Dr. Gary Steinberg: How to Improve Brain Health & Offset Neurodegeneration
In this episode of Huberman Lab, Dr. Gary Steinberg provides insights into preserving brain health and function. He offers an overview of strokes and traumatic brain injuries (TBIs), covering prevention strategies and innovative treatments like clot removal techniques and stem cell therapy.
Steinberg discusses the role of neuroplasticity in recovery from stroke and TBI, highlighting promising approaches such as vagus nerve stimulation and constraint-induced movement therapy. He also emphasizes the importance of lifestyle factors like exercise, diet, sleep, and stress management in promoting overall brain health and preventing neurodegeneration.
This is a preview of the Shortform summary of the May 20, 2024 episode of the Huberman Lab
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1-Page Summary
Strokes and Cerebrovascular Health
Dr. Gary Steinberg explains that strokes occur due to clots or hemorrhages disrupting blood flow to the brain. Ischemic strokes (87%) are caused by clots blocking arteries, while hemorrhagic strokes (13%) result from burst blood vessels. Steinberg notes that lifestyle factors like smoking, alcohol, and drug use contribute to stroke risk, along with medical conditions like hypertension and heart disease. However, declining smoking rates and better hypertension management have reduced stroke incidence.
For treatment, timely restoration of blood flow via clot-busting drugs and mechanical clot removal is crucial. Steinberg references innovations like catheters for clot extraction and potential curative drugs. He advocates physical therapy to regain function by engaging neuroplasticity, as well as protective measures like mild hypothermia and statins. He supports the new blood pressure guideline of 120/80 or lower for stroke prevention.
Traumatic Brain Injuries and Concussions
Concussions cause temporary neurological deficits like disorientation and imbalance, while severe traumatic brain injuries (TBIs) can lead to lasting disabilities. Steinberg explains that repeated concussions, even in non-contact sports, can cause chronic traumatic encephalopathy (CTE). Post-concussion, rest and gradual return to activity are recommended. Techniques like eye tracking can assess recovery, and constraints on uninjured limbs can promote plasticity.
Neuroplasticity and Regenerative Treatments
Challenging past beliefs, Steinberg discusses research showing stem cell transplantation and vagus nerve stimulation as promising for functional recovery post-TBI or stroke. Stem cells may aid recovery by secreting growth factors that induce angiogenesis, neurogenesis, and synaptogenesis, rather than directly replacing damaged cells. Early studies suggest stem cell treatments improve outcomes for chronic patients.
Vagus nerve stimulation coupled with therapy also enhances plasticity. It likely works by directly stimulating brain regions, rather than peripheral effects. This FDA-approved chronic stroke treatment has shown meaningful improvements years post-injury.
Neuroprotective Measures
Steinberg and Dr. Huberman highlight lifestyle factors like exercise, diet, stress management, and sleep hygiene as key for brain health and preventing cerebrovascular issues. Avoiding excess alcohol, smoking, and drugs reduces stroke and TBI risks, as noted by Steinberg.
Therapeutically, mild brain cooling can block cell death and inflammation pathways post-injury. Physical and cognitive activity may also promote neuroplasticity and endogenous stem cell activation, per Steinberg.
1-Page Summary
Additional Materials
Clarifications
- Chronic Traumatic Encephalopathy (CTE) is a degenerative brain condition linked to repeated head injuries, such as concussions. Over time, these repeated brain traumas can lead to the accumulation of an abnormal protein called tau in the brain. CTE is commonly associated with athletes in contact sports like football, boxing, and hockey, but it can also affect individuals in other high-risk professions or situations. Symptoms of CTE can include memory loss, confusion, impaired judgment, aggression, depression, and eventually, progressive dementia.
- Stem cell transplantation involves the introduction of stem cells into the body to aid in the recovery process after a traumatic brain injury (TBI) or stroke. These stem cells can release growth factors that promote the formation of new blood vessels (angiogenesis), nerve cells (neurogenesis), and connections between nerve cells (synaptogenesis). While the stem cells themselves may not directly replace damaged cells, their ability to stimulate these regenerative processes shows promise in improving outcomes for individuals dealing with the long-term effects of TBI or stroke.
