognitive function, such as a 1% drop, can significantly impact daily activities.

Sleep, TBI, Concussion & Executive Function; BrainHQ (01:25:22)

• Poor sleep quality can significantly impair cognitive performance, especially prefrontal cortical function.
• Traumatic brain injuries and concussions can disrupt sleep, worsening cognitive deficits.
• Optimizing sleep, nutrition, and physical activity are essential for brain health and recovery from brain injuries.
• Gradual return to activities and cognitive tasks is recommended after a brain injury, rather than complete rest.
• Technology-based brain training programs like Brain HQ and games developed by Posit Science, such as those created by Dr. Merzenich, can be helpful tools for cognitive rehabilitation and improving specific cognitive functions.
• Dr. Merzenich's work has shown that neuroplasticity continues beyond adolescence and into adulthood, allowing individuals to improve their cognitive abilities through focused effort and work.

Aging & Frontal Executive System; Brain Health (01:31:57)

• Regularly engaging in mentally challenging activities, such as reading books and avoiding distractions, can help maintain and improve cognitive health, especially working memory and frontal lobe function.
• While aging naturally affects cognitive function, particularly the frontal executive system, optimizing brain health and function is crucial rather than solely focusing on preventing decline.
• Simple practices like reading a book chapter without distractions, redirecting focus when it wanders, getting enough sleep, and maintaining physical health through regular exercise and adequate sleep can help maintain and enhance working memory and cognitive function.
• Unlike physical health, brain health optimization lacks a structured approach and a standardized measure or test for assessment.
• The Brain Health Project at UT Dallas aims to develop a comprehensive brain health index that encompasses cognitive function, social engagement, lifestyle factors like sleep, and overall well-being, allowing individuals to track their brain health over time and assess the effectiveness of interventions aimed at optimizing brain health.

Tools: Brain Health & Boosting Executive Function, Books (01:39:26)

• Optimizing brain health involves measurable actions beyond sleep, exercise, and nutrition, such as reading fiction, learning new skills, and engaging in social interactions.
• Tracking brain health progress, similar to tracking physical health, would increase confidence in brain health practices.
• Disciplined engagement in activities that promote cognitive richness, such as reading fiction and following cohesive plots, is essential for brain health.
• Boosting executive function requires human interaction and coaching, and should be taught in schools alongside school management theory.
• Life coaches can offer simple and obvious advice that can make a big difference in brain health.
• Activities like chess and improv can improve working memory and cognitive function, while novel and challenging activities that require goal-setting, multitasking, and distraction filtering can enhance cognitive abilities.

Alzheimer’s Disease, Genetics, Pharmacology (01:47:26)

• Alzheimer's disease is a neurodegenerative disorder that affects the hippocampus and is characterized by the presence of plaques and tangles in the neurons.
• There is a genetic link to Alzheimer's, but it is not as straightforward as other diseases like Huntington's disease.
• The amyloid hypothesis, which suggests that the buildup of amyloid plaques is a primary cause of Alzheimer's, has been debated in recent years due to accusations of false data.
• The only approved treatment for Alzheimer's disease is donepezil, which boosts acetylcholine levels, but it has limited effectiveness.
• Finding a primary mechanism or neurotransmitter that can make a significant difference in Alzheimer's has been challenging, leading to the lack of transformative drug treatments.
• Despite the lack of effective treatments, understanding the disease, managing behaviors, and providing social support are important for families dealing with Alzheimer's.

Parkinson’s Disease, L-Dopa; Coping with Alzheimer’s; Nicotine (01:51:48)

• L-Dopa, commonly found in energy drinks and supplements, is ineffective for Parkinson's disease due to its limited ability to cross the blood-brain barrier.
• For early-stage Alzheimer's, maintaining social engagement, cognitive stimulation, and good sleep habits can slow cognitive decline.
• Behavioral symptoms in Alzheimer's, such as delusions and agitation, can be managed with medications used for other conditions, but treatment remains purely symptomatic.
• Socialization and activities that evoke emotional responses, like listening to familiar music, can benefit Alzheimer's patients.
• Nicotine may have protective effects against Parkinson's and Alzheimer's, but it can raise blood pressure and has other health risks.
• Boosting the cholinergic system may be beneficial for Alzheimer's, as some patients given anticholinesterase inhibitors show symptomatic improvements.
• Pharmaceutical companies have focused on single neuromodulators like acetylcholine for Alzheimer's disease instead of trying a combination of neuromodulators.
• The author believes that panels or committees should be in charge of large organizations instead of individuals to ensure diversity and better decision-making.