- Vagus nerve stimulation involves the use of a device to send electrical impulses to the vagus nerve, a major nerve that runs from the brain to various organs in the body. This stimulation has shown promise in aiding functional recovery after traumatic brain injuries (TBI) or strokes by potentially enhancing neuroplasticity and promoting brain region activity. The therapy is believed to work by influencing the brain directly rather than through peripheral effects, leading to improvements in motor or cognitive functions. Vagus nerve stimulation has been FDA-approved for chronic stroke treatment and has demonstrated meaningful benefits even years after the initial injury.
- Angiogenesis is the formation of new blood vessels, neurogenesis is the generation of new neurons, and synaptogenesis is the creation of new connections between neurons. Stem cells can induce these processes by releasing growth factors that stimulate the growth of blood vessels, the generation of new neurons, and the formation of new connections between neurons in the brain. This can help in repairing damaged brain tissue and improving brain function after injuries like strokes or traumatic brain injuries.
- Endogenous stem cell activation for neuroplasticity involves the body's own stem cells being stimulated to promote brain healing and adaptability. This process can enhance the brain's ability to reorganize and form new connections after injury or disease. By activating these internal stem cells, the brain can potentially repair itself and improve function without the need for external interventions. This mechanism plays a crucial role in the brain's natural healing processes and can contribute to recovery and rehabilitation following neurological conditions like strokes or traumatic brain injuries.
Counterarguments
- While lifestyle factors like smoking, alcohol, and drug use are significant contributors to stroke risk, genetics and environmental factors also play a crucial role that might not be as easily modifiable.
- The statement that declining smoking rates and better hypertension management have reduced stroke incidence might overlook other factors that could contribute to stroke trends, such as changes in population demographics or the prevalence of other risk factors like obesity and diabetes.
- The emphasis on the new blood pressure guideline of 120/80 or lower for stroke prevention may not account for individual patient variability and the potential risks of aggressive blood pressure management in certain populations.
- The effectiveness of physical therapy and neuroplasticity engagement post-stroke might vary significantly among individuals, and some patients may not experience substantial recovery despite therapy.
- While stem cell transplantation and vagus nerve stimulation are promising, they are still relatively new treatments and may not be widely accessible or proven effective for all patients.
- The idea that stem cells aid recovery mainly through the secretion of growth factors might be an oversimplification, as the mechanisms of stem cell therapy are complex and not fully understood.
- The FDA approval of vagus nerve stimulation for chronic stroke treatment implies a level of endorsement, but it's important to note that FDA approval does not guarantee treatment efficacy for all patients or that it is the best option available.
- The role of lifestyle factors in preventing cerebrovascular issues, while important, may not be sufficient on their own without considering the impact of social determinants of health, such as access to healthcare, education, and socioeconomic status.
- The recommendation for mild brain cooling post-injury as a neuroprotective measure may not be practical or feasible in many clinical settings, and its effectiveness may vary.
- The suggestion that physical and cognitive activity may promote neuroplasticity and endogenous stem cell activation is an area of ongoing research, and the extent to which these activities can influence recovery is still being determined.
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Strokes and Cerebrovascular Health
Dr. Gary Steinberg, a distinguished expert in cerebrovascular health, elucidates the intricacies of strokes, their risks, treatments, and rehabilitation, underscoring the pressing need for public awareness and medical preparedness.
Strokes are disruptions in brain blood flow, either from clots or hemorrhages
Steinberg vividly describes a stroke as a "heart attack of the brain," caused by an obstruction in blood flow due to either a blocked vessel or a hemorrhage. He details that ischemic strokes, accounting for approximately 87% of all cases, often result from arterial clots which may originate near the heart or in the carotid artery and then lodge in the brain. On the other hand, hemorrhagic strokes, which make up about 13% of strokes, arise from a burst blood vessel, depriving neurons of oxygen and nutrients.
The transient ischemic attack (TIA) is another cerebrovascular event that Steinberg touches upon. Originally defined as neurologic deficits lasting less than 24 hours, TIAs are now more accurately diagnosed with advanced imaging like MR scans, sometimes reclassified as strokes due to detectable brain abnormalities.
Steinberg also cautions about artery dissection caused by neck manipulation, such as that performed by chiropractors, which can lead to ischemic strokes by obstructing vital arterial blood flow to the brain.
Furthermore, Steinberg shares a clinical anecdote about operating on a patient with a vascular malformation in the speech area, a condition that can cause hemorrhagic strokes if it ruptures.