Estrogen & Dopamine, Cognition; Tool: Physical Exercise (01:58:37)

• Estrogen plays a significant role in cognitive function and brain health, particularly in frontal lobe function and working memory.
• Low estrogen levels, combined with low dopamine, can lead to decreased frontal lobe function and impaired working memory.
• Optimizing estrogen levels is crucial for both men and women for cognitive and vascular health.
• Physical exercise, such as aerobic exercise, can improve working memory and cognition, independent of its cardiovascular benefits.
• Aerobic exercise is important for cognitive function and brain health.
• Neurologists are starting to recognize the importance of exercise, nutrition, and sleep for brain health.

Tool: Mindfulness Meditation & Executive Function (02:04:43)

• Mindfulness training, combined with goal management training, enhances executive function and improves focus.
• Tailoring mindfulness approaches can be beneficial, and the field of neuroscience is becoming more open to discussions on mindfulness, nutrition, and alternative therapies like psychedelics.
• Personal experience with mindfulness, such as non-sleep deep rest and mindfulness meditation, positively impacts mental and physical vigor, problem-solving, and time orientation.
• Simple tools like putting the phone in another room can improve focus.
• Meditation is crucial for optimizing cognitive function and brain health, which can be measured through various methods to determine the effectiveness of different therapies.
• The state of brain networks and neurochemical profiles play a vital role in predicting responses to therapies and determining their benefits.

Brain Networks; Modularity (02:10:31)

• Dr. Mark D'Esposito emphasizes the importance of viewing the brain as a complex network, with hubs like the prefrontal cortex playing a crucial role in overall brain function.
• Diseases such as Alzheimer's and schizophrenia disrupt the brain's network, providing a new target for treatments.
• Measuring brain network structure, particularly modularity, can predict well-being and response to interventions, making it a valuable metric for assessing brain health.
• Higher modularity is associated with better cognitive function and brain health.
• Modularity has been found to predict outcomes in various populations, including traumatic brain injury patients, older adults experiencing cognitive decline, and individuals undergoing behavioral therapy for obsessive-compulsive disorder.

Modularity, Brain Indices (02:17:08)

• Neuroscience should focus on understanding the "verb states" or action states of brain areas rather than overemphasizing specific brain regions.
• There is a lack of a naming system and metrics for waking states of mind, despite the rich understanding of sleep states.
• Modularity, which measures the large-scale organization of the brain, can serve as a metric for cognitive function and brain health.
• Real-time measurement of modularity could revolutionize the assessment of cognitive function and brain health, but it requires practical and non-invasive development.
• Dr. Mark D'Esposito and his team are working on a project to measure brain modulation and physiological data to determine brain states.
• The aim is to create a simple device that can read out brain states, similar to how smartwatches read out other physiological information.

Psilocybin; Transcranial Magnetic Stimulation (02:22:53)

• Increased resting-state connectivity, as seen in psilocybin studies, may benefit social-emotional function but not cognitive function.
• Modularity, or the segregation of brain networks, is crucial for cognitive function and can vary in individuals and different states.
• Combining drug therapies, cognitive training, and transcranial magnetic stimulation (TMS) may improve brain health and cognitive function.
• TMS has shown promise in enhancing working memory, but further research is needed to determine its generalizability and effectiveness.
• Brain health interventions should focus on restoring the balance of brain networks rather than solely increasing or decreasing activity in specific regions.
• Dr. Mark D'Esposito emphasizes the importance of interventions and possibilities to alleviate cognitive deficits and brain health issues, challenging the traditional role of neurologists as mere describers of conditions.
• Potential interventions mentioned include bromocryptine, mindfulness, and exercise.
• Patients should advocate for their own health and seek information about various possibilities to optimize brain health.

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• Cognitive function and memory are essential for daily activities.
• The brain is a complex organ responsible for cognition and memory.
• Optimizing cognitive function and brain health is crucial for overall well-being.