Risk factors for strokes include genetics, lifestyle, and medical conditions
Identifying several risk factors for strokes, Andrew Huberman and Steinberg discuss genetic predispositions like Factor V Leiden, which Huberman carries. Such mutations can lead to increased risk of clotting and bleeding, influenced by lifestyle choices and the mutation's homozygosity or heterozygosity.
They examine behavioral and health factors that can elevate stroke vulnerability, including smoking, high alcohol consumption, and drug use — especially of substances such as cocaine and methamphetamines that result in vascular damage. Huberman and Steinberg also note the involvement of medical conditions like high blood pressure, high cholesterol, and heart disease.
However, recent shifts in lifestyle choices, such as reduced smoking rates and better hypertension management, have contributed to a declining stroke incidence.
Treatments and therapies for strokes
When discussing interventions, Steinberg explains that timely treatments to restore blood flow, including clot-busting drugs and mechanical removals of clots, are critical. He mentions innovations in acut ...
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Strokes and Cerebrovascular Health
Additional Materials
Clarifications
- Factor V Leiden is a genetic mutation that increases the risk of blood clot formation. It affects the protein Factor V, making it resistant to inactivation by protein C, leading to a higher tendency for clotting. Individuals with Factor V Leiden may have an increased risk of both arterial and venous blood clots. Lifestyle choices and the specific genetic makeup of an individual can influence how this mutation impacts their health.
- Homozygosity and heterozygosity are terms used to describe the presence of identical or different versions of a gene on a pair of chromosomes. Homozygosity means having two identical copies of a particular gene, while heterozygosity means having two different versions of the gene. This genetic variation can influence the expression of traits and the risk of certain conditions. In the context of genetic mutations like Factor V Leiden, the homozygous form may have a more pronounced effect on clotting and bleeding risks compared to the heterozygous form.
- Artery dissection from neck manipulation occurs when the arteries in the neck are damaged, leading to tears in the arterial walls. This can disrupt blood flow to the brain, potentially causing a stroke. Neck manipulation, often performed by chiropractors, can sometimes result in these arterial tears, which may lead to serious health complications. It is essential to be cautious with neck manipulations, especially if there are underlying risk factors for stroke.
- Vascular malformations in the brain are abnormal tangles of blood vessels that can disrupt normal blood flow and increase the risk of hemorrhagic strokes. These malformations can weaken vessel walls over time, making them prone to rupture and bleed into the brain tissue. Depending on the type and location of the malformation, the risk of a hemorrhagic stroke varies. Treatment options for vascular malformations may include surgery, embolization, or radiation therapy to prevent future bleeding events.
- Pharmacological interventions for stroke treatment involve the use of drugs to address various aspects of stroke, such as clot dissolution and neuroprotection. These medications are often time-sensitive and aim to restore blood flow to the affected areas of the brain. Some drugs show promise in preclinical studies for their potential to improve outcomes when administered promptly after a stroke. The development of pharmacological treatments for strokes continues to be an active area of research in the field of cerebrovascular health.
- Mild hypothermia as a therapy for stroke recovery involves intent ...
Counterarguments
- While the text emphasizes the role of lifestyle choices in stroke risk, it's important to note that not all risk factors are modifiable, and some individuals with healthy lifestyles still suffer from strokes.
- The effectiveness of clot-busting drugs and mechanical clot removal can vary significantly depending on the timing of treatment and the individual's specific condition.
- The recommendation for a systolic blood pressure of 120 or lower to prevent strokes may not be suitable for all individuals, as overly aggressive blood pressure management can sometimes lead to adverse effects, especially in older adults or those with certain medical conditions.
- While physical activity and therapy are crucial for recovery, the degree of recovery can vary widely among individuals, and some may not regain their previous level of function despite intensive rehabilitation.
- The benefits of statins in reducing cognitive decline risk are still a subject of ongoing research, and there may be cases where the risks of statins outweigh the benefits, particularly concerning potential side effects.
- The use of aspirin post-stroke or TIA is generally supported, but its role in primary prevention of cardiovascular events is more controversial, with some studies suggesting a more nuanced approach based on individual risk profiles.
- The classification of TIAs and strokes based on advanced imaging may not capture the full spectrum of cerebrovascular disease, as some patients with negative imaging results may still have significant vascular pathology.
- While the text mentions the risk of arter ...
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Traumatic Brain Injuries and Concussions
The prevalence of concussions and traumatic brain injuries (TBI) in sports and other fields has led to deeper discussions on their treatment and management.
Symptoms and effects of concussions and TBIs
Steve Young's experience as a former 49ers quarterback who retired due to a bad concussion brings attention to the serious nature of head injuries. In the past, the long-term sequelae of concussions weren't fully understood, especially when they were not repeated. However, it is now known that repeated concussions can lead to chronic traumatic encephalopathy (CTE), a condition found even among high school football players who have suffered multiple concussions. Nerve cells in the brain can become injured or start dying after a head injury—in a process that could unfold over minutes to days.
Concussions can cause temporary neurological deficits like disorientation, vision changes, and imbalance
Symptoms like dizziness after hitting one's head can indicate concussions, resulting in temporary neurological deficits such as disorientation, vision changes, and imbalance.
More severe TBIs can lead to lasting neurological damage and disability
Gary Steinberg points out that more severe TBIs can cause lasting damage and disability, with evidence of CTE found in autopsies even in those who experienced multiple concussions in less impact-heavy sports like soccer, which has a surprisingly high incidence of concussions, especially in female players.
Approaches to managing and recovering from concussions/TBIs
To manage and recover from concussions and TBIs, several key practices are recommended.
Avoiding further head impacts, getting rest, and gradually resuming activity are important
Avoiding further head injury, obtaining sufficient rest without overdoing it, and gradually returning to normal activity are crucial in the aftermath of a concussion according to experts Steinberg and Huberman. In the event of a severe concussion, an MR scan might be advised, though such scans often do not reveal the molecular abnormalities associated with a concussion ...
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Traumatic Brain Injuries and Concussions
Additional Materials
Clarifications
- Chronic Traumatic Encephalopathy (CTE) is a degenerative brain condition associated with repeated head injuries. It is commonly found in athletes engaged in contact sports and military personnel with a history of head trauma. CTE can lead to cognitive and behavioral symptoms that worsen over time, eventually resulting in dementia. Diagnosis of CTE is typically confirmed post-mortem through examination of brain tissue for specific markers.
- Chronic Traumatic Encephalopathy (CTE) is a degenerative brain condition linked to repeated head injuries, particularly concussions. Autopsies can reveal physical signs of CTE in the brain, such as abnormal protein deposits and damaged nerve cells. These post-mortem examinations provide crucial evidence of the impact of head trauma on brain health. CTE is a significant concern in contact sports and has raised awareness about the long-term consequences of repetitive brain injuries.
- An MR scan, short for magnetic resonance imaging scan, is a medical imaging technique that uses a magnetic field and radio waves to create detailed images of the body's internal structures, including the brain. In the context of severe concussions, an MR scan may be recommended to assess the extent of brain injury and detect any structural abnormalities that could help guide treatment decisions. This imaging tool can provide valuable information about the brain's condition post-injury, aiding healthcare professionals in understanding the impact of the concussion on the brain's tissues. MR scans are non-invasive and can offer insights into potential complications or areas of concern following a severe concussion.
- Pre-season eye tracking is a method used in sports medicine to establish a baseline measurement of an athlete's eye movements and coordination before the start of a season. This baseline serves as a reference point for comparison in case of a head injury or concussion during the season. By comparing post-injury eye tracking results to the p ...
Counterarguments
- While repeated concussions have been linked to CTE, the relationship is not fully understood, and not everyone who experiences repeated concussions will develop CTE.
- The process by which nerve cells are injured or die after a head injury is complex and can vary greatly between individuals, with some people experiencing significant recovery and others not.
- While concussions can cause temporary neurological deficits, the duration and severity of these symptoms can vary, and some individuals may recover more quickly than others.
- The assertion that severe TBIs can cause lasting neurological damage and disability may not account for the full spectrum of recovery outcomes, as some individuals with severe TBIs can make remarkable recoveries.
- The presence of CTE in autopsies does not necessarily indicate the level of functional impairment the individual experienced during life, and the clinical significance of CTE findings is still a subject of debate.
- The recommended management strategies for concussions, such as avoiding further head impacts and getting rest, are general guidelines and may need to be tailored to the individual circumstances of each case.
- Eye tracking as a method for assessing and monitoring rec ...
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Neuroplasticity and Regenerative Treatments
Recent studies have challenged the long-standing belief that nerve cells in the brain do not regenerate after damage. Dr. Gary Steinberg shares groundbreaking research indicating that stem cells and vagus nerve stimulation are promising avenues for brain repair and functional recovery after conditions like TBI, stroke, and concussions.
Stem cell therapies show promise for promoting brain repair and functional recovery
Clinical trials have shown encouraging signs that stem cell transplantation into the brain can help patients recover functions such as control over their arms, legs, and speech, even years after a stroke. Steinberg discusses the primary ways stem cells aid in recovery, not by directly replacing damaged cells but by secreting proteins and growth factors that promote native recovery. These include angiogenesis (formation of new blood vessels), neurogenesis (growth of new nerve cells), gliogenesis (formation of glial cells), and synaptogenesis (formation of synaptic connections).
Stem cells may work by secreting growth factors and modulating the immune system, rather than directly replacing damaged cells
Stem cells, sometimes derived from bone marrow donors or fetal neural tissue, have the ability to modulate the immune system, producing an environment that encourages plasticity and the recovery of function. Steinberg emphasizes that their trial utilizing stem cells has shown that these cells are safe, effective, and do not cause tumors.
Preliminary studies suggest stem cell treatments can improve outcomes for chronic stroke and TBI patients
Almost all patients in Steinberg's trials have recovered to some degree, with many experiencing meaningful improvements. Nevertheless, he warns against clinics offering unproven treatments, such as the case in Florida where patients were blinded by unauthorized stem cell injections. The road to FDA approval and commercialization is fraught with funding challenges, and collaboration between academia and industry may be necessary to finance the costly trials required.
Vagus nerve stimulation, coupled with physical therapy, may also enhance brain plasticity and recovery
In addition to stem cell therapies, vagus nerve stimulation in conjunction with physical therapy has been FDA-approved as a treatment for chronic stroke. Contrary to previous beliefs tha ...
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Neuroplasticity and Regenerative Treatments
Additional Materials
Clarifications
- Stem cells promote brain repair by secreting proteins and growth factors that stimulate processes like angiogenesis, neurogenesis, gliogenesis, and synaptogenesis. These processes involve the formation of new blood vessels, nerve cells, glial cells, and synaptic connections, respectively. Stem cells also modulate the immune system, creating an environment conducive to recovery and plasticity. Rather than directly replacing damaged cells, stem cells support native repair mechanisms and aid in functional recovery.
- Vagus nerve stimulation involves sending electrical impulses to the vagus nerve in the neck, which has extensive connections with various brain functions. This stimulation is believed to activate specific brain areas, potentially reviving neural circuits or promoting plasticity to aid in stroke recovery or depression treatment. The exact brain regions affected by this stimulation are not fully understood, but the process involves triggering brain activity that encourages neural plasticity. This approach has shown promising results in enhancing brain plasticity and facilitating recovery in conditions like chronic stroke.
- Gaining FDA approval for treatments involves rigorous testing to ensure safety and efficacy. Clinical trials are conducted to gather data on the treatment's benefits and potential risks. The FDA reviews this data to determine if the treatment meets regulatory standards. Approval can be a lengthy process, involving collaboration between researchers, regulators, and industry partne ...
Counterarguments
- While stem cell therapies show promise, the long-term effects and potential risks are not fully understood, and more extensive research is needed to establish safety and efficacy.
- The improvements seen in patients undergoing stem cell treatments could be partially due to the placebo effect or natural recovery over time, rather than the treatment itself.
- The cost and accessibility of stem cell therapies and vagus nerve stimulation may limit their widespread use, especially in low-income regions or among underinsured populations.
- There may be ethical concerns regarding the source of stem cells, particularly those derived from fetal tissue, which could affect public acceptance and regulatory approval.
- The degree of recovery varies greatly among individuals, and not all patients may experience meaningful improvements, suggesting that these treatments may not be universally effective.
- The FDA approval of vagus nerve stimulation for chronic stroke is based on modest improvements, and it may not represent a significant ad ...
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Neuroprotective Measures
In the realm of health and wellness, neuroprotective measures are becoming increasingly pivotal for long-term brain health. Experts Dr. Huberman and Steinberg delve into lifestyle choices and therapeutic approaches that support brain health and offer neuroprotection.
Lifestyle factors that support brain health
Exercise, healthy diet, stress management, and adequate sleep are important for preventing cerebrovascular issues
Dr. Huberman stresses the importance of a sleeping environment with controlled temperature for maintaining brain health, as a cooler body temperature is needed for deep sleep, and a rise in temperature is required to wake up feeling refreshed. Steinberg and Huberman highlight the significance of blood pressure and LDL cholesterol regulation and agree that what benefits the heart also benefits the brain, emphasizing blood flow’s importance to cerebrovascular health. The incidence of stroke has decreased, in part, due to better self-care regarding exercise and other lifestyle factors.
Avoiding excess alcohol, smoking, and recreational drug use reduces stroke and TBI risks
Indulging in substances such as alcohol, cocaine, and methamphetamines is directly linked to strokes, and avoiding these substances is essential for maintaining better brain health and lowering the risks of stroke and Traumatic Brain Injury (TBI). Steinberg notes that recent studies suggest that abstaining from alcohol might be beneficial for health, countering previous beliefs that moderate drinking provided some benefits. Moderation and informed choices in lifestyle are considered crucial for longevity and brain health. Smoking and the use of hard drugs are also identified as risk factors for strokes, which should be avoided.
Therapeutic approaches that may provide neuroprotection
Mild brain cooling can block pathways of cell death and inflammation after injuries
Steinberg outlines the advantages of mild hypothermia as a multi-target therapeutic approach, which can block several detrimental pathways, such as the release of excitatory amino acids, calcium influx, inflammation, and programmed cell death. Clinical trials have shown that cooling the brain to 32-34 degrees centigrade in cases of ...
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Neuroprotective Measures
Additional Materials
Clarifications
- Regulating blood pressure and LDL cholesterol is crucial for brain health as it ensures proper blood flow to the brain, reducing the risk of cerebrovascular issues like stroke. High blood pressure can damage blood vessels in the brain, leading to cognitive decline and an increased risk of stroke. LDL cholesterol, when elevated, can contribute to the buildup of plaques in blood vessels, potentially impeding blood flow to the brain and increasing the risk of stroke and other neurological conditions. Maintaining optimal levels of these factors through lifestyle choices can support long-term brain health and reduce the risk of cerebrovascular diseases.
- Alcohol, cocaine, and methamphetamines are substances that, when abused, can significantly increase the risk of strokes. These substances can lead to various cardiovascular issues, including high blood pressure and disrupted blood flow, which are key factors in the development of strokes. Avoiding excessive consumption of alcohol and illicit drugs is crucial for maintaining brain health and reducing the risk of stroke. Studies have shown a direct link between the abuse of these substances and an elevated likelihood of experiencing a stroke.
- Mild hypothermia can help block harmful pathways after brain injuries by reducing excitatory amino acid release, limiting calcium influx, decreasing inflammation, and preventing programmed cell death. This therapeutic approach has shown promise in improving cognitive outcomes in cases of cardiac arrest or hypoxic ischemic injury. Overcooling should be avoided as it may disrupt metabolic functions and increase infection risks.
- Endogenous stem cell activation involves the body's own stem cells being stimulated to repair and regenerate damaged tissues in the brain. This process can be promoted through activities like physical exercise and cognitive t ...
Counterarguments
- While exercise and a healthy diet are generally recommended for brain health, individual responses to different types of exercise and dietary components can vary, and what is beneficial for one person may not be for another.
- The optimal temperature for sleep can be subjective and may vary from person to person; some individuals may find they sleep better in warmer or cooler conditions than the general recommendations.
- The relationship between alcohol consumption and health is complex, and some research suggests that moderate consumption of certain types of alcohol, like red wine, may have cardiovascular benefits for some individuals.
- The decrease in stroke incidence could also be attributed to improvements in healthcare access, emergency response, and advancements in medical technology, not solely to lifestyle changes.
- While avoiding smoking and hard drug use is widely accepted as beneficial for health, the impact of these substances can be influenced by genetic predispositions and other social and environmental factors.
- The benefits of mild brain cooling are still being researched, and it may not be universally effective for all types of brain injuries or for all patients.
- Overcooling risks may vary, and there might be individual differences in how patients respond to hypothermia treatment, necessitating personalized treatment protocols.
- The role of phys ...
